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The development of phosphorescent materials with ultrapure emission is of great significance for wide‐color‐gamut organic light‐emitting diodes (OLEDs). Herein, a ligand steric interlocking strategy is introduced to achieve the narrowband emission of phosphorescent Ir(III) complexes. The steric interlocking effect contributed by the short distance between ligands leads to enhanced rigidity, and suppresses the high‐frequency vibrations of oICz‐Ir. In this context, oICz‐Ir exhibits an ultrapure green phosphorescence with a small full width at half maximum (FWHM) of 23 nm peaking at 521 nm in solution. Furthermore, the oICz‐Ir‐based OLED achieves a maximum external quantum efficiency (EQEmax) of 18.9%, an excellent color purity with Commission Internationale de L'Eclairage coordinate y (CIEy) of 0.69, making it the purest green bottom‐emitting phosphorescent OLEDs. Meanwhile, with oICz‐Ir as the sensitizer, a phosphorescence sensitized fluorescent OLED shows an excellent EQEmax of 31.1% with the CIEy of 0.7. [ABSTRACT FROM AUTHOR]

• ZnIn 2 S 4 /Mn 0.3 Cd 0.7 S 1-x photocatalysts with a Mn-S bond interface were synthesized. • fs-TA probed the kinetics and lifetime of active photogenerated charge carriers. • Various in-situ characteriazations demonstrated a rational Z-Scheme mechanism. • The quantum efficiency for the optimal photocatalyst achieved 32.71 % at 420 nm. Developing a highly effective solar-to-H 2 conversion system is a promising strategy for carbon neutrality. Here, we report a chemically bonded Z-scheme photocatalyst by specifically linking the conduction band site of ZnIn 2 S 4 with the valence band site of Mn 0.3 Cd 0.7 S 1-x. Deviates from the typical van der Waals interactions between two semiconductors, the in-built robust binding force (Mn-S bond) and charge transfer channel facilitates the electron mobility, minimizes detrimental deep charge trapping, and prolongs the active charge lifetime from 983 ps to 4250 ps. The sulfur vacancies in Mn 0.3 Cd 0.7 S 1-x are partially refilled by atoms of the same element in ZnIn 2 S 4 during the in-situ formation of heterojunctions, which promotes and solidates the establishment of interfacial chemical bonds. The optimal photocatalyst achieves a high quantum efficiency of 32.71 % at 420 nm. This study offers a new insight into the development of Z-Scheme heterojunctions via a synergistic approach involving doping, vacancy filling and strong interfacial chemical bonds. [ABSTRACT FROM AUTHOR]

Background: Human MARCH5 is a mitochondria-localized E3 ubiquitin-protein ligase that is essential for the regulation of mitochondrial dynamics. A large body of evidence suggests that imbalances in mitochondrial dynamics are strongly associated with cancer. However, the expression, biological function and prognostic significance of MARCH5 in hepatocellular carcinoma (HCC) have not been determined. Materials and methods: The mRNA and protein expression of MARCH5 in HCC cell lines and tumor tissues was assessed by real-time quantitative PCR, Western blot analysis and immunohistochemistry. The clinical prognostic significance of MARCH5 was evaluated in 135 HCC patients. Knockdown or overexpression of MARCH5 in HCC cells was determined by in vitro cell proliferation, migration and invasion assays, and in vivo tumor growth and metastasis assays. In addition, the intrinsic mechanisms by which MARCH5 regulates HCC cell growth and metastasis were explored. Results: MARCH5 was significantly overexpressed in HCC cells and was closely associated with patients' poor postoperative prognosis. In vivo and in vitro experiments revealed that MARCH5 significantly promoted the increase and invasive and migratory ability of hepatocellular carcinoma cells, which was mainly due to the promotion of autophagy by MARCH5. Mechanistic studies revealed that MARCH5 promoted autophagy through ubiquitination degradation of p53 leading to malignant progression of hepatocellular carcinoma. Conclusion: Our findings suggest that MARCH5 plays a critical oncogenic role in HCC cells, which provides experimental evidence for the use of MARCH5 as a potential target for HCC therapy. [ABSTRACT FROM AUTHOR]

Abstract Quinone methides are important reactive intermediates in photobiology and photochemistry, with little known regarding the photo-induces generation of reactive quinone methides species from relevant precursors in aqueous solutions. Here, the time-resolved spectroscopy methods including the transient absorption experiments and time-resolved Resonance Raman were employed to directly study the photophysics and photochemical processes of 6,6′-Bis(hydroxymethyl)-1,1′-binaphthyl-2,2′-diol (BQMP-a) in neat MeCN and 1:1 MeCN:H 2 O aqueous solutions. In aqueous solution, the intramolecular excited state proton transfer (ESIPT) process was observed where the water molecules help deliver the proton on the hydroxyl group to the naphthol ring within 125 ps in the singlet excited state of BQMP-a. This solvent mediated ESIPT will then lead to the leaving of the H 2 O group in 906 ps followed by the generation of the binol quinone methide (BQM-a) intermediate with a lifetime of 1.7 μs. As a result, the BQMP-a provides a different production rate of quinone methides compared with the 1,1′-(2,2′-Dihydroxy-1,1′-binaphthyl-6,6′-diyl) bis( N,N,N -trimethylmethanaminium) bromide system, which indicates the leaving group is an important factor in the generation of the reactive DNA alkylated intermediates. [ABSTRACT FROM AUTHOR]

Abstract: Imatinib is a synthetic tyrosinase inhibitor that is employed for the treatment of some kinds of human cancer. This drug has a low phototoxicity towards DNA, but its pyridylpyrimidine (1) fragment by itself exhibits significant phototoxicitiy. The intrinsic mechanism that leads to the enhanced photosafety of Imatinib is not yet known. Here, the properties of the excited state and interchromophoric interactions of Imatinib have been explored by using ultrafast laser flash photolysis and agarose electrophoresis studies. An intramolecular charge separation was directly observed for the irradiated Imatinib, which accounts for the relaxation of its excited state. An anionic form of pyridylpyrimidine (1) was deduced from the results of time‐resolved resonance Raman spectra and by quenching experimental studies on compound 1 and diaminotoluene. In contrast, compound 1 efficiently transformed into triplet excited states with a long lifetime, which explained the phototoxicity associated with this fragment. This work provides insight into how to design drugs with lower phototoxicitiy or improved photostability by using interchromophoric interactions. [ABSTRACT FROM AUTHOR]

Neutral stochastic delay differential equations often appear in various fields of science and engineering. The aim of this article is to investigate the strong convergence of the split-step theta (SST) method for the neutral stochastic delay differential equations, where the corresponding coefficients may be highly nonlinear with respect to the delay variables. In particular, we reveal that the SST method with θ ∈ [ 0 , 1 ] strongly converges to the exact solution with the order 1 2 . Some numerical results are presented to confirm the obtained results. [ABSTRACT FROM AUTHOR]

