Unraveling the hydrogeochemical characteristics and pollution sources of groundwater in an intensive industrial area, East China.

It is challenging to interpret hydrogeochemical datasets with complex natural and anthropogenic genesis in intensive industrial areas. This paper elucidates the hydrogeochemical characteristics and pollution sources of groundwater in an industrial park, East China, combining the self-organizing map (SOM), hydrochemical graphs, and correlation analysis. The results show that the total dissolved solids of groundwater range from 73.45 to 997.92 mg/L and can be regarded as freshwater. The pH varies greatly from 6.44 to 9.90, most of samples belonging to weakly acidic-weakly alkaline. The groundwater can be classified into five clusters by SOM, representing the non- or least-polluted groundwater (cluster D), high salt groundwater (cluster A), high NH4+-N and HCO3- groundwater (cluster B), high Fe and Mn groundwater (cluster C), and high pH groundwater (cluster E), which were contaminated by industrial salts, historical agriculture activity, industrial reducing substances, and industrial alkali, respectively. The natural evolution of groundwater (cluster D) in the study area is mainly controlled by mineral weathering/dissolution. The contributions of calcite, dolomite, gypsum, halite, and silicate mineral to groundwater solute are 55.8-66.3%, 15.1-18.0%, 9.0-10.7%, 2.5-10.1%, and 2.3-9.4%, respectively, based on the mass conservation. The contaminated groundwaters (all other clusters except for cluster D) have different hydrochemical characteristics associated with the pollution sources. In addition, the relatively reductive environment in quaternary flu-lacustrine sediments favored the formation of high level of Fe, Mn, and NH4+-N in groundwater. This study provides a new insight into the characteristic contaminants and their distributions in groundwater and the associated pollution sources based on the large datasets in an intensive industrial area. The data evaluation methods and results of this study could be useful to the groundwater usage management and pollution control in this area and other industrial areas.

Effect of Specific mode electroacupuncture stimulation combined with NGF during the ischaemic stroke: Study protocol for a randomized controlled trial.

BACKGROUND: The emergence of the Nerve Growth Factor (NGF) has promoted the development of neuroprotective therapy; however, it has little effect on cerebral ischemia because of its poor Blood-Brain Barrier (BBB) permeability. Specific Mode Electroacupuncture Stimulation (SMES) can open BBB safely and effectively; however, it has shown inconclusive clinical effects and indirect clinical evidence in the recovery phase. Hence, the authors conducted a multicentre, randomized, placebo-controlled, assessor-blinded clinical trial to assess the effectiveness and safety of SMES combined with NGF treatment used during ischaemic stroke recovery. METHODS: A total of 288 stroke patients from three hospitals will be recruited and randomly allocated to four groups: acupuncture + placebo, acupuncture + NGF, SMES + placebo, and SMES + NGF, in a 1:1:1:1 ratio. Assessment data will be collected at baseline, 2-weeks, and 4-weeks during the treatment period, as well as at the 4-week and 8-week follow-up after treatment completion. The primary outcome measure will be the basic cure rate. The secondary outcome measures include the simplified Modified Barthel Index, Timed Up and Go Test, Fugl-Meyer Assessment of Motor Function Score, Tinetti Performance Oriented Mobility Assessment, Montreal Cognitive Assessment, and Loewenstein Occupational Therapy Cognitive Assessment. Moreover, resting-state functional magnetic resonance imaging and Functional near-infrared spectroscopy can detect changes in cerebral blood flow and brain function and investigate the relationship between the clinical efficacy and mechanism of the prescribed interventions. CONCLUSION: This study will provide clinical evidence for the efficacy and safety of SMES combined with NGF in the treatment of stroke patients.

