Transcriptional regulation of Znt family members znt4, znt5 and znt10 and their function in zinc transport in yellow catfish (Pelteobagrus fulvidraco).

The study characterized the transcriptionally regulatory mechanism and functions of three zinc (Zn) transporters (znt4, znt5 and znt10) in Zn2+ metabolism in yellow catfish (Pelteobagrus fulvidraco), commonly freshwater fish in China and other countries. We cloned the sequences of znt4 promoter, spanning from -1217 bp to +80 bp relative to TSS (1297 bp); znt5, spanning from -1783 bp to +49 bp relative to TSS (1832 bp) and znt10, spanning from -1923 bp to +190 bp relative to TSS (2113 bp). In addition, after conducting the experiments of sequential deletion of promoter region and mutation of potential binding site, we found that the Nrf2 binding site (-607/-621 bp) and Klf4 binding site (-5/-14 bp) were required on znt4 promoter, the Mtf-1 binding site (-1674/-1687 bp) and Atf4 binding site (-444/-456 bp) were required on znt5 promoter and the Atf4 binding site (-905/-918 bp) was required on znt10 promoter. Then, according to EMSA and ChIP, we found that Zn2+ incubation increased DNA affinity of Atf4 to znt5 or znt10 promoter, but decreased DNA affinity of Nrf2 to znt4 promoter, Klf4 to znt4 promoter and Mtf-1 to znt5 promoter. Using fluorescent microscopy, it was revealed that Znt4 and Znt10 were located in the lysosome and Golgi, and Znt5 was located in the Golgi. Finally, we found that znt4 knockdown reduced the zinc content of lysosome and Golgi in the control and zinc-treated group; znt5 knockdown reduced the zinc content of Golgi in the control and zinc-treated group and znt10 knockdown reduced the zinc content of Golgi in the zinc-treated group. High dietary zinc supplement up-regulated Znt4 and Znt5 protein expression. Above all, for the first time, we revealed that Klf4 and Nrf2 transcriptionally regulated the activities of znt4 promoter; Mtf-1 and Atf4 transcriptionally regulated the activities of znt5 promoter and Atf4 transcriptionally regulated the activities of znt10 promoter, which provided innovative regulatory mechanism of zinc transporting in yellow catfish. Our study also elucidated their subcellular location, and regulatory role of zinc homeostasis in yellow catfish.

[Screening and Identification of lncRNA Related to Adipocity of Bone Marrow Microenvironment in Aplastic Anemia].

OBJECTIVE: To systematically screen and identify long noncoding RNA (lncRNA) associated with bone marrow adiposity changes in aplastic anemia (AA). METHODS: The PPARγ and C/EBPα ChIP-Seq data in ChIPBase was analyzed by bioinformatics and the potential lncRNA co-transcriptionally regulated by PPARγ and C/EBPα was screened. The expression of candidate lncRNA was verified by qRT-PCR in the in vitro adipogenic differentiation model of BM-MSC, BM-MSC infected with lenti-shPPARγ and lenti-shC/EBPα as well as clinical BM-MSC samples derived from AA and controls. RESULTS: PPARγ and C/EBPα were significantly highly expressed in AA BM-MSC, and knock-down of PPARγ and C/EBPα impaired the adipogenic capacity of AA BM-MSC. PPARγ and C/EBPα cotranscriptionally activate LINC01230 promoter activity in binding sites dependant manner. The LINC01230 was also aberrantly highly expressed in AA BM-MSC compared with controls. CONCLUSION: PPARγ and C/EBPα are aberrantly expressed in AA BM-MSC and may promote the adipogenic differentiation of AA BM-MSC, and to a certain extent mediate the bone marrow adiposity alteration by transcriptionally activating LINC01230 expression.

Combined anti-PD-1, HDAC inhibitor and anti-VEGF for MSS/pMMR colorectal cancer: a randomized phase 2 trial.