The amorphous carbon derived from a “molten salt CO 2 capture and electrochemical transformation” process, was characterized and studied for the adsorption of aqueous solutes. XRF and TG measurements showed that the electrolytic carbon (E-carbon) had a higher purity than the commonly available biochars and activated carbons due to its unique growth mechanism in molten salts. The analysis on morphology, diameter distribution and porosity indicated that the E-carbon, with an inhomogeneous porous structure, exhibited an average particle size of 9.8 μm in aqueous solution, and a BET surface area of 614 m 2 g −1 . The major surface oxygen-containing functional group for E-carbon was carboxyl group, which was primarily due to the cathodic deoxygenation of carbonate ions and the surface modifying effect of melt. The spontaneous Cu(II) adsorption by E-carbon followed the pseudo-second-order kinetic model and the Langmuir isotherm. Through the surface complexation and surface-precipitation processes, the E-carbon exhibited a maximum adsorptive capacity of 29.9 mg g −1 for Cu (II) adsorption. It also showed a good performance on methylene blue adsorption due to its favorable adsorption-related features, such as high purity, porosity and having a large number of surface functional groups. The E-carbon is envisaged to be used as an adsorptive material for decontamination. [ABSTRACT FROM AUTHOR]

Purpose To investigate the safety and feasibility of intraluminal brachytherapy using 125 I seed strand for locally advanced pancreatic ductal adenocarcinoma with obstructive jaundice. Methods and Materials From January 2010 to February 2015, 18 consecutive patients diagnosed with locally advanced, nonmetastatic, inoperable pancreatic ductal adenocarcinoma with obstructive jaundice were enrolled and underwent intraluminal brachytherapy using 125 I seed strand. Dose calculation was performed using a software. The procedure-related and radiation complications were assessed. Obstruction-free survival and overall survival were calculated using the Kaplan–Meier method. Results The technique successful rate of 125 I seed strand implantation was 100%. Successful bile drainage was achieved in all patients. The estimated mean accumulating dose (R = 5 mm, z = 0, 240 days) was 167.2 Gy, from 164.19 to 170.05 Gy. Two patients had adverse event of Grade 3, one of Grade 4. Stent dysfunction occurred in 1/18 (5.6%) patients. The mean and median obstruction-free survival time were 10.61 months (95% confidence interval [CI]: 7.04, 14.18) and 7.26 months (95% CI: 2.14, 12.38). The mean and median overall survival time were 11.91 months (95% CI: 7.39, 16.43) and 7.26 months (95% CI: 2.14, 12.38). Conclusions Intraluminal brachytherapy using 125 I seed strand may be consider as a safe treatment option for the therapy of locally advanced pancreatic duct adenocarcinoma complicated by obstructive jaundice with acceptable complication rates. [ABSTRACT FROM AUTHOR]

[Display omitted] • Ibrutinib inhibits the expression and secretion of inflammatory cytokines and chemokines in macrophages induced by multiple TLR agonists. • Ibrutinib selectively suppresses the activation, superoxide release, and calcium influx of neutrophils stimulated by zymosan. • Ibrutinib exerts excellent therapeutic effects on zymosan-induced mice acute peritonitis. • Ibrutinib blocks the activation of BTK-PLCγ2-DAG/IP3-PKC-ERK1/2 signaling pathways in neutrophils induced by zymosan. Timely treatment of acute inflammatory reactions induced by fungi or bacteria is essential to prevent infectious damage. Ibrutinib is a Bruton's tyrosine kinase (BTK) inhibitor which is used to treat various lymphoid cancers. It is also known that BTK plays important roles in innate immunity and inflammatory response. In the present study, we investigated the regulatory effects of Ibrutinib on the activation of neutrophils and macrophages and its therapeutic effects on acute peritonitis. In addition, we also studied its anti-inflammatory mechanisms. The results showed that Ibrutinib inhibited the expression and secretion of inflammatory factors in macrophages induced by multiple Toll-like receptor (TLR) agonists. In the study of neutrophils, Ibrutinib selectively suppressed the activation, superoxide release, and calcium influx of neutrophils stimulated by zymosan. Furthermore, in zymosan-induced mice acute peritonitis, Ibrutinib significantly reduced the infiltration of neutrophils into peritoneal cavity, the release of myeloperoxidase (MPO) and β-glucuronidase as well as the production of inflammatory factors in peritoneal cavity. In mechanism study, Ibrutinib selectively inhibited the phosphorylation of PLCγ2, PKCδ, and ERK1/2 in neutrophils induced by zymosan. Collectively, Ibrutinib can significantly inhibit the activation of neutrophils and macrophages by inhibiting BTK-PLCγ2-PKC signaling pathway, and has great potential to be developed into therapeutic drug for acute inflammatory diseases. [ABSTRACT FROM AUTHOR]

[Display omitted] • Ibrutinib inhibits the expression and secretion of inflammatory cytokines and chemokines in macrophages induced by multiple TLR agonists. • Ibrutinib selectively suppresses the activation, superoxide release, and calcium influx of neutrophils stimulated by zymosan. • Ibrutinib exerts excellent therapeutic effects on zymosan-induced mice acute peritonitis. • Ibrutinib blocks the activation of BTK-PLCγ2-DAG/IP3-PKC-ERK1/2 signaling pathways in neutrophils induced by zymosan. Timely treatment of acute inflammatory reactions induced by fungi or bacteria is essential to prevent infectious damage. Ibrutinib is a Bruton's tyrosine kinase (BTK) inhibitor which is used to treat various lymphoid cancers. It is also known that BTK plays important roles in innate immunity and inflammatory response. In the present study, we investigated the regulatory effects of Ibrutinib on the activation of neutrophils and macrophages and its therapeutic effects on acute peritonitis. In addition, we also studied its anti-inflammatory mechanisms. The results showed that Ibrutinib inhibited the expression and secretion of inflammatory factors in macrophages induced by multiple Toll-like receptor (TLR) agonists. In the study of neutrophils, Ibrutinib selectively suppressed the activation, superoxide release, and calcium influx of neutrophils stimulated by zymosan. Furthermore, in zymosan-induced mice acute peritonitis, Ibrutinib significantly reduced the infiltration of neutrophils into peritoneal cavity, the release of myeloperoxidase (MPO) and β-glucuronidase as well as the production of inflammatory factors in peritoneal cavity. In mechanism study, Ibrutinib selectively inhibited the phosphorylation of PLCγ2, PKCδ, and ERK1/2 in neutrophils induced by zymosan. Collectively, Ibrutinib can significantly inhibit the activation of neutrophils and macrophages by inhibiting BTK-PLCγ2-PKC signaling pathway, and has great potential to be developed into therapeutic drug for acute inflammatory diseases. [ABSTRACT FROM AUTHOR]