Astragalus mongholicus Bunge extract improves ulcerative colitis by promoting PLCB2 to inhibit colonic epithelial cell pyroptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Astragalus mongholicus Bunge (AM) and its active ingredients are mainly used for anti-inflammatory, antiviral, antioxidant, immune regulation, cardiovascular and nervous system protection, anti-cancer, anti-tumor and so on. AIM OF THE STUDY: To explore the Astragalus mongholicus Bunge extract pharmacological mechanisms and biology processes which improves ulcerative colitis (UC). MATERIALS AND METHODS: Dextran sulfate sodium (DSS)-induced UC models in C57BL/6 mice were established, and the mice were treated with Astragalus mongholicus Bunge extract or salazosulfapyridine (SASP). DSS-induced mice- and human-derived colonic epithelial cell lines were used to reveal the inflammatory environment of UC. After treatment with Astragalus mongholicus Bunge extract, the expression of phospholipase C-ß 2 (PLCB2) in the cells was detected by quantitative real-time PCR (qRT-PCR), and cell proliferative activity was detected by cell counting kit 8 (CCK-8) assay. Finally, the levels of pyroptosis-related inflammatory factors in cell culture supernatants was detected by ELISA. RESULTS: Treatment of UC mice with Astragalus mongholicus Bunge extract do significantly improved DAI scores and histopathological damage scores, and decreased the levels of Eotaxin, GCSF, KC, MCP-1, TNF-α, and IL-6. Besides, Astragalus mongholicus Bunge extract inhibited the expression of nucleotide-binding oligomerization segment-like receptor family 3 (NLRP3), cleaved Caspase-1, and GSDMD-N in the colonic tissues, and reduced the levels of inflammation-related factors IL-1ß and IL-18 in serum and tissues. In vitro, Astragalus mongholicus Bunge extract partially reversed the DSS-induced reduction of PLCB2 expression in CP-M030 and NCM460, promoted cell proliferative activity, and reduced the levels of IL-1ß and IL-18. CONCLUSIONS: In DDS-induced UC mice, Astragalus mongholicus Bunge extract improves ulcerative colitis by inhibiting colonic epithelial cell pyroptosis through PLCB2 promotion.

Interface Engineering Modulated Valley Polarization in MoS2/hBN Heterostructure.

Layered transition metal dichalcogenides (TMDs) provide a favorable research platform for the advancement of spintronics and valleytronics because of their unique spin-valley coupling effect, which is attributed to the absence of inversion symmetry coupled with the presence of time-reversal symmetry. To maneuver the valley pseudospin efficiently is of great importance for the fabrication of conceptual devices in microelectronics. Here, we propose a straightforward way to modulate valley pseudospin with interface engineering. An underlying negative correlation between the quantum yield of photoluminescence and the degree of valley polarization was discovered. Enhanced luminous intensities were observed in the MoS2/hBN heterostructure but with a low value of valley polarization, which was in stark contrast to those observed in the MoS2/SiO2 heterostructure. Based on the steady-state and time-resolved optical measurements, we reveal the correlation between exciton lifetime, luminous efficiency, and valley polarization. Our results emphasize the significance of interface engineering for tailoring valley pseudospin in two-dimensional systems and probably advance the progression of the conceptual devices based on TMDs in spintronics and valleytronics.

Association between dietary knowledge and overweight and obesity in Chinese children and adolescents: Evidence from the China Health and Nutrition Survey in 2004-2015.

OBJECTIVE: To assess whether dietary knowledge of Chinese children and adolescents and their mothers was associated with childhood and adolescent overweight and obesity. METHODS: This cross-sectional study obtained data from the China Health and Nutrition Survey (CHNS) between 2004 and 2015. Dietary knowledge of children and adolescents and their mothers was assessed by asking questions and statements on diets, and clustered by K-means clustering. Body mass index (BMI) and waist circumference (WC) were used to evaluate overweight and obesity among children and adolescents. The association of dietary knowledge with childhood and adolescent overweight and obesity was evaluated by multivariate regression analysis, with odds ratios (ORs) and 95% confidence intervals (CIs) calculated. RESULTS: A total of 2,338 children and adolescents were included. Children and adolescents with low dietary knowledge were demonstrated to have significantly higher risks of BMI-defined overweight or obesity (OR = 1.66, 95%CI = 1.21-2.28, P = 0.002), and WC-defined obesity (OR = 1.52, 95%CI = 1.12-2.06, P = 0.007) than those with high dietary knowledge. Compared with high dietary knowledge in mothers, low dietary knowledge was associated with significantly elevated risks of BMI-defined overweight or obesity (OR = 1.48, 95%CI = 1.08-2.02, P = 0.014), and WC-defined obesity (OR = 1.59, 95%CI = 1.18-2.16, P = 0.003). Furthermore, significantly increased odds of BMI-defined overweight or obesity and WC-defined non-obesity in children and adolescents were related to low dietary knowledge versus high dietary knowledge of children and adolescents (OR = 1.72, 95%CI = 1.08-2.74, P = 0.023), while there was no association of BMI-defined non-overweight and non-obesity and WC-defined obesity with dietary knowledge among children and adolescents (OR = 1.35, 95%CI = 0.89-2.04, P = 0.161). Additionally, no association was found between dietary knowledge of mothers and BMI-defined overweight or obesity and WC-defined non-obesity among children and adolescents (OR = 1.39, 95%CI = 0.89-2.17, P = 0.155), while low dietary knowledge of mothers was associated with increased odds of BMI-defined non-overweight and non-obesity and WC-defined obesity in children and adolescents (OR = 1.58, 95%CI = 1.03-2.43, P = 0.036). CONCLUSION: Dietary knowledge of children and adolescents and their mothers was associated with childhood and adolescent overweight and obesity. Dietary knowledge of children and adolescents negatively related to the risk of BMI-defined overweight or obesity, and dietary knowledge of mothers to odds of WC-defined obesity.