Epigenetic modifications of chromatin, including histone acetylation, and tumor angiogenesis play pivotal roles in creating an immunosuppressive tumor microenvironment. In the randomized phase 2 CAPability-01 trial, we investigated the potential efficacy of combining the programmed cell death protein-1 (PD-1) monoclonal antibody sintilimab with the histone deacetylase inhibitor (HDACi) chidamide with or without the anti-vascular endothelial growth factor (VEGF) monoclonal antibody bevacizumab in patients with unresectable chemotherapy-refractory locally advanced or metastatic microsatellite stable/proficient mismatch repair (MSS/pMMR) colorectal cancer. Forty-eight patients were randomly assigned to either the doublet arm (sintilimab and chidamide, n = 23) or the triplet arm (sintilimab, chidamide and bevacizumab, n = 25). The primary endpoint of progression-free survival (PFS) rate at 18 weeks (18wPFS rate) was met with a rate of 43.8% (21 of 48) for the entire study population. Secondary endpoint results include a median PFS of 3.7 months, an overall response rate of 29.2% (14 of 48), a disease control rate of 56.3% (27 of 48) and a median duration of response of 12.0 months. The secondary endpoint of median overall survival time was not mature. The triplet arm exhibited significantly improved outcomes compared to the doublet arm, with a greater 18wPFS rate (64.0% versus 21.7%, P = 0.003), higher overall response rate (44.0% versus 13.0%, P = 0.027) and longer median PFS rate (7.3 months versus 1.5 months, P = 0.006). The most common treatment-emergent adverse events observed in both the triplet and doublet arms included proteinuria, thrombocytopenia, neutropenia, anemia, leukopenia and diarrhea. There were two treatment-related fatalities (hepatic failure and pneumonitis). Analysis of bulk RNA sequencing data from the patients suggested that the triplet combination enhanced CD8+ T cell infiltration, resulting in a more immunologically active tumor microenvironment. Our study suggests that the combination of a PD-1 antibody, an HDACi, and a VEGF antibody could be a promising treatment regimen for patients with MSS/pMMR advanced colorectal cancer. ClinicalTrials.gov registration: NCT04724239 .

MnO2 nanoparticles trigger hepatic lipotoxicity and mitophagy via mtROS-dependent Hsf1Ser326 phosphorylation.

Manganese (Mn) is an essential element for maintaining normal metabolism in vertebrates. Mn dioxide nanoparticles (MnO2 NPs), a novel Mn source, have shown great potentials in biological and biomedical applications due to their distinct physical and chemical properties. However, little is known about potential adverse effects on animal or cellular metabolism. Here, we investigated whether and how dietary MnO2 NPs affect hepatic lipid metabolism in vertebrates. We found that, excessive MnO2 NPs intake increased hepatic and mitochondrial Mn content, promoted hepatic lipotoxic disease and lipogenesis, and inhibited hepatic lipolysis and fatty acid ß-oxidation. Moreover, excessive MnO2 NPs intake induced hepatic mitochondrial oxidative stress, damaged mitochondrial function, disrupted mitochondrial dynamics and activated mitophagy. Importantly, we uncovered that mtROS-activated phosphorylation of heat shock factor 1 (Hsf1) at Ser326 residue mediated MnO2 NPs-induced hepatic lipotoxic disease and mitophagy. Mechanistically, MnO2 NPs-induced lipotoxicity and mitophagy were via mtROS-induced phosphorylation and nucleus translocation of Hsf1 and its DNA binding capacity to plin2/dgat1 and bnip3 promoters, respectively. Overall, our findings uncover novel mechanisms by which mtROS-mediated mitochondrial dysfunction and phosphorylation of Hsf1S326 contribute to MnO2 NPs-induced hepatic lipotoxicity and mitophagy, which provide new insights into the effects of metal oxides nanoparticles on hepatotoxicity in vertebrates.

Machine Learning Methods Based on CT Features Differentiate G1/G2 From G3 Pancreatic Neuroendocrine Tumors.

RATIONALE AND OBJECTIVES: To identify CT features for distinguishing grade 1 (G1)/grade 2 (G2) from grade 3 (G3) pancreatic neuroendocrine tumors (PNETs) using different machine learning (ML) methods. MATERIALS AND METHODS: A total of 147 patients with 155 lesions confirmed by pathology were retrospectively included. Clinical-demographic and radiological CT features was collected. The entire cohort was separated into training and validation groups at a 7:3 ratio. Least absolute shrinkage and selection operator (LASSO) algorithm and principal component analysis (PCA) were used to select features. Three ML methods, namely logistic regression (LR), support vector machine (SVM), and K-nearest neighbor (KNN) were used to build a differential model. Receiver operating characteristic (ROC) curves and precision-recall curves for each ML method were generated. The area under the curve (AUC), accuracy rate, sensitivity, and specificity were calculated. RESULTS: G3 PNETs were more likely to present with invasive behaviors and lower enhancement than G1/G2 PNETs. The LR classifier yielded the highest AUC of 0.964 (95% confidence interval [CI]: 0.930, 0.972), with 95.4% accuracy rate, 95.7% sensitivity, and 92.9% specificity, followed by SVM (AUC: 0.957) and KNN (AUC: 0.893) in the training group. In the validation group, the SVM classier reached the highest AUC of 0.952 (95% CI: 0.860, 0.981), with 91.5% accuracy rate, 97.3% sensitivity, and 70% specificity, followed by LR (AUC: 0.949) and KNN (AUC: 0.923). CONCLUSIONS: The LR and SVM classifiers had the best performance in the training group and validation group, respectively. ML method could be helpful in differentiating between G1/G2 and G3 PNETs.

