NUFIP1-engineered exosomes derived from hUMSCs regulate apoptosis and neurological injury induced by propofol in newborn rats.

BACKGROUND: Propofol can increase neurotoxicity in infants but the precise mechanism is still unknown. Our previous study revealed that nuclear FMR1 interacting protein 1 (NUFIP1), a specific ribophagy receptor, can alleviate T cell apoptosis in sepsis. Yet, the effect of NUFIP1-engineered exosomes elicited from human umbilical cord blood mesenchymal stem cells (hUMSCs) on nerve injury induced by propofol remains unclear. This study intended to investigate the effect of NUFIP1-engineered exosomes on propofol-induced nerve damage in neonatal rats. METHODS: Firstly, NUFIP1-engineered exosomes were extracted from hUMSCs serum and their identification was conducted using transmission electron microscopy (TEM), Flow NanoAnalyzer, quantitative real-time polymerase chain reaction (qRT-PCR), and western blot (WB). Subsequently, the optimal exposure duration and concentration of propofol induced apoptosis were determined in SH-SY5Y cell line using WB. Following this, we co-cultured the NUFIP1-engineered exosomes in the knockdown group (NUFIP1-KD) and overexpression group (NUFIP1-OE) with SH-SY5Y cells and assessed their effects on the apoptosis of SH-SY5Y cells using terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) assay, Hoechst 33258 staining, WB, and flow cytometry, respectively. Finally, NUFIP1-engineered exosomes were intraperitoneally injected into neonatal rats, and their effects on the learning and memory ability of neonatal rats were observed through the righting reflex and Morris water maze (MWM) test. Hippocampi were extracted from different groups for hematoxylin-eosin (HE) staining, immunohistochemistry, immunofluorescence, and WB to observe their effects on apoptosis in neonatal rats. RESULTS: TEM, Flow NanoAnalyzer, qRT-PCR, and WB analyses confirmed that the exosomes extracted from hUMSCs serum exhibited the expected morphology, diameter, surface markers, and expression of target genes. This confirmed the successful construction of NUFIP1-KD and NUFIP1-OE-engineered exosomes. Optimal exposure duration and concentration of propofol were determined to be 24 hours and 100 µg/ml, respectively. Co-culture of NUFIP1 engineered exosomes and SH-SY5Y cells resulted in significant up-regulation of pro-apoptotic proteins Bax and c-Caspase-3 in the KD group, while anti-apoptotic protein Bcl-2 was significantly decreased. The OE group showed the opposite trend. TUNEL apoptosis assay, Hoechst 33258 staining, and flow cytometry yielded consistent results. Animal experiments demonstrated that intraperitoneal injection of NUFIP1-KD engineered exosomes prolonged the righting reflex recovery time of newborn rats, and MWM tests revealed a significant diminution in the time and number of newborn rats entering the platform. HE staining, immunohistochemistry, immunofluorescence, and WB results also indicated a significant enhancement in apoptosis in this group. Conversely, the experimental results of neonatal rats in the OE group revealed a certain degree of anti-apoptotic effect. CONCLUSIONS: NUFIP1-engineered exosomes from hUMSCs have the potential to regulate nerve cell apoptosis and mitigate neurological injury induced by propofol in neonatal rats. Targeting NUFIP1 may hold great significance in ameliorating propofol-induced nerve injury.

Induced dipole moments in amorphous ZnCdS catalysts facilitate photocatalytic H2 evolution.

Amorphous semiconductors without perfect crystalline lattice structures are usually considered to be unfavorable for photocatalysis due to the presence of enriched trap states and defects. Here we demonstrate that breaking long-range atomic order in an amorphous ZnCdS photocatalyst can induce dipole moments and generate strong electric fields within the particles which facilitates charge separation and transfer. Loading 1 wt.% of low-cost Co-MoSx cocatalysts to the ZnCdS material increases the H2 evolution rate to 70.13 mmol g-1 h-1, which is over 5 times higher than its crystalline counterpart and is stable over the long-term up to 160 h. A flexible 20 cm × 20 cm Co-MoSx/ZnCdS film is prepared by a facile blade-coating technique and can generate numerous observable H2 bubbles under natural sunlight, exhibiting potential for scale-up solar H2 production.

