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Background: Dental pulp stem cells (DPSCs) refer to a type of stem cells which is characterized by great differentiation potential and is easy to obtain. DPSCs are able to be employed for treating immune diseases and tissue regeneration. However, the differentiation ability exhibited by aging DPSCs is reduced, thereby limiting the application. As speculated by the microarray analysis, different expression of miRNAs might be involved in DPSC senescence, whereas comprehensive transcriptome level detection has been rare. Objective and Methods: To gain insights into the molecular mechanisms involved, RNA-seq, pathway enrichment and Gene Ontology Analysis were conducted on aging and young DPSCs. Results: In this study, the differences in lncRNA and mRNA expressions of the aging and young DPSCs were demonstrated, and the vital factors and the relevant pathways were speculated. On the whole, 18950 mRNAs and 21854 lncRNAs were detected, among which 14 mRNAs and 7 lncRNAs were differentially expressed. Furthermore, hsa-miR-6724-5p may be a vital node in the aging process of DPSCs, and its target genes was involved in the dopaminergic synapse. Conclusion: In brief, the aging of DPSCs was significantly dependent of different expressed genes (DEGs) which is related to dopaminergic synapse. However, the specific function and internal relationship of the DEGs should be verified in depth.

The present work aims to evaluate the tolerance, osmoregulation, metabolism, and antioxidant ability of saline water immersed grass goldfish (Carassius auratus) during the recovery in freshwater. Grass goldfish (38.15 ±5.48g) acclimated in freshwater were immersed by two salinities (20 ‰ or 30 ‰) for different time durations (10min, 20min, 30min, and 60min); and the physiological stress responses were measured during a recovery period of 24 h. Resultly, osmotic pressure kept unchanged in all treated fish, whereas the decline of sodium ions, potassium ions, and the ratio of Na+/Cl- was observed in saline treated fish. Differently, concentrations of chloride ion in saline treated fish were higher than control fish, but decreased as recovery time went. Soon after freshwater recovery, the gill Na+/K+—ATPase in saline treated fish kept lower than control group except for the fish immersed by salinity 20 for 10 – 30 min. Specifically, gill Na+/K+—ATPase levels showed a decreased trend in all saline treated fish, but the mRNA of NKA-α and NKA-β both significantly increased at 1h and 6h in salinity 20 treated fish.Compared with control group, cortisol levels were increased in all salinity 20 treated fish at 1h of recovery, but then gradually declined. However, in salinity 30 treated group, cortisol levels showed a rise trend and maintained high levels until 24 h post recovery. As for serum lactic acid, fish treated by salinity 20 for 10 or 20 min did not show any fluctuation. Whereas there was a rise trend of lactic acid in fish immersed by salinity 20 for 30 min and 60 min as recovery time went on. Fish treated by salinity 30 exhibited a relative high level of serum lactic acid at 1h and then gradually decreased at 24 post recovery. What’s more, antioxidant capacities were higher at salinity 20 treated fish than salinity 30 immersed fish. The limited results indicated that grass goldfish could well osmoregulate and survive by immersion in salinity 20 less than 60 min or salinity 30 less than 30min, even though immersion by salinity 20 could minimize the negative effect.

Under the influence of the epidemic, the number of tourists and the overall income of the Gulongshan Grand Canyon has been greatly reduced, which also highlights the problem that the Gulongshan Grand Canyon is susceptible to external factors due to its sensitivity and vulnerability. Two years after the start of the epidemic, it was not able to resume development. In the late stage of the epidemic, the domestic epidemic entered a state of steady development, but there were still cases of infection rebounding. At the same time, the overseas epidemic has spread widely and entered a state of high incidence of cases. The Guangxi Gulongshan tourism market itself has not fully recovered, and the development of the overseas tourism market has been restricted, making the recovery of the Gulongshan Grand Canyon even more difficult. The traditional development is also severely limited, so we will use the 4P and swot theory to analyze the current situation of the Gulongshan Grand Canyon, and at the same time refer to the literature review at home and abroad, correctly view the challenges brought by these epidemics, seize the emerging opportunities, and discuss The strategy for the recovery and development of the Gulongshan Grand Canyon after the outbreak of the epidemic will promote the innovation and sustainable development of the Gulongshan Grand Canyon. This topic includes the following aspects: one is to analyze the current situation of the impact of the epidemic on the Gulongshan Grand Canyon scenic spot; the second is the opportunities and challenges faced by the Gulongshan Grand Canyon in the post-epidemic era; the third is the countermeasures and suggestions for the marketing of the Gulongshan Grand Canyon in the post-epidemic era. This paper completes the writing of this topic from these three aspects.