Tuning the optical absorption performance of MoS2 monolayers with compressive strain.

Strain engineering has been extensively applied as a promising strategy in the regulation of physical and chemical properties of two-dimensional (2D) materials, which remarkably broadens their application prospects in flexible electronics and chip manufacturing. However, the difficulty in fixing a flexible substrate under compression and the challenge in adjusting the focal distance have hindered the in-depth investigation of compressive strain. Here, we fabricated a home-made strain loading device and proposed a compressive strain measurement method, via which the strain-dependent optical absorption properties of MoS2 monolayers under compression has been studied. According to the measured optical absorption spectra, the first blueshift and then redshift trend under compression was obviously observed. The reliability of the experimentally observed trend in peak position shift was theoretically verified by density functional theory calculation. Our work offers a feasible way to characterize optical properties of 2D materials under compressive strain and expands the space for the development of next-generation micro/nano-scale optoelectronic devices.

Electroacupuncture of the trigeminal nerve causes N-methyl-D-aspartate receptors to mediate blood-brain barrier opening and induces neuronal excitatory changes.

The blood-brain barrier (BBB) is an important structure for maintaining environmental stability in the central nervous system (CNS). Our previous study showed that specific parameters of electroacupuncture (EA) at the head points Shuigou (GV26) and Baihui (GV20) can open the BBB; however, the mechanism by which stimulation of body surface acupuncture points on the head results in peripheral stimulation and affects the status of the central BBB and the neuronal excitatory changes has not been elucidated. We used laser spectroscopy, the In Vivo Imaging System (IVIS), immunofluorescence and immunoblotting to verified the role of the trigeminal nerve in BBB opening during EA, and we applied the central N-methyl-D-aspartate (NMDA) receptors blocker MK-801 to verify the mediating role of NMDA receptors in EA-induced BBB opening. Next, electroencephalogram (EEG) and in vivo calcium imaging techniques were applied to verify the possible electrical patterns of BBB opening promoted by different intensities of EA stimulation. The results showed that the trigeminal nerve plays an important role in the alteration of BBB permeability promoted by EA stimulation of the head acupoints. Brain NMDA receptors play a mediating role in promoting BBB permeability during EA of the trigeminal nerve, which may affect the expression of the TJ protein occludin, and thus alter BBB permeability. The analysis of the electrical mechanism showed that there was no significant change in the rhythm of local field potentials (LFP) in different brain regions across frequency bands immediately after EA of the trigeminal nerve at different intensities. However, the local primary somatosensory (S1BF) area corresponding to the trigeminal nerve showed a transient reduction in the delta rhythm of LFP with no change in the high-frequency band, and the action potential (spike) with short inter spike interval (ISI) varied with EA intensity. Meanwhile, EA of the trigeminal nerve resulted in rhythmic changes in calcium waves in the S1BF region, which were influenced by different EA intensities. This study provides a research perspective and a technical approach to further explore the mechanism of EA-induced BBB opening and its potential clinical applications.

Synthesis of graphene nanomesh with symmetrical fractal patterns via hydrogen-free chemical vapor deposition.

Graphene nanomesh (GNM), an emerging graphene nanostructure with a tunable bandgap, has gained tremendous interests owing to its great potentials in the fields of high-performance field-effect transistors, electrochemical sensors, new generation of spintronics and energy converters. In previous works, GNM has been successfully obtained on copper foil surface by employing hydrogen as an etching agent. A more facile, and low-cost strategy for the preparation of GNM is required. Here, we demonstrated a direct and feasible means for synthesizing large-area GNM with symmetrical fractal patterns via a hydrogen-free chemical vapor deposition method. The influences of the growth time and the gas source flow on the morphology of GNM patterns were systematically investigated. Then, we exhibited the key reaction details and proposed a growth mechanism of the GNM synthesis during the hydrogen-free chemical vapor deposition process. This work provides a valuable guidance for quality control in GNM mass production.