Background: Measuring the portal pressure gradient from the portal vein (PV) to the inferior vena cava (IVC) or to the right atrium (RA) remains controversial. The aim of our study was to compare the predictive ability of portoatrial gradient (PAG) and portocaval gradient (PCG) for variceal rebleeding. Methods: The data of 285 cirrhotic patients with variceal bleeding undergoing elective transjugular intrahepatic portosystemic shunt (TIPS) in our hospital were analyzed retrospectively. The variceal rebleeding rates were compared between groups categorized by established or modified thresholds. The median follow-up time was 30.0 months. Results: After TIPS, PAG was equal to (n = 115) or more than (n = 170) PCG. The pressure of IVC was defined as an independent predictor for a PAG-PCG difference of ≥ 2 mmHg (p < 0.001, OR 1.23, 95% CI 1.10–1.37). Using a threshold of 12 mmHg, PAG (p = 0.081, HR 0.63, 95% CI 0.37–1.06) could not predict variceal rebleeding but PCG could (p = 0.003, HR 0.45, 95% CI 0.26–0.77). This pattern was unchanged when a ≥ 50% reduction from baseline was also considered as a threshold (PAG/PCG: p = 0.114 and 0.001). Subgroup analyses showed that only in patients with post-TIPS IVC pressure < 9 mmHg (p = 0.018), PAG could predict variceal rebleeding. Because PAG was on average 1.4 mmHg higher than PCG, patients were classified by a PAG of 14 mmHg, and there was no difference in rebleeding rates between these two groups (p = 0.574). Conclusions: For patients with variceal bleeding, the predictive ability of PAG is limited. The portal pressure gradient should be measured between the PV and IVC. [ABSTRACT FROM AUTHOR]

Portal vein thrombosis (PVT) is commonly classified into acute (symptom duration <60 days and absence of portal carvernoma and portal hypertension) and chronic types. However, the rationality of this classification has received little attention. In this study, 60 patients (40 men and 20 women) with PVT were examined using contrast-enhanced computed tomography (CT). The percentage of vein occlusion, including portal vein (PV) and superior mesenteric vein (SMV), was measured on CT image. Of 60 patients, 17 (28.3%) met the criterion of acute PVT. Symptoms occurred more frequently in patients with superior mesenteric vein thrombosis (SMVT) compared to those without SMVT (p<0.001). However, there was no significant difference in PV occlusion between patients with and without symptoms. The frequency of cavernous transformation was significantly higher in patients with complete PVT than those with partial PVT (p<0.001). Complications of portal hypertension were significantly associated with cirrhosis (p<0.001) rather than with the severity of PVT and presence of cavernoma. These results suggest that the severity of PVT is only associated with the formation of portal cavernoma but unrelated to the onset of symptoms and the development of portal hypertension. We classified PVT into complete and partial types, and each was subclassified into with and without portal cavernoma. In conclusion, neither symptom duration nor cavernous transformation can clearly distinguish between acute and chronic PVT. The new classification system can determine the pathological alterations of PVT, patency of portal vein and outcome of treatment in a longitudinal study. [ABSTRACT FROM AUTHOR]

In this present paper, cobalt oxide (CoO x ) is studied as an effective cocatalyst in a photocatalytic hydrogen production system. CoO x -loaded titanium dioxide/cadmium sulfide (TiO 2 /CdS) semiconductor composites were prepared by a simple solvothermal method and characterized by powder X-ray diffraction (XRD), transmission electron microscopy (TEM), ultraviolet–visible diffuse reflectance spectroscopy (UV–Vis DRS), and X-ray photoelectron spectroscopy (XPS). Photocatalytic hydrogen production was studied using the as-synthesized photocatalysts in aqueous solution containing sodium sulfide (Na 2 S)/sodium sulfite (Na 2 SO 3 ) as hole scavengers under visible light irradiation ( λ > 400 nm). The optimal cobalt content in CoO x -loaded TiO 2 /CdS composite is determined to be 2.1 wt% and the corresponding rate of hydrogen evolution is 660 μmol g −1 h −1 , which is about 7 times higher than TiO 2 /CdS and CdS photocatalysts under the same condition. Visible light-driven photocurrents of the semiconductor composites were further measured on a photoelectrochemical electrode, revealing that the photocorrosion of CdS can be prevented due to the presence of TiO 2 –CoO x . [ABSTRACT FROM AUTHOR]

Purpose: This study is aimed at evaluating the safety and efficacy of transarterial chemoembolization (TACE) for patients with hypervascular painful metastatic spinal tumors refractory to percutaneous vertebroplasty (PVP). Methods: A total of 11 patients with hypervascular painful metastatic spinal tumors refractory to PVP were recruited for testing the safety and efficacy of TACE. Individual patients were subjected to infusion with 40 mg/m epirubicin and 20-60 mg polyvinyl alcohol foam (PVA) particles (300-500 μm) or gel-foam strips for embolization through the dominant arteries to the tumor. The degrees of pain the patients suffered were evaluated using the visual analogue scale (VAS) score one day before, 5 days, and 2 weeks after TACE. The neurologic symptoms and skin/muscle complications were observed. Results: A total of 12 lumbar vertebrae from 11 patients were treated with TACE through 21 vertebral arteries. Twelve out of 21 arteries were embolized with PVA particles, and other nine arteries were embolized with gel-foam strips. The analgesic rate of TACE in those patients was 90.9 % at 5 and 14 days postprocedure. The VAS scores in those patients were reduced from preoperative 8.6 ± 1.1 to 3.9 ± 1.38 on day 5 and to 3.6 ± 1.7 at 2 weeks post-TACE, respectively. There was no obvious neurologic symptom or skin/muscle necrosis in those patients. Conclusions: Transarterial chemoembolization (TACE) is a safe and effective therapy for pain relief in patients with hypervascular painful metastatic spinal tumors refractory to PVP. [ABSTRACT FROM AUTHOR]

• 0D/1D heterojunctions of CdS quantum dots /TiO 2 nanotube arrays were fabricated by a simple vapor transport method. • Femtosecond transient absorption (fs-TA) spectroscopy was employed to investigate the dynamics of the charge carriers. • Internal electric field was formed between CdS quantum dots and TiO 2 nanotube arrays. • Z-scheme mechanism was proposed in the heterostructure, enabling 5-fold improvement of photocatalytic activities. Heterojunctions of CdS quantum dots (QDs)/TiO 2 nanotube arrays (NTAs) were synthesized via a simple vapor transport approach. The 0D/1D QDs/NTAs electrodes exhibited 5-fold improvement efficiency for photocatalytic dye degradation and hydrogen evolution compared to pure TiO 2 NTAs in a photoelectrochemistry cell, which was attributed to the faster transportation and retarded recombination of electron-hole pairs in the 0D/1D heterostructures. Femtosecond transient absorption offers deep insights into the dynamics of the charge carriers, showing that surface-trapped electrons were generated within 1.2 ps. The lifetimes for recombination of electrons at shallow trap sites with holes and deep trapped electrons with holes are prolonged to 73.2 ps and 622.6 ps, respectively. The reduced charge transfer resistance is verified by electrochemical impedance spectroscopy. Mott-Schottky plots indicated downward shifts for both the conduction band and valence band in the heterostructure. Finally, a Z-scheme photoreactive mechanism is proposed to explain the enhanced catalytic activities. [ABSTRACT FROM AUTHOR]

