Paeoniflorin promotes PPARγ expression to suppress HSCs activation by inhibiting EZH2-mediated histone H3K27 trimethylation.

BACKGROUND: The alleviating effect of paeoniflorin (Pae) on liver fibrosis has been established; however, the molecular mechanism and specific target(s) underlying this effect remain elusive. PURPOSE: This study was to investigate the molecular mechanism underlying the regulatory effect of Pae on hepatic stellate cells (HSCs) activation in liver fibrosis, with a specific focus on the role of Pae in modulating histone methylation modifications. METHODS: The therapeutic effect of Pae was evaluated by establishing in vivo and in vitro models of carbon tetrachloride (CCl4)-induced mice and transforming growth factor ß1 (TGF-ß1)-induced LX-2 cells, respectively. Molecular docking, surface plasmon resonance (SPR), chromatin immunoprecipitation-quantitative real time PCR (ChIP-qPCR) and other molecular biological methods were used to clarify the molecular mechanism of Pae regulating HSCs activation. RESULTS: Our study found that Pae inhibited HSCs activation and histone trimethylation modification in liver of CCl4-induced mice and LX-2 cells. We demonstrated that the inhibitory effect of Pae on the activation of HSCs was dependent on peroxisome proliferator-activated receptor γ (PPARγ) expression and enhancer of zeste homolog 2 (EZH2). Mechanistically, Pae directly binded to EZH2 to effectively suppress its enzymatic activity. This attenuation leaded to the suppression of histone H3K27 trimethylation in the PPARγ promoter region, which induced upregulation of PPARγ expression. CONCLUSION: This investigative not only sheds new light on the precise targets that underlie the remission of hepatic fibrogenesis induced by Pae but also emphasizes the critical significance of EZH2-mediated H3K27 trimethylation in driving the pathogenesis of liver fibrosis.

Dual-mode fluorimetric and colorimetric sensors based on iron and nitrogen co-doped carbon dots for the detection of dopamine.

Determination of dopamine (DA) is crucial for its intimate relationship with clinical trials and biological environment. Herein, Fe, N co-doped carbon dots (AFC-CDs) were fabricated by optimizing precursors and reaction conditions for fluorimetric/colorimetric dual-mode sensing of DA. With synergistic influence of Förster resonance energy transfer and static quenching effect, DA significantly quenched the blue luminescence of AFC-CDs at 442 nm, the production of recognizable tan-brown complex caused evident colorimetric response, achieved the dual-mode fluorimetric/colorimetric sensing for DA. The excellent selectivity and satisfied sensitivity can be confirmed with the limit of detection at 0.29 µM and 2.31 µM via fluorimetric/colorimetric mode respectively. The reliability and practicability were proved by recovery of 94.81-101.61% in real samples. Notably, the proposed electron transfer way between AFC-CDs and DA was hypothesized logically, indicated dual-mode probe provided a promising platform for the sensing of trace DA, and could be expanded in environment and food safety.

Portable smartphone platform utilizing AIE-featured carbon dots for multivariate visual detection for Cu2+, Hg2+ and BSA in real samples.

Heavy metals cause serious toxic threats to both environment and human health. The multivariate, instrument-free, portable, and rapid detection strategy is crucial for determination of heavy metals. Herein, aggregation-induced emission (AIE) featured carbon dots (SN-CDs) were fabricated hydrothermally by optimizing co-doping precursors. With bright yellow emission at 560 nm, the SN-CDs were utilized for multivariate sensing Cu2+, Hg2+ and bovine serum albumin (BSA) based on AIE behavior and static quenching effect, with detection limits of 0.46 µmol·L-1, 25.8 nmol·L-1 and 1.52 µmol·L-1. A portable smartphone platform was constructed to enable portable, prompt, and sensitive analysis for Cu2+, Hg2+, and BSA via different strategies in real water and food samples with satisfied recovery. Moreover, a logic gate circuit was designed to provide the possibilities for utilization of intelligent facility. The proposed AIE SN-CDs possessing great contribution in preferable sensing performance, present promising prospects in real-time monitoring of environment and food safety.