The influence of electronic acupuncture at a specific frequency in facilitating the passage of NGF through the blood-brain barrier and its effect on learning and memory in MCAO/R rats.

BACKGROUND: The blood-brain barrier (BBB) maintains the balance of the internal environment of the brain and strictly controls substance exchange between the brain and blood dynamically but stably. Transient increases in the permeability of the BBB plays an important role in helping macromolecular drugs enter the brain to exert their pharmacological effects. Previous research has revealed that electronic acupuncture (EA) stimulation connecting Baihui (GV20) and Shuigou (GV26) at a specific frequency can enhance the permeability of the BBB at 8 minutes after the intervention and induce the entry of 20 kDa fluorescein isothiocyanate-dextran (FITC-dextran) into the cerebral cortex, but whether it can also allow drugs to pass the BBB remains unknown. We hypothesized that EA at a specific frequency could open the BBB and induce the entry of nerve growth factor (NGF) into the brain to exert its therapeutic effect. METHODS: First, the middle cerebral artery occlusion (MCAO) model is adopted and changes in the permeability and structure of the BBB are assessed by measuring both the intensity of Evans blue (EB) staining and the cerebral infarction volume, and by evaluating the ultrastructure of the BBB. Then, a laser spectrometer and immunofluorescence are used to observe entry of NGF into the brain. Finally, the learning and memory ability of rats are assessed and the DeadEndTM Fluorometric TUNEL System is applied to assess apoptosis in the hippocampus. RESULTS: Our results showed that, in the first, the BBB was essentially repaired three weeks after MCAO operation. Secondly, Electronic Acupuncture (EA) stimulation at a specific frequency can enhance BBB permeability in the prefrontal cortex and induce NGF uptake by prefrontal neurons. Finally, in the presence of EA stimulation, entry of NGF into the brain promoted learning and memory in rats and inhibited the apoptosis of neurons in the hippocampus. CONCLUSIONS: In this study, the timing of BBB repair in the MCAO model was determined under pathological conditions and the EA stimulation can induce the entry of NGF into the brain to exert its therapeutic effect. EA could serve as a new strategy for delivering therapeutics to the central nervous system (CNS), given that EA stimulation at a specific frequency was shown to increase the permeability of the BBB. Further study of the mechanism underlying the opening of the BBB and its timing is needed.

Factors influencing the blood-brain barrier permeability.

The blood-brain barrier (BBB) is a dynamic structure that protects the brain from harmful blood-borne, endogenous and exogenous substances and maintains the homeostatic microenvironment. All constituent cell types play indispensable roles in the BBB's integrity, and other structural BBB components, such as tight junction proteins, adherens junctions, and junctional proteins, can control the barrier permeability. Regarding the need to exchange nutrients and toxic materials, solute carriers, ATP-binding case families, and ion transporter, as well as transcytosis regulate the influx and efflux transport, while the difference in localisation and expression can contribute to functional differences in transport properties. Numerous chemical mediators and other factors such as non-physicochemical factors have been identified to alter BBB permeability by mediating the structural components and barrier function, because of the close relationship with inflammation. In this review, we highlight recently gained mechanistic insights into the maintenance and disruption of the BBB. A better understanding of the factors influencing BBB permeability could contribute to supporting promising potential therapeutic targets for protecting the BBB and the delivery of central nervous system drugs via BBB permeability interventions under pathological conditions.

Transcriptomic Analysis of Rat Cerebral Cortex Reveals the Potential Mechanism of Electroacupuncture Opening Blood Brain Barrier.