Exopolysaccharides from endophytic Glutamicibacter halophytocota KLBMP 5180 functions as bio-stimulants to improve tomato plants growth and salt stress tolerance.

Microbial exopolysaccharides (EPSs) can promote plants growth and protect them against various abiotic stresses, but the role of actinobacteria-produced EPSs in plant growth promoting is still less known. Here, we aim to explore the effect of EPSs from an endophyte Glutamicibacter halophytocota KLBMP 5180 on tomato seeds germination and seedlings growth under salt stress. Our study revealed that 2.0 g/L EPSs resulted in increased seed germination rate by 23.5 % and 11.0 %, respectively, under 0 and 200 mM NaCl stress conditions. Further pot experiment demonstrated that EPSs significantly promoted seedlings growth under salt stress, with increased height, root length and fibrous roots number. Plant physiological traits revealed that EPSs increased chlorophyll content, enhanced the activity of antioxidant enzymes, soluble sugar, and K+ concentration in seedlings; malondialdehyde and Na+ contents were reduced. Additionally, auxin, abscisic acid, jasmonic acid, and salicylic acid were accumulated significantly in seedlings after EPSs treatment. Furthermore, we identified 1233 differentially expressed genes, and they were significantly enriched in phytohormone signal transmission, phenylpropanoid biosynthesis, and protein processing in endogenous reticulum pathways, etc. Our results suggest that KLBMP 5180-produced EPSs effectively ameliorated NaCl stress in tomato plants by triggering complex regulation mechanism, and showed application potentiality in agriculture.

MnO2 nanoparticles and MnSO4 differentially affected hepatic lipid metabolism through miR-92a/acsl3-dependent de novo lipogenesis in yellow catfish Pelteobagrusfulvidraco.

With the increasing production and use of MnO2 NPs and MnSO4 in various fields, their discharge into the aquatic environment is inevitable, which poses potential threats to aquatic organisms and humans. However, to date, few studies have been conducted to investigate the potential mechanism of the toxicity of MnO2 NPs, and a comprehensive understanding of the differences between this mechanism and the toxicity mechanism of inorganic Mn (MnSO4) is still lacking. Since lipid metabolism-relevant parameters have been widely recognized as novel biomarkers for risk assessment of environmental contaminants, the present study investigated the differential mechanisms of how MnO2 NPs and MnSO4 affect hepatic lipid metabolism in a freshwater fish yellow catfish. Compared to MnSO4, dietary MnO2 NPs caused liver injury, increased hepatic lipid accumulation and induced lipotoxicity, and up-regulated mRNA expression of de novo lipogenic genes. Moreover, MnO2 NPs downregulated the expression of miR-92a and miR-92b-3p, microRNAs involved in regulation of lipid metabolism, in the liver. Mechanistically, we found that acls3, an acetyl-coenzyme A synthetase, is target gene of miR-92a, and miR-92a-acsl3-dependent de novo lipogenesis contributes to lipid accumulation and lipotoxicity induced by MnO2 NPs. Collectively, these findings provided novel insights into mechanism whereby miRNAs mediate nanoparticles- and inorganic Mn-induced hepatic lipotoxicity and changes of lipid metabolism in vertebrates. Our findings also shed new perspective for ecotoxicity and ecological risk of MnO2 NPs and MnSO4 in aquatic environment.

Adherence, belief, and knowledge about oral anticoagulants in patients with bioprosthetic heart valve replacement: a cross-sectional study.

