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Exploring the spatial distribution of tourist attractions and comprehending the spatio-temporal behaviors of tourists within tourist attractions can provide local planning agencies, destination marketing organizations, and government departments with essential evidence for decision-making processes. This study examines the spatio-temporal behavior patterns of tourists in the Kushan Scenic Area by analyzing GPS trajectory data acquired from social media platforms. The investigation primarily utilizes three research methodologies: grid analysis, Markov chain, and K-means clustering. The grid analysis results reveal three spatial distribution patterns within the scenic area, while the outcomes from the Markov chain and K-means clustering delineate six tourist movement patterns, along with three choices regarding travel time. This finding holds significant practical implications for enhancing the attractiveness of scenic areas, optimizing spatial layout, and improving tourists’ experiences.

As China’s urbanization progresses, the urban heat island (UHI) effect has become more pronounced, impacting the health of residents and the activity intentions of visitors within historic urban areas. This study focuses on the historic district of the Three Lanes and Seven Alleys Tourist Area (SFQX) in Fuzhou, where simulations were conducted on four representative streets across various times during a typical summer meteorological day. Typological methods were employed to simplify neighborhood modeling, and Phoenics software was utilized to simulate the neighborhood’s wind environment and the outdoor pedestrian thermal comfort index. Aspect ratio (AR), sky view factor (SVF), air velocity (Va), and universal thermal climate index (UTCI) values at specific locations were collected for statistical analysis. The findings reveal that: (1) the N–S orientation exhibits more significant correlations between Va, the UTCI, and street geometry compared to the E–W orientation; (2) the relationship between SVF and the UTCI fluctuates with time; (3) areas with higher AR values, such as medium and deep canyons, offer better thermal comfort for outdoor pedestrians; and (4) at 8:00, the UTCI and wind speed show minimal correlations with street geometry and direction, being predominantly influenced by objective climatic factors. These insights are expected to significantly inform the geometric design and planning of streets in Fuzhou’s historic districts, aiming to create more comfortable outdoor environments for inhabitants and visitors alike.

Multiple myeloma (MM) is a hematological malignancy characterized by the unrestricted proliferation of plasma cells that secrete immunoglobulin in the bone marrow. Extracted primarily from Anemone raddeana regel , Raddeanin A (RA) is a natural triterpenoid saponin compound with anti-inflammatory and anti-tumor activities. However, most research on the anti-tumor effects of RA has concentrated on solid tumors, with little exploration into non-solid tumors like MM. Furthermore, there is a dearth of research investigating the interplay between RA and MM, encompassing their interaction targets and mechanisms. This study aims to delve into the biological activity and molecular mechanism of RA’s anti-MM properties through the lens of network pharmacology and experimental validation. The findings from GO enrichment analysis, KEGG enrichment analysis, and molecular docking prediction suggested a potential correlation between the MAPK signaling pathway, including the MAPK1 gene (also known as ERK2), and the impact of RA on MM. Results from the CCK-8 assay revealed a time-dependent and concentration-dependent inhibition of proliferation in MM cell lines treated with RA. Notably, in the cell lines used for the test, the IC50 values for MM.1 S cells were 1.616 µM at 24 H and 1.058 µM at 48 H, for MM.1R cells were 3.905 µM at 24 H and 2.18 µM at 48 H, while for RPMI 8226 cells, they were 6.091 µM at 24 H and 3.438 µM at 48 H. The PI, Annexin V-FITC/PI, and JC-1 staining showed that RA could arrest the cell cycle in the G2 phase, cause apoptosis, and induce the change of mitochondrial membrane potential (MMP) in MM cells. Treated with RA, the Western blot analysis showed that the expression levels of Bim, Cleaved Caspase 3/9, and Cleaved PARP were increased, and the expression level of Mcl-1 was decreased in MM cells. Concurrently, the phosphorylated protein expression levels of p-ERK1/2, p-MSK1, p-P90RSK, and p-MEK1/2 were diminished following RA treatment. These results suggest that RA has the activity of anti-MM, and the MAPK/ERK signaling pathway is involved in the growth inhibition effect of RA on MM cells via cycle arrest and mitochondrial-pathway-dependent apoptosis.