Therapeutic treatment options for central nervous system (CNS) diseases are greatly limited by the blood-brain barrier (BBB). Electroacupuncture (EA) can be used to induce an increase in BBB permeability on rats, providing a potential approach for the delivery of drugs from the systemic circulation into the brain. However, there remains a large gap in our knowledge regarding the impact of EA on brain gene expression. This work is focused on investigating the transcriptional changes of rat cerebral cortex following EA and expression changes in genes and bioinformatic analysis was performed. We found that the potential mechanism of EA opening BBB involves receptor-mediated/carrier-mediated endocytosis (RMT/CMT), and related genes include solute carrier (SLC) transporter genes and ATP-binding cassette (ABC) transporter genes. The results also suggested that EA may affect the expression of tight junction (TJ) proteins in endothelial cells by affecting integrin binding, autophagy pathway and calcium signaling pathway, thus further affecting the permeability of blood-brain barrier. Our results provide a valuable resource that will guide mechanism research of EA opening BBB and other ways to mediate drug delivery into the brain.

MiR-1236-3p Inhibits the Proliferation, Invasion, and Migration of Colon Cancer Cells and Hinders Epithelial-Mesenchymal Transition by Targeting DCLK3.

BACKGROUND: Dysregulated microRNAs (miRNAs) are common in human cancer and are involved in the proliferation, promotion, and metastasis of tumor cells. Therefore, this study aimed to evaluate the expression and biological function of miR-1236-3p in colon cancer. METHODS: This study screened the miRNA in normal and colon cancer tissues through array analysis. In addition, quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) analysis was performed to validate the expression of miR-1236-3p in normal and tumor tissues from colon cancer patients and cancer cell lines. Online predicting algorithms and luciferase reporter assays were also employed to confirm Doublecortin Like Kinase 3 (DCLK3) was the target for miR-1236-3p. Moreover, the impact of miR-1236-3p on the progression of colon cancer was evaluated in vitro and in vivo. Western blotting and qRT-PCR were also performed to investigate the interactions between miR-1236-3p and DCLK3. RESULTS: MiR-1236-3p was significantly downregulated in colon cancer tissues and its expression was associated with the TNM stage and metastasis of colon. In addition, the in vitro and in vivo experiments showed that miR-1236-3p significantly promoted cancer cell apoptosis and inhibited the proliferation, invasion, and migration of cancer cells. The results also showed that miR-1236-3p hindered Epithelial-mesenchymal Transition (EMT) by targeting DCLK3. Moreover, the expression of DCLK3 mediated the effects of miR-1236-3p on the progression of cancer. CONCLUSIONS: MiR-1236-3p functions as a tumor suppressor in colon cancer by targeting DCLK3 and is therefore a promising therapeutic target for colon cancer.

Gene co-expression analysis identifies modules related to insufficient sleep in humans.

BACKGROUND: Insufficient sleep and circadian rhythm disruption may cause cancer, obesity, cardiovascular disease, and cognitive impairment. The underlying mechanisms need to be elucidated. METHOD: Weighted gene co-expression network analysis (WGCNA) was used to identify co-expressed modules. Connectivity Map tool was used to identify candidate drugs based on top connected genes. R ptestg package was utilized to detected module rhythmicity alteration. A hypergeometric test was used to test the enrichment of insomnia SNP signals in modules. Google Scholar was used to validate the modules and hub genes by literature. RESULTS: We identified a total of 45 co-expressed modules. These modules were stable and preserved. Eight modules were correlated with sleep restriction duration. Module rhythmicity was disrupted in sleep restriction subjects. Hub genes that involve in insufficient sleep also play important roles in sleep disorders. Insomnia GWAS signals were enriched in six modules. Finally, eight drugs associated with sleep disorders were identified. CONCLUSION: Systems biology method was used to identify sleep-related modules, hub genes, and candidate drugs. Module rhythmicity was altered in sleep insufficient subjects. Thiamphenicol, lisuride, timolol, and piretanide are novel candidates for sleep disorders.

The application of magnetic resonance imaging and diffusion-weighted imaging in the diagnosis of hypoxic-ischemic encephalopathy and kernicterus in premature infants.

BACKGROUND: To explore the application of magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI) in the diagnosis of hypoxic-ischemic encephalopathy and kernicterus in premature infants. METHODS: Fifty-eight premature infants with hypoxic-ischemic encephalopathy and fifty-eight premature infants with kernicterus who were examined and treated in our hospital between January 2018 and January 2021 were assigned to the observation group or the control group. All patients were examined by MRI imaging and DWI imaging, and the examination results were compared between the two groups. RESULTS: No significant differences were found in sensitivity, specificity, positive predictive value, or negative predictive value between the observation group and the control group (P>0.05). MRI could clearly visualize the signal changes of patients, whereas DWI did not show any signal changes. There was no significant difference between MRI and DWI in the diagnosis of hypoxic-ischemic encephalopathy in premature infants. Further, there was no significant difference in the diagnostic performance of MRI between the observation group and the control group (P>0.05). However, the diagnostic performance of DWI in the control group was better than that in the observation group, and the difference was statistically significant (P<0.05). CONCLUSIONS: MRI and DWI imaging have high detection rates for the diagnosis of hypoxic-ischemic encephalopathy and kernicterus in premature infants. These imaging methods can benefit the treatment of premature infants and have important clinical application value.

HNRNPL affects the proliferation and apoptosis of colorectal cancer cells by regulating PD-L1.

Colorectal cancer (CRC) ranks fourth among all human cancers in the world. HNRNPL plays an oncogenic role in various cancers, but is not discussed yet in CRC. The presents study aims to investigate the role of HNRNPL in CRC development. The mRNA and protein levels of HNRNPL in CRC cells were measured by RT-qPCR and western blot. The cell viability, colony formation, and apoptosis were evaluated after CRC cells were transfected with shRNA-HNRNPL. Also, the invasion and migration of transfected cells were respectively detected by transwell and wound-healing assays. Besides, tumor-bearing mice were established after C57BL/6 mice received injection of CRC cells with or without overexpression plasmid of HNRNPL, accompanied with anti-PD-L1 treatment. Expression of Ki67 in tumor tissue was detected using immunohistochemistry. HNRNPL was up-regulated in CRC cells, and transfection with shRNA-HNRNPL led to the decreases in cell viability, migration, invasion, and the increase in apoptosis of CRC cells. HNRNPL was verified to be a potential binding protein of PD-L1. Overexpression of HNRNPL promoted tumor growth in vivo, which was attenuated by anti-PD-L1 treatment. HNRNPL promotes the tumor growth and development of CRC by regulating PD-L1, which may direct us a new method to treat CRC.

Manipulating the Raman scattering rotation via magnetic field in an MoS2 monolayer.

Magneto-optical effects, which originate from the interactions between light and magnetism, have provided an important way to characterize magnetic materials and hosted abundant applications, such as light modulators, magnetic field sensors, and high-density data storage. However, such effects are too weak to be detected in non-magnetic materials due to the absence of spin degree of freedom. Here, we demonstrated that applying a perpendicular magnetic field can produce a colossal Raman scattering rotation in non-magnetic MoS2, for A-mode representing the out-of-plane breathing vibration. Our experimental results show that linearly polarized scattering light is rotated by ∓125°, more apparent than the valley Zeeman splitting effect (∓1.2 meV) under the same experimental conditions (±5 T), near room temperature. A detailed and systematic analysis on the polarization-resolved magnetic field-dependent micro-zone Raman intensity offers a feasible way to manipulate the inelastically scattered light via a magnetic technique. This explored phenomenology and physical mechanism arouse a new ramification of probing burgeoning magneto-optical effects in the field of two-dimensional laminar materials.

N6-Methyladenosine Regulators Promote Malignant Progression of Gastric Adenocarcinoma.

N6-methyladenosine (m6A) RNA methylation is dynamically and reversibly regulated by methyltransferases, binding proteins, and demethylases. The restoration of m6A to adenosine could result in demethylation modifications. Abnormalities in m6A epigenetic modifications in cancer are of increasing interest in recent years. According to the progression and prognostic performance of m6A epigenetic modifications in gastric adenocarcinoma (STAD), this study comprehensively analyzed the m6A modification patterns of gastric adenocarcinoma specimens in The Cancer Genome Atlas (TCGA) database based on 20 m6A regulators. Here, we found that 20 m6A RNA methylation regulators were high-expressed in gastric adenocarcinoma. m6A RNA methylation regulators were closely associated with pT staging of gastric cancer. Based on such findings, we developed a prognostic model using four m6A RNA methylation regulators (IGF2BP1, RBM15, FTO, ALKBH5), and the FTO was confirmed as an independent prognostic marker.

Interaction between regulatory T cells and mast cells via IL-9 and TGF-ß production.