Aims: To investigate adherence to oral anticoagulants among patients after mechanical heart valve (BHV) replacement and further examine the mediating role of medication belief in the relationship between knowledge and medication adherence. Background: The number of patients who undergo BHV replacement has increased in recent years. Short-term anticoagulant therapy is recommended for patients after BHV replacement. However, little is known about adherence to oral anticoagulant therapy and the underlying mechanisms among patients with BHV replacement. Methods: A cross-sectional study was conducted between September 2022 and November 2022. A convenience sample of 323 patients who underwent BHV replacement was recruited from a tertiary public hospital in Southwest China. Data were collected by using the 8-item Morisky Medication Adherence Scale, Beliefs about Medicines Questionnaire-specific, and the Knowledge of Anticoagulation Questionnaire. The mediation model was tested by Hayes's PROCESS macro. The STROBE checklist was used. Results: Approximately 17.3% of participants had low adherence, 47.1% had medium adherence, and only 35.6% reported high adherence to oral anticoagulants. Knowledge and necessity beliefs were positively related to medication adherence, while concern beliefs were negatively correlated with medication adherence. Medication belief mediated the relationship between knowledge and adherence to oral anticoagulants. Conclusion: Patients with BHV replacement demonstrated relatively low adherence to oral anticoagulant therapy. Efforts to enhance medication adherence should consider improving patients' knowledge and medication beliefs.

Corrigendum: Phyllanthus niruri L. exerts protective effects against the calcium oxalate-induced renal injury via ellgic acid.

[This corrects the article DOI: 10.3389/fphar.2022.891788.].

Visible Light-Induced Oxidation of Alcohols by a Luminescent Osmium(VI) Nitrido Complex: Evidence for the Generation of PhIO+ as a Highly Active Oxidant in the Presence of PhIO.

Although alcohols are readily oxidized by a variety of oxidants, their oxidation by metal nitrido complexes is yet to be studied. We report herein visible-light-induced oxidation of primary and secondary alcohols to carbonyl compounds by a strongly luminescent osmium(VI) nitrido complex (OsN). The proposed mechanism involves initial rate-limiting hydrogen-atom transfer (HAT) from the α-carbon of the alcohol to OsN*. Attempts to develop catalytic oxidation of alcohols by OsN* using PhIO as the terminal oxidant resulted in the formation of novel osmium(IV) iminato complexes in which the nitrido ligand is bonded to a δ-carbon of the alcohol. Experimental and theoretical studies suggest that OsN* is reductively quenched by PhIO to generate PhIO+, which is a highly active oxidant that readily undergoes α- and δ-C-H activation of alcohols.

Curcumol Exerts Antitumor Effect via Inhibiting EGFR-Akt-Mcl-1 Signaling.

Dysfunction of epidermal growth factor receptor (EGFR) signaling plays a critical role in the tumorigenesis of oral squamous cell carcinoma (OSCC). In the present study, the data analysis results of immunohistochemistry and the TCGA database verified that the expression of EGFR is significantly upregulated in OSCC tumor tissues, and depletion of EGFR inhibits the growth of OSCC cells in vitro and in vivo. Moreover, these results showed that the natural compound, curcumol, exhibited a profound antitumor effect on OSCC cells. Western blotting, MTS, and immunofluorescent staining assays indicated that curcumol inhibited cell proliferation and induced intrinsic apoptosis in OSCC cells via downregulating myeloid cell leukemia 1 (Mcl-1). A mechanistic study revealed that curcumol inhibited the EGFR-Akt signal pathway, which activated GSK-3[Formula: see text]-mediated Mcl-1 phosphorylation. Further research showed that curcumol-induced Mcl-1 Ser159 phosphorylation is required to disrupt the interaction between deubiquitinase JOSD1 and Mcl-1 and eventually induce Mcl-1 ubiquitination and degradation. In addition, curcumol administration can effectively inhibit CAL27 and SCC25 xenograft tumor growth and is well-tolerated in vivo. Finally, we demonstrated that Mcl-1 is upregulated and positively correlates with p-EGFR and p-Akt in OSCC tumor tissues. Collectively, the present results provide new insights into the antitumor mechanism of curcumol, identifying it as an attractive therapeutic agent that reduces Mcl-1 expression and inhibits OSCC growth. Targeting EGFR/Akt/Mcl-1 signaling could be a promising option in the clinical treatment of OSCC.

Ring Nitrogenation of Aromatic Amines by the Excited State of an Osmium(VI) Nitrido Complex.