H3K27ac-activated LncRNA NUTM2A-AS1 Facilitates the Progression of Colorectal Cancer Cells via MicroRNA-126-5p/FAM3C Axis.

OBJECTIVE: Long non-coding RNAs (lncRNAs) are of great importance in the process of colorectal cancer (CRC) tumorigenesis and progression. However, the functions and underlying molecular mechanisms of the majority of lncRNAs in CRC still lack clarity. METHODS: A Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to detect lncRNA NUTM2A-AS1 expression in CRC cell lines. Cell counting kit 8 (CCK-8) assay and flow cytometry were used to examine the biological functions of lncRNA NUTM2A-AS1 in the proliferation and apoptosis of CRC cells. RT-qPCR and western blot were implemented for the detection of cell proliferation-, apoptosis-related proteins, and FAM3C. Bioinformatics analysis and dual- luciferase reporter assays were utilized to identify the mutual regulatory mechanism of ceRNAs. RESULTS: lncRNA NUTM2A-AS1 notably elevated in CRC cell lines and the silencing of NUTM2A- AS1 declined proliferation and facilitated apoptosis. Mechanistically, NUTM2A-AS1 was transcriptionally activated by histone H3 on lysine 27 acetylation (H3K27ac) enriched at its promoter region, and NUTM2A-AS1 acted as a sponge for miR-126-5p, leading to the upregulation of FAM3C expression in CRC cell lines. CONCLUSION: Our research proposed NUTM2A-AS1 as an oncogenic lncRNA that facilitates CRC malignancy by upregulating FAM3C expression, which might provide new insight and a promising therapeutic target for the diagnosis and treatment of CRC.

Quantifying population-level conservation impacts for a perpetual conservation program on private land.

Area-based targets, such as percentages of regions protected, are popular metrics of success in the protection of nature. While easily quantified, these targets can be uninformative about the effectiveness of conservation interventions and should be complemented by program impact evaluations. However, most impact evaluations have examined the effect of protected areas on deforestation. Studies that have extended these evaluations to more dynamic systems or different outcomes are less common, largely due to data availability. In these cases, simulations might prove to be a valuable tool for gaining an understanding of the potential range of program effect sizes. Here, we employ simulations of wetland drainage to estimate the impact of the United States Fish and Wildlife Service Small Wetlands Acquisition Program (SWAP) across a ten-year period in terms of wetland area, and breeding waterfowl and brood abundance in the Prairie Pothole Region of North Dakota, South Dakota, and Montana. Using our simulation results, we estimate a plausible range of program impact for the SWAP as an avoided loss of between 0.00% and 0.02% of the carrying capacity for broods and breeding waterfowl from 2008-2017. Despite the low programmatic impact that these results suggest, the perpetual nature of SWAP governance provides promising potential for a higher cumulative conservation impact in the long term if future wetland drainage occurs.

Imperfect makes perfect: defect engineering of photoelectrodes towards efficient photoelectrochemical water splitting.

Photoelectrochemical (PEC) water splitting for hydrogen evolution has been considered as a promising technology to solve the energy and environmental issues. However, the solar-to-hydrogen (STH) conversion efficiencies of current PEC systems are far from meeting the commercial demand (10%) due to the lack of efficient photoelectrode materials. The recent rapid development of defect engineering of photoelectrodes has significantly improved the PEC performance, which is expected to break through the bottleneck of low STH efficiency. In this review, the category and the construction methods of different defects in photoelectrode materials are summarized. Based on the in-depth summary and analysis of existing reports, the PEC performance enhancement mechanism of defect engineering is critically discussed in terms of light absorption, carrier separation and transport, and surface redox reactions. Finally, the application prospects and challenges of defect engineering for PEC water splitting are presented, and the future research directions in this field are also proposed.

Corrigendum: Loss of hepatic Surf4 depletes lipid droplets in the adrenal cortex but does not impair adrenal hormone production.

[This corrects the article DOI: 10.3389/fcvm.2021.764024.].