Urban noise pollution poses a significant obstacle to sustainable development by compromising public health and well-being. Within this context, the soundscape emerges as a critical component in creating healthier and more livable cities. To further investigate the relationship between urban land-use planning characteristics and soundscape distribution, this study examines the spatial distribution of urban soundscapes and urban spatial functions. It explores the influence of urban land-use types on both the acoustic environment and soundscape perception and evaluation, aiming to better understand the influencing factors and dynamics of composite soundscapes in urban environments. The results show that (a) acoustic environment characteristics and soundscape perception evaluations are influenced by urban land-use function, exhibit a spatial aggregation effect, and are affected by the surrounding environment. (b) The key acoustic indices affecting the perception and evaluation of urban soundscapes are the equivalent continuous A-weighted sound pressure level (L[sub.Aeq]), the background sound level (L[sub.90]), the difference between C-weighted and A-weighted levels (L[sub.C]–L[sub.A]), and loudness. People perceive quiet environments more positively and report strong discomfort in noisy environments. (c) Urban land-use planning significantly impacts the urban soundscape, with significant differences observed in both the acoustic environment and soundscape perception evaluations across different land-use types. This study deepens the understanding of the acoustic environment and demonstrates that soundscape-oriented land-use planning can function as an effective tool for fostering inclusive, healthy, and socially sustainable communities.

With the increasing frequency of extreme disasters, effectively utilizing park green spaces in both daily life and disaster scenarios has emerged as a new challenge, particularly in county-level cities. In this context, the core planning area of Anxi County in Quanzhou was selected as the study site. By adjusting the layout and scale of park green spaces, this research investigates how such modifications influence the quality of the urban wind environment and green space accessibility in county-level cities. The results show the following: (1) Under the vegetation ratio of trees–shrubs–herbaceous plants, the ventilation performance of the urban wind environment improved at a daily wind speed of 5 m/s. The wind speed increased from the current low base speed (0–1 m/s) to a moderate speed (2–5 m/s), significantly enhancing the comfort of the population. (2) Under the vegetation ratio of trees–shrubs–herbaceous plants, the overall disaster-prevention performance of the county improved. During typhoon wind speeds (50 m/s), the wind speed gradually decreased from partially higher speeds (40–50 m/s) to lower speeds (10–20 m/s), resulting in a significant improvement in the wind environment. (3) After optimizing the layout of park green spaces, accessibility was greatly enhanced, better meeting the needs of the population in the developed area.

TiO2 was employed as the waste form for disposal of simulated nuclide Sr. Preparation of Sr bearing rutile was explored under different sintering temperatures and Sr contents. The optimal treatment temperature was confirmed as 1300 ℃ for the incorporation of SrO in rutile Ti O2. Perovskite type Sr TiO3 was prepared as the resultant product. The limited containment capacity of SrO in rutile was speculated to be 56.5wt%. As the SrO content increases, the as-synthesized sample exhibits more porosity because Sr TiO3 phase demonstrates higher density than rutile and SrO. The 28 day normalized leaching rate（LRi） of Sr and Ti will decrease congruously as the SrO incorporation increases. The LRSr value is lower than 0.1g·m^-2·d^-1, which is about 3 orders of magnitude higher than the LR（Ti） value.

Spermatogonial stem cells （SSCs） can produce numerous male gametes after transplantation into recipient testes, presenting a valuable approach for gene therapy and continuous production of gene-modified animals. However, successful genetic manipulation of SSCs has been limited, partially due to complexity and low efficiency of currently available genetic editing techniques. Here, we show that efficient genetic modifications can be introduced into SSCs using the CRISPR-Cas9 system. We used the CRISPR-Cas9 system to mutate an EGFP transgene or the endogenous Crygc gene in SCCs. The mutated SSCs underwent spermatogenesis after transplantation into the seminiferous tubules of infertile mouse testes. Round spermatids were generated and, after injection into mature oocytes, supported the production of heterozygous offspring displaying the corresponding mutant phenotypes. Furthermore, a disease-causing mutation in Crygc （Crygc-/-） that pre-existed in SSCs could be readily repaired by CRISPR-Cas9-induced nonhomologous end joining （NHEJ） or homology-directed repair （HDR）, resulting in SSC lines carrying the corrected gene with no evidence of off-target modifications as shown by whole-genome sequencing. Fertilization using round spermatids generated from these lines gave rise to offspring with the corrected phenotype at an efficiency of 100%. Our results demonstrate efficient gene editing in mouse SSCs by the CRISPR-Cas9 system, and provide the proof of principle of curing a genetic disease via gene correction in SSCs.