The reactivity of electrophilic OsVI and RuVI nitrides toward various aliphatic and aromatic amines have been previously reported; these reactions all go through an initial nucleophilic addition of the amine nitrogen to MVI≡N (M = Os, Ru) to generate a MIV hydrazido species. Herein, we report that the excited state of a luminescent osmium(VI) nitrido complex, [OsVI(N)(L)(CN)3]- (OsN, HL = 2-(2-hydroxy-5-nitrophenyl)benzoxazole), undergoes unprecedented ring nitrogenation of aromatic amines. Visible-light irradiation of OsN generates OsN*, which predominantly attacks the aromatic ring of 2,6-dimethylaniline (Me2PhNH2) to give an Os(II) benzoquinone diimine compound (PPh4)[OsII(L)(CN)3(p-NH═Me2Ph═NH2)] [(PPh4)2] in 60% yield, while nucleophilic addition of the amine N to OsN* also occurs to give the osmium(II) diazonium compound (PPh4)[OsII(L)(CN)3(N = N-Me2Ph)] [(PPh4)1] as a minor product (10% yield). On the other hand, OsN* undergoes exclusive ring nitrogenation of diphenylamine, indole, and carbazole to give the corresponding osmium(II) benzoquinone diimines. All products have been characterized by various spectroscopic techniques and by X-ray crystallography. The reaction between OsN* and Ar2N is proposed to proceed via an initial 1e- transfer (ET) followed by proton transfer (PT) to generate OsVNH and Ar2N• intermediates, which then further combine to give the product. The benzoquinone diimine ligands are susceptible to oxidation. Oxidation of 2 with H2O2 at ambient conditions affords [OsIV(L)(CN)3(N═PhMe2(O)═O)]-, which bears the previously unknown (epoxy)benzoquinone iminato ligand.

Synthesis and insecticidal activities of 4-(propargyloxy) benzenesulfonamide derivatives.

A series of 4-(propargyloxy) benzenesulfonamide derivatives with different substituents on the benzene ring were synthesized and evaluated for their insecticidal activity. Some of the compounds showed good insecticidal activity against Mythimna separata, and the LC50 value of the most active compound B2.5 was 0.235 mg/ml. Ultrastructural changes in the midgut epithelial cells of Mythimna separata were observed using transmission electron microscopy, and severe structural damage was found in microvilli, mitochondria and rough endoplasmic reticulum. It indicates that the possible site of action of these benzenesulfonamides is the cytoplasmic membrane and endomembrane system of the midgut epithelial cells. The above provides a basis for the development of novel insecticidal active compounds with a novel mechanism of action.

Effect of the dangling aromatic ring on neutral luminescent bis(phosphine) Cu(i)/Ag(i) complexes with the asymmetric pyridyl-tetrazolate ligands.

A series of neutral luminescent bis(phosphine) Cu(i) complexes of pyridyl-tetrazolate ligands (L1-L3) with the general formula [CuI(L n )(P^P)] (1-6) were synthesized, which have been well characterized by IR, UV/vis, CV, 1H NMR and 31P NMR. For comparison, an Ag(i) complex [AgI(L2)(PPh3)2] (7) was also synthesized. The crystal structures of 2 and 7 have been further determined by X-ray crystallography. All these Cu(i) compounds show bright luminescence in the solid state with photoluminescence quantum yields (PLQYs) in the range of 25.8% to 85.0%. More interestingly, the Cu(i) complexes bearing an additional dangling aromatic ring on the diimine ligands exhibit enhanced luminescent performance in various solutions and their PLQYs are significantly higher than those of related Cu(i) complexes without steric protection. Compared with 1, the Cu(i) complexes with an additional dangling tetrazole moiety show a significant solvatochromic effect, which is uncommon for luminescent Cu(i) complexes. Moreover, [CuI(L2)(PPh3)2] (2) was further designed as an OLED material, which showed a high external quantum efficiency of 7.7%.

[Correlation between Cyclic GMP-AMP Synthase-Stimulator of Interferon Genes Signaling Pathway and Non-infectious Diseases].

As a DNA receptor in the cytoplasm,cyclic GMP-AMP synthase (cGAS) can recognize abnormal DNA in the cytoplasm and activate stimulator of interferon genes (STING) to regulate the immune response. The recent studies have demonstrated that this pathway plays a role in non-infectious inflammatory diseases by promoting the expression of type Ⅰ interferon and interferon-stimulated gene.This article reviews the activation and regulation of cGAS-STING pathway in multiple systems and the effect of this pathway on the occurrence and progression of non-infectious inflammatory diseases,providing theoretical reference for future application of cGAS-STING pathway-related drugs in non-infectious inflammatory diseases.