Quantitative Phosphoproteome Analysis of the Interaction Between Fusarium graminearum and Triticum aestivum.

Quantitative proteomics is a powerful method for distinguishing protein abundance changes in a biological system across conditions. In addition to recent advances in computational power and bioinformatics methods, improvements to sensitivity and resolution of mass spectrometry (MS) instrumentation provide an innovative approach for studying host-pathogen interaction dynamics and posttranslational modifications. In this protocol, we provide a workflow for state-of-the-art MS-based proteomics to assess changes in phosphorylated protein abundance upon interaction between the worldwide cereal crop, Triticum aestivum (wheat), and the global cereal crop fungal pathogen, Fusarium graminearum, during infection. This protocol mimics a time course of infection of T. aestivum by F. graminearum in the greenhouse, and the harvested samples undergo Fe-NTA phosphoenrichment combined with label-free quantification (LFQ) for detection by liquid-chromatography (LC)-coupled with tandem MS/MS. Our approach provides an in-depth view of changes in phosphorylation from both the host and pathogen perspectives in a single experiment across infection time points and different host cultivars.

A strategy of local hydrogen capture and catalytic hydrogenation for enhanced therapy of chronic liver diseases.

Background: Chronic liver diseases (CLD) frequently derive from hepatic steatosis, inflammation and fibrosis, and become a leading inducement of cirrhosis and hepatocarcinoma. Molecular hydrogen (H2) is an emerging wide-spectrum anti-inflammatory molecule which is able to improve hepatic inflammation and metabolic dysfunction, and holds obvious advantages in biosafety over traditional anti-CLD drugs, but existing H2 administration routes cannot realize the liver-targeted high-dose delivery of H2, severely limiting its anti-CLD efficacy. Method: In this work, a concept of local hydrogen capture and catalytic hydroxyl radical (·OH) hydrogenation is proposed for CLD treatment. The mild and moderate non-alcoholic steatohepatitis (NASH) model mice were intravenously injected with PdH nanoparticles firstly, and then daily inhaled 4% hydrogen gas for 3 h throughout the whole treatment period. After the end of treatment, glutathione (GSH) was intramuscularly injected every day to assist the Pd excretion. Results: In vitro and in vivo proof-of-concept experiments have confirmed that Pd nanoparticles can accumulate in liver in a targeted manner post intravenous injection, and play a dual role of hydrogen captor and ·OH filter to locally capture/store the liver-passing H2 during daily hydrogen gas inhalation and rapidly catalyze the ·OH hydrogenation into H2O. The proposed therapy significantly improves the outcomes of hydrogen therapy in the prevention and treatment of NASH by exhibiting a wide range of bioactivity including the regulation of lipid metabolism and anti-inflammation. Pd can be mostly eliminated after the end of treatment under the assistance of GSH. Conclusion: Our study verified a catalytic strategy of combining PdH nanoparticles and hydrogen inhalation, which exhibited enhanced anti-inflammatory effect for CLD treatment. The proposed catalytic strategy will open a new window to realize safe and efficient CLD treatment.

Hydrogen inhalation ameliorates hepatic inflammation and modulates gut microbiota in rats with high-fat diet-induced non-alcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is a multisystem metabolic disease associated with gut microflora dysbiosis and inflammation. Hydrogen (H2) is a novel and effective antiinflammatory agent. The present study was aimed to clarify the effects of 4% H2 inhalation on NAFLD and its mechanism of action. Sprague-Dawley rats were fed a high-fat diet for 10 weeks to induce NAFLD. Rats in treatment group inhaled 4% H2 each day for 2 h. The protective effects on hepatic histopathology, glucose tolerance, inflammatory markers, and intestinal epithelial tight junctions were assessed. Transcriptome sequencing of liver and 16 S-seq of cecal contents were also performed to explore the related mechanisms of H2 inhalation. H2 improved the hepatic histological changes and glucose tolerance, decreased the liver function parameters of plasma alanine aminotransferase and aspartate aminotransferase, and relieved liver inflammation. Liver transcriptomic data suggested that H2 treatment significantly downregulated inflammatory response genes, and the lipopolysaccharide (LPS)/Toll-like receptor (TLR) 4/nuclear transcription factor kappa B (NF-κB) signaling pathway might be involved, and the expressions of critical proteins were further validated. Meanwhile, the plasma LPS level was significantly decreased by the H2 intervention. H2 also improved the intestinal tight junction barrier by enhancing the expressions of zonula occludens-1 and occluding. Based on 16S rRNA sequencing, H2 altered the composition of gut microbiota, improving the relative abundance of Bacteroidetes-to-Firmicutes. Collectively, our data show that H2 could prevent NAFLD induced by high-fat diet, and the anti-NAFLD effect is associated with the modulation of gut microbiota and inhibition of LPS/TLR4/NF-κB inflammatory pathway.