Nitrenium ions are common reactive intermediates with high activities towards some biological nucleophiles. In this paper, we employed femtosecond transient absorption (fs-TA) and nanosecond transient absorption (ns-TA) as well as nanosecond time-resolved resonance Raman (ns-TR3) spectroscopy and density function theory (DFT) calculations to study the spectroscopic properties of the N(4,4′–dibromodiphenylamino)–2,4,6–trimethylpyridinium BF4− salt (1) in an acidic aqueous solution. Efficient cleavage of the N–N bond (4 ps) to form the N,N–di(4–bromophenyl)nitrenium ion (DN) was also observed in the acidic aqueous solution. As a result, the dication intermediate 4 appears more likely to be produced after abstracting a proton for the nitrenium ion DN in the acid solution first, followed by an electron abstraction to form the radical cation intermediate 3. These new and more extensive time-resolved spectroscopic data will be useful to help to develop an improved understanding of the identity, nature, and properties of nitrenium ions involved in reactions under acidic aqueous conditions. [ABSTRACT FROM AUTHOR]

Background: Thyroid nodule (TN) patients in China are subject to overdiagnosis and overtreatment. The implementation of existing technologies such as thyroid ultrasonography has indeed contributed to the improved diagnostic accuracy of TNs. However, a significant issue persists, where many patients undergo unnecessary biopsies, and patients with malignant thyroid nodules (MTNs) are advised to undergo surgery therapy. Methods: This study included a total of 293 patients diagnosed with TNs. Differential methylation haplotype blocks (MHBs) in blood leukocytes between MTNs and benign thyroid nodules (BTNs) were detected using reduced representation bisulfite sequencing (RRBS). Subsequently, an artificial intelligence blood leukocyte DNA methylation (BLDM) model was designed to optimize the management and treatment of patients with TNs for more effective outcomes. Results: The DNA methylation profiles of peripheral blood leukocytes exhibited distinctions between MTNs and BTNs. The BLDM model we developed for diagnosing TNs achieved an area under the curve (AUC) of 0.858 in the validation cohort and 0.863 in the independent test cohort. Its specificity reached 90.91% and 88.68% in the validation and independent test cohorts, respectively, outperforming the specificity of ultrasonography (43.64% in the validation cohort and 47.17% in the independent test cohort), albeit with a slightly lower sensitivity (83.33% in the validation cohort and 82.86% in the independent test cohort) compared to ultrasonography (97.62% in the validation cohort and 100.00% in the independent test cohort). The BLDM model could correctly identify 89.83% patients whose nodules were suspected malignant by ultrasonography but finally histological benign. In micronodules, the model displayed higher specificity (93.33% in the validation cohort and 92.00% in the independent test cohort) and accuracy (88.24% in the validation cohort and 87.50% in the independent test cohort) for diagnosing TNs. This performance surpassed the specificity and accuracy observed with ultrasonography. A TN diagnostic and treatment framework that prioritizes patients is provided, with fine-needle aspiration (FNA) biopsy performed only on patients with indications of MTNs in both BLDM and ultrasonography results, thus avoiding unnecessary biopsies. Conclusions: This is the first study to demonstrate the potential of non-invasive blood leukocytes in diagnosing TNs, thereby making TN diagnosis and treatment more efficient in China. [ABSTRACT FROM AUTHOR]

The 3′,5′-dimethoxybenzoin (DMB) system has been widely investigated as a photoremovable protecting group (PRPG) for the elimination of various functional groups and has been applied in many fields. The photolysis of DMB fluoride leads to a highly efficient photocyclization–deprotection reaction, resulting in a high yield of 3′,5′-dimethoxybenzofuran (DMBF) in a MeCN solution, while there is a competitive reaction that produces DMB in an aqueous solution. The yield of DMB increased as the volume ratio of water increased. To understand the solvent effect of the photolysis of selected DMB-based compounds, a combination of femtosecond to nanosecond transient absorption spectroscopies (fs-TA and ns-TA), nanosecond time-resolved resonance Raman spectroscopy (ns-TR3) and quantum chemical calculation was employed to study the photophysical and photochemical reaction mechanisms of DMB fluoride in different solutions. Facilitated by the bichromophoric nature of DMB fluoride with electron-donating and -withdrawing chromophores, the cyclized intermediates could be found in a pure MeCN solution. The deprotection of a cyclic biradical intermediate results in the simultaneous formation of DMBF and a cyclic cation species. On the other hand, in aqueous solution, fs-TA experiments revealed that α-keto cations could be observed after excitation directly, which could easily produce the DMB through the addition of a hydroxyl within 8.7 ps. This work provides comprehensive photo-deactivation mechanisms of DMB fluoride in MeCN and aqueous conditions and provides critical insights regarding the biomedical application of DMB-based PRPG compounds. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to assess the safety and efficacy of endovascular managements, including splenic vein recanalization (SVR), partial splenic embolization (PSE), and percutaneous transsplenic gastric varices embolization combined with PSE (PSE+GVE), for management of SPH-related variceal hemorrhage (VH). Methods: A total of 61 patients with SPH-related VH from three hospitals were enrolled and classified into three groups: the SVR group (Group 1, n=24), the PSE+GVE group (Group 2, n=17), and the PSE group (Group 3, n=20). Baseline characteristics and clinical outcomes were compared among the groups. Results: The technical success rates for transhepatic and transsplenic SVR were 27.8% and 34.6%, respectively. No major complications were observed during any of the procedures. The median follow-up period was 53.2 months. The 2-year GI rebleeding rates for Group 1, 2, and 3 were 0%, 5.9%, and 35%, respectively. Groups 1 and 2 have a lower GI rebleeding rate (p = 0.002, p = 0.048, respectively) and better results of the degree of GV (p = 0.003, p = 0.044, respectively) compared to Group 3. No significant differences were found in 2-year GI rebleeding rates and the degree of GV between Group 1 and 2 (p = 0.415, p = 0.352, respectively). Conclusion: SVR, PSE+GVE, and PSE seem safe and effective for management of SPH-related VH. SVR appears to be the superior treatment option. Transsplenic access may further increase the SVR success rate. PSE+GVE seems to have comparable outcomes in GV control and GI rebleeding rates compared to SVR, while superior to PSE. [ABSTRACT FROM AUTHOR]