An integrated network pharmacology, molecular docking and experiment validation study to investigate the potential mechanism of Isobavachalcone in the treatment of osteoarthritis.

BACKGROUND: In many different plants, including Dorstenia and Psoralea corylifolia L., Isobavachalcone (IBC) is a naturally occurring flavonoid chemical having a range of biological actions, including anti-inflammatory, immunomodulatory, and anti-bacterial. The "Theory of Medicinal Properties" of the Tang Dynasty states that Psoralea corylifolia L. has the ability to alleviate discomfort in the knees and waist. One of the most widespread chronic illnesses, osteoarthritis (OA), is characterized by stiffness and discomfort in the joints. However, there hasn't been much research done on the effectiveness and underlying processes of IBC in the treatment of osteoarthritis. AIM OF THE STUDY: To investigate the potential efficacy and mechanism of IBC in treating osteoarthritis, we adopted an integrated strategy of network pharmacology, molecular docking and experiment assessment. MATERIALS AND METHODS: The purpose of this research was to determine the impact of IBC on OA and the underlying mechanisms. IBC and OA possible targets and processes were predicted using network pharmacology, including the relationship between IBC and OA intersection targets, Cytoscape protein-protein interaction (PPI) to obtain key potential targets, and GO and KEGG pathway enrichment analysis to reveal the probable mechanism of IBC on OA. Following that, in vitro tests were carried out to confirm the expected underlying processes. Finally, in vivo tests clarified IBC's therapeutic efficacy on OA. RESULTS: We anticipated and validated that the impact of IBC on osteoarthritis is mostly controlled by the PI3K-AKT-NF-κB signaling pathway by combining the findings of network pharmacology analysis, molecular docking and Experiment Validation. CONCLUSIONS: This study reveals the IBC has potential to delay OA development.

Goal-directed fluid therapy using stroke volume variation on length of stay and postoperative gastrointestinal function after major abdominal surgery-a randomized controlled trial.

BACKGROUND AND OBJECTIVE: The effectiveness of goal-directed fluid therapy (GDFT) in promoting postoperative recovery remains unclear, the aim of this study was to evaluate the effect of GDFT on length of hospital stay and postoperative recovery of GI function in patients undergoing major abdominal oncologic surgery. METHODS: In this randomized, double- blinded, controlled trial, adult patients scheduled for elective major abdominal surgery with general anesthesia, were randomly divided into the GDFT protocol (group G) or conventional fluid therapy group (group C). Patients in group C underwent conventional fluid therapy based on mean arterial pressure (MAP) and central venous pressure (CVP) whereas those in group G received GDFT protocol associated with the SVV less than 12% and the cardiac index (CI) was controlled at a minimum of 2.5 L/min/m2. The primary outcomes were the length of hospital stay and postoperative GI function. RESULTS: One hundred patients completed the study protocol. The length of hospital stay was significantly shorter in group G compared with group C [9.0 ± 5.8 days versus 12.0 ± 4.6 days, P = 0.001]. Postoperative gastrointestinal dysfunction (POGD) occurred in two of 50 patients (4%) in group G and 16 of 50 patients (32%) in the control group (P < 0.001). GDFT significantly also shorten time to first flatus by 11 h (P = 0.009) and time to first tolerate oral diet by 2 days (P < 0.001). CONCLUSIONS: Guided by SVV and CI, the application of GDFT has the potential to expedite postoperative recovery of GI function and reduce hospitalization duration after major abdominal surgery. TRIAL REGISTRATION: This study was registered on www. CLINICALTRIALS: gov on 07/05/2019 with registration number: NCT03940144.

Effect of statins on pulmonary function in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis of randomized controlled trials.

Background: Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease, and its treatment is still controversial. Statins have been proven to have anti-inflammatory and immunomodulatory effects, but their effectiveness in the treatment of COPD is still unclear. We conducted this meta-analysis to more accurately evaluate the therapeutic effect of statins on COPD patients. Methods: Randomized controlled studies published in PubMed, Cochrane Library, Embase, Wiley Online Library, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang databases from inception to July 2022 were retrieved to evaluate the effect of statins on COPD patients. Two evaluators conducted literature screening based on inclusion and exclusion criteria, and conducted a bias risk assessment on them. Meta analysis was conducted using Stata17.0 statistical software. Results: A total of 1,463 patients from 10 studies were included. After statin treatment, the percentage of predicted forced expiratory volume in the first second (FEV1%pred) of COPD patients was improved [weighted mean difference (WMD): 7.89; 95% confidence interval (CI): 7.19-8.60; P<0.05], and the level of the inflammatory factor C-reactive protein (CRP) decreased (WMD: -0.63; 95% CI: -1.84, 0.58; P<0.05). The 6-minute walking distance (6MWD) of patients in the statin treatment group demonstrated a significant benefit (WMD: 26.27; 95% CI: 24.02-28.51; P<0.05). Compared to the placebo control group, statins significantly reduced COPD Assessment Test (CAT) (WMD: -2.45; 95% CI: -3.62, -1.27). Conclusions: Preliminary evidence suggests that statins may have a certain effect on improving lung function, reducing inflammatory factor levels, and improving clinical symptoms in COPD patients. However, due to the quality and quantity limitations of the included studies, these results need to be further verified through a larger, higher quality randomized controlled trial (RCT).

Construction of the molecularly imprinted adsorbent based on shaddock peel biochar sphere for highly sensitive detection of ribavirin in food and water resources.

Ribavirin (RBV) that is not metabolically released into the environment can contaminate the environment and even make organisms resistant to it. Therefore, it is of great significance to establish a simple and effective method for adsorbing RBV in the environment. In this study, a novel biochar-based boronate affinity molecularly imprinted polymers (C@H@B-MIPs) were synthesized. This is the first time that shaddock peel biochar sphere was used as a carrier for specific recognition of RBV. The polymerization conditions were optimized and the binding properties of RBV were studied. Benefiting from the synergistic effect of boronate affinity and surface imprinting, the C@H@B-MIPs showed rapid equilibrium kinetics of 15 min, high adsorption capacity of 18.30 mg g-1, and excellent reusability for RBV. The linear range was 0.05-100 mg L-1, and the detection limit was 0.023 mg L-1. This method was triumphant applied to the selective adsorption of RBV in food and water resources with recovery rates of 81.4-97.7%. This study provides a practical platform for the manufacture of efficient biomass-based adsorbents.

Controllable synthesis of bifunctional magnetic carbon dots for rapid fluorescent detection and reversible removal of Hg2.

Mercury is one of the most toxic heavy metals, whose identification and separation are crucial for environmental remediation. Till now, it remains a significant challenge upon simultaneous detection and removal of Hg2+. Herein, bifunctional probe magnetic carbon dots were synthesized and optimized via systematic structure manipulation of the carbon and iron precursors towards fluorescence, Hg2+ adsorption and magnetic separation. The probe exhibited blue emission at 440 nm with high quantum yield of 55 % and a high paramagnetism with the saturation magnetization value of 22.70 emu/g. Furthermore, the fluorescent detection of Hg2+ with limit of 5.40 nM and high selectivity were achieved through surface structure manipulation with moderate -NH2, -SH and Fe contents. As a result, the magnetic removal of Hg2+ was consecutively effectuated with high removal efficiency of 98.30 %. The detection and recovery of Hg2+ in real samples were further verified and demonstrated the excellent environmental tolerance of probe. The reusability was viable with recycling at least three turns by external magnet. This work not only provides a promising approach for simultaneous detection and removal of heavy metal pollution, but also provides an excellent example as a versatile platform for multifunction integration via the structure manipulation for other applications.

Grain Refinement Mechanism of 5A06 Aluminum Alloy Sheets during Cold Rotary Forging.

This paper studies the grain refinement mechanisms of 5A06 aluminum alloy sheets in cold rotary forging (CRF). The results show that the grains are clearly refined from 25.1 µm to 11.8 µm during the CRF process. The grain refinement mechanism can be divided into two modes: (1) The grains with a small Schmid factor (SF) are activated by multi-slip systems, and dense dislocations are segregated along the boundaries of interior regions with different slip systems, which results in a rapidly increasing strain localization along these boundaries. Since the strain localization restrains the coordinate slip deformation between different interior regions, the grains are directly separated into several finer grains. (2) The grains with a large SF are primarily activated by a single slip system, and the dislocation migrates smoothly along most microband boundaries. Then, a more severe lattice rotation causes a transformation to a hard orientation and multi-slip system activation, which contributes to an increase in the rapid misorientation across microband boundaries and thus promotes significant SF grain refinement.

Portable smartphone-integrated AuAg nanoclusters electrospun membranes for multivariate fluorescent sensing of Hg2+, Cu2+ and l-histidine in water and food samples.

Detection of heavy metals have been pivotal due to their non-biodegradability and food chain accumulation. Herein, a multivariate ratiometric sensor was developed by in situ integrating AuAg nanoclusters (NCs) into electrospun cellulose acetate nanofibrous membranes (AuAg-ENM) for visual detection of Hg2+, Cu2+ and consecutive sensing of l-histidine (His), which was integrated into a smartphone platform for quantitative on-site detection. AuAg-ENM achieved multivariate detection of Hg2+ and Cu2+ by fluorescence quenching, and subsequent selective recovery of the Cu2+-quenched fluorescence by His, which distinguished Hg2+ and Cu2+ and fulfilled determination of His simultaneously. Notably, AuAg-ENM achieved selective monitoring of Hg2+, Cu2+ and His in water, food and serum samples with high accuracy comparable to ICP and HPLC tests. A logic gate circuit was devised to further explain and promote the application of AuAg-ENM detection by smartphone App. This portable AuAg-ENM provides a promising reference for fabricating intelligent visual sensors for multiple detection.

The synthesis of gold nanoclusters with high stability and their application in fluorometric detection for Hg2+ and cell imaging.

Sensing Hg2+ is significant to protecting human health and environmental ecosystems, for its toxicity and genotoxicity. Here, highly stable fluorescent folic acid (FA)-protected Au nanoclusters (FA-AuNCs) were synthesized by optimizing the reactive parameters with high quantum yield of 34.7%. Main components of Au4L were confirmed by MALDI-TOF, and the electron-rich residues of FA shell enabled FA-AuNCs excellent photostability. FA-AuNCs exhibited sensitive response behavior to Hg2+ with a minimum detectability of 1.3 nM, and presented extreme effect to the detection of Hg2+ in real water. Notably, the cellular imaging and in-situ detection of Hg2+ in cells can be achieved visually. The high selectivity was attributed to the chemical bond formed between Au+ (4f145d10) and Hg2+ (4f145d10). And the internal filter effect and static quenching effect were proved triggering the quenching of FA-AuNCs. The ultra-stable FA-AuNCs provide a potential promising opportunity for the in-situ tracing Hg2+ from environmental and biological samples.

The fabrication of N-doped carbon dots by methionine and their utility in sensing Cu2+ in real water.

Copper ions (Cu2+) are ubiquitous in the ecosystem and cause serious environmental pollution, posing a threat to human health. Therefore, sensitive detection of Cu2+ is urgently needed. Herein, we employed a solvothermal method to prepare blue-emitting carbon dots (Met-CDs) using formamide (FA) and methionine (Met) as precursors, with a high quantum yield (QY) of 38%. Based on the good optical stability of Met-CDs and selective quenching by Cu2+, a sensitive probe using Met-CDs for the detection of Cu2+ in water was successfully designed. Within the linear range of 0.15-2 µM, the limit of detection (LOD) was determined to be as low as 47.7 nM, enabling the quantitative detection of Cu2+. Moreover, the recovery data of the spiked analysis of lake/river water samples were also satisfactory and verified the feasibility of the probe by the analysis of Cu2+ in natural conditions.

The synthesis of carbon dots by folic acid and utilized as sustainable probe and paper sensor for Hg2+ sensing and cellular imaging.

In this work, the blue emission carbon dots (FA-CDs) are synthesized by one-pot solvothermal method by using folic acid as precursor. The FA-CDs emitted bright emission at 445 nm when excited at 360 nm with the QY of 31.2 %. The FA-CDs exhibit sensitive quenching response to Hg2+ with variable concentrations systematically, which determined FA-CDs can be employed as fluorescent probe, with a reliable linear relationship between fluorescence intensity and Hg2+ concentration, and a limit of detection (LOD) of 1.29 nM. Notably, the quenched FA-CDs can be recovered by using EDTA saturated solution with the emission comparable to initial in succession. The FA-CDs based paper sensor can be explored with similar detection performance, and it can also be restored by EDTA saturated solution. Both the restored CDs and paper sensor can be reused in the next turn for detecting Hg2+, which allowed the FA-CDs and their paper sensor can be serviced as sustainable probe for Hg2+ detection. The visual LOD of paper sensor can be determined at 0.1 µM, notably, the paper sensor can be reused at least 3 times with good performance, which is beneficial to environmental protection and saving resources. Possess excellent water solubility and non-toxic properties, the cellular imaging of FA-CDs was evaluated with excellent quality fluorescent image results. The FA-CDs provide a promising convenient fluorescent probe for multi-application in detection and imaging.

Amino acid-immobilized copper ion-modified carbon-based adsorbent for selective adsorption of bovine hemoglobin.

We prepared an amino acid-immobilized copper ion-modified carbon-based adsorbent (C@TA@P@A-Cu) for selective bovine hemoglobin (BHb) adsorption in biological samples. Carbon nanoparticles were used as the matrix, and copper ions were attached to the amino acid-modified carbon nanoparticles as metal chelate complexes via immobilized metal affinity. BSA, Lyz, OVA, and HRP were chosen as reference proteins for further study. Furthermore, the synthesis conditions of adsorbents, SPE conditions, selectivity, competitivity, reproducibility, and reusability were extensively investigated. The results showed that the maximum adsorption capacity of C@TA@P@A-Cu microspheres for BHb under optimal conditions was 673.0 mg g-1. The addition of a TiO2 layer with an increased specific surface area of the adsorbent and the addition of poly-l-lysine (PLL) inhibited the adsorbent's binding ability to non-BHb proteins, but chelated Cu2+ increased the adsorbent's specific binding ability to BHb. Furthermore, after six adsorption-desorption cycles, the adsorbent has satisfactory reusability with no significant change in adsorption capacity. Furthermore, C@TA@P@A-Cu was successfully used to identify BHb from real blood samples, as confirmed by SDS-PAGE, and it is expected to have potential applications in protein purification and disease diagnosis.

The role of GRP78 in oxidative stress induced by tunicamycin in trabecular meshwork cells.

OBJECTIVE: To clarify the regulatory effect of GRP-78 induced by tunicamycin on endoplasmic reticulum (ER) stress. METHODS: Tunicamycin was used to induce ER stress in trabecular meshwork cells (HTMC and GTM3). Cell apoptosis and ROS content were detected by flow cytometry to reveal the effect of tunicamycin on trabecular meshwork cells. RESULTS: Tunicamycin could significantly increase the ROS content and the apoptosis rate in HTMC and GTM3 (p<0.01). The results showed that tunicamycin could increase the Ca2+ flow in cells. Tunicamycin can also increase expression levels of GRP78,VDAC1, ATF4, PERK, eIF2a, and CHOP (p<0.01). Overexpression of GRP78 protected cells from ER stress. Co-IP test showed that GRP78 directly bound to eIF2. These results suggest that GRP78 may play a regulatory role by regulating eIF2. CONCLUSION: Tunicamycin induces oxidative stress in trabecular meshwork cells, and the increase in GRP78 expression can protect the cells during ER stress by regulating eIF2.

The 100 most cited articles in lateral epicondylitis research: A bibliometric analysis.

Introduction: Lateral epicondylitis is a significant clinical problem in orthopaedics. There have been numerous articles written about this. Bibliometric analysis is critical for determining a field's most influential study. We attempt to identify and analyze the top 100 citations in lateral epicondylitis research. Materials and methods: On December 31, 2021, an electronic search was conducted in the Web of Science Core Collection and the Scopus search engine with no restrictions on publication years, language, or study design. We reviewed each article's title and abstract until the top 100 were documented and evaluated in various ways. Results: Between 1979 and 2015, the 100 most cited articles were published in 49 journals. The total number of citations ranged from 75 to 508 (mean ± SD, 145.5 ± 90.9), with citation densities ranging from 2.2 to 37.6 citations per year (mean ± SD, 8.7 ± 6.5). The United States is the most productive country, and the 2000s witnessed a surge in lateral epicondylitis research. The year of publication had a moderately positive correlation with citation density. Conclusion: Our findings offer readers a fresh perspective on historical development hotspot areas of lateral epicondylitis research. Disease progression, diagnosis, and management have always been topics of discussion in articles. PRP-based biological therapy has emerged as a promising area for future research.

The synthesis of Cu nanoclusters and their dual mode colorimetric and fluorescent sensing for 2,4-dinitrophenol.

Herein, we have reported a facile one-pot strategy to synthesize fluorescent Cu nanclusters (Cu NCs) by using ʟ-histidine as stabilizer, and ascorbic acid as reducing agent. Cu NCs are stable, water-dispersible, and emit bright cyan emission with a quantum yield 26.08%. The Cu NCs can be employed as colorimetric and fluorimetric dual-mode detector, exhibiting excellent selectivity and sensitivity for detecting 2,4-dinitrophenol (DNP) specifically. Notably, Cu NCs were a sensitive sensor, which had speciality to detect DNP in range of linearity from 0.01 to 0.15 mM with a discernable limit as low as 3.96µM. The mechanism of efficiently selective detection of DNP by Cu NCs was analyzed by UV absorption, fluorescence decay spectrum, and the performance of 'turn off' towards DNP was determined as the inner filter effect and static quenching effect. Further, the environmental tolerance of the Cu NCs probe was estimated by using the different natural water samples, demonstrating its great promise in the field of DNP monitoring and water sample analysis.

Carbon dots-magnetic nanocomposites for the detection and removal of Hg2.

The dual functional detection and removal of heavy ion metals by carbon dots has become an urgent matter of concern. Here, a unique fluorescent carbon dot-magnetic nanocomposite (Fe3O4/CDs) was prepared by hydrothermal methods for sensitive detection of Hg2+. The Fe3O4/CDs serve as fluorescent probes with higher selectivity and sensitivity for Hg2+, with the lowest detectable limit of 0.3 nM. Hg2+ statically quenched the blue emission of Fe3O4/CDs, which can be restored in the presence of saturated EDTA solution. The utilization of Fe3O4/CDs was fulfilled by recovering their emission conveniently. The recovery of Hg2+ in Chagan Lake water, tap water and drinks was calculated at 96.5 ~ 108.8%, which demonstrates the feasibility of the Fe3O4/CDs sensing system in natural samples. Notably, the Fe3O4/CDs can drive the effective removal of Hg2+ from samples, which is of outstanding significance as a promising probe in environmental monitoring.

Preparation of fluorescent bimetallic silver/copper nanoparticles and their utility of dual-mode fluorimetric and colorimetric probe for Hg2.

A dual-mode colorimetric and fluorimetric probe was successfully established based on silver/copper bimetallic nanoparticles (AgCu-BNPs). The AgCu-BNPs were confirmed as individually bimetallic nanoparticles with a mean size of 7.7 ± 0.2 nm, as characterized by high resolution transmission electron microscopy. Intriguingly, the AgCu-BNPs possess both surface plasmon resonances (SPR) and fluorescence emission. AgCu-BNPs emanate bright blue fluorescence with optical emission centered at 442 nm with high quantum yield of 30.3%, and AgCu-BNPs were attenuated or even quenched by Hg2+ via both static and dynamic quenching, coincidently accompanied by a visible color change, which endow AgCu-BNPs a unique utility as dual-mode colorimetric and fluorimetric probes. The detection limits as low as 89 nM and 9 nM were determined by dual-mode of AgCu-BNPs, respectively. The recovery rates in real samples were found to be 97.3-118.8%, and 89.5-112.7% by colorimetric and fluorescent methods separately, demonstrates the good environmental tolerance of the dual-mode probe.