Efficacy and safety of Qingda granule versus valsartan capsule in Chinese grade 1 hypertensive patients with low-moderate risk: A randomized, double-blind, double dummy, non-inferiority, multi-center trial.

BACKGROUND: The efficacy and safety of Qingda granule (QDG) in managing blood pressure (BP) among grade 1 hypertensive patients with low-moderate risk remain uncertain. METHODS: In the randomized, double-blind, double dummy, non-inferiority and multicenter trial, 552 patients with grade 1 hypertension at low-moderate risk were assigned at a ratio of 1:1 to receive either QDG or valsartan for 4 weeks, followed up by a subsequent 4 weeks. RESULTS: Post-treatment, clinic systolic/diastolic BPs (SBP/DBP) were reduced by a mean change of 9.18/4.04 mm Hg in the QDG group and 9.85/5.05 mm Hg in the valsartan group (SBP P = 0.47, DBP P = 0.16). Similarly, 24-hour, daytime and nighttime BPs were proportional in both groups (P > 0.05) after 4 weeks treatment. After discontinuing medications for 4 weeks, the mean reduction of clinic SBP/DBP were 0.29/0.57 mm Hg in the QDG group compared to -1.59/-0.48 mm Hg in the valsartan group (SBP P = 0.04, DBP P = 0.04). Simultaneously, the 24-hour SBP/DBP were reduced by 0.9/0.31 mm Hg in the QDG group and -1.66/-1.08 mm Hg in the valsartan group (SBP P = 0.006, DBP P = 0.02). And similar results were observed regarding the outcomes of daytime and nighttime BPs. There was no difference in occurrence of adverse events between two groups (P > 0.05). CONCLUSION: QDG proves to be efficacious for grade 1 hypertension at a low-to-medium risk, even after discontinuation of the medication for 4 weeks. These findings provide a promising option for managing grade 1 hypertension and suggest the potential for maintaining stable BP through intermittent administration of QDG. TRIAL REGISTRATION: ChiCTR2000033890.

Quantitative measurement of cell-surface displayed proteins based on split-GFP assembly.

BACKGROUND: Microbial cell surface display technology allows immobilizing proteins on the cell surface by fusing them to anchoring motifs, thereby endowing the cells with diverse functionalities. However, the assessment of successful protein display and the quantification of displayed proteins remain challenging. The green fluorescent protein (GFP) can be split into two non-fluorescent fragments, while they spontaneously assemble and emit fluorescence when brought together through complementation. Based on split-GFP assembly, we aim to: (1) confirm the success display of passenger proteins, (2) quantify the number of passenger proteins displayed on individual cells. RESULTS: In this study, we propose two innovative methods based on split-green fluorescent protein (split-GFP), named GFP1-10/GFP11 and GFP1-9/GFP10-11 assembly, for the purpose of confirming successful display and quantifying the number of proteins displayed on individual cells. We evaluated the display efficiency of SUMO and ubiquitin using different anchor proteins to demonstrate the feasibility of the two split-GFP assembly systems. To measure the display efficiency of functional proteins, laccase expression was measured using the split-GFP assembly system by co-displaying GFP11 or GFP10-11 tags, respectively. CONCLUSIONS: Our study provides two split-GFP based methods that enable qualitative and quantitative analyses of individual cell display efficiency with a simple workflow, thus facilitating further comprehensive investigations into microbial cell surface display technology. Both split-GFP assembly systems offer a one-step procedure with minimal cost, simplifying the fluorescence analysis of surface-displaying cells.

Comparison of laparoscopic hepatectomy and percutaneous radiofrequency ablation for the treatment of small hepatocellular carcinoma: a meta-analysis.

AIM: The purpose of this study was to compare the long-term outcomes of laparoscopic hepatectomy (LH) and percutaneous radiofrequency ablation (PRFA) for the treatment of small hepatocellular carcinoma. METHODS: We systematically searched PubMed, Embase, Web of Science, and Medline from January 2000 to May 2022 for literature comparing the efficacy of LH and PRFA in the treatment of small hepatocellular carcinoma (largest tumour diameter ≤ 3 cm, number of intrahepatic tumours ≤3, or diameter of a single intrahepatic lesion ≤5 cm. ). We assessed overall survival (OS), recurrence-free survival (RFS), local recurrence and complication rates. RESULTS: A total of 1886 patients with small HCC were included in the 8 studies included in this study, of which 839 underwent LH and 1047 underwent PRAF. The results of the meta-analysis showed that the two groups had the same 3-year (HR: 0.99, 95% CI: 0.67 to 1.47) and 5-year (HR: 1.30, 95% CI: 0.90 to 1.87) OS rates, and the LH group had better 3-year (HR: 0.58, 95% CI: 0.49 to 0.68) and 5-year (HR: 0.56, 95% CI: 0.37 to 0.85) RFS rates. The LH group had a lower local recurrence rate (OR: 0.19, 95% CI: 0.12 to 0.32), but the PRFA group had a lower complication rate (OR: 2.49, 95% CI: 1.76 to 3.54). CONCLUSION: There was no difference in OS between LH and PRFA in the treatment of small HCC. LH had a higher RFS rate and a lower local recurrence rate, but PRFA had a lower complication rate. In general, the long-term efficacy of LH in the treatment of small HCC is better than that of PRFA. Considering the advantages of less trauma and a low complication rate of PRFA, a large number of RCT studies are needed for further verification in the future.

