Mesoporous Carbon for High-Performance Near-Neutral Zinc-Air Batteries.

Near-neutral zinc-air batteries (ZABs) have garnered significant research interest due to their high energy density, exceptional electrochemical reversibility, and adaptability to ambient air. However, these batteries suffer from substantial electrochemical polarization, low energy efficiency, and poor rate performance. In this study, a mesoporous carbon (meso-C) with a high specific surface area (1081 m2 g-1 ) and abundant porous structure for the cathode of near-neutral ZABs using a scalable synthesis method is prepared. The meso-C-based cathode is endowed with stable hydrophobicity and abundant electrochemical active sites, which considerably improve the energy efficiency, rate performance, and cycle life of the battery compare to commercial carbon black-based cathode when applied to near-neutral ZABs with 1 mol kg-1 (1 m) zinc acetate and 1 m zinc trifluoromethanesulfonate electrolytes. Additionally, the mesopores of meso-C facilitate the construction of better three-phase reaction interfaces and contribute to better electrochemical reversibility. The work presents a general and scalable approach for carbon materials in the cathode of near-neutral ZABs.

One-Step Molten-Salt-Assisted Approach for Direct Preparation and Regeneration of LiNi0.6Co0.2Mn0.2O2 Cathode.

Single-crystal lithium-nickel-manganese-cobalt-oxide (SC-NMC) is attracting increasing attention due to its excellent structural stability. However, its practical production faces challenges associated with complex precursor preparation processes and severe lithium-nickel cation mixing at high temperatures, which restricts its widespread application. Here, a molten-salt-assisted method is proposed using low-melting-point carbonates. This method obviates the necessity for precursor processes and simplified the synthetic procedure for SC-NMC down to a single isothermal sintering step. Multiple characterizations indicate that the acquired SC-LiNi0.6Mn0.2Co0.2O2 (SC-622) exhibits favorable structural capability against intra-granular fracture and suppressive Li+/Ni2+ cation mixing. Consequently, the SC-622 exhibits superior electrochemical performance with a high initial specific capacity (174 mAh g-1 at 0.1 C, 3.0-4.3 V) and excellent capacity retention (87.5% after 300 cycles at 1C). Moreover, this molten-salt-assisted method exhibits its effectiveness in directly regenerating SC-622 from spent NMC materials. The recovered material delivered a capacity of 125.4 mAh g-1 and retained 99.4% of the initial capacity after 250 cycles at 1 C. This work highlights the importance of understanding the process-structure-property relationships and can broadly guide the synthesis of other SC Ni-rich cathode materials.

Cytokine profiles and virological markers highlight distinctive immune statuses, and effectivenesses and limitations of NAs across different courses of chronic HBV infection.

PURPOSE: The characteristics of cytokine/chemokine(CK) profiles across different courses of chronic hepatitis B virus infection and the effects of NAs antiviral therapy on cytokine profiles remain unclear. METHODS: This report provides evidence from 383 patients with chronic HBV infection. The Luminex multiple cytokine detection technology was used to detect CK profiles. The predictive power of CKs across course of disease was assessedusing univariate analyses and with receiver operating characteristic (ROC) curves. RESULTS: Compared to healthy control (HC), expression levels of interleukin 6 (IL)-6, IL-8, IL-21, matrix metalloproteinases (MMP)-2 and tumor necrosis factor receptor (TNFR)-1 showed a significant increasing trend during chronic HBV infection. IL-23 and IL-33 increased respectively in chronic hepatitis B patients (CHB). interferon (IFN)-gamma and TNF-α changed significantly only in liver cirrhosis (LC) patients. Whereas, myeloid-related markers decreased dramatically in those with hepatocellular carcinoma (HCC). The ROC result suggests that combining IL-6, IL-8, CXCL9 and CXCL13 into a nomogram has closely correlation with HCC during chronic HBV infection. In addition, nucleotide analogues (NAs) antiviral treatments are capable of recoveringnormal liver functions and significantly reducing the viral loads, however, they seem to have a limited effect in changing CKs, especially specific antiviral factors. CONCLUSION: The differential CK and virological markers may serve as potential indicators of distinct immune statuses in chronic HBV infection. They also underscore the varying efficacy and limitations of NAs antiviral therapies. This next step would to break new ground in the optimization of current anti-HBV treatment programs although this requires further research.