Surf4 (Surfeit Locus Protein 4) Deficiency Reduces Intestinal Lipid Absorption and Secretion and Decreases Metabolism in Mice.

BACKGROUND: Postprandial dyslipidemia is a causative risk factor for cardiovascular disease. The majority of absorbed dietary lipids are packaged into chylomicron and then delivered to circulation. Previous studies showed that Surf4 (surfeit locus protein 4) mediates very low-density lipoprotein secretion from hepatocytes. Silencing hepatic Surf4 markedly reduces the development of atherosclerosis in different mouse models of atherosclerosis without causing hepatic steatosis. However, the role of Surf4 in chylomicron secretion is unknown. METHODS: We developed inducible intestinal-specific Surf4 knockdown mice (Surf4IKO) using Vil1Cre-ERT2 and Surf4flox mice. Metabolic cages were used to monitor mouse metabolism. Enzymatic kits were employed to measure serum and tissue lipid levels. The expression of target genes was detected by qRT-PCR and Western Blot. Transmission electron microscopy and radiolabeled oleic acid were used to assess the structure of enterocytes and intestinal lipid absorption and secretion, respectively. Proteomics was performed to determine changes in protein expression in serum and jejunum. RESULTS: Surf4IKO mice, especially male Surf4IKO mice, displayed significant body weight loss, increased mortality, and reduced metabolism. Surf4IKO mice exhibited lipid accumulation in enterocytes and impaired fat absorption and secretion. Lipid droplets and small lipid vacuoles were accumulated in the cytosol and the endoplasmic reticulum lumen of the enterocytes of Surf4IKO mice, respectively. Surf4 colocalized with apoB and co-immunoprecipitated with apoB48 in differentiated Caco-2 cells. Intestinal Surf4 deficiency also significantly reduced serum triglyceride, cholesterol, and free fatty acid levels in mice. Proteomics data revealed that diverse pathways were altered in Surf4IKO mice. In addition, Surf4IKO mice had mild liver damage, decreased liver size and weight, and reduced hepatic triglyceride levels. CONCLUSIONS: Our findings demonstrate that intestinal Surf4 plays an essential role in lipid absorption and chylomicron secretion and suggest that the therapeutic use of Surf4 inhibition requires highly cell/tissue-specific targeting.

Phenylethanoid glycosides extract from Cistanche deserticola ameliorates atherosclerosis in apolipoprotein E-deficient mice and regulates intestinal PPARγ-LXRα-ABCA1 pathway.

OBJECTIVES: This study was aimed to evaluate the protective effects of phenylethanoid glycosides extract from Cistanche deserticola against atherosclerosis and its molecular mechanism. METHODS: Total phenylethanoid glycosides were extracted and purified from C. deserticola, and the C. deserticola extract (CDE) was used to treat a mice model of atherosclerosis. KEY FINDINGS: CDE containing 81.00% total phenylethanoid glycosides, with the contents of echinacoside and acteoside being 31.36% and 7.23%, respectively. A 13-week of CDE supplementation (1000 mg/kg body weight/day) significantly reduced atherosclerotic lesions in the aortic sinus and entire aorta in ApoE-/- mice fed with a high-fat diet. In addition, varying doses of CDE (250, 500 and 1000 mg/kg body weight/day) lowered plasma total cholesterol, triglyceride and non-high-density lipoprotein cholesterol levels. Transcriptomic analysis of the small intestine revealed the changes enriched in cholesterol metabolic pathway and the activation of Abca1 gene. Further validation using real-time quantitative PCR and western blot confirmed that CDE significantly increased the mRNA levels and protein expressions of ABCA1, LXRα and PPARγ. CONCLUSIONS: Our results demonstrate the beneficial effects of C. deserticola on atherosclerotic plaques and lipid homeostasis, and it is, at least partially, by activating PPARγ-LXRα-ABCA1 pathway in small intestine.