Binol quinone methides (BQMs) can be generated from 1,1′-(2,2′-dihydroxy-1,1′-binaphthyl-6,6′-diyl)bis(N,N,N-trimethylmethanamiuium) bromide (BQMP-b) in a 1:1 MeCN:H2O mixed solution via a ground state intramolecular proton transfer (GSIPT), as mentioned in our previously reported studies. Here, the photoreaction of BQMP-b in neutral and basic aqueous solution (pH = 7, 10, 12) was investigated to explore the possible mechanisms and the key intermediates produced in the process of the photoreaction and to examine whether they are different from those in a neutral mild-mixed MeCN:H2O solution. The studies were conducted using femtosecond transient absorption (fs-TA), nanosecond transient absorption (ns-TA), and nanosecond time-resolved resonance Raman spectroscopy (ns-TR3) in conjunction with results from density functional theory (DFT) computations. The results showed that BQMP-b was deprotonated initially and produced BQMs species more effectively through an E1bc elimination reaction in a strong basic aqueous condition (pH = 12), which differed from the reaction pathway that took place in the solution with pH = 7 or 10. A related single naphthol ring molecule 1-(6-hydroxynaphthalen-2-yl)-N,N,N-trimethylmethanaminium bromide (QMP-b) that did not contain a second naphthol ring was also investigated. The related reaction mechanisms are elucidated in this work, and it is briefly discussed how the mechanisms vary as a function of aqueous solution pH conditions. [ABSTRACT FROM AUTHOR]

To compare the safety and efficacy of intraluminal brachytherapy with iodine-125 (125I) seed strand implantation combined with and without stent placement to treat patients with obstructive jaundice induced by tumor thrombus. Between January 2018 and June 2022, 42 patients with malignant obstructive jaundice (MOJ) induced by tumor thrombus were included. 20 patients received 125I seed strand implantation and stent placement (group A). The remaining 22 patients, implanted 125I seed strands only, served as control (group B). The two groups' overall survival and jaundice-free survival were compared using the Kaplan-Meier method and log-rank test. During the follow-up period, the mean survival time of group A was 38.0 ± 4.1 months (95%CI, 30.0–46.1 months), while that of group B was 25.1 ± 2.8 (95% CI, 19.5–30.6 months) (p = 0.406). The mean survival rates of 12 months for all patients, group A, and group B was 66.7%, 65%, and 68%, respectively. The mean jaundice-free survival of group A and group B were 34.0 ± 3.6 months (95% CI, 27.9–41.2months) and 22.9 ± 2.7 months (95%CI, 17.5–28.2months) (p = 0.254), respectively. Two PTBD drainage tube infection cases occurred in group A and group B separately. 125I intraluminal brachytherapy is an effective and safe therapy for treating patients with obstructive jaundice induced by tumor thrombus. [ABSTRACT FROM AUTHOR]

Sphingosine 1-phosphate (S1P) plays an important role in hepatocarcinogenesis. We previously demonstrated that S1P induced epithelial–mesenchymal transition of hepatocellular carcinoma (HCC) cells via an MMP-7/Syndecan-1/TGF-β autocrine loop. In the present study, we investigated the regulative role of S1P in cell survival and progression of HCC cells, and tested whether syndecan-1 is required in the S1P action. After transfected with syndecan-1 shRNA, HepG2 and SMMC7721 cells were treated with S1P for 72 h, and then cell proliferation was detected by CCK8 assay, and cell cycle progression and cell apoptosis were detected by flow cytometry. The levels of apoptosis markers including cleaved-Caspase-3 and cleaved-PARP in SMMC7721 cells were examined by western blotting. Results showed that S1P significantly enhanced cell proliferation in HCC cells, which was significantly inhibited by syndecan-1 shRNA. S1P induced the cell proportion in S phase in HCC cells, whereas S1P decreased the proportion of cells in both early and late apoptosis. Syndecan-1 shRNA induced the G2/M arrest in the presence of S1P. In the syndecan-1 shRNA transfected HCC cells, the proportions of late and early apoptotic cells, and levels of cleaved-Caspase-3 and cleaved-PARP were significantly increased in cells with or without S1P treatment. Thus, S1P augments the proportion of cells in S phase of the cell cycle that might translate to enhance HCC cell proliferation and inhibit the cell apoptosis via syndecan-1. [ABSTRACT FROM AUTHOR]

Introduction: Gastroesophageal varices (GOV) bleeding is a common and serious complication of advanced liver cirrhosis with a median survival of less than 2 years. Multiple guidelines have pointed out that transjugular intrahepatic portosystemic shunt (TIPS) is the rescue treatment of acute variceal hemorrhage (AVB) after failure of standard therapy and an effective second-line treatment for preventing patients with high risks from rebleeding of GOV. The safety and stability of TIPS have been greatly improved due to the improvements of related technologies and the emergence of various novel devices, but the incidence of hepatic encephalopathy (HE) after shunting (10–50%) hindered the widespread use of TIPS. The target portal vein branch might affect the incidence of HE after TIPS. The aim of this study is to compare the rate of HE in patients with hepatitis B virus (HBV) related cirrhosis receiving TIPS either the left or right branch of the portal vein with 8mm Viatorr stent for preventing rebleeding from GOV. Methods and analysis: This study is a multicenter randomized controlled trial comparing the influence of shunting left or right portal vein branch on post-TIPS hepatic encephalopathy for preventing rebleeding from GOV in patients with HBV-related cirrhosis. A total of 130 patients will be recruited over a period of 24 months across 5 centers in China. Eligible patients will be stratified 1:1 to constructing either a left or right portal vein shunt with an 8-mm Viatorr stent. The primary objective was to compare the incidence of post-TIPS hepatic encephalopathy between the two groups. The secondary objectives were to compare the grade and duration of hepatic encephalopathy, the rate of shunt dysfunction, the rate of variceal rebleeding, the HE-free survival, the cumulative patency rate of the stent, and the overall survival at 12 months and 24 months between two groups. Ethics and dissemination: This study was approved by the ethics committee of Zhongshan Hospital of Fudan University (No. B2018-292R) and was registered at ClinicalTrials.gov (NCT03825848). All participants give written informed consent. Trial registration: ClinicalTrials.gov NCT03825848. Registered on January 31, 2019 Trial status: The first patient was recruited into our study on June 19, 2019. A total of 55 patients were recruited till May 27, 2021 (27 and 28 patients assigned to shunting the left (L Group) and right (R Group) branches of the portal vein, respectively). [ABSTRACT FROM AUTHOR]