Phyllanthus Niruri L. Exerts Protective Effects Against the Calcium Oxalate-Induced Renal Injury via Ellgic Acid.

Background: Urolithiasis or kidney stones is a common and frequently occurring renal disease; calcium oxalate (CaOx) crystals are responsible for 80% of urolithiasis cases. Phyllanthus niruri L. (PN) has been used to treat urolithiasis. This study aimed to determine the potential protective effects and molecular mechanism of PN on calcium oxalate-induced renal injury. Methods: Microarray data sets were generated from the calcium oxalate-induced renal injury model of HK-2 cells and potential disease-related targets were identified. Network pharmacology was employed to identify drug-related targets of PN and construct the active ingredient-target network. Finally, the putative therapeutic targets and active ingredients of PN were verified in vitro and in vivo. Results: A total of 20 active ingredients in PN, 2,428 drug-related targets, and 127 disease-related targets were identified. According to network pharmacology analysis, HMGCS1, SQLE, and SCD were identified as predicted therapeutic target and ellagic acid (EA) was identified as the active ingredient by molecular docking analysis. The increased expression of SQLE, SCD, and HMGCS1 due to calcium oxalate-induced renal injury in HK-2 cells was found to be significantly inhibited by EA. Immunohistochemical in mice also showed that the levels of SQLE, SCD, and HMGCS1 were remarkably restored after EA treatment. Conclusion: EA is the active ingredient in PN responsible for its protective effects against CaOx-induced renal injury. SQLE, SCD, and HMGCS1 are putative therapeutic targets of EA.

ARNI or ARB Treats Residual Left Ventricular Remodelling after Surgery for Valvular Regurgitation: ReReRe study protocol.

AIMS: Patients with persistent or de novo left ventricular (LV) dilation and/or reduced ejection fraction (EF) after correction for primary aortic (AR) or mitral (MR) regurgitation (i.e. residual LV remodelling) have not been well studied with regard to guideline-directed medical therapy after successful aetiology-reversing surgery. We aim to (i) compare the effectiveness of sacubitril/valsartan vs. valsartan in promoting LV reverse remodelling and (ii) explore the safety of medication withdrawal after LV recovery. METHODS AND RESULTS: The ReReRe study is a multicentre, randomized, open-label, parallel trial that consists of two consecutive parts. A total of 371 patients with an LV end-diastolic diameter (LVEDD) > 60 mm or LVEF < 50%, assessed by transthoracic echocardiography (TTE) 7-14 days after valve surgery for significant AR or primary MR will be enrolled. The 1st randomization into the sacubitril/valsartan or valsartan groups and structured follow-up (1, 3, 6, 9, and 12 months after randomization) will be conducted to observe the primary objective as the rate of complete recovery of LV remodelling (i.e. LVEDD < 55 mm and LVEF ≥ 60% by TTE at two consecutive visits). Those who have complete recovery of LV remodelling will be enrolled in Study Part 2; consequently, they will receive the 2nd randomization into the medication withdrawal or maintenance group and 6-monthly visits for the observation of the primary objective as the rate of LV remodelling relapse (LVEDD > 60 mm or LVEF < 50%). The secondary objectives include the rate of composite clinical outcomes and the degree of change in 6-min walk distance and Kansas City Cardiomyopathy Questionnaire scores. CONCLUSIONS: The ReReRe study will provide new evidence for the treatment of patients with residual LV remodelling after curable unloaded surgery, as well as the duration of treatment. The study results will fill the gap in identifying an appropriate medical therapy regimen for this group of patients and perhaps for those with reversible aetiologies of heart failure.

Quantitative analysis of enhanced CT in differentiating well-differentiated pancreatic neuroendocrine tumors and poorly differentiated neuroendocrine carcinomas.