Dual Engineering of Lattice Strain and Valence State of NiAl-LDHs for Photoreduction of CO2 to Highly Selective CH4.

Converting CO2 to clean-burning fuel such as natural gas (CH4 ) with high activity and selectivity remains to be a grand challenge due to slow kinetics of multiple electron transfer processes and competitive hydrogen evolution reaction (HER). Herein, the fabrication of surfactants (C11 H23 COONa, C12 H25 SO4 Na, C16 H33 SO4 Na) intercalated NiAl-layered double hydroxides (NiAl-LDH) is reported, resulting in the formation of LDH-S1 (S1 = C11 H23 COO- ), LDH-S2 (S2 = C12 H25 SO4 - ) and LDH-S3 (S3 = C16 H33 SO4 - ) with curved morphology. Compared with NiAl-LDH with a 1.53% selectivity of CH4 , LDH-S2 shows higher selectivity of CH4 (83.07%) and lower activity of HER (3.84%) in CO2 photoreduction reaction (CO2 PR). Detailed characterizations and DFT calculation indicates that the inherent lattice strain in LDH-S2 leads to the structural distortion with the presence of VNi/Al defects and compressed MOM bonds, and thereby reduces the overall energy barrier of CO2 to CH4 . Moreover, the lower oxidation states of Ni in LDH-S2 enhances the adsorption of intermediates such as OCOH* and *CO, promoting the hydrogenation of CO to CH4 . Therefore, the coupling effect of both lattice strain and electronic structure of the LDH-S2 significantly improves the activity and selectivity for CO2 PR.

Revealing the Kinetic Balance between Proton-Feeding and Hydrogenation in CO2 Electroreduction.

Electrocatalytic reduction of CO2 to high-value-added chemicals provides a feasible path for global carbon balance. Herein, the fabrication of NiNP x @NiSA y -NG (x,y = 1, 2, 3; NG = nitrogen-doped graphite) is reported, in which Ni single atom sites (NiSA ) and Ni nanoparticles (NiNP ) coexist. These NiNP x @NiSA y -NG presented a volcano-like trend for maximum CO Faradaic efficiency (FECO ) with the highest point at NiNP2 @NiSA2 -NG in CO2 RR. NiNP2 @NiSA2 -NG exhibited ≈98% of maximum FECO and a large current density of -264 mA cm-2 at -0.98 V (vs. RHE) in the flow cell. In situ experiment and density functional theory (DFT) calculations confirmed that the proper content of NiSA and NiNP balanced kinetic between proton-feeding and CO2 hydrogenation. The NiNP in NiNP2 @NiSA2 -NG promoted the formation of H* and reduced the energy barrier of *CO2 hydrogenation to *COOH, and CO desorption can be efficiently facilitated by NiSA sites, thereby resulting in enhanced CO2 RR performance.

LncRNA DNAJC3-AS1 promotes the biological functions of papillary thyroid carcinoma via regulating the microRNA-27a-3p/CCBE1 axis.

Long noncoding RNA DNAJC3-AS1 (lncRNA DNAJC3-AS1) has been probed in many studies, while the regulatory mechanism of DNAJC3-AS1 on papillary thyroid carcinoma (PTC) via regulating microRNA (miR)-27a-3p remains inadequate. This research aims to depict the role of DNAJC3-AS1, miR-27a-3p, collagen, and calcium-binding EGF domain-containing protein 1 (CCBE1) on PTC development. DNAJC3-AS1, miR-27a-3p, and CCBE1 expression levels in PTC tissues and adjacent normal tissues were tested. The relation of DNAJC3-AS1, miR-27a-3p, and CCBE1 was analyzed. DNAJC3-AS1 and miR-27a-3p and CCBE1-related oligonucleotides were transfected into IHH-4 cells to investigate their role in PTC development. Cell tumorigenicity was detected by in vivo assay. DNAJC3-AS1 and CCBE1 expressed highly and miR-27a-3p expressed lowly in PTC. Downregulation of DNAJC3-AS1, upregulating miR-27a-3p or downregulating CCBE1 impaired the malignant behaviors of IHH-4 cells. Depletion of miR-27a-3p reversed the DNAJC3-AS1 suppression-induced phenotypic inhibition of IHH-4 cells. DNAJC3-AS1 bound to miR-27a-3p and CCBE1 as a target of miR-27a-3p. Our study highlights that DNAJC3-AS1 inhibits miR-27a-3p to promote CCBE1 expression, thereby facilitating PTC development. This study affords distinguished therapeutic strategies and novel research directions for PTC treatment.

Extended application of defective metal oxide BiO2-x: Liquid phase low-temperature thermal catalysis for the removal of phenolic pollutants.

