Comprehensive genomic analysis of puerarin in inhibiting bladder urothelial carcinoma cell proliferation and migration.

BACKGROUND: Bladder urothelial carcinoma (BUC) ranks second in the incidence of urogenital system tumors, and the treatment of BUC needs to be improved. Puerarin, a traditional Chinese medicine (TCM), has been shown to have various effects such as anti-cancer effects, the promotion of angiogenesis, and anti-inflammation. This study investigates the effects of puerarin on BUC and its molecular mechanisms. METHODS: Through GeneChip experiments, we obtained differentially expressed genes (DEGs) and analyzed these DEGs using the Ingenuity® Pathway Analysis (IPA®), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) pathway enrichment analyses. The Cell Counting Kit 8 (CCK8) assay was used to verify the inhibitory effect of puerarin on the proliferation of BUC T24 cells. String combined with Cytoscape® was used to create the Protein-Protein Interaction (PPI) network, and the MCC algorithm in cytoHubba plugin was used to screen key genes. Gene Set Enrichment Analysis (GSEA®) was used to verify the correlation between key genes and cell proliferation. RESULTS: A total of 1617 DEGs were obtained by GeneChip. Based on the DEGs, the IPA® and pathway enrichment analysis showed they were mainly enriched in cancer cell proliferation and migration. CCK8 experiments proved that puerarin inhibited the proliferation of BUC T24 cells, and its IC50 at 48 hours was 218µmol/L. Through PPI and related algorithms, 7 key genes were obtained: ITGA1, LAMA3, LAMB3, LAMA4, PAK2, DMD, and UTRN. GSEA showed that these key genes were highly correlated with BUC cell proliferation. Survival curves showed that ITGA1 upregulation was associated with poor prognosis of BUC patients. CONCLUSION: Our findings support the potential antitumor activity of puerarin in BUC. To the best of our knowledge, bioinformatics investigation suggests that puerarin demonstrates anticancer mechanisms via the upregulation of ITGA1, LAMA3 and 4, LAMB3, PAK2, DMD, and UTRN, all of which are involved in the proliferation and migration of bladder urothelial cancer cells.

Research progress of therapeutic effects and drug resistance of immunotherapy based on PD-1/PD-L1 blockade.

The binding of programmed death-1 (PD-1) on the surface of T cells and PD-1 ligand 1 (PD-L1) on tumor cells can prevent the immune-killing effect of T cells on tumor cells and promote the immune escape of tumor cells. Therefore, immune checkpoint blockade targeting PD-1/PD-L1 is a reliable tumor therapy with remarkable efficacy. However, the main challenges of this therapy are low response rate and acquired resistance, so that the outcomes of this therapy are usually unsatisfactory. This review begins with the description of biological structure of the PD-1/PD-L1 immune checkpoint and its role in a variety of cells. Subsequently, the therapeutic effects of immune checkpoint blockers (PD-1 / PD-L1 inhibitors) in various tumors were introduced and analyzed, and the reasons affecting the function of PD-1/PD-L1 were systematically analyzed. Then, we focused on analyzing, sorting out and introducing the possible underlying mechanisms of primary and acquired resistance to PD-1/PD-L1 blockade including abnormal expression of PD-1/PD-L1 and some factors, immune-related pathways, tumor immune microenvironment, and T cell dysfunction and others. Finally, promising therapeutic strategies to sensitize the resistant patients with PD-1/PD-L1 blockade treatment were described. This review is aimed at providing guidance for the treatment of various tumors, and highlighting the drug resistance mechanisms to offer directions for future tumor treatment and improvement of patient prognosis.

[Efficiency and safety of microsurgical cluster ligation of the spermatic vein].