Background Ginsenoside Rg3 is a low toxic inhibitor of vascular endothelial growth factor (VEGF), which is implicated in angiogenesis in hepatocellular carcinoma (HCC). This single-centre, open-label, randomised, controlled trial evaluated the efficacy and safety of ginsenoside Rg3 plus transarterial chemoembolisation (TACE) in patients with advanced HCC. Methods Advanced HCC patients (Child-Pugh A) who had no prior systemic therapy were randomly assigned (2:1 ratio) to receive 20 mg twice daily orally ( n = 152) combined with TACE or TACE alone ( n = 76). The primary endpoint was overall survival (OS). Secondary endpoints included time to progression (TTP), time to untreatable progression (TTUP), disease control rate (DCR) based on modified Response Evaluation Criteria in Solid Tumors, and safety. Results Median overall survival was 13.2 months (95% confidence interval (CI) 11.15–15.26) in the TACE + Rg3 group compared with 10.1 months (95% CI 9.14–11.06) for those receiving TACE alone (hazard ratio (HR) 0.63 [95% CI 0.46–0.85], p = 0.002). Median TTP was 4.3 months (95% CI 3.32–5.28) in the TACE + Rg3 group compared with 3.2 months (95% CI 2.51–3.89) in the TACE group (HR 0.82 [95% CI 0.62–1.08], p = 0.151). Patients in the TACE + Rg3 group had longer median TTUP (8.3 months [95% CI 7.05–9.55]) than in the TACE group (7.3 months [95% CI 6.40–8.20]; HR 0.76 [95% CI 0.57–1.02], p = 0.063). The most frequently reported Rg3-related grade 3–4 adverse events in 152 patients were constipation (two [1.3%]) and hypertension (six [3.9%]). The incidence of ascites was lower in the TACE + Rg3 group than in the TACE group (23.7% versus 48.7%, p = 0.002), as was the incidence of anorexia [12.5% versus 44.7%, p = 0.000], fatigue (9.9% versus 50.0% p = 0.000), anaemia (36.8% versus 51.3%, p = 0.037), leukopenia (46.7% versus 76.3%, p = 0.000), thrombocytopenia (32.9% versus 50.0%, p = 0.012), and hyperbilirubinaemia (17.8% versus 34.2%, p = 0.028). Interpretation In patients with advanced HCC and sufficient liver function, median survival was nearly 3 months longer for patients treated with TACE and ginsenoside Rg3 than for those who received TACE only. [ABSTRACT FROM AUTHOR]

Background: To evaluate the prognostic value of the pre-treatment aspartate transaminase (AST)/alanine transaminase (ALT) ratio in hepatocellular carcinoma (HCC) patients receiving radiofrequency ablation (RFA)/microwave ablation (MWA) combined with simultaneous TACE. Methods: The data for 117 patients were retrospectively analyzed in this study. The endpoint of prognosis was overall survival (OS). The Youden index was used to choose the optimal cut-off value of the pre-treatment AST/ALT ratio for OS prediction. Univariate and multivariate analyses were used to identify independent risk factors, then integrated to establish the nomogram. Results: The AST/ALT ratio cut-off value for OS prediction was 0.89, and patients with a higher AST/ALT ratio had poorer OS. The median OS for the high-value AST/ALT group was not reached, while the median OS for the low-value AST/ALT group was 48.5 months (P = 0.0047). The univariate and multivariate analysis showed that AST/ALT ratio, AFP, and tumor numbers were independent prognostic indicators for OS. The integrated nomogram showed higher predictive accuracy for OS (C-index 0.674, 95%CI: 0.600–0.748). Conclusions: The preoperative AST/ALT ratio could be a prognostic indicator for HCC patients receiving thermal ablation combined with simultaneous TACE. [ABSTRACT FROM AUTHOR]

Background: Portal vein puncture (PVP) is a critical step during transjugular intrahepatic portosystemic shunt (TIPS) and correlates to several complications. Techniques guiding PVP are needed. Purpose: To evaluate the safety, feasibility, and efficiency of digital subtraction angiography (DSA) overlay reference during TIPS creation and compare it with transhepatic portal vein (THPV) guiding. Material and Methods: The clinical records of 185 patients at three medical centers who underwent TIPS placement were reviewed. Portal vein access was guided by THPV guiding in 120 cases and DSA overlay reference in 60 cases. The number of punctures, portal vein entry time, procedural adverse events, technical and hemodynamic success rate were analyzed to compare the safety, feasibility, and efficiency of the two methods. Results: The median numbers of punctures in group 1 and group 2 were 2 (1–4) and 2 (1–5), respectively (P = 0.094). There was no statistical difference between two groups in needle passes. The median portal vein entry time of group 1 was 12 min (8–16 min) and 13 min (8–16 min) in group 2. No significant difference was found in the PVP time (P = 0.802). Arterioportal fistula formation occurred in 15 patients in group 1; two patients in group 2 had hepatic artery injury. The patients in group 2 had lower rates of procedural adverse events (P = 0.047). Median dose area product of G1 was lower than G2 statistically (P <0.001). There was no significant difference in total fluoroscopy time (P = 0.856). Conclusion: DSA overlay reference has lower procedural adverse events rates compared with THPV guiding TIPS. It seems to be a safe and effective method for guiding PVP. [ABSTRACT FROM AUTHOR]

Objectives: Patients with colorectal liver metastases (CRLM) who underwent hepatic resection after conversion therapy had a high recurrence rate of nearly 90%. Preoperative DEB-TACE has the potential to prevent postoperative recurrence which has not been elucidated. The objective of this study was to evaluate the safety and efficacy of preoperative DEB-TACE. Materials and methods: Patients with CRLM who underwent liver resection from June 1, 2016, to June 30, 2021, were collected and those who received conversional hepatectomy were included in this study. Patients with preoperative DEB-TACE were propensity-score matched in a 1:1 ratio to patients without preoperative DEB-TACE. Short-term outcomes and recurrence-free survival (RFS) were compared between the two groups. Results: After PSM, 44 patients were included in each group. The toxicities of DEB-TACE were mild and could be managed by conservative treatment. Overall response rate (ORR) of conversion therapy (75.0% vs. 81.2%, p = 0.437) and postoperative complication of hepatic resection (27.3% vs. 20.5%, p = 0.453) were similar between the two groups. The median RFS of the DEB-TACE group (10.7 months, 95%CI: 6.6–14.8 months) was significantly longer than that of the control group (8.1 months, 95%CI: 3.4–12.8 months) (HR: 0.60, 95%CI: 0.37–0.95, p = 0.027). Conclusions: In patients who became resectable after conversion therapy, preoperative DEB-TACE might be a safe option to achieve longer RFS. Key Points: • This is a propensity-score matching study comparing patients who underwent conversional hepatectomy with or without preoperative DEB-TACE. • The preoperative DEB-TACE was safe and with mild toxicities (without toxicities more than CTCAE grade 3). • The preoperative DEB-TACE significantly prolonged the RFS of those patients who underwent conversional hepatectomy (10.7 vs. 8.1 months, p = 0.027). [ABSTRACT FROM AUTHOR]