Research on the immunosuppression of cancer cells has attracted much attention in recent years. The present study sought to provide a new strategy for tumor immunotherapy targeting mast cells by studying the mechanisms underlying mast cell function in cancer immunosuppression. Between January 2015 and December 2017, the tumor tissues of 40 patients with gastric cancer (GC) were collected and grouped in Lihuili Hospital of Ningbo City, China. Pathological sections were prepared and an immunofluorescence assay was performed to analyze the expression of forkhead Box Protein P3 (FOXP3), tryptase, TGFß1, TGF-ßR, IL-9, IL-9R and Oxford 40 ligand (OX40L). Then, the correlations between FOXP3 and tryptase, TGFß1 and tryptase expression, and the expression of OX40L in patients with GC with different stages were analyzed. The results revealed that high levels of mast cells were present in patients GC, and tryptase and FOXP3 expressions were positively correlated. Mast cells regulate T regulatory (reg) cells in the gastric tumor microenvironment by secreting TGFß1. Tregs, in turn, promote the survival of mast cells in the tumor microenvironment by producing IL-9. Furthermore, OX40L expression in mast cells was significantly associated with Tumor-Node-Metastasis staging of GC. Overall, the present study reported a positive feedback system that functions through TGFß1 and IL-9 to allow cross-talk between Tregs and mast cells. Moreover, OX40L may be a potential target for the diagnosis and treatment of GC. These results may provide a new strategy for tumor immunotherapy targeting mast cells.

Specific Frequency Electroacupuncture Stimulation Transiently Enhances the Permeability of the Blood-Brain Barrier and Induces Tight Junction Changes.

The blood-brain barrier (BBB) plays an important role in both the physiological state and pharmacological state of the brain. Transiently enhancing the permeability of the BBB may allow the use of more types of medications for neuropsychiatric diseases. Our previous research revealed that electroacupuncture (EA) stimulation at certain parameters can enhance the permeability of the BBB in Sprague-Dawley rats, but this phenomenon is not well characterized. We propose that specific frequency EA can transiently open the BBB and may be related to the change of tight junctions (TJ). To find the best EA frequency among commonly used frequencies, preliminarily explore the mechanism, we detected BBB permeability by measuring the intensity of Evans Blue and 20 kDa FITC-dextran fluorescence in the cerebral cortex. Then, we used a laser spectrometer, immunofluorescence, western blotting, and transmission electron microscopy to detect the mechanism of BBB opening. Finally, measured brain water content, AQP4, GFAP, Iba1, and used the DeadEndTM Fluorometric TUNEL System to clear whether the stimulation caused obvious negative effects. The results show that EA stimulation at 2/100 Hz maximally increased BBB permeability, and the BBB closed within 12 h after EA stimulation was removed. EA stimulation increased blood perfusion, c-fos levels, and Substance P expression in the cerebral cortex, decreased ZO-1 and occludin levels and induced ultrastructural changes in TJ morphology. EA stimulation at specific parameters did not cause brain edema, activation of glial cells, or cell apoptosis. This study shows that EA stimulation induces a reversible, frequency-dependent alteration of BBB permeability and proposes a hypothetical mechanism of BBB opening related to vasodilation and TJ disruption. Transiently enhancing the permeability of the BBB with EA at specific parameters may be a new strategies for delivering therapeutics to the central nervous system. Further study of this technology is needed.

Electroacupuncture: a new approach to open the blood-brain barrier in rats recovering from middle cerebral artery occlusion.

OBJECTIVE: To examine for an opening effect on the blood-brain barrier (BBB) in intact rats and rats with experimental ischaemia-reperfusion (I/R) during the recovery period after various electroacupuncture (EA) treatments with different time courses, and to determine whether there is a time-dependent effect. An additional objective was to determine whether this method could induce the penetration of nerve growth factor (NGF) through the BBB. METHODS: A middle cerebral artery occlusion (MCAO) model was first established. We chose different stimulation time courses and observed the effects of EA treatment (100 Hz frequency; 2 mA intensity) at GV20 and GV26 on the BBB in rats recovering from MCAO 3 weeks after modelling. The rats were injected with 2% Evans blue (EB) saline. The brain water content was measured using a wet/dry weighing method. The degree of penetration of EB was detected using spectrophotometry and laser confocal microscopy. The rats were then injected with NGF, and the concentration of NGF in the brain tissues was measured using ELISA. RESULTS: The increase in the BBB permeability was most notable following the 8 min EA stimulation (P<0.05), which may be advantageous for the targeted delivery of drugs (such as NGF) into the brain. Additionally, this effect did not appear to cause brain oedema (P>0.05) in healthy or MCAO rats. CONCLUSIONS: EA treatment for a certain stimulation time at GV20 and GV26 in MCAO rats can increase BBB permeability.