Bismuth oxide (BiO2-x) with oxygen vacancies was created using a hydrothermal process and was found to exhibit good catalytic oxidation performance under low-temperature heating without the addition of external oxidants. The catalytic activity of BiO2-x was tested using 4-chlorophenol (4-CP) as the target aqueous pollutant. We observed that 10 ppm of 4-CP was completely degraded within 40 min at a reaction temperature of 65 °C. The effective elimination of 4-CP was attributed to active oxygen species produced by the release of lattice oxygen. Furthermore, the low-temperature thermal catalytic activity of BiO2-x was affected by the electron transfer characteristics of pollutants, leading to the rapid degradation of electron-rich pollutants. This study reveals the unique application of BiO2-x as a catalyst for removing phenolic pollutants under low-temperature thermal catalysis, thereby expanding its catalytic application scenarios and offering a new approach for the degradation of phenolic pollutants.

Conditional Knockout of Hypoxia-Inducible Factor 1-Alpha in Tumor-Infiltrating Neutrophils Protects against Pancreatic Ductal Adenocarcinoma.

Large numbers of neutrophils infiltrate tumors and comprise a notable component of the inflammatory tumor microenvironment. While it is established that tumor cells exhibit the Warburg effect for energy production, the contribution of the neutrophil metabolic state to tumorigenesis is unknown. Here, we investigated whether neutrophil infiltration and metabolic status promotes tumor progression in an orthotopic mouse model of pancreatic ductal adenocarcinoma (PDAC). We observed a large increase in the proportion of neutrophils in the blood and tumor upon orthotopic transplantation. Intriguingly, these tumor-infiltrating neutrophils up-regulated glycolytic factors and hypoxia-inducible factor 1-alpha (HIF-1α) expression compared to neutrophils from the bone marrow and blood of the same mouse. This enhanced glycolytic signature was also observed in human PDAC tissue samples. Strikingly, neutrophil-specific deletion of HIF-1α (HIF-1αΔNφ) significantly reduced tumor burden and improved overall survival in orthotopic transplanted mice, by converting the pro-tumorigenic neutrophil phenotype to an anti-tumorigenic phenotype. This outcome was associated with elevated reactive oxygen species production and activated natural killer cells and CD8+ cytotoxic T cells compared to littermate control mice. These data suggest a role for HIF-1α in neutrophil metabolism, which could be exploited as a target for metabolic modulation in cancer.

Optical reflectometric measurement of SARS-CoV-2 (COVID-19) RNA based on cationic cysteamine-capped gold nanoparticles.

The coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged as a major public health outbreak in late 2019 and was proclaimed a global pandemic in March 2020. A reflectometric-based RNA biosensor was developed by using cysteamine-stabilized gold nanoparticles (cysAuNPs) as the colorimetric probe for bioassay of COVID-19 RNA (SARS-CoV-2 RNA) sequence. The cysAuNPs aggregated in the presence of DNA probes via cationic and anionic electrostatic attraction between the positively charged cysteamine ligands and the negatively charged sugar-phosphate backbone of DNA, whilst in the presence of target RNAs, the specific recognition between DNA probes and targets depleted the electrostatic interaction between the DNA probes and cysAuNPs signal probe, leading to dispersed particles. This has rendered a remarkable shifting in the surface plasmon resonance (SPR) on the basis of visual color change of the RNA biosensor from red to purplish hue at the wavelength of 765 nm. Optical evaluation of SARS-CoV-2 RNA by means on reflectance transduction of the RNA biosensor based on cysAuNPs optical sensing probes demonstrated rapid response time of 30 min with high sensitivity, good linearity and high reproducibility across a COVID-19 RNA concentration range of 25 nM to 200 nM, and limit of detection (LOD) at 0.12 nM. qPCR amplification of SARS-CoV-2 viral RNA showed good agreement with the proposed RNA biosensor by using spiked RNA samples of the oropharyngeal swab from COVID-19 patients. Therefore, this assay is useful for rapid and early diagnosis of COVID-19 disease including asymptomatic carriers with low viral load even in the presence of co-infection with other viruses that manifest similar respiratory symptoms.

Rational Regulation of Electronic Structure in Layered Double Hydroxide Via Vanadium Incorporation to Trigger Highly Selective CO2 Photoreduction to CH4.

To realize excellent selectivity of CH4 in CO2 photoreduction (CO2 PR) is highly desirable, yet which is challenging due to the limited active sites for CH4 generation and severe electron-hole recombination on photocatalysts. Herein, based on the theoretically calculated effects of vanadium incorporation into the laminate of layered double hydroxides (LDHs), V into NiAl-LDH to synthesize a series of LDHs with various V contents is introduced. NiV-LDH is revealed to afford a high CH4 selectivity (78.9%), and extremely low H2 selectivity (only 0.4%) under λ > 400 nm irradiation. By further tuning the molar ratio of Ni to V, a CH4 selectivity of as high as 90.1% is achieved on Ni4 V-LDH, and H2 is completely prohibited on Ni2 V-LDH. Fine structural characterizations and comprehensive optical and electrochemical studies uncover V incorporation creates the lower-valence Ni species as active sites for generating CH4 , and enhances the generation, separation, and transfer of photogenerated carriers.