Background/aims: Cavernous transformation of the portal vein (CTPV) in cirrhotic patients with extrahepatic portal vein obstruction (EHPVO) was a relatively rare disease and had no consensus on the treatment. Our study aimed to explore the value of anticoagulation with warfarin treatment for CTPV cirrhotic patients with EHPVO. Methods: From January 2015 to December 2019, the clinical characteristics of cirrhotic patients who were diagnosed as CTPV with EHPVO were retrospectively analyzed. Eligible patients were distributed into the anticoagulation group (n = 46) and control group (n = 38). The change of portal vein thrombosis, hepatic decompensation, survival and adverse events were evaluated between the two groups. Results: The median follow-up of our patients was 51 months in the anticoagulation group and 44 months in the control group. The progress rate of the portal vein was higher in patients from the control groups (n = 12) than in patients from the anticoagulation group (n = 4, p = 0.008). There was no significant difference between the partial recanalization rate and stable rate between the two groups. Patients in anticoagulation group developed less hepatic decompensation than those in control group (13.0% vs 34.2%, p = 0.021). The Kaplan-Meier curve showed that patients in the anticoagulation group had a better prognosis than patients in the control group (P < 0.022). There were no serious complications due to warfarin treatment. Conclusion: For CTPV cirrhotic patients with EHPVO, anticoagulation with warfarin treatment was effective and safe. Anticoagulants could prevent portal vein thrombosis progression, hepatic decompensation and death. In addition, our results showed little benefit of anticoagulants on thrombosis recanalization. [ABSTRACT FROM AUTHOR]

This work was aimed at investigating the predictive value on prognosis, response to immunotherapy, and association with the immune landscape of costimulatory molecules in HCC patients. We acquired the clinicopathological information and gene expression of HCC patients from public available database (TCGA and GEO). The prognostic model in TCGA database was established with LASSO regression and Cox regression analysis. Through the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis, the enrichment analysis was implemented for analyzing the biological function and associated pathways. Immune microenvironment, immune escape, immune therapy, and tumor mutation were analyzed between both risk groups. TNFRSF4, the critical costimulatory molecule, was chosen for the in-depth investigation in vitro experiments. A novel risk signature based on 8 costimulatory molecules associated with prognosis was constructed from TCGA and proved in the database of GEO. The ROC and Kaplan-Meier curves confirmed that this risk model has good predictive accuracy. Our functional analysis demonstrated costimulatory molecular genes might associate with immune-related functions and pathways. Statistical differences were not shown between both groups, in the aspect of immune landscape, response to immune therapy, and tumor mutation. Knocking down TNFRSF4 expression significantly reduced the proliferation ability and increased the apoptosis ability. On the basis of the costimulatory molecule expression in HCC, a novel risk model was constructed and had an excellent value to predict prognosis, immune microenvironment, and response to immune therapy. TNFRSF4 was identified as an underlying oncogene in HCC and deserves further exploration. [ABSTRACT FROM AUTHOR]