OBJECTIVE: To study the effect and safety of microscopic varicocele cluster ligation (MVCL). METHODS: We selected 28 patients undergoing bilateral microscopic spermatic vein ligation in Xuzhou Central Hospital from July 2021 to June 2022. Using the computerized randomization method, we performed MVCL or microscopic varicocele ligation (MVL) for the right or the left spermatic cord, respectively. We recorded the operation time, intraoperative blood loss, the numbers of the spermatic veins ligated and the arteries and lymphatic vessels preserved in each surgical side. A surgeon unaware of the surgical approach on the operative side collected the Visual Analogue Scale (VAS) pain scores, nodular foreign body sensation, relief of scrotal cramps, complications, and long-term recurrence from the patients. RESULTS: Compared with the MVL group, the MVCL group showed significantly shorter time for spermatic vein ligation (ï¼»56.21±13.96ï¼½ vs ï¼»31.43±10.13ï¼½ min, P<0.01), lower VAS scores on the 1st postoperative day (P <0.05) and a lower incidence of intra-scrotal nodular foreign body sensation in the 1st postoperative month (P <0.05). There were no statistically significant differences in the intraoperative blood loss, numbers of spermatic veins ligated and arteries and lymphatic vessels preserved, VAS scores at 3 and 7 postoperative days, incidence of complications and long-term recurrence between the two groups (P >0.05). CONCLUSION: MVCL is superior to MVL in reducing the time of spermatic vein ligation and improving the efficiency, efficacy and safety of the procedure, and therefore worthy of clinical promotion.

Role of protein phosphorylation in cell signaling, disease, and the intervention therapy.

Protein phosphorylation is an important post-transcriptional modification involving an extremely wide range of intracellular signaling transduction pathways, making it an important therapeutic target for disease intervention. At present, numerous drugs targeting protein phosphorylation have been developed for the treatment of various diseases including malignant tumors, neurological diseases, infectious diseases, and immune diseases. In this review article, we analyzed 303 small-molecule protein phosphorylation kinase inhibitors (PKIs) registered and participated in clinical research obtained in a database named Protein Kinase Inhibitor Database (PKIDB), including 68 drugs approved by the Food and Drug Administration of the United States. Based on previous classifications of kinases, we divided these human protein phosphorylation kinases into eight groups and nearly 50 families, and delineated their main regulatory pathways, upstream and downstream targets. These groups include: protein kinase A, G, and C (AGC) and receptor guanylate cyclase (RGC) group, calmodulin-dependent protein kinase (CaMK) group, CMGC [Cyclin-dependent kinases (CDKs), Mitogen-activated protein kinases (MAPKs), Glycogen synthase kinases (GSKs), and Cdc2-like kinases (CLKs)] group, sterile (STE)-MAPKs group, tyrosine kinases (TK) group, tyrosine kinase-like (TKL) group, atypical group, and other groups. Different groups and families of inhibitors stimulate or inhibit others, forming an intricate molecular signaling regulatory network. This review takes newly developed new PKIs as breakthrough point, aiming to clarify the regulatory network and relationship of each pathway, as well as their roles in disease intervention, and provide a direction for future drug development.

ERH Interacts With EIF2α and Regulates the EIF2α/ATF4/CHOP Pathway in Bladder Cancer Cells.

Background: There is a lack of research on the molecular interaction of the enhancers of rudimentary homolog (ERH) in bladder cancer (BC) cells. This study aimed to determine the interacting proteins of ERH in human T24 cells. Methods: First, the ERH gene was overexpressed in human T24 cells. Coimmunoprecipitation (co-IP) and shotgun mass spectrometry (MS) analyses were performed to obtain a list of proteins that interact with ERH. Subsequently, bioinformatic analyses with Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein interaction (PPI) studies were performed to analyze the ERH-interactive protein list (ERH-IPL). Then, we selected one of the interacting proteins, EIF2α for verification. An immunofluorescence colocalization assay was performed to validate the co-expression of the selected protein, and the binding sites of the two proteins were predicted by ZDOCK technology. Finally, PCR analysis on the downstream molecules of the interacting protein was performed for verification. Results: ERH protein was successfully overexpressed in human T24 cells. We obtained a list of 205 proteins that might directly or indirectly interact with the ERH protein by mass spectrometric analysis. The bioinformatic analysis showed that ERH-interacting proteins were related to "ribonucleoprotein complex", "ATPase activity", "nuclear speck", and "translation factor activity, RNA binding". We further identified one of the key genes, EIF2S1, and confirmed that the corresponding protein EIF2α is co-expressed and may bind with ERH in human T24 cells. The mRNA levels of molecules ATF4 and CHOP were found to be upregulated by ERH. Conclusion: ERH protein affects "ribonucleoprotein complex", "ATPase activity", "nuclear speck", and "translation factor activity, RNA binding". The ERH protein can interact with EIF2α and regulate the EIF2α-ATF4/CHOP signaling pathway in human T24 cells.

Effects of Multimedia Assisted Song Integrated Teaching on College Students' English Learning Interests and Learning Outcomes.

In the process of globalization, the English language not only represents British and American culture, but it has also gradually become a language used all over the world, and it has become essential for many people to learn it as a second language. Education is the century business of a nation. At the same time, to meet the needs of E generation, I generation, and touch-screen generation students, teachers are increasingly undertaking multimedia-integrated curriculum design and instruction. Teachers are no longer knowledge providers, but they are expected to provide students with a personalized learning model and guide and support them in a timely manner. This study included a sample of business students from Guilin University of technology. A total of 216 students participated in a 16-week (3 h per week, a total of 48 h) course of experimental teaching. The research results showed that 1. multimedia assisted, song integrated English teaching affected learning interest, 2. That multimedia assisted, song integrated English teaching affected learning outcomes, and 3. That learning interest had significantly positive effects on learning outcome. Based on these results, this study contributes to improving college students' English listening, speaking, reading, and writing skills via multimedia teaching, which also facilitated their interest and ability to achieve the learning outcomes.

ERH Gene and Its Role in Cancer Cells.

Cancer is a major public health problem worldwide. Studies on oncogenes and tumor-targeted therapies have become an important part of cancer treatment development. In this review, we summarize and systematically introduce the gene enhancer of rudimentary homolog (ERH), which encodes a highly conserved small molecule protein. ERH mainly exists as a protein partner in human cells. It is involved in pyrimidine metabolism and protein complexes, acts as a transcriptional repressor, and participates in cell cycle regulation. Moreover, it is involved in DNA damage repair, mRNA splicing, the process of microRNA hairpins as well as erythroid differentiation. There are many related studies on the role of ERH in cancer cells; however, there are none on tumor-targeted therapeutic drugs or related therapies based on the expression of ERH. This study will provide possible directions for oncologists to further their research studies in this field.

Discussion of Students' E-book Reading Intention With the Integration of Theory of Planned Behavior and Technology Acceptance Model.

The emergence of e-books with the characteristics of easy access and reading any time anywhere is a subject of debate in academia. Topics include the use of e-books in libraries, their use in support teaching, new possibilities for reading activities, potential uses for library archives, and the motivation and intention of e-book users. Students at Guilin University of Technology participated in a survey. Of the 300 copies of the questionnaire distributed, 263 valid copies were returned, a retrieval rate of 88%. The research results show that (1) Usability and reading need are the key factors in e-book usage. Usability refers to convenient keyword searches, portability, and any time reading. E-books are considered to make searching and reading large amounts of data easier. (2) E-books are not restricted to time and space so that the overall reading quantity is increasing. Readers become accustomed to reading e-books, and the quality of their digital reading is gradually enhanced. (3) Students should complete e-book use courses offered by libraries to enhance their familiarity with e-books and their use of e-book software, thereby enhancing postgraduate student readers' e-book information literacy. The results of the research prompt suggestions to enhance the promotion of reading and e-book information to encourage student readers' e-book reading intention.

Decoupling of Medical Public-Private Partnership Efficiency and Pollution to Improve Public Health: A Three-Stage DEA Analysis.

This study investigates the spatiotemporal evolution of the efficiency of medical public-private partnerships (PPPs) and the decoupling of environmental pollution to promote public health, balanced development, and environmentalism. Based on the 2011-2020 data of medical PPPs in China, the results of a three-stage data envelopment analysis (DEA) and decoupling model show that, firstly, the spatiotemporal evolution of PPP efficiency of China in healthcare has forward periodic twists and turns, and alternating peaks and valleys, which fall into two stages: extensive development, and transformation and upgrading. Secondly, this development is either a type of stable, steady or a surge increase. Thirdly, PPP efficiency and environmental pollution show a weak decoupling state. That is, Northeast China (NEC) and Southwest China (SWC) are in a state of increasing connection, whereas Northwest China (NWC) is in an expanding negative decoupling state. The remaining regions are in a weak decoupling state. This study recommends the mode of ecology-oriented development (EOD) to promote a high-quality, integrated development of PPPs in medicine and healthcare that are especially conducive to a "green economy." There should be a more coordinated development across regions in China as well.

Xanthatin induces glioma cell apoptosis and inhibits tumor growth via activating endoplasmic reticulum stress-dependent CHOP pathway.

Xanthatin is a natural sesquiterpene lactone purified from Xanthium strumarium L., which has shown prominent antitumor activity against a variety of cancer cells. In the current study, we investigated the effect of xanthatin on the growth of glioma cells in vitro and in vivo, and elucidated the underlying mechanisms. In both rat glioma C6 and human glioma U251 cell lines, xanthatin (1-15 µM) dose-dependently inhibited cell viability without apparent effect on the cell cycle. Furthermore, xanthatin treatment dose-dependently induced glioma cell apoptosis. In nude mice bearing C6 glioma tumor xenografts, administration of xanthatin (10, 20, 40 mg·kg-1·d-1, ip, for 2 weeks) dose-dependently inhibited the tumor growth, but did not affect the body weight. More importantly, xanthatin treatment markedly increased the expression levels of the endoplasmic reticulum (ER) stress-related markers in both the glioma cell lines as well as in C6 xenografts, including glucose-regulated protein 78, C/EBP-homologous protein (CHOP), activating factor 4, activating transcription factor 6, spliced X-box binding protein-1, phosphorylated protein kinase R-like endoplasmic reticulum kinase, and phosphorylated eukaryotic initiation factor 2a. Pretreatment of C6 glioma cells with the ER stress inhibitor 4-phenylbutyric acid (4-PBA, 7 mM) or knockdown of CHOP using small interfering RNA significantly attenuated xanthatin-induced cell apoptosis and increase of proapoptotic caspase-3. These results demonstrate that xanthatin induces glioma cell apoptosis and inhibits tumor growth via activating the ER stress-related unfolded protein response pathway involving CHOP induction. Xanthatin may serve as a promising agent in the treatment of human glioma.

Accuracy and stability improvement for meat species identification using multiplicative scatter correction and laser-induced breakdown spectroscopy.

An efficient method has been developed to identify meat species by using laser-induced breakdown spectroscopy (LIBS). To improve the accuracy and stability of meat species identification, multiplicative scatter correction (MSC) was adopted to first pretreat the spectrum for correction of spectrum scatter. Then the corrected spectra were identified by using the K-nearest neighbor (KNN) model. The results showed that the identification rate improved from 94.17% to 100% and the prediction coefficient of variance (CV) decreased from 5.16% to 0.56%. This means that the accuracy and stability of meat species identification using MSC and LIBS simultaneously improved. In light of the findings, the proposed method can be a valuable tool for meat species identification using LIBS.

A Novel Linking Strategy of Using 9,10-Dihydroacridine to Construct Efficient Host Materials for Red Phosphorescent Organic Light-Emitting Diodes.

Three novel 9,10-dihydroacridine derivatives, 4'-(10-methyl-9,9-diphenyl-9,10-dihydroacridin-4-yl)[1,1'-biphenyl]-4-carbonitrile (MeAcPhCN), 4'-(9,9,10-triphenyl-9,10-dihydroacridin-4-yl)[1,1'-biphenyl]-4-carbonitrile (PhAcPhCN), and 5-[4-(9,9,10-triphenyl-9,10-dihydroacridin-4-yl)phenyl]picolinonitrile (MeAcPyCN), were prepared by the attachment of [1,1'-biphenyl]-4-carbonitrile or 5-phenylpicolinonitrile to the 4-position of 9,10-dihydroacridine. This special linking strategy limited the conjugation length, maintained the triplet energy, and inhibited the intermolecular charge-transfer (ICT) characteristics of these compounds. Notably, the enhanced accepting strength of the picolinonitrile segment relative to that of benzonitrile led to relatively strong ICT characteristics, a low energy gap, and a low triplet energy for MeAcPyCN. The thermal, photophysical, electrochemical, and electroluminescent properties of these host materials were studied systematically. Consequently, (acetylacetonato)bis(2-methyldibenzo[f,h]quinoxaline)iridium(III) [Ir(MDQ)2 (acac)]-based red phosphorescent organic light-emitting diodes (PHOLEDs) were fabricated with these three host materials. As a result, the device hosted by MeAcPhCN showed good device performance with a maximum external quantum efficiency of 20.5 %.