As a novel sales strategy, live-streamed selling has drawn considerable interest. In this paper, we study a dual-channel live-streaming supply chain consisted of a single manufacturer, a moderate live streamer and a live-streaming platform. We construct two scenarios, the retail live streaming and commissioned live streaming modes, under manufacturer self-live streaming and investigates the optimal mode with the Stackelberg games. The study discovers: (1) Under the commissioned live streaming mode, the price of Internet celebrity live streaming is less expensive than that under manufacturer self-live streaming within a specific commission ratio and is proportionate to the commission ratio. (2) Under the retail live streaming mode, only when consumers' preferences are more concentrated on the manufacturer self-live streaming, the price of Internet celebrity live streaming is less than the manufacturer self-live stream channel. (3) In both scenarios, Internet celebrity live-streaming sales effort is consistently lower than the manufacturer self-live stream channel. Additionally, the consumer's sensitivity coefficient and the trust degree in Internet-celebrity streamer, the personal impact of Internet-celebrity streamer, and the proportion of impulsive consumers are all positively correlated with the price, sales effort, and profit of both channels.

Cytospora canker, caused by Cytospora mali, is the most destructive disease in production of apples (Malus domestica). Adding potassium (K) to apple trees can effectively control this disease. However, the underlying mechanisms of apple resistance to C. mali under high-K (HK) status remain unknown. Here, we found that HK (9.30 g/kg) apple tissues exhibited high disease resistance. The resistance was impeded when blocking K channels, leading to susceptibility even under HK conditions. We detected a suite of resistance events in HK apple tissues, including upregulation of resistance genes, callose deposition, and formation of ligno-suberized tissues. Further multiomics revealed that the phenylpropanoid pathway was reprogrammed by increasing K content from low-K (LK, 4.30 g/kg) status, leading to increases of 18 antifungal chemicals. Among them, the physiological concentration of coumarin (1,2-benzopyrone) became sufficient to inhibit C. mali growth in HK tissues, and exogenous application could improve the C. mali resistance of LK apple branches. Transgenic apple calli overexpressing beta-glucosidase 40 (MdBGLU40), which encodes the enzyme for coumarin synthesis, contained higher levels of coumarin and exhibited high resistance to C. mali even under LK conditions. Conversely, the suppression of MdBGLU40 through RNAi reduced coumarin content and resistance in HK apple calli, supporting the importance of coumarin accumulation in vivo for apple resistance. Moreover, we found that the upregulation of transcription factor MdMYB1r1 directly activated MdBGLU40 and the binding affinity of MdMYB1r1 to the MdBGLU40 promoter increased in HK apple tissue, leading to high levels of coumarin and resistance in HK apple. Overall, we found that the accumulation of defensive metabolites strengthened resistance in apple when raising K from insufficient to optimal status, and these results highlight the optimization of K content in fertilization practices as a disease management strategy.