Inflammatory bowel disease （IBD） is an important factor in the induction of colon cancer, but its mechanism is unclear. Colitis and colitis-associated colorectal cancer （CAC） models induced using both dextran sulfate sodium （DSS） and the azoxymethane/DSS protocol were established in wild-type （WT） and CTRP4 transgenic （CTRP4-tg） C57BL6/J mice. Body weight, stool consistency and the presence of blood in the stool were analyzed; tumor quantity, size and histological characteristics were analyzed during the development of CAC. The CTRP4-tg mice exhibited significantly reduced colitis and developed far fewer macroscopic tumors; these tumors were smaller in size, and a majority of the colon tumors in these mice were restricted to the superficial mucosa. Tumors of lower grades were observed in the CTRP4-tg mice. Interleukin-6 was markedly downregulated in the CTRP4-tg mice during CAC tumorigenesis. The phosphorylation of ERK, signal transducer and activator of transcription 3 and Akt in the colon and the proliferation of intestinal epithelial cells were decreased in the CTRP4-tg mice. The injection of recombinant CTRP4 protein significantly reduced the colitis symptoms of the WT mice. CTRP4 plays an important role in inflammation and inflammation-associated colon tumorigenesis, and our research may provide a novel method for the treatment of IBD and CAC.

Background Mounting evidence indicates that long noncoding RNAs (lncRNAs) could play a pivotal role in cancer biology. However, the overall biological role and clinical significance of PVT1 in gastric carcinogenesis remains largely unknown. Methods Expression of PVT1 was analyzed in 80 GC tissues and cell lines by qRT-PCR. The effect of PVT1 on proliferation was evaluated by MTT and colony formation assays, and cell apoptosis was evaluated by Flow-cytometric analysis. GC cells transfected with sh PVT1 were injected into nude mice to study the effect of PVT1 on tumorigenesis in vivo. RIP was performed to confirm the interaction between PVT1 and EZH2. ChIP was used to study the promoter region of related genes. Results The higher expression of PVT1 was significantly correlated with deeper invasion depth and advanced TNM stage. Multivariate analyses revealed that PVT1 expression served as an independent predictor for overall survival (p = 0.031). Further experiments demonstrated that PVT1 knockdown significantly inhibited the proliferation both in vitro and in vivo. Importantly, we also showed that PVT1 played a key role in G1 arrest. Moreover, we further confirmed that PVT1 was associated with enhancer of zeste homolog 2 (EZH2) and that this association was required for the repression of p15 and p16. To our knowledge, this is the first report showed that the role and the mechanism of PVT1 in the progression of gastric cancer. Conclusions Together, these results suggest that lncRNA PVT1 may serve as a candidate prognostic biomarker and target for new therapies in human gastric cancer.

Background Accumulating evidence indicates that the long non-coding RNA HOTAIR plays a critical role in cancer progression and metastasis. However, the overall biological role and clinical significance of HOTAIR in gastric carcinogenesis remains largely unknown. Methods HOTAIR expression was measured in 78 paired cancerous and noncancerous tissue samples by real-time PCR. The effects of HOTAIR on gastric cancer cells were studied by overexpression and RNA interference approaches in vitro and in vivo. Insights of the mechanism of competitive endogenous RNAs (ceRNAs) were gained from bioinformatic analysis, luciferase assays and RNA binding protein immunoprecipitation (RIP). The positive HOTAIR/HER2 interaction was identified and verified by immunohistochemistry assay and bivariate correlation analysis. Results HOTAIR upregulation was associated with larger tumor size, advanced pathological stage and extensive metastasis, and also correlated with shorter overall survival of gastric cancer patients. Furthermore, HOTAIR overexpression promoted the proliferation, migration and invasion of gastric carcinoma cells, while HOTAIR depletion inhibited both cell invasion and cell viability, and induced growth arrest in vitro and in vivo. In particular, HOTAIR may act as a ceRNA, effectively becoming a sink for miR-331-3p, thereby modulating the derepression of HER2 and imposing an additional level of post-transcriptional regulation. Finally, the positive HOTAIR/HER2 correlation was significantly associated with advanced gastric cancers. Conclusions HOTAIR overexpression represents a biomarker of poor prognosis in gastric cancer, and may confer malignant phenotype to tumor cells. The ceRNA regulatory network involving HOTAIR and the positive interaction between HOTAIR and HER2 may contribute to a better understanding of gastric cancer pathogenesis and facilitate the development of lncRNA-directed diagnostics and therapeutics against this disease.