Deciphering m6A signatures in hepatocellular carcinoma: Single-cell insights, immune landscape, and the protective role of IGFBP3.

RNA m6 methyladenosine (m6A) modifications impact tumor biology and immune processes, particularly in hepatocellular malignant tumors. Using a consensus clustering algorithm on 371 hepatocellular carcinoma (HCC) samples, we identified three m6A-modified subtypes and correlated them with positive tumor microenvironment (TME) markers for distinct immune phenotypes. Stratifying patients based on m6A scores revealed a low presentation group with better immune penetration, lower tumor mutation load, and increased expression of immune checkpoint markers like CTLA-4 and PD-1, suggesting enhanced responsiveness to immunization therapy. A machine-learning model of 23 m6A genes was constructed. Single-cell analysis revealed a surprising enrichment of IGFBP3 in astrocytes, prompting the exploration of associated signaling pathways. Experimental verification shows that IGFBP3 is significantly enhanced in normal tissues, while immunohistochemical analysis shows that its expression is lower in tumor tissues, indicating its protective effect in HCC and a good prognosis. Importantly, high IGFBP3 expression is associated with better outcomes in patients receiving immunotherapy. Moreover, cytotoxic T lymphocyte (CTL) experiments have confirmed that high expression of IGFBP3 is associated with stronger T cell-killing ability. In summary, the comprehensive evaluation of m6A modification, immune characteristics, and single-cell analysis in this study not only revealed the TME of HCC but also made significant contributions to the progress of personalized HCC immunotherapy targeting IGFBP3. This study provides a solid theoretical foundation for clinical translation and emphasizes its potential impact on developing effective treatment strategies.

Effect of Intrinsic Ferroelectric Phase Transition on Hydrogen Evolution Electrocatalysis.

Heterogeneous electrocatalysis closely relies on the electronic structure of the catalytic materials. The ferroelectric-to-paraelectric phase transition of the materials also involves a change in the state of electrons that could impact the electrocatalytic activity, but such correlation remains unexplored. Here, we demonstrate experimentally and theoretically that the intrinsic electrocatalytic activity could be regulated as exampled by hydrogen evolution reaction catalysis over two-dimensional ferroelectric CuInP2S6. The obvious discontinuity in the overpotential and apparent activation energy values for CuInP2S6 electrode are illustrated during the ferroelectric-to-paraelectric phase transition caused by copper displacement around Tc point (318 K), revealing the ferroelectro-catalytic effect on thermodynamics and kinetics of electrocatalysis. When loading Pt single atom on the CuInP2S6, the paraelectric phase one showed an improved hydrogen evolution activity with smaller apparent activation energy over the ferroelectric phase counterpart. This is attributed to the copper hopping between two sulfur planes, which alternate between strong and weak H adsorption at the Pt sites to simultaneously promote H+ reactant adsorption and H2 product desorption.

Hydrophobic and Homogeneous Conductive Carbon Matrix for High-Rate Non-Alkaline Zinc-Air Batteries.

Non-alkaline zinc-air batteries (ZABs) that use reversible O2 /ZnO2 chemistry exhibit excellent stability and superior reversibility compared to conventional alkaline ZABs. Unlike alkaline ZABs, ZnO2 discharge products are generated on the surface of the air cathodes in non-alkaline ZABs, requiring more gas-liquid-solid three-phase reaction interfaces. However, the kinetics of reported ZABs based on carbon black (CB) is far from satisfactory due to the insufficient reaction areas. The rational structural design of the air cathode is an effective way to increase active surfaces to further enhance the performance of non-alkaline ZABs. In this study, multi-walled carbon nanotubes (MW-CNTs) with unique mesoporous structures and high pore volumes are selected to replace CB in the air cathode preparation. Due to the larger electrochemically active surface area, superior hydrophobicity, and uniform electroconductibility of MW-CNTs-based cathodes, primary ZABs exhibit high specific capacity (704 mAh gZn-1 ) with a Zn utilization ratio of 85.85% at 1.0 mA cm-2 , excellent discharge rate performance, and negligible self-discharge. Furthermore, rechargeable ZABs also demonstrate outstanding rate capability and excellent cycling stability at various current densities. This work provides a fundamental understanding of the criteria for the cathode design of non-alkaline ZABs, thus opening a new pathway for more sustainable ZABs.