A BiVO4 Photoanode with a VOx Layer Bearing Oxygen Vacancies Offers Improved Charge Transfer and Oxygen Evolution Kinetics in Photoelectrochemical Water Splitting.

Sluggish oxygen evolution kinetics are one of the key limitations of bismuth vanadate (BiVO4 ) photoanodes for efficient photoelectrochemical (PEC) water splitting. To address this issue, we report a vanadium oxide (VOx ) with enriched oxygen vacancies conformally grown on BiVO4 photoanodes by a simple photo-assisted electrodeposition process. The optimized BiVO4 /VOx photoanode exhibits a photocurrent density of 6.29 mA cm-2 at 1.23 V versus the reversible hydrogen electrode under AM 1.5 G illumination, which is ca. 385 % as high as that of its pristine counterpart. A high charge-transfer efficiency of 96 % is achieved and stable PEC water splitting is realized, with a photocurrent retention rate of 88.3 % upon 40 h of testing. The excellent PEC performance is attributed to the presence of oxygen vacancies in VOx that forms undercoordinated sites, which strengthen the adsorption of water molecules onto the active sites and promote charge transfer during the oxygen evolution reaction. This work demonstrates the potential of vanadium-based catalysts for PEC water oxidation.

Inhalation of 4% and 67% hydrogen ameliorates oxidative stress, inflammation, apoptosis, and necroptosis in a rat model of glycerol-induced acute kidney injury.

Acute kidney injury (AKI) is the major complication of rhabdomyolysis (RM) clinically, which is usually mimicked by glycerol injection in basic research. Oxidative stress, inflammatory response and apoptosis are recognized to play important roles in development of this disease. Recently, numerous studies have reported the therapeutic effects of molecular hydrogen (H2) on oxidative stress and inflammation-related diseases. Here, the effects of H2 against glycerol-induced AKI and the underlying mechanisms were explored in rats. Low (4%) and high (67%) concentrations of H2 were prepared using a self-made device to investigate the dose-response. After 72 hours of glycerol injection (8 mL/kg), we found that glycerol triggered oxidative stress, inflammatory reactions, and apoptotic events. These caused subsequent renal damage, evidenced by a significant reduction of antioxidases and up-regulation of the relevant damaged biomarkers. H2 inhalation reversed the above alterations and exerted renoprotective effects. Interestingly, for RM/AKI-related factors, no consistent dose-response benefits of H2 were observed. However, higher concentration of H2 inhalation improved histological and morphological changes better. This study suggests that H2 is a potential alternative therapy to prevent or minimize RM induced AKI possibly via its antioxidant, anti-inflammatory, anti-apoptotic and anti-necroptotic properties.

[Effects of Qilan Prescription on the proliferation and apoptosis of human prostate cancer DU145 cells and its action mechanism].