Purpose To summarize the magnetic resonance imaging manifestations of hepatocellular carcinoma (HCC) with and without progression after stereotactic body radiation therapy (SBRT) and evaluate the treatment effect using the modified Liver Reporting and Data System (LI-RADS). Methods Between January 2015 and December 2020, 102 patients with SBRT-treated HCC were included. Tumor size, signal intensity, and enhancement patterns at each follow-up period were analyzed. Three different patterns of enhancement: APHE and wash-out, non-enhancement, and delayed enhancement. For modified LI-RADS, delayed enhancement with no size increase were considered to be a “treatment-specific expected enhancement pattern” for LR-TR non-viable. Results Patients were divided into two groups: without (n = 96) and with local progression (n = 6). Among patients without local progression, APHE and wash-out pattern demonstrated conversion to the delayed enhancement (71.9%) and non-enhancement (20.8%) patterns, with decreased signal intensity on T1WI(92.9%) and DWI(99%), increased signal intensity on T1WI (99%), and decreased size. The signal intensity and enhancement patterns stabilized after 6–9 months. Six cases with progression exhibited tumor growth, APHE and wash-out, and increased signal intensity on T2WI/DWI. Based on the modified LI-RADS criteria, 74% and 95% showed LR-TR-nonviable in 3 and 12 months post-SBRT, respectively. Conclusions After SBRT, the signal intensity and enhancement patterns of HCCs showed a temporal evolution. Tumor growth, APHE and wash-out, and increased signal intensity on T2WI/DWI indicates tumor progression. Modified LI-RADS criteria showed good performance in evaluating nonviable lesions after SBRT.

Background: Alzheimer’s disease (AD) disturbs many patients and family. However, little progress has been made in finding effective treatments. Given AD is a multifactorial disease, luteolin and exercise combination therapy may be more effective than monotherapy. Objective: To explore the therapeutic effect and underlying mechanisms of luteolin and exercise combination therapy in AD treatment. Methods: This study utilized a validated mouse model of AD by bilateral injection of amyloid-β (Aβ)1-42 oligomers into the CA1 region of the hippocampus. By combining with animal behavioral test, thioflavin T detection, immunofluorescence and western blot test, the cognitive-enhancing effects of luteolin and exercise combination therapy and the underlying mechanisms were investigated. Results: Luteolin (100 mg/kg/d) combined with exercise could significantly improve the performance of AD model mice in novel object recognition test, and the improvement was greater than that of monotherapy. Further experiments showed that luteolin and exercise alone or in combination could reverse the increase of Aβ content, the activation of astrocytes and microglia, and the decrease of the level of autophagy in hippocampus and cortex in AD model induced by Aβ1-42 oligomers. While the combination therapy involved more intact hippocampal and cortical areas, with greater degree of changes. Conclusion: Luteolin and exercise combination therapy prevented Aβ1-42 oligomers-induced cognitive impairment, possibly by decreasing neuroinflammation and enhancing autophagy. The luteolin and exercise combination therapy may be a useful therapeutic option for preventing and/or delaying the progression of memory dysfunction of AD.

Background: Parkinson’s disease (PD) is the second most common neurodegenerative disease with a significant public health burden. It is characterized by the gradual degeneration of dopamine neurons in the central nervous system. Although symptomatic pharmacological management remains the primary therapeutic method for PD, clinical experience reveals significant inter-individual heterogeneity in treatment effectiveness and adverse medication responses. The mechanisms behind the observed interindividual variability may be elucidated by investigating the role of genetic variation in human-to-human variances in medication responses and adverse effects. Objective: This review aims to explore the impact of gene polymorphism on the efficacy of antiparkinsonian drugs. The identification of factors associated with treatment effectiveness variability might assist the creation of a more tailored pharmacological therapy with higher efficacy, fewer side outcomes, and cheaper costs. Methods: In this review, we conducted a thorough search in databases such as PubMed, Web of Science, and Google Scholar, and critically examined current discoveries on Parkinson's disease pharmacogenetics. The ethnicity of the individuals, research methodologies, and potential bias of these studies were thoroughly compared, with the primary focus on consistent conclusions. Results: This review provides a summary of the existing data on PD pharmacogenetics, identifies its limitations, and offers insights that may be beneficial for future research. Previous studies have investigated the impact of gene polymorphism on the effectiveness and adverse effects of levodopa. The trendiest genes are the COMT gene, DAT gene, and DRD2 gene. However, limited study on other anti-Parkinson's drugs has been conducted. Conclusion: Therefore, In order to develop an individualized precision treatment for PD, it is an inevitable trend to carry out multi-center, prospective, randomized controlled clinical trials of PD pharmacogenomics covering common clinical anti-PD drugs in large, homogeneous cohorts.