Ce Site in Amorphous Iron Oxyhydroxide Nanosheet toward Enhanced Electrochemical Water Oxidation.

Iron oxyhydroxide has been considered an auspicious electrocatalyst for the oxygen evolution reaction (OER) in alkaline water electrolysis due to its suitable electronic structure and abundant reserves. However, Fe-based materials seriously suffer from the tradeoff between activity and stability at a high current density above 100 mA cm-2 . In this work, the Ce atom is introduced into the amorphous iron oxyhydroxide (i.e., CeFeOx Hy ) nanosheet to simultaneously improve the intrinsic electrocatalytic activity and stability for OER through regulating the redox property of iron oxyhydroxide. In particular, the Ce substitution leads to the distorted octahedral crystal structure of CeFeOx Hy , along with a regulated coordination site. The CeFeOx Hy electrode exhibits a low overpotential of 250 mV at 100 mA cm-2 with a small Tafel slope of 35.1 mVdec-1 . Moreover, the CeFeOx Hy electrode can continuously work for 300 h at 100 mA cm-2 . When applying the CeFeOx Hy nanosheet electrode as the anode and coupling it with the platinum mesh cathode, the cell voltage for overall water splitting can be lowered to 1.47 V at 10 mA cm-2 . This work offers a design strategy for highly active, low-cost, and durable material through interfacing high valent metals with earth-abundant oxides/hydroxides.

Predictive Value of Ablative Margin Assessment After Microwave Ablation for Local Tumor Progression in Medium and Large Hepatocellular Carcinoma: Computed Tomography-Computed Tomography Image Fusion Method Versus Side-by-Side Method.

OBJECTIVE: This study aimed to explore the feasibility and predictive value for local tumor progression (LTP) of the computed tomography (CT)-CT image fusion method versus side-by-side method to assess ablative margin (AM) in hepatocellular carcinoma ≥3 cm in diameter. MATERIALS AND METHODS: We selected patients with hepatocellular carcinoma ≥3 cm in diameter who underwent microwave ablation and had complete tumor ablation. We used the CT-CT image fusion method and side-by-side method to assess AM separately and divided the lesions into 3 groups: group I, minimum ablative margin (min-AM) <0 mm (the ablation zone did not fully cover the tumor); group II, 0 mm ≤ min-AM <5 mm; and group III, min-AM ≥5 mm. RESULTS: A total of 71 patients involving 71 lesions were included. The κ coefficient for the agreement between the CT-CT image fusion method and the side-by-side method in assessing min-AM was 0.14 (P = 0.028). Cumulative LTP rate was significantly different between groups by min-AM from the CT-CT image fusion method (P < 0.05) but not by min-AM from the side-by-side method (P = 0.807). Seventeen of the 20 LTP lesions were located at min-AM on fused CT images, with consistency rate of 85%. CONCLUSIONS: Compared with the side-by-side method, the CT-CT image fusion method is more accurate in assessing the AM of eccentrically ablated lesions and shows better predictive value for LTP. The min-AM based on CT-CT image fusion assessment is an important influencing factor for LTP.

Pairing of Aqueous and Nonaqueous Electrosynthetic Reactions Enabled by a Redox Reservoir Electrode.

Paired electrolysis methods are appealing for chemical synthesis because they generate valuable products at both electrodes; however, development of such reactions is complicated by the need for both half-reactions to proceed under mutually compatible conditions. Here, a modular electrochemical synthesis (ModES) strategy bypasses these constraints using a "redox reservoir" (RR) to pair electrochemical half-reactions across aqueous and nonaqueous solvents. Electrochemical oxidation reactions in organic solvents, the conversion of 4-t-butyltoluene to benzylic dimethyl acetal and aldehyde in methanol or the oxidative C-H amination of naphthalene in acetonitrile, and the reduction of oxygen to hydrogen peroxide in water were paired using nickel hexacyanoferrate as an RR that can selectively store and release protons (and electrons) while serving as the counter electrode for these reactions. Selective proton transport through the RR is optimized and confirmed to enable the ion balance, and thus the successful pairing, between redox half-reactions that proceed with different rates, on different scales, and in different solvents (methanol, acetonitrile, and water).