Background and aims: The placement of Transjugular intrahepatic portosystemic shunt (TIPS) results in a sudden increase in central circulating blood volume, which requires proper regulation of the cardiovascular system. We aimed to investigate the impact of TIPS on cirrhotic cardiomyopathy (CCM).A consecutive case series of patients with cirrhosis who underwent TIPS were evaluated by echocardiography and pressure measurements before, immediately after TIPS and 2–4 days later (delayed). Furthermore, all patients underwent a one-year follow-up.In this study, 107 patients were enrolled, 38 (35.5%) with CCM. Echocardiography revealed an increase in postoperative left ventricular filling pressure accompanied by an elevation in left ventricular ejection fraction (LVEF). However, patients in the CCM group exhibited lower LVEF and mean arterial pressure (MAP) compared to the non-CCM group. Post-TIPS, CCM patients showed increased right atrium pressure (RAP) that normalized within 2–4 days, whereas non-CCM patients had lower RAP than baseline. Compared to patient without CCM, CCM patients revealed lower immediate (16.7 ± 4.4 vs. 18.9 ± 4.8, p = 0.022) and delayed 15.9 ± 3.7 vs. 17.7 ± 5.3, p = 0.044) portal vein pressures (PVP) and portal pressure gradients (PPG) (7.7 ± 3.4 vs. 9.2 ± 3.6, p = 0.032 and 10.1 ± 3.1 vs. 12.3 ± 4.9, p = 0.013). The 1-year mortality rates were 13.2% for CCM patients and 4.3% for non-CCM patients (log-rank test, p = 0.093), with MELD score, and preoperative RAP significantly associated with the mortality.Cirrhotic patients with CCM exhibit lower PVP and PPG immediately after TIPS and 2–4 days later, without significantly impacting one-year survival outcomes.Method: The placement of Transjugular intrahepatic portosystemic shunt (TIPS) results in a sudden increase in central circulating blood volume, which requires proper regulation of the cardiovascular system. We aimed to investigate the impact of TIPS on cirrhotic cardiomyopathy (CCM).A consecutive case series of patients with cirrhosis who underwent TIPS were evaluated by echocardiography and pressure measurements before, immediately after TIPS and 2–4 days later (delayed). Furthermore, all patients underwent a one-year follow-up.In this study, 107 patients were enrolled, 38 (35.5%) with CCM. Echocardiography revealed an increase in postoperative left ventricular filling pressure accompanied by an elevation in left ventricular ejection fraction (LVEF). However, patients in the CCM group exhibited lower LVEF and mean arterial pressure (MAP) compared to the non-CCM group. Post-TIPS, CCM patients showed increased right atrium pressure (RAP) that normalized within 2–4 days, whereas non-CCM patients had lower RAP than baseline. Compared to patient without CCM, CCM patients revealed lower immediate (16.7 ± 4.4 vs. 18.9 ± 4.8, p = 0.022) and delayed 15.9 ± 3.7 vs. 17.7 ± 5.3, p = 0.044) portal vein pressures (PVP) and portal pressure gradients (PPG) (7.7 ± 3.4 vs. 9.2 ± 3.6, p = 0.032 and 10.1 ± 3.1 vs. 12.3 ± 4.9, p = 0.013). The 1-year mortality rates were 13.2% for CCM patients and 4.3% for non-CCM patients (log-rank test, p = 0.093), with MELD score, and preoperative RAP significantly associated with the mortality.Cirrhotic patients with CCM exhibit lower PVP and PPG immediately after TIPS and 2–4 days later, without significantly impacting one-year survival outcomes.Results: The placement of Transjugular intrahepatic portosystemic shunt (TIPS) results in a sudden increase in central circulating blood volume, which requires proper regulation of the cardiovascular system. We aimed to investigate the impact of TIPS on cirrhotic cardiomyopathy (CCM).A consecutive case series of patients with cirrhosis who underwent TIPS were evaluated by echocardiography and pressure measurements before, immediately after TIPS and 2–4 days later (delayed). Furthermore, all patients underwent a one-year follow-up.In this study, 107 patients were enrolled, 38 (35.5%) with CCM. Echocardiography revealed an increase in postoperative left ventricular filling pressure accompanied by an elevation in left ventricular ejection fraction (LVEF). However, patients in the CCM group exhibited lower LVEF and mean arterial pressure (MAP) compared to the non-CCM group. Post-TIPS, CCM patients showed increased right atrium pressure (RAP) that normalized within 2–4 days, whereas non-CCM patients had lower RAP than baseline. Compared to patient without CCM, CCM patients revealed lower immediate (16.7 ± 4.4 vs. 18.9 ± 4.8, p = 0.022) and delayed 15.9 ± 3.7 vs. 17.7 ± 5.3, p = 0.044) portal vein pressures (PVP) and portal pressure gradients (PPG) (7.7 ± 3.4 vs. 9.2 ± 3.6, p = 0.032 and 10.1 ± 3.1 vs. 12.3 ± 4.9, p = 0.013). The 1-year mortality rates were 13.2% for CCM patients and 4.3% for non-CCM patients (log-rank test, p = 0.093), with MELD score, and preoperative RAP significantly associated with the mortality.Cirrhotic patients with CCM exhibit lower PVP and PPG immediately after TIPS and 2–4 days later, without significantly impacting one-year survival outcomes.Conclusion: The placement of Transjugular intrahepatic portosystemic shunt (TIPS) results in a sudden increase in central circulating blood volume, which requires proper regulation of the cardiovascular system. We aimed to investigate the impact of TIPS on cirrhotic cardiomyopathy (CCM).A consecutive case series of patients with cirrhosis who underwent TIPS were evaluated by echocardiography and pressure measurements before, immediately after TIPS and 2–4 days later (delayed). Furthermore, all patients underwent a one-year follow-up.In this study, 107 patients were enrolled, 38 (35.5%) with CCM. Echocardiography revealed an increase in postoperative left ventricular filling pressure accompanied by an elevation in left ventricular ejection fraction (LVEF). However, patients in the CCM group exhibited lower LVEF and mean arterial pressure (MAP) compared to the non-CCM group. Post-TIPS, CCM patients showed increased right atrium pressure (RAP) that normalized within 2–4 days, whereas non-CCM patients had lower RAP than baseline. Compared to patient without CCM, CCM patients revealed lower immediate (16.7 ± 4.4 vs. 18.9 ± 4.8, p = 0.022) and delayed 15.9 ± 3.7 vs. 17.7 ± 5.3, p = 0.044) portal vein pressures (PVP) and portal pressure gradients (PPG) (7.7 ± 3.4 vs. 9.2 ± 3.6, p = 0.032 and 10.1 ± 3.1 vs. 12.3 ± 4.9, p = 0.013). The 1-year mortality rates were 13.2% for CCM patients and 4.3% for non-CCM patients (log-rank test, p = 0.093), with MELD score, and preoperative RAP significantly associated with the mortality.Cirrhotic patients with CCM exhibit lower PVP and PPG immediately after TIPS and 2–4 days later, without significantly impacting one-year survival outcomes. [ABSTRACT FROM AUTHOR]

In this work, a confined-doped fiber oscillator model considering the spatial hole-burning effect is established to help understand the underlying physical mechanism of the gain filtering effect. The influences of the relative doping ratio on the gain filtering effect are systematically analyzed in a fiber oscillator under different power levels, which reveals the possibility of achieving near pure fundamental mode laser operation by carefully designing the relative doping ratio of the confined-doped fiber. Simultaneously, the comparison experiment adopting homemade large-mode-area confined-doped fiber and fully-doped fiber is conducted to verify the gain filtering effect of confined-doped fiber in high-power oscillators. This work could provide a practical reference for optimizing the design of the confined-doped fiber laser systems for high-power high-brightness laser operation. This work highlights the first comprehensive study on the gain filtering effect in high-power confined-doped fiber oscillators both experimentally and theoretically. The gain filtering effect in kilowatt-level confined-doped fiber oscillators is verified through comparison experiments, and a numerical model considering the spatial hole-burning effect is established to analyze the influence of the relative doping ratio on the gain filtering effect under different gain saturation levels. This work could provide valuable guidance for the confined-doped fiber design and laser system optimization for high-power high-brightness laser output. [ABSTRACT FROM AUTHOR]

Ultrafast excited‐state decay and intrinsic charge carrier recombination restrain the photoactivity enhancement for solar‐to‐H2 production. Here, a CdS‐fullerene/graphene (CdS‐F/G) photocatalyst is synthesized for enhancing visible‐light‐driven hydrogen generation from earth‐abundant water. The CdS‐F/G shows ultrafast interfacial electrons/holes transfer and holes self‐trapping process in photocatalysis. The in‐situ dynamic study from transient absorption spectroscopy reveals the sub‐microsecond‐lived excited states (≈172.6 ns), interfacial electron transfer (≈30.3 ps), and hole trapping (≈44.0 ps) in the CdS‐F/G photocatalyst. The efficient active species transportation and prolonged lifetime significantly enhance the charge separation state survival, increasing the photoactivity and photostability. Consequently, visible‐light activity enhancement (>400%) of H2 evolution reaction (HER) is obtained at the CdS‐F/G photocatalyst with high stability (>36 h). The 127.2 µmol h−1 g−1 performance corresponding to a quantum efficiency of 7.24% at 420 nm is not only higher than the case of pristine CdS (29.2 µmol h−1 g−1) but also much higher than that of CdS‐Pt photocatalyst (73.8 µmol h−1 g−1). The cost‐effective CdS‐F/G photocatalyst exhibits a great potential for sustainable and high‐efficiency photocatalytic water splitting into clean energy carriers. Moreover, the optimized electronic structure associated with interfacial electrons/holes transfer and holes self‐trapping promotes overall water splitting for H2 and O2 generation. [ABSTRACT FROM AUTHOR]

Purpose: There was no standard treatment for hepatocellular carcinoma with portal vein tumour thrombosis (PVTT). This prospective, randomised, two-arm clinical trial aims to investigate the feasibility, safety and effectiveness of transarterial chemoembolisation (TACE) combined with the endovascular implantation of an iodine-125 seed strand for the treatment of hepatocellular carcinoma with portal vein tumