Arginine deprivation enriches lung cancer proteomes with cysteine by inducing arginine-to-cysteine substitutants.

Many types of human cancers suppress the expression of argininosuccinate synthase 1 (ASS1), a rate-limiting enzyme for arginine production. Although dependency on exogenous arginine can be harnessed by arginine-deprivation therapies, the impact of ASS1 suppression on the quality of the tumor proteome is unknown. We therefore interrogated proteomes of cancer patients for arginine codon reassignments (substitutants) and surprisingly identified a strong enrichment for cysteine (R>C) in lung tumors specifically. Most R>C events did not coincide with genetically encoded R>C mutations but were likely products of tRNA misalignments. The expression of R>C substitutants was highly associated with oncogenic kelch-like epichlorohydrin (ECH)-associated protein 1 (KEAP1)-pathway mutations and suppressed by intact-KEAP1 in KEAP1-mutated cancer cells. Finally, functional interrogation indicated a key role for R>C substitutants in cell survival to cisplatin, suggesting that regulatory codon reassignments endow cancer cells with more resilience to stress. Thus, we present a mechanism for enriching lung cancer proteomes with cysteines that may affect therapeutic decisions.

Shaoxia: a web-based interactive analysis platform for single cell RNA sequencing data.

BACKGROUND: In recent years, Single-cell RNA sequencing (scRNA-seq) is increasingly accessible to researchers of many fields. However, interpreting its data demands proficiency in multiple programming languages and bioinformatic skills, which limited researchers, without such expertise, exploring information from scRNA-seq data. Therefore, there is a tremendous need to develop easy-to-use software, covering all the aspects of scRNA-seq data analysis. RESULTS: We proposed a clear analysis framework for scRNA-seq data, which emphasized the fundamental and crucial roles of cell identity annotation, abstracting the analysis process into three stages: upstream analysis, cell annotation and downstream analysis. The framework can equip researchers with a comprehensive understanding of the analysis procedure and facilitate effective data interpretation. Leveraging the developed framework, we engineered Shaoxia, an analysis platform designed to democratize scRNA-seq analysis by accelerating processing through high-performance computing capabilities and offering a user-friendly interface accessible even to wet-lab researchers without programming expertise. CONCLUSION: Shaoxia stands as a powerful and user-friendly open-source software for automated scRNA-seq analysis, offering comprehensive functionality for streamlined functional genomics studies. Shaoxia is freely accessible at http://www.shaoxia.cloud , and its source code is publicly available at https://github.com/WiedenWei/shaoxia .

Metformin overcomes chemoresistance by regulating stemness via KLF4 in oral squamous cell carcinoma.

OBJECTIVE: Chemoresistance is a common event after chemotherapy, including oral squamous cell carcinoma (OSCC). Accumulated evidence suggests that the cancer stemness significantly contributes to therapy resistance. An unresolved question remains regarding how to effectively overcome OSCC chemoresistance by targeting stemness. This study aims to investigate the antitumor effect of metformin and clarify the potential molecular mechanisms. METHODS: Cellular models resistant to chemotherapy were established, and their viability and sphere-forming ability were assessed using CCK-8 and soft agar formation assays, respectively. RNA-seq and Western blotting analyses were employed to delve into the molecular pathways. Furthermore, to corroborate the inhibitory effects of metformin and cisplatin at an animal level, a subcutaneous tumor transplantation model was instituted. RESULTS: Metformin as a monotherapy exhibited inhibition of stemness traits via Krüppel-like factor 4 (KLF4). Metformin and cisplatin can synergically inhibit cell proliferation and induce cell apoptosis. Animal experiments confirmed the inhibitory effect of cisplatin and metformin on tumor in mice. CONCLUSION: Our study proposes a potential therapeutic approach of combining chemotherapy with metformin to overcome chemoresistance in OSCC.

Comparative analysis of two arecoline-induced oral submucous fibrosis models.

OBJECTIVE: The limited understanding of the molecular mechanism for oral submucosal fibrosis (OSF) poses challenges to the development of effective prevention and treatment strategies. The lack of suitable animal models is a major hindrance. Therefore, this study aimed to address this issue by comparing commonly used arecoline-induced water drinking and injection mouse models. MATERIALS AND METHODS: The mice were subjected to two protocols: receiving 2 mg/mL arecoline in drinking water and 4 mg/mL arecoline saline solution injections every other day. Tissues were collected at regular 4-week intervals, with a final time point of 20 weeks. Stereo microscopy and histomorphological analysis were performed on live and harvested tissues, respectively. RESULTS: During arecoline treatment, collagen deposition and myofibroblast proliferation progressively increased in both models. Changes in the collagen I/III ratio indicated that both models exhibited characteristics of the early and intermediate stages of OSF after 20 weeks of arecoline induction. The water-drinking model also demonstrated multi-organ fibrosis involving the tongue, lungs, and small intestine. CONCLUSION: Both the water drinking and injection mouse models effectively induced OSF, but the water-drinking model better mirrored the observed pathogenesis in patients with OSF. These models provide valuable tools for investigating the mechanisms underlying OSF.

Countermeasures and Application Effect of Nursing Interventions in Maintenance Hemodialysis Patients with Complications of Secondary Hyperparathyroidism.

Background: Secondary hyperparathyroidism commonly arises in individuals with end-stage kidney disease, especially those who undergo maintenance hemodialysis (MHD). This study investigated strategies and effectiveness of nursing interventions in MHD patients with secondary hyperparathyroidism complications. Methodology: This study is a retrospective analysis conducted at the General Hospital of Northern Theater Command. From June 2021 to June 2023, 212 patients undergoing MHD were selected for the study. They were divided into 2 groups based on their parathyroid hormone levels: a hyperthyroidism group and a standard group. Within the hyperthyroidism group, participants were randomly assigned to either the control group (CG), which received routine nursing, or the observation group (OG), which received targeted nursing. The study assessed several primary outcome measures, including patient risk factors, nursing satisfaction, psychological status, quality of life, treatment compliance, and nutritional indexes. Results: Significant disparities existed in the age, diabetes presence, pulse pressure, duration of dialysis, and levels of creatinine, C-reactive protein, phosphorus, triglyceride, albumin, calcium, and phosphorus product between the hyperthyroidism and the standard group. The duration of dialysis, presence of diabetes, C-reactive protein, and blood phosphorus were identified as independent risk factors for maintaining secondary hyperparathyroidism in patients undergoing hemodialysis. Overall satisfaction with nursing care and compliance with treatment were significantly higher in the observation group compared to the CG. Following nursing care, the scores on the Self-rating Anxiety Scale and the Self-rating Depression Scale were substantially lower in the OG compared to the CG. After nursing care, the biochemical indicators were lower, the nutritional indicators were higher, and the quality of life scores were significantly improved in the OG compared to the CG. Conclusion: Targeted nursing interventions in the care of hemodialysis patients with hyperparathyroidism enhanced serological markers, alleviated negative emotions, and improved patients' quality of life and nutritional status.

18 F-DCFPyL positron emission tomography/magnetic resonance imaging-guided ultrasound fusion biopsy is an identical pathway in prostate cancer diagnosis.

BACKGROUND: Prostate biopsy is still unavoidable in patients with a rising prostate-specific antigen even though multiparametric magnetic resonance imaging (MRI) is widely used. 18 F-DCFPyL positron emission tomography (PET)/MRI was proved to be promising both in sensitivity and specificity. But its guiding fusion biopsy and the advantages in the diagnosis of prostate disease is seldom reported. This study aimed to verify the feasibility and advantage of 18 F-DCFPyL PET/MRI-guided fusion targeted biopsy (TB) over whole-mount histopathology (WMH) for prostate cancer diagnosis. METHODS: A prospective study of 94 biopsy-naïve patients were conducted using 18 F-DCFPyL PET/MRI scans and scored on a scale of 1-4. Systematic biopsy was performed for all patients. Patients with suspicious lesions also underwent PET/MRI/transrectal ultrasound-guided fusion biopsy. Patients with pathologically confirmed cancer underwent surgery and WMH sections. Systematic biopsy was compared with TB for the detection of index tumors (ITs). Significant cancer was defined as Grade group (GG) 2 or higher no matter the length of the cancer core. RESULTS: 18 F-DCFPyL PET/MRI detected 30/94 (32%) patients with a score of 4, all of whom were verified to have prostate cancer. While it detected 10 patients with a score of 1 (10.6%), they were shown to have no cancer. The sensitivity and specificity of 18 F-DCFPyL PET/MRI were 94.4% and 75%, respectively, if images with a score of 3 are defined as positive. Systematic biopsy detected 18% (203/1128) samples as prostate cancer; conversely, TB detected 113 samples out of 259 scores (43.6%). A statistically significant difference was seen between the PCa detection rates by TB and SB (p < 0.001). All targeted lesions were pathologically proven to be the IT on WMH. CONCLUSIONS: In biopsy-naïve patients, the ultrasound fusion biopsy targeted by 18 F-DCFPyL PET/MRI is an identical pathway for the detection of prostate cancer.

Calcium signaling induces a partial EMT.

Epithelial plasticity, or epithelial-to-mesenchymal transition (EMT), is a well-recognized form of cellular plasticity, which endows tumor cells with invasive properties and alters their sensitivity to various agents, thus representing a major challenge to cancer therapy. It is increasingly accepted that carcinoma cells exist along a continuum of hybrid epithelial-mesenchymal (E-M) states and that cells exhibiting such partial EMT (P-EMT) states have greater metastatic competence than those characterized by either extreme (E or M). We described recently a P-EMT program operating in vivo by which carcinoma cells lose their epithelial state through post-translational programs. Here, we investigate the underlying mechanisms and report that prolonged calcium signaling induces a P-EMT characterized by the internalization of membrane-associated E-cadherin (ECAD) and other epithelial proteins as well as an increase in cellular migration and invasion. Signaling through Gαq-associated G-protein-coupled receptors (GPCRs) recapitulates these effects, which operate through the downstream activation of calmodulin-Camk2b signaling. These results implicate calcium signaling as a trigger for the acquisition of hybrid/partial epithelial-mesenchymal states in carcinoma cells.

Association of Globodera rostochiensis (Nematoda) with Stunted and Chlorotic Potato Plants in Yunnan and Sichuan Provinces in China.

On a global basis, potato cyst nematodes (Globodera spp. Skarbilovich 1959 [Behrens 1975]) are one of the most serious soilborne pathogens in potato (Solanum tuberosum L.) production. In 2019 to 2020, 188 soil samples were taken from rhizosphere soil associated with the roots of stunted and chlorotic potato plants in the main potato-growing areas of Yunnan and Sichuan Provinces of China. Globodera rostochiensis Wollenweber 1923 (Skarbilovich 1959) was recovered from 112 of the samples. Nematode identification was as confirmed by morphometric, light microscopy, electron microscopy, and molecular methodologies. Population densities of G. rostochiensis ranged from 47.0 to 69.0 eggs/g of soil. A BLASTn homology search program was used to compare the sequences of populations of G. rostrochienses from Yunnan and Sichuan Provinces with populations of other Heteroderinae spp. and populations of G. rostochiensis from other nations. Although potato has been grown in China for at least 400 years and the nation produces more potato than any other country, potato cyst nematodes were not reported in China until 2022.

Surgical treatment of Shone's syndrome and patent ductus arteriosus in an adult.

BACKGROUND: Shone's syndrome is a rare complex congenital anomaly. The classical definition consists of four anomalies: supravalvular mitral membrane, parachute mitral valve (PMV), subaortic stenosis, and coarctation of the aorta (CoA). Few studies have been reported on Shone's syndrome in adults, particularly the primary surgical correction of the anomalies. CASE PRESENTATION: A 22-year-old female patient presented with chest distress and tachypnea. Echocardiography and CT revealed supravalvular mitral membrane, PMV, Bicuspid aortic valve stenosis, CoA and patent ductus arteriosus. She underwent primary definitive surgical correction successfully and was discharged from hospital with symptoms free. CONCLUSIONS: Our case report highlights the importance of echocardiographic evaluation in the diagnosis of Shone's syndrome. The surgical strategy should be tailored according to both the patient's profile and the surgeon's personal surgical experience. Extra-anatomical bypass procedure is an appropriate technique for adult patients with long-segment coarctation and concomitant cardiac lesions. The outcomes of the case study indicate that the primary definitive surgery is encouraging.

A rapid and highly effective approach for SARS-CoV-2 nucleic acid daily testing in more than four thousand single-tube samples.

BACKGROUND: Presently, the global spread of COVID-19 is still going on, with more than 0.6 million new cases confirmed per day (as of November 20, 2021). However, since China entered a post-epidemic phase in mid-March 2020, the daily number of new domestic infections in the Chinese mainland has been maintained at almost zero or single digits, which was attributed to a series of effective measures for COVID-19 prevention and control adopted by the Chinese government. Among these measures, SARS-CoV-2 nucleic acid testing holds key role for the timely confirmation and isolation of the infections to prevent further transmission. METHODS: Referring to the national policy requirements, since April 30, 2020, The Affiliated Hospital of Qingdao University has conducted SARS-CoV-2 nucleic acid testing in its PCR laboratory for patients and social workers, as well as for environmental monitoring and employee screening. As of mid-November 2020, the daily amount of single-tube samples for nucleic acid testing rose above 4,000. RESULTS: In this article, a rapid and highly effective approach for SARS-CoV-2 nucleic acid daily testing is presented, allowing five technicians to complete nucleic acid testing in 6,500 single-tube samples in one day with a high level of quality. Using this approach, since the samples entered the PCR laboratory, all testing results were reported in 2.5-3 h with satisfactory quality control and precise reporting criterion as prerequisites. CONCLUSION: This testing approach provides a referable workflow for other testing institutions and is expected to play an important role in COVID-19 prevention and control.

First detection of the potato cyst nematode (Globodera rostochiensis) in a major potato production region of China.

The potato cyst nematodes (PCN) Globodera rostochiensis and Globodera pallida are the very important quarantine nematode pests of potato [Stone 1973]. Both species cause serious potato tuber yield losses. These species are subjected to strict quarantine regulations in many countries (EPPO 2017). G. rostochiensis was detected in Sichuan and Yunnan province, China in 2022 (Jiang et al. 2022). A survey for cyst nematodes in potato fields was conducted in Guizhou Province from 2018 to 2020. A total of 200 samples, including roots and soil, were collected from 40 potato fields in Hezhang (N27 06.145, E104 39.153) and Weining (N26 50.541, E104 09.885) counties in Guizhou Province, China. The Cobb decanting and sieving method was used to isolate cysts and J2s from the soil samples (Southey 1986). The potato roots were stained with acid fusion to observe cyst development. Morphological and molecular analyses indicated that 27 (13.5%) of the samples contained G. rostochiensis. The cyst density ranged between 1-85 cysts per 100 cm3 of soil and a mean density was 15 cysts per 100 cm3 soil. The smoothly rounded cysts were in brown and golden color, and the terminal cone was absent and circumfenestrate. The key morphometrics of cysts (n=20) were 695 ± 26 (685-757) µm in length excluding neck and 690 ± 30 (668 to769) µm in width; the number of cuticular ridges between anus and vulval fenestra was 16.3 ±2.1 (14 to 18); fenestral length was 15.1 ± 2.1 µm (13.18 to 19.27); distance from anus to the edge of fenestra was 61.12 ± 8.9 (49.22 to76.27) µm; and Granek's ratio was 4.54 ± 0.8 (3.97-5.26). The key morphometrics of J2 (n = 20): 468.0 ± 20.1 (427 to - 521) µm in body length, 20.58 ± 0.7 (20.2 to 21.8) µm in stylet length, 43.9 ± 5.6 (40.3 to 53.9) µm in tail length, and 23.1 ± 1.8 (21.77 to 25.32) µm in hyaline region length. The cyst and J2 morphologies were consistent with those of G. rostochiensis (Subbotin et al. 2010, EPPO 2017). Genomic DNA was isolated from cysts (n=20). DNA extraction was performed in a volume of 20 µl containing 3 µl 10× PCR buffer, 3 µl Proteinase K (600 µg µl-1), 14 µl distilled water and a single cyst was added and ground in an ice bath as described by Ou et al. (2008). The internal transcribed spacer (ITS) regions were amplified using the universal primers: rDNA1 (5'-TTGATTACGTCCCTGCCCTTT-3') and rDNA2 (5'-TTTCACTCGCCGTTACTAAGG-3') (Fleming 1998 ), and the 28S rDNA-D2/D3 regions were amplified using the primers: D2A (5´-ACAAGTACCGTGAGGGAAAGTTG-3´) and D3B (5´-TCGGAAGGAACCAGCTACTA-3´) (Subbotin et al. 2006). After the brackets at the beginning and end of the sequences were closed-up, the ITS rDNA sequences (GenBank Accession No. MZ042367 and MZ042368) showed 99.66% - 99.92% identity to G. rostochiensis sequences available in GenBank (FJ212166.1, GQ294513, FJ212164.1 and KJ409617.1). Sequences from the 28S region (GenBank Accession No. MZ057597 and MZ057598) were 99.23% - 99.74% similar to those of G. rostochiensis isolate from Slovakia (KJ409625.1), Italy (KJ409631.1) and United Kingdom (KJ409633.1). We used species specific primers ITS5（5'-GGAAGTAAAAGTCGTAACAAGG-3'）and PITSr3 (5'AGCGCAGACATGCCGCAA-3') to amplify the product (Bulman & Marshall 1997; EPPO 2017). A single 434bp fragment was obtained from Hezhang and Weining populations. A host test for the Hezhang and Weining populations were performed by inoculating 1,000 eggs per plant of varieties Qingshu 9, Huize 2 and Hezuo 88 grown in the pots containing 800 cm3 of sterilized soil (soil: sand ratio was 3:1), and four replications were tested in greenhouse under 16 h light, 22°C in the day and 8 h dark in the night. At 90 days post inoculation, 32.6 ± 7, 31.2 ± 8, and 29.5 ± 8 females and cysts were extracted from the infected roots and soils of the varieties Qingshu 9, Huize 2 and Hezuo 88, respectively. No females and cysts were observed on the control plants. The trial indicated that potato cultivars Qingshu 9, Huize 2 and Hezuo 88 are hosts for the Hezhang and Weining populations of Globodera rostochiensis. To the best of our knowledge, this is the first detection of potato cyst nematode Globodera rostochiensis in Guizhou Province, China.

Application of constructivism and cognitive flexibility theory to build a Comprehensive, Integrated, Multimodal Interprofessional Education and Practice (CIM-IPEP) program.

Interprofessional Education (IPE) is challenging to implement and assess due to barriers preventing interprofessional communication, inadequately defined accreditation criteria, ambiguous professional roles and responsibilities, and the inherently "ill-structured" educational construct of IPE. To address these gaps, a novel comprehensive, integrated, and multimodal interprofessional education and practice (CIM-IPEP) curriculum involving students from pharmacy, medicine, psychology, and nursing professional degree programmes was created. CIM-IPEP was carefully designed based on cognitive flexibility theory (CFT) to reinforce the complexities associated with teaching and learning for multi-faceted and dynamic domains such as IPE. CFT emphasises pluralistic representation, repetition, and cognitive layering in experiential learning for ill-structured domains. Thus, CIM-IPEP was vertically and horizontally aligned within individual colleges and included diverse IPE experiences in required courses such as Foundations of IPE, and high-fidelity simulation events, culminating in an IPE-Hotspotting elective, which exposed learners to real-world patient cases. Cases were presented in a format of increasing complexity emphasising the integration of foundational and skills-based learning using constructivist methods such as Team-Based and Case-Based Learning. CIM-IPEP offers a novel IPE model. Here we present a stepwise development and implementation blueprint for similar IPE programmes that is readily transferable to other health profession education (HPE) programmes.

Co-amorphous Drug Delivery Systems: a Review of Physical Stability, In Vitro and In Vivo Performance.

Over the past few decades, co-amorphous solids have been used as a promising approach for delivering poorly water-soluble drugs. Co-amorphous solids, comprising pharmacologically relevant drug substances or excipients, improve physical stability, solubility, dissolution, and bioavailability compared with single amorphous ingredients. In this review, we have summarized recent advances in physical stability and in vitro and in vivo performances of co-amorphous solids. We have highlighted the role of molar ratio, molecular interaction, and mobility that affects the physical stability of co-amorphous solids. This review delves deep as to how co-amorphous solids affect the physicochemical properties in vitro and in vivo. We also described the challenges to the formulation of co-amorphous solids. A better understanding of the mechanisms of the physical stability, in vitro and in vivo performance of co-amorphous solids, and proper selection of the co-former is likely to expedite the development of robust co-amorphous-based pharmaceutical formulations and can address the challenges associated with the delivery of poorly soluble drugs.

The functions of autophagy at the tumour-immune interface.

Autophagy is frequently induced in the hypoxic tumour microenvironment. Accumulating evidence reveals important functions of autophagy at the tumour-immune interface. Herein, we propose an update on the roles of autophagy in modulating tumour immunity. Autophagy promotes adaptive resistance of established tumours to the cytotoxic effects of natural killer cells (NKs), macrophages and effector T cells. Increased autophagic flux in tumours dampen their immunogenicity and inhibits the expansion of cytotoxic T lymphocytes (CTLs) by suppressing the activation of STING type I interferon signalling (IFN-I) innate immune sensing pathway. Autophagy in suppressive tumour-infiltrating immune subsets maintains their survival through metabolic remodelling. On the other hand, autophagy is involved in the antigen processing and presentation process, which is essential for anti-tumour immune responses. Genetic deletion of autophagy induces spontaneous tumours in some models. Thus, the role of autophagy is context-dependent. In summary, our review has revealed the dichotomous roles of autophagy in modulating tumour immunity. Broad targeting of autophagy may not yield maximal benefits. The characterization of specific genes regulating tumour immunogenicity and innovation in targeted delivery of autophagy inhibitors into certain tumours are among the most urgent tasks to sensitize cold cancers to immunotherapy.

A genome-wide RNAi screen reveals a Trio-regulated Rho GTPase circuitry transducing mitogenic signals initiated by G protein-coupled receptors.

Activating mutations in GNAQ and GNA11, encoding members of the Gα(q) family of G protein α subunits, are the driver oncogenes in uveal melanoma, and mutations in Gq-linked G protein-coupled receptors have been identified recently in numerous human malignancies. How Gα(q) and its coupled receptors transduce mitogenic signals is still unclear because of the complexity of signaling events perturbed upon Gq activation. Using a synthetic-biology approach and a genome-wide RNAi screen, we found that a highly conserved guanine nucleotide exchange factor, Trio, is essential for activating Rho- and Rac-regulated signaling pathways acting on JNK and p38, and thereby transducing proliferative signals from Gα(q) to the nucleus independently of phospholipase C-ß. Indeed, whereas many biological responses elicited by Gq depend on the transient activation of second-messenger systems, Gq utilizes a hard-wired protein-protein-interaction-based signaling circuitry to achieve the sustained stimulation of proliferative pathways, thereby controlling normal and aberrant cell growth.

Isorhamnetin induces the paraptotic cell death through ROS and the ERK/MAPK pathway in OSCC cells.

OBJECTIVE: There were rarely investigations on the effects and molecular mechanisms of oral squamous cell carcinoma (OSCC) cells when treated with isorhamnetin. This article assesses the anti-cancer effect of isorhamnetin. METHODS AND MATERIALS: Oral squamous cell carcinoma cells were treated with or without isorhamnetin. Cell proliferation, cell cycle arrest, cell migration, cell death, and the related signaling pathways were evaluated. RESULTS: The results revealed that cell proliferation was inhibited in a dose- and time-dependent manner, which was confirmed by diminished cell viability and revealed by decreased in the number of cell colonies. In addition, the cell cycle arrested in the G2/M phase, and the protein levels of cyclin B1 and CDC2 were suppressed. Moreover, the cell migration was inhibited, and the protein levels of related proteins were modulated. Furthermore, it could be observed that abundant cytoplasmic vacuoles existed which that were derived from mitochondria and the endoplasmic reticulum. It was confirmed that cell death did not result from apoptosis and may have which may be apt to paraptosis. Isorhamnetin was observed to upregulate phosphorylated ERK cascades and increase intracellular reactive oxygen species levels. CONCLUSIONS: Our study suggested that the anti-cancer effect of isorhamnetin might trigger paraptosis, which may indicate a new therapeutic approach to OSCC.

Mechanism of deglutition stage acupuncture for treating deglutition disorder after stroke.

This research analyzed the efficacy of dysphagia after stroke and evaluated the clinical curative effect after treatment by the staging acupuncture method in comparison with traditional acupuncture method. We tried to study the curative effect of the staging acupuncture treatment after stroke and the possible mechanism of action. Then it could provide the basis of evidence-based medicine and lead for further research. There were 30 patients in the experimental group and the control group, including 15 patients at the middle oral stage and pharynx stage, respectively. The patients were divided into groups who met the standards according to the time sequence of hospitalization using the randomized controlled trial method. Comparing the curative effect between the experimental group control group after 12 days the therapeutic effect evaluation criteria were the water intake test score and the standard swallowing function score (SSA) score and recorded the occurrence of adverse events. There was no statistically significant difference (P>0.05) of oral and pharyngeal period in the baseline data between the two groups in gender, age, course of disease before treatment, and SSA scores before treatment. After treatment, there was statistically significant difference between the two groups. For dysphagia after stroke, the effect of acupuncture in deglutition stage was better than that in routine acupuncture group. Comparison of the efficacy between the oral and pharyngeal phases showed that the staged acupuncture group was superior to the traditional acupuncture group.

MicroRNA-22 suppresses cell proliferation, migration and invasion in oral squamous cell carcinoma by targeting NLRP3.

MicroRNAs (miRNAs) have been implicated as important regulators of carcinogenesis and tumor development. Recently, microRNA-22 (miR-22) has been reported to be a cancer-related miRNA in several types of tumors. In this study, we aimed to investigate the role of miR-22 in oral squamous cell carcinoma (OSCC). We found that miR-22 expression was significantly decreased in OSCC tissues compared with that in the adjacent noncancerous tissues. Furthermore, lentivirus-mediated miR-22 overexpression markedly reduced OSCC cell viability, migration and invasion, whereas miR-22 inhibitor promoted these parameters. Mechanistically, NLR family pyrin domain containing three (NLRP3) was identified as a direct target of miR-22. miR-22 expression was inversely correlated with NLRP3 expression both in OSCC tissues and cell lines. Moreover, overexpression of miR-22 in OSCC cells could reverse the tumor-promoting effect of the activated NLRP3 inflammasome and vice versus. Therefore, our results indicate that miR-22 may play a suppressive role in OSCC by targeting NLRP3, which offer new insights into the molecular mechanisms of the growth and metastasis of OSCC.

Terahertz radiation in graphene hyperbolic medium excited by an electric dipole.

In this Letter, the enhanced and directional radiation in a wide terahertz (THz) frequency range in a graphene hyperbolic medium excited by an electric dipole is presented. The numerical simulations and theoretical analyses indicate that the enhanced radiation comes from the strong surface plasmon couplings in the graphene hyperbolic medium, consisting of alternative graphene and dielectric substrate layers. The simulation results also show that the peak power flow of the enhanced THz radiation in the graphene hyperbolic medium is dramatically enhanced by more than 1 order of magnitude over that in a general medium within a certain distance from the dipole, and the electromagnetic fields are strongly concentrated in a narrow angle. Also, the radiation fields can be manipulated, and the fields' angular distributions can be tuned by adjusting the dielectric permittivity and thickness of the substrates, and the chemical potential of graphene. Accordingly, it provides a good opportunity for developing miniature, integratable, high-power-density, and tunable radiation sources in the THz band at room temperature.

NLRP3 promotes tumor growth and metastasis in human oral squamous cell carcinoma.

BACKGROUND: Inflammasomes are reported to be abnormally expressed and activated in several malignancies and play important roles in tumor development. The present study was designed to investigate the expression and function of the NLR family pyrin domain containing protein 3 (NLRP3) inflammasome in oral squamous cell carcinoma (OSCC). METHODS: NLRP3 expression in OSCC cell lines and the normal human immortalized oral epithelial cells (HIOEC) was determined by real-time PCR and western blot. Immunohistochemistry was used to examine the expression of NLRP3 and IL-1ß in the paraffin-embedded OSCC tissues. The proliferation of OSCC cells was detected by the 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and cell colony formation ability of the OSCC cells was also evaluated. Tumor cell migration or invasion was measured by the transwell assay and related protein markers were determined by western blot. A mouse xenograft model was established to investigate the OSCC tumor growth in vivo. RESULTS: Significant higher expression of NLRP3 was observed in the OSCC cells. Obvious expression of NLRP3 and IL-1ß was found in the paraffin-embedded OSCC tissues, and the NLRP3 expression levels were correlated with the tumor size, lymphonode metastatic status and IL-1ß expression. Downregulating NLRP3 expression markedly reduced the cleavage of caspase-1 and production of IL-1ß in OSCC cells. NLRP3 knockdown also inhibited the proliferation, migration and invasion of OSCC cells. Further investigation indicated that expressions of E-cadherin and vimentin in OSCC cells were increased, while N-cadherin expression was decreased after NLRP3 knockdown. Downregulating NLRP3 expression in OSCC cells significantly reduced the tumor growth in vivo. CONCLUSIONS: Our data suggested that the increased expression of NLRP3 in OSCC was associated with tumor growth and metastasis. NLRP3 may be considered as a potential target for OSCC therapy.