Associations of left renal vein entrapment with IgA nephropathy and Henoch-Schönlein purpura nephritis.

OBJECTIVES: The aims of the study were to identify whether left renal vein (LRV) entrapment was more prevalent in IgA nephropathy (IgAN) and Henoch-Schönlein purpura nephritis (HSPN) compared with other types of renal diseases, and the association of LRV entrapment with glomerular incidental IgA and galactose-deficient-IgA1 (Gd-IgA1) deposition. METHODS: A total of 797 patients with biopsy-proven kidney diseases have been screened for LRV entrapment by color Doppler ultrasound, and the prevalence of LRV entrapment in different types of renal diseases were then analyzed. Propensity score matching analysis was used to adjust for age, gender, and body mass index. Immunostaining of Gd-IgA1 with KM55 was performed in paraffin-embedded sections of renal biopsy specimens. RESULTS: LRV entrapment was diagnosed in 47 patients (6%) with several kinds of renal diseases in our cohort. A total of 32 (68%) LRV entrapments were combined with expanded IgAN (idiopathic IgAN and HSPN). The prevalence of LRV entrapment in expanded IgAN was significantly higher than that in non-expanded IgAN (17 vs. 2%, p < 0.001), even after adjustment for age, gender, and body mass index by propensity score matching analysis (13 vs. 2%, p < 0.001). Removing expanded IgAN and LN, glomerular incidental IgA deposition was observed to be significantly more common in patients with LRV entrapment compared with patients without it (43 vs. 9%, p < 0.001). Furthermore, in glomerular diseases with incidental IgA deposits, significantly much larger proportion of patients with LRV entrapment were positive for glomerular Gd-IgA1 in contrast to patients without LRV entrapment (5/5 vs. 5/17, p = 0.01). CONCLUSIONS: LRV entrapment coexisted with several kinds of renal diseases, with a significantly higher prevalence in patients with idiopathic IgAN and HSPN. In patients of LN and IgAN-unrelated disease with LRV entrapment, glomerular IgA and Gd-IgA1 deposition was more common compared with patients without LRV entrapment.

The efficacy and safety of second dinoprostone pessary or balloon catheter after unsuccessful primary ripening with dinoprostone pessary.

We investigated which treatment should be applied if primary cervical ripening with a dinoprostone pessary is unsuccessful. We included 281 women who experienced unsuccessful cervical ripening with a dinoprostone pessary and continued on induction of labour (IOL). Of the 281 women recruited, 177 were given a second dose of dinoprostone; 104 women received a balloon catheter. The second dinoprostone pessary was successful in achieving vaginal delivery in 88 of the 177 (48.6%) women, while the balloon catheter was successful in 42 of the 104 women (40.4%); there was no significant difference between the two treatments with regards to successful vaginal delivery. However, of the women who experienced successful vaginal delivery, the delivery rate in the dinoprostone group was significantly higher than that in the balloon catheter group 12, 24, 36, or 48 h after insertion (p = .0094, .0005, .0258, .0483, respectively). The neonatal outcomes, the proportion of maternal infection and postpartum haemorrhage were similar between the two groups.IMPACT STATEMENTWhat is already known on this subject? Labour induction is a common procedure in obstetrics in a bid to achieve vaginal delivery in China, because vaginal delivery is more beneficial and associated with a better quality of life as compared to a Caesarean delivery. There is consensus relating to the preferred method of IOL after unsuccessful IOL with a dinoprostone pessary.What do the results of this study add? This is the first study in a Chinese population to compare the dinoprostone pessary and balloon catheter for women with no response to dinoprostone for cervical ripening with a sample size greater than 100. We found that a second dose of dinoprostone can reduce the time from the re-initiation of IOL to vaginal delivery compared with the balloon catheter. Our data also indicated that all other outcomes relating to the mother and infant were similar.What are the implications of these findings for clinical practice and/or future research? A second dose of dinoprostone is a superior choice for women who experience unsuccessful IOL with dinoprostone to further accelerate vaginal delivery.

Clinical relevance of glomerular IgM deposition in patients with lupus nephritis.