OBJECTIVE: To investigate the effects of different concentrations of Qilan Prescription (QLP) on the proliferation and apoptosis of human PCa DU145 cells and its underlying mechanism. METHODS: We treated human PCa DU145 cells with QLP at 400, 200, 100, 50, 25, 12.5, 6.25, 3.125 or 1.56 µg/ml for 24, 48 and 72 hours respectively. Then we observed the morphological changes of the cells, examined their viability by CCK-8 assay, detected their cell cycle and apoptosis by flow cytometry, and determined the protein expressions of cyclin D1, Bax, Bcl-2 and cleaved-caspase 3 in the DU145 cells by Western blot, followed by comparison of the parameters with those obtained from the blank control group. RESULTS: QLP significantly inhibited the growth, reduced the contour clarity and adhesion ability of the DU145 cells at the concentrations of 100, 200 and 400 µg/ml, and markedly decreased the activity of the cells at 200 and 400 µg/ml, most significantly at 400 µg/ml. The number of the G2-phase DU145 cells was dramatically increased in all the concentration groups (P < 0.01), so was the total number of apoptotic DU145 cells (P < 0.01), while that of the S-phase cells remarkably decreased in the 400 µg/ml QLP (P < 0.01) and 200 µg/ml QLP (P < 0.05) groups. The expression of the cyclin D1 protein was significantly down-regulated in the 400 µg/ml QLP group (P < 0.01). That of Bcl-2 was also down-regulated (P < 0.01) while those of Bax and cleaved-caspase 3 up-regulated in the 400 and 200 µg/ml QLP groups (P < 0.01). CONCLUSION: QLP can inhibit the proliferation and promote the apoptosis of human PCa DU145 cells, which may be associated with its effects of down-regulating the expression of the cell cycle-related protein cyclin D1, disrupting the Bax-Bcl-2 balance, and up-regulating the expression of cleaved-caspase 3.

Clinical application of a digital positioning guide template during the extraction of maxillary wholly impacted supernumerary teeth / 口腔疾病防治

Objective@#To evaluate the clinical efficacy of positioning guide templates for maxillary wholly impacted supernumerary teeth to provide technological solutions for clinical applications. @*Methods @#After approval by the hospital ethics committee and informed consent given by the patients. Data from 136 patients with maxillary wholly impacted supernumerary teeth from January 2016 to April 2022 were analyzed retrospectively. The patients were divided into two groups according to the usage of the positioning guide template. The experimental group included patients using the positioning guide template (71 cases), and the control group did not use the positioning guide template (65 cases). The operation time and complications were statistically analyzed to evaluate the clinical efficacy after surgery. @*Results @# All operations were successfully completed. The average operation time in the experimental group was (21.5 ± 3.4) min, significantly shorter than that in the control group (27.2 ± 4.9) min. There were statistically significant differences between the experimental and control groups (t = 7.599, P<0.001). One week after the operation, there were no complications in the experimental group, and there were 2 cases of adjacent tooth injury and 3 cases of gingival numbness in the control group.@* Conclusion @# A digital positioning guide template can effectively shorten the time of maxillary wholly impacted supernumerary teeth extraction and is an effective means to assist clinical maxillary wholly impacted supernumerary teeth extraction.

Accurate in vivo real-time determination of the hydrogen concentration in different tissues of mice after hydrogen inhalation.

As an antioxidant, anti-inflammatory and anti-apoptotic agent, hydrogen (H2) shows a promising potential in basic and clinical research against various diseases owing to its safety and efficacy. However, knowledge involving its underlying mechanisms of action, dosage effects, and dose duration remains limited. Previously, the dynamics of H2 concentrations in different tissues of rats after exogenous H2 inhalation had been detected by our team. Here, sequential changes of H2 concentrations in different tissues of another most commonly used experimental rodent mice were monitored in real time with an electrochemical H2 gas sensor during continuous different concentrations of H2 inhalation targeting on five tissues including brain, liver, spleen, kidney, and gastrocnemius. The results showed that the H2 saturation concentrations varied among tissues significantly regardless of the concentration of H2 inhaled, and they were detected the highest in the kidney but the lowest in the gastrocnemius. Meantime, it required a significant longer time to saturate in the thigh muscle. By comparing the H2 saturation concentrations of mice and rats, we found that there were no differences detected in most tissues except the kidney and spleen. Both gas diffusion and bloodstream transport could help the H2 reach to most organs. The results provide data reference for dosage selection, dose duration determination to ensure optimal therapeutic effects of H2 for mice experiments.

The effect of a low dose hydrogen-oxygen mixture inhalation in midlife/older adults with hypertension: A randomized, placebo-controlled trial.