OBJECTIVE: To identify quantitative CT features for distinguishing well-differentiated pancreatic neuroendocrine tumors (PNETs) from poorly differentiated pancreatic neuroendocrine carcinomas (PNECs). MATERIALS AND METHODS: Seventeen patients with PNECs and 131 patients with PNETs confirmed by biopsy or surgery were retrospectively included. General demographic (sex, age) and CT quantitative parameters (arterial/portal absolute enhancement, arterial/portal relative enhancement ratio, arterial/portal enhancement ratio) were collected. Univariate and multivariate logistic regression analyses were performed to confirm independent variables for differentiating PNECs from PNETs. Receiver operating characteristic (ROC) curves for each quantitative parameter were generated to determine their diagnostic ability. RESULTS: PNECs had a much lower mean arterial/portal absolute enhancement value (19.5 ± 11.0 vs. 78.8 ± 47.2; 28.1 ± 15.8 vs. 77.0 ± 39.4), arterial/portal relative enhancement ratio (0.57 ± 0.36 vs. 2.03 ± 1.31; 0.80 ± 0.52 vs. 1.99 ± 1.13), and arterial/portal enhancement ratio (0.62 ± 0.27 vs. 1.22 ± 0.49; 0.74 ± 0.19 vs. 1.21 ± 0.36) than PNETs (all p < 0.001). After multivariable analysis, arterial absolute enhancement (odds ratio [OR]: 0.96, 95% confidence interval [CI]: 0.93, 0.99) and portal absolute enhancement (OR: 0.96, 95% CI: 0.92, 0.99) were independent factors for differentiating PNECs from PNETs. For each quantitative parameter, arterial lesion enhancement yielded the highest diagnostic performance, with an area under the curve (AUC) of 0.922 (95% CI: 0.867-0.960), followed by portal absolute enhancement. CONCLUSIONS: Arterial/portal absolute enhancements were independent predictors with good diagnostic accuracy for differentiating between PNETs and PNECs. Quantitative parameters of enhanced CT can distinguish PNECs from PNETs. KEY POINTS: • PNECs were hypovascular and had a much lower enhanced CT attenuation in both arterial and portal phases than well-differentiated PNETs. • Quantitative parameters derived from enhanced CT can be used to distinguish PNECs from PNETs. • Arterial absolute enhancement and portal absolute enhancement were independent predictive factors for differentiating between PNETs and PNECs.

Oxidative C-O bond cleavage of dihydroxybenzenes and conversion of coordinated cyanide to carbon monoxide using a luminescent Os(VI) cyanonitrido complex.

The photoreactions of a luminescent osmium(VI) nitrido complex, [OsVI(N)(L)(CN)3]- (OsN, HL = 2-(2-hydroxy-5-nitrophenyl)benzoxazole), with catechol (H2Cat) and hydroquinone (H2Q) lead to the cleavage of strong C-OH bonds (ca. 120 kcal mol-1) of the dihydroxybenzenes with concomitant conversion of the coordinated cyanide to carbon monoxide.

Wrist-Ankle Acupuncture as Additional Therapy for Postoperative Multimodal Analgesia in Orthopedic Surgery: Systematic Review and Meta-Analysis.

BACKGROUND: The present meta-analysis analyzed the efficacy and safety of wrist-ankle acupuncture (WAA) as an additional therapy for postoperative multimodal analgesia after orthopedic surgery. METHODS: Electronic databases, including Cochrane Library, PubMed, EMBASE, Web of Science, CNKI, SinoMed, Wanfang, and VIP, were searched to identify randomized controlled trials and cohort studies that reported details of WAA as an additional therapy for postoperative multiple analgesia in orthopedic surgery before October 1, 2021. Analyzed outcomes included time points of the visual analog scale, use of patient-controlled intravenous analgesia (PCIA), and postoperative adverse events. Subgroup analysis was performed according to time points and complication type. RESULTS: Eleven randomized controlled trials and one cohort study were included in the meta-analysis. Among a total of 845 patients, there were 422 patients in the WAA groups and 423 patients in the control groups. The WAA groups showed a better analgesic effect (standard mean difference [SMD] = -1.34; 95% confidence interval [CI]: -1.76 to -0.91; P < 0.00001; I2 = 0.94), lower use of PCIA (SMD = -1.48; 95% CI: -2.26 to -0.69; P = 0.0002; I2 = 0.94), and lower occurrence of postoperative adverse events (risk ratio = 0.38; 95% CI: 0.30 to 0.49; P < 0.00001; I2 = 0) than did the control groups. CONCLUSION: WAA as an additional therapy for postoperative multimodal analgesia in orthopedic surgery showed advantages over control treatment in terms of pain relief, use of PCIA, and occurrence of postoperative adverse events.