BACKGROUND: The aim of the study was to investigate the clinical relevance of IgM deposition in patients with lupus nephritis (LN) in a large cohort. RESULTS: 217 patients with renal biopsy-proven active LN were enrolled. The associations between glomerular IgM deposition and clinicopathological parameters were further analyzed. IgM deposition was positively correlated with glomerular C1q and C3 deposition moderately (r = 0.436, P < 0.001; r = 0.408, P < 0.001, respectively), and inversely correlated with plasma levels of C3 and CFH mildly (r = - 0.138, P = 0.043; r = - 0.147, P = 0.037, respectively). By multivariate analysis, we found that glomerular IgM deposition independently contributed to glomerular C3 deposition in patients with LN (OR = 2.002, 95% CI 1.295-3.094, P = 0.002). In addition, we also found that patients with IgM 0-2+ had similar plasma CFH levels, but in patients with IgM3+-4+, plasma CFH levels were significantly lower (300.4 ± 155.8 µg/mL vs. 429.9 ± 187.5 µg/mL, P < 0.001). Furthermore, patients with high density of glomerular IgM and low levels of CFH had heavier proteinuria, higher serum creatinine and lower plasma C3 levels (5.7 ± 3.1 g/d vs. 4.7 ± 3.5 g/d, P = 0.037; 150.1 ± 121.0 µmol/L vs. 105.6 ± 97.1 µmol/L, P = 0.005; 0.3 ± 0.2 µg/L vs. 0.4 ± 0.2 µg/L, P = 0.04, respectively), comparing with those with low density of glomerular IgM and low levels of CFH. CONCLUSIONS: Our results suggested the involvement of glomerular deposited IgM in complement activation and renal injury in LN.

Contrast-enhanced ultrasound LI-RADS 2017: comparison with CT/MRI LI-RADS.

OBJECTIVE: To compare the classification based on contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) with that of contrast-enhanced CT and MRI (CECT/MRI) LI-RADS for liver nodules in patients at high risk of hepatocellular carcinoma. METHODS: Two hundred thirty-nine patients with 273 nodules were enrolled in this retrospective study. Each nodule was categorized according to the CEUS LI-RADS version 2017 and CECT/MRI LI-RADS version 2017. The diagnostic performance of CEUS and CECT/MRI was compared. The reference standard was histopathology diagnosis. Inter-modality agreement was assessed with Cohen's kappa. RESULTS: The inter-modality agreement for CEUS LI-RADS and CECT/MRI LI-RADS was fair with a kappa value of 0.319 (p < 0.001). The positive predictive values (PPVs) of hepatocellular carcinoma (HCC) in LR-5, LR-4, and LR-3 were 98.3%, 60.0%, and 25.0% in CEUS, and 95.9%, 65.7%, and 48.1% in CECT/MRI, respectively. The sensitivities and specificities of LR-5 for diagnosing HCC were 75.6% and 93.8% in CEUS, and 83.6% and 83.3% in CECT/MRI, respectively. The positive predictive values of non-HCC malignancy in CEUS LR-M and CECT/MRI LR-M were 33.9% and 93.3%, respectively. The sensitivity, specificity, and accuracy for diagnosing non-HCC malignancy were 90.9%, 84.5%, and 85.0% in CEUS LR-M and 63.6%, 99.6%, and 96.7% in CECT/MRI LR-M, respectively. CONCLUSIONS: The inter-modality agreement of the LI-RADS category between CEUS and CECT/MRI is fair. The positive predictive values of HCCs in LR-5 of the CEUS and CECT/MRI LI-RADS are comparable. CECT/MRI LR-M has better diagnostic performance for non-HCC malignancy than CEUS LR-M. KEY POINTS: • The inter-modality agreement for the final LI-RADS category between CEUS and CECT/MRI is fair. • The LR-5 of CEUS and CECT/MRI LI-RADS corresponds to comparable positive predictive values (PPVs) of HCC. For LR-3 and LR-4 nodules categorized by CECT/MRI, CEUS examination should be performed, at least if they can be detected on plain ultrasound. • CECT/MRI LR-M has better diagnostic performance for non-HCC malignancy than CEUS LR-M. For LR-M nodules categorized by CEUS, re-evaluation by CECT/MRI is necessary.