Objective: To explore the effect of a low-dose hydrogen-oxygen (H2-O2) mixture inhalation in midlife/older adults with hypertension. Methods: This randomized, placebo-controlled trial included 60 participants with hypertension aged 50-70 years who were randomly divided into Air group (inhaled placebo air) or H2-O2 group [inhaled H2-O2 mixture (66% H2/33% O2)]. Participants in both groups were treated 4 h per day for 2 weeks. Four-limb blood pressure and 24-h ambulatory blood pressure were monitored before and after the intervention, and levels of plasma hormones related to hypertension were determined. Results: A total of 56 patients completed the study (27 in the Air group and 29 in the H2-O2 group). The right and left arm systolic blood pressure (SBP) were significantly decreased in H2-O2 group compared with the baseline levels (151.9 ± 12.7 mmHg to 147.1 ± 12.0 mmHg, and 150.7 ± 13.3 mmHg to 145.7 ± 13.0 mmHg, respectively; all p < 0.05). Meanwhile, the H2-O2 intervention significantly decreased diastolic nighttime ambulatory blood pressure by 2.7 ± 6.5 mmHg (p < 0.05). All blood pressures were unaffected in placebo group (all p > 0.05). When stratified by age (aged 50-59 years versus aged 60-70 years), participants in the older H2-O2 group showed a larger reduction in right arm SBP compared with that in the younger group (p < 0.05). In addition, the angiotensin II, aldosterone, and cortisol levels as well as the aldosterone-to-renin ratio in plasma were significantly lower in H2-O2 group compared with baseline (p < 0.05). No significant differences were observed in the Air group before and after the intervention. Conclusion: Inhalation of a low-dose H2-O2 mixture exerts a favorable effect on blood pressure, and reduces the plasma levels of hormones associated with hypertension on renin-angiotensin-aldosterone system and stress in midlife/older adults with hypertension.

Photoactive terahertz metasurfaces for ultrafast switchable sensing of colorectal cells.

Metasurfaces with a strongly enhanced local field are envisioned as a powerful platform for ultrasensitive optical sensors to significantly amplify imperceptible differences between compatible bioanalytes. Through the use of phototunable silicon-based terahertz (THz) metasurfaces, we experimentally demonstrate ultrafast switchable sensing functions. It is found that the THz responses of the coupled-resonances in the metasurfaces shift from Lorentz-lattice mode to electromagnetism-induced transparency (EIT) mode under optical pumping within an ultrashort time of 32 ps, enabling an ultrafast sensitive sensor. For the Lorentz-lattice mode, the THz time-domain signal directly shows a highly sensitive response to detect tiny analytes without extra Fourier transformation as the mismatch between the two modes increases. Once the metasurfaces are switched to the EIT mode, the silicon-metal hybrid structure supports frequency-domain sensing ability due to strong field confinement with a sensitivity of 118.4 GHz/RIU. Both of the sensing configurations contribute to more subtle information and guarantee the accuracy of the sensor performance. Combined with the aforementioned advantages, the proposed metasurfaces have successfully identified colorectal cells between normal, adenoma, and cancer states in experiments. This work furnishes a new paradigm of constructing reliable and flexible metasurface sensors and can be extended to other optics applications.

Correlation between apparent diffusion coefficient and tumor-stroma ratio in hybrid 18F-FDG PET/MRI: preliminary results of a rectal cancer cohort study.

Background: To explore possible correlations between the tumor-stroma ratio (TSR) and different imaging features of fluorine-18-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging (18F-FDG PET/MRI) in untreated rectal cancer patients. Methods: A patients with rectal cancer were included in this study. All participants were examined preoperatively with whole-body 18F-FDG PET/MRI. Two pathologists evaluated the TSR of tumors together. Apparent diffusion coefficient (ADC) values and PET-related parameters of the primary lesions were measured and compared between the stroma-high and stroma-low groups. Pearson's correlation or Spearman's rank correlation were used to evaluate the correlation between the ADC values, PET-related parameters, and pathological indices. Results: Our results showed that in the untreated rectal cancer patients, the ADC mean values correlated with the TSR (r=0.327; P=0.007), and stroma-high (low TSR) rectal cancer corresponded to relatively lower ADC mean values (813.54±88.68 vs. 879.92±133.18; P=0.018). The ADC mean and ADC minimum (ADCmin) values were found to be negatively correlated with the pathological T stages (r=-0.384, P=0.001; r=-0.416, P=0.001, respectively) as well as the largest tumor diameters (r=-0.340, P=0.005; r=-0.314, P=0.010, respectively) of rectal cancer. In addition, the pathological T stages correlated with all PET-related metabolic parameters, including mean standard uptake value (SUV), maximum SUV (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) (r=0.338, P=0.006; r=0.350, P=0.004; r=0.326, P=0.007; and r=0.472, P<0.001, respectively). Our results also identified associations between the ADCmin values and SUVmean, SUVmax, and TLG (r=-0.335, P=0.006; r=-0.343, P=0.005; and r=-0.343, P=0.005, respectively). However, there were no statistical correlations between the PET/MRI parameters and the immunohistochemical (IHC) results. Conclusions: This study indicated that the intratumoral heterogeneity measured by PET/MRI may reflect characteristics of the tumor microenvironment. Hence, PET/MRI parameters might be helpful in predicting tumor aggressiveness and prognosis.

miR-887-3p Inhibits the Progression of Colorectal Cancer via Downregulating DNMT1 Expression and Regulating P53 Expression.

Colorectal cancer (CRC) is the third most diagnosed cancer worldwide and the second leading cause of cancer-related deaths. Many researchers have reported that abnormal microRNAs (miRs) were expressed in CRC and participated in the occurrence and progression of CRC. However, there are few reports of miR-887-3p regulating CRC development. In the current study, we investigated the abnormal expression of miR-887-3p and also demonstrated its regulatory role and detailed molecular mechanism in CRC. Initially, miRNA expression data were obtained from TCGA-COAD that consisted of 453 CRC samples and 8 normal tissue samples. These were downloaded and analyzed to compare the expression level of miR-887-3p in CRC tissues to that in normal tissues. Moreover, 32 pairs of surgically resected CRC tumors and para-cancer tissues from our hospital were collected. Quantitative real-time PCR (qRT-PCR) was performed to detect miR-887-3p expression levels in CRC tissues, para-cancer tissues, several CRC cell lines, and an intestinal epithelial cell line. Following miR-887-3p mimic transfection in colon cancer SW480 cell line, the regulatory roles of miR-887-3p on cell proliferation, apoptosis, invasion, migration, and epithelial-mesenchymal transition (EMT) were detected through CCK-8, flow cytometry, transwell assay, and Western blot. After potential targeting protein was predicted by bioinformatic websites, the luciferase reporter assay and Western blot were used to confirm the target of miR-887-3p. The targeting protein expressions were detected by Western blot and qRT-PCR. The relationship between miR-887-3p level and the effect of miR-887-3p on P53 expression was evaluated by Western blot and qRT-PCR. The effects of miR-887-3p on CRC cell growth in vivo by xenograft tumor experiments were investigated, and Ki-67 in tumor tissue was determined by immunohistochemistry. Results. The COAD data demonstrated that the expression levels of miR-887-3p in CRC clinical sample tissues and cell line cultures were remarkably lower than para-cancer normal tissues and NCM460 cells (normal colonic epithelial cell line). Functional experiments demonstrated that overexpression of miR-887-3p in SW480 cells significantly reduced proliferation, migration, invasion, and EMT, and promoted cancer cell apoptosis. Additionally, Western blot, qRT-PCR, and luciferase reporter assays confirmed that DNMT1 was a downstream target of miR-887-3p. Moreover, the blocking of DNMT1 by miR-887-3p mimics also promoted P53 expression. Finally, overexpression of DNMT1 in SW480 cells could partially reverse the regulatory effect of miR-887-3p mimics on CRC cell development. From in vivo experiments, overexpression of miR-887-3p could inhibit tumor growth in CRC xenograft mice and reduce the Ki-67 level. Conclusion. The microRNA miR-887-3p is a potential biomarker of CRC. It inhibited CRC cell proliferation, invasion, and EMT, and promoted cell apoptosis through targeting and downregulating DNMT1 and promoting P53 expression. Therefore, miR-887-3p may be a good biomarker and therapeutic target for CRC treatment.