High hepatitis C virus cure rates with approved interferon-free direct-acting antivirals among diverse mainland Chinese patients including genotypes 3a and 3b.

BACKGROUND AND AIM: Globally, China has the highest chronic hepatitis C (CHC) burden, but its real-world direct-acting antiviral (DAA) data are limited. Our aim is to investigate the real-world outcome of China Food and Drug Administration-approved DAA therapies across mainland China including those with genotype (GT) 3. METHODS: The REAL-C is a multinational real-world interferon-free DAA-treated CHC registry of several mainland China and other Asian centers. We evaluated the sustained virological response rate 12 weeks after end of treatment (SVR12), adverse events, and treatment effect on liver function and fibrosis (fibrosis-4 index). RESULTS: We analyzed 859 DAA-treated CHC patients (6/1/2017-5/30/2019) from 12 mainland China centers (three municipalities and nine provinces): median age 52, 49.9% male, 33.1% cirrhosis, 95% treatment naïve, and 2.5% HBsAg+ . The most common GT was GT1b (523, 62.2%), followed by GT2a (156, 18.5%), GT3b (74, 8.8%), GT3a (41, 4.9%), and GT6 (37, 4.4%). SVR12 rates were 98.0% overall (95% confidence interval 96.9-98.8%), 98.1% for GT1b, 96.8% GT2a, 100% GT3a, 97.3% GT3b, and 100% GT6. Baseline cirrhosis and male sex but not prior treatment history, renal dysfunction, age, and GTs were associated with SVR12. For both cirrhotic and non-cirrhotic patients, there were significant improvement in liver function tests, alpha fetoprotein, and fibrosis-4 index with SVR12. Serious adverse events were rare (1.1%) with only nine patients discontinuing therapy prematurely and anemia being the most common adverse event (13.1%, mostly with ribavirin). CONCLUSIONS: In real-world Chinese patients with diverse GTs, Chinese Food and Drug Administration-approved interferon-free DAAs were well tolerated, provided high cure rates (98.0% overall) including GT3a/3b, and led to improvement of liver function.

Nucleoside transporter-guided cytarabine-conjugated liposomes for intracellular methotrexate delivery and cooperative choriocarcinoma therapy.

Gestational trophoblastic tumors seriously endanger child productive needs and the health of women in childbearing age. Nanodrug-based therapy mediated by transporters provides a novel strategy for the treatment of trophoblastic tumors. Focusing on the overexpression of human equilibrative nucleoside transporter 1 (ENT1) on the membrane of choriocarcinoma cells (JEG-3), cytarabine (Cy, a substrate of ENT1)-grafted liposomes (Cy-Lipo) were introduced for the targeted delivery of methotrexate (Cy-Lipo@MTX) for choriocarcinoma therapy in this study. ENT1 has a high affinity for Cy-Lipo and can mediate the endocytosis of the designed nanovehicles into JEG-3 cells. The ENT1 protein maintains its transportation function through circulation and regeneration during endocytosis. Therefore, Cy-Lipo-based formulations showed high tumor accumulation and retention in biodistribution studies. More importantly, the designed DSPE-PEG2k-Cy conjugation exhibited a synergistic therapeutic effect on choriocarcinoma. Finally, Cy-Lipo@MTX exerted an extremely powerful anti-choriocarcinoma effect with fewer side effects. This study suggests that the overexpressed ENT1 on choriocarcinoma cells holds great potential as a high-efficiency target for the rational design of active targeting nanotherapeutics.

Additional Diagnostic Value of Fusion Imaging of CEUS and First CEUS of Invisible Hepatic Lesions ≤2 cm.

OBJECTIVE: To explore the clinical value of image fusion of contrast-enhanced ultrasonography (CEUS) and contrast-enhanced computed tomography (CECT) in the diagnosis of invisible lesions with a size ≤2 cm on conventional ultrasound imaging, and compare it with the clinical value of "first CEUS" . METHODS: A total of 132 patients with 147 lesions with abnormal blood supply with a size ≤2 cm on CECT were included in this study. "first CEUS" was performed for these lesions. Then "fusion CEUS," that is, CEUS administered after fusion of US and CECT images, was carried out. The detection rates of the "first CEUS" and "fusion CEUS" were compared. How "fusion CEUS" corrects the misdiagnosis of liver lesions on CECT was analyzed. RESULTS: One hundred nine lesions considered as HCC and 38 lesions considered as benign lesions on CECT were included. The detection rates for the lesions of "first CEUS" and "fusion CEUS" were 71.4% and 96.6%, respectively (P < 0.001). Among the 147 lesions, 68 were with a diameter ≤ 1 cm. The detection rate of "first CEUS" and "fusion CEUS" were 55.9% and 95.6%, respectively (P < 0.001) for the lesions with a size ≤1 cm. "Fusion CEUS" and "first CEUS" corrected the misdiagnosis in 2 lesions on CECT. CONCLUSION: The "first CEUS" and "fusion CEUS" can improve the lesion conspicuity. Compared with "first CEUS," "fusion CEUS" has a higher diagnostic ability and hence can detect most of the invisible lesions on the former.

MicroRNA26a inhibits cisplatin-induced renal tubular epithelial cells apoptosis through suppressing the expression of transient receptor potential channel 6 mediated dynamin-related protein 1.

Acute kidney injury (AKI) is a common adverse reaction of the anticancer drug. Among these chemotherapeutic agents, cisplatin, an effective chemotherapeutic drug, is extensively applied to the treatment of solid tumours, yet various adverse reactions, especially AKI, often limit their use. However, the pathogenesis of AKI caused by cisplatin remains poorly clarified. Therefore, we tested whether microRNAs, which have been certified as key regulators of disease are involved in this process. AKI mouse and HK2 cells were treated with cisplatin. Annexin V/PI staining and cleaved caspase-3 were used to assess apoptosis. Western blot analyses and qRT-PCR were used to evaluate the protein and mRNA level of TRPC6 and DRP1. miR-26a was remarkably decreased in cisplatin-induced AKI and in cisplatin co-cultured HK2 cells. Furthermore, we used a miR-26a mimics in vitro and found that apoptosis was alleviated than that in the control cells. We further verified that miR-26a protected against cisplatin-induced cell apoptosis by acting on transient receptor potential channel 6 (TRPC6) which can regulate the expression of dynamin-related protein 1 (DRP1), thus inhibited the mitochondrial apoptosis pathway. Therefore, the study unveiled that miR-26a/TRPC6/DRP1 is a novel protective pathway in cisplatin-induced AKI and may be targeted for the prevention and treatment of drug-related renal injury. SIGNIFICANCE OF THE STUDY: Our study found that miR-26a was significantly downregulated during cisplatin-induced AKI and during cisplatin co-cultured HK2 cells. Further, in vitro we used miR-26a mimic to intervene cells and found that apoptosis alleviated compared with control group. We further verified that miR-26a protected cisplatin-induced apoptosis by target transient receptor potential channel 6 (TRPC6) which can regulate the expression of dynamic-related protein 1 (DRP1) and inhibit the mitochondrial apoptosis pathway. Thus, miR-26a/TRPC6/DRP1 is a new protective pathway in cisplatin-induced AKI and may be targeted for the prevention and treatment of drug-related acute kidney injury.

LINE-1 Methylation in Chronic HBV Infected Patients: Association with HCC, Gender and MTHFR C677T Polymorphism.

BACKGROUND: Polymorphism of methylene tetrahydrofolate reductase (MTHFR) C677T has been reported to be associated with HBV-related hepatocellular carcinoma (HCC) risk. However, the underlying mechanism remains elusive. DNA methylation has been suggested to be associated with HCC onset. MTHFR is the key enzyme in folic acid metabolism, thus, it influences the production of the main donor of methyl groups for DNA methylation. This study aimed to determine the association of global DNA methylation with MTHFR C677T polymorphism in chronic HBV infected patients, as well as its association with HCC and gender. METHODS: In all, 130 chronic hepatitis B (CHB) and 131 HBV-related HCC patients were enrolled in the study. The methylation level of long interspersed nuclear element-1 (LINE-1), the surrogate marker of global DNA methylation, and MTHFR C677T genotypes were determined. RESULTS: The HCC group showed significantly lower LINE-1 methylation than the CHB group (p = 0.016). Females were observed to have a markedly lower LINE-1 methylation level than males in both CHB and HCC groups (p = 0.000, p = 0.014, respectively). A significant relationship between MTHFR C677T polymorphism and LINE-1 methylation was observed in the CHB group (F = 5.985, p = 0.003). CT, TT, and CT + TT genotypes were significantly associated with lower LINE-1 methylation level compared with the CC genotype (p = 0.005, p = 0.018, p = 0.001, respectively). In addition, the association between MTHFR C677T and LINE-1 methylation was more significant in females (F= 5.036, p = 0.011) than in males (F = 3.083, p = 0.051); further, the association was significant in the subjects older than 60 years (F = 3.865, p = 0.028), but not in the subgroup aged less than 60 years (F = 2.496, p = 0.089). CONCLUSIONS: LINE-1 methylation level in chronic HBV infected patients was associated with the occurrence of HBV-related HCC, gender, and MTHFR C677T polymorphism.

Artemisinin attenuates tubulointerstitial inflammation and fibrosis via the NF-κB/NLRP3 pathway in rats with 5/6 subtotal nephrectomy.

Artemisinin (Art) is isolated from Artemisia annua L. and known as the most effective antimalaria drugs. Previous studies demonstrated that it could exert an immune-regulatory effect on autoimmune diseases. In this study, we first investigated its potential role in tubulointerstitial inflammation and fibrosis in rats with 5/6 nephrectomy. Subtotal nephrectomized (SNx) rats were orally administered Art (100 mg·kg -1 ·d - 1) for 16 weeks. Blood and urine samples were collected for biochemical examination. Kidney tissues were collected for immunohistochemistry and Western blot analyses. Ang II-induced injury of the human kidney 2 (HK-2) cells was used for in vitro study. It was shown that Art could significantly attenuate the renal function decline in SNx rats compared with control. More importantly, Art treatment significantly reduced the tubulointerstitial inflammation and fibrosis, as demonstrated by the evaluation of renal pathology. Furthermore, Art inhibited the activation of NLRP3 inflammasome and NF-κB in the kidneys. In in vitro study, Art pretreatment could significantly prevent the activation of NLRP3 inflammasome and NF-κB in Ang II-treated HK-2 cells, while BAY11-7082 (an inhibitor of NF-κB) significantly inhibited Ang II-induced NLRP3 inflammasome activation. This study suggested that Art could provide renoprotective role by attenuating the tubulointerstitial inflammation and fibrosis in SNx rats by downregulating the NF-κB/NLRP3 signaling pathway.

Calcium-sensing receptor activation attenuates collagen expression in renal proximal tubular epithelial cells.

316: F1006-F1015, 2019. First published March 6, 2019; doi: 10.1152/ajprenal.00413.2018 .-Experimental studies have shown that pharmacological activation of calcium-sensing receptor (CaSR) attenuates renal fibrosis in some animal models beyond modification of bone and mineral homeostasis; however, its underlying mechanisms remain largely unknown. Since excessive collagen deposition is the key feature of fibrosis, the present study aimed to examine whether CaSR was involved in the regulation of collagen expression in rats with adenine diet-induced renal fibrosis and in profibrotic transforming growth factor (TGF)-ß1-treated renal proximal tubular epithelial cells (PTECs). The results showed that the CaSR agonist cinacalcet significantly attenuated renal collagen accumulation and tubular injury in adenine diet-fed rats. Additionally, the in vitro experiment showed that profibrotic TGF-ß1 significantly increased the expression of collagen and decreased CaSR expression at the mRNA and protein levels in a concentration- and time-dependent manner. Furthermore, the CaSR CRISPR activation plasmid and cinacalcet partially abrogated the upregulation of collagen induced by TGF-ß1 treatment. Blockade of CaSR by the CRISPR/Cas9 KO plasmid or the pharmacological antagonist Calhex231 further enhanced TGF-ß1-induced collagen expression. Mechanistic experiments found that Smad2 phosphorylation and Snail expression were markedly increased in PTECs treated with TGF-ß1, whereas the CaSR CRISPR activation plasmid and cinacalcet substantially suppressed this induction. In summary, this study provides evidence for a direct renal tubular epithelial protective effect of CaSR activation in renal fibrosis, possibly through suppression of collagen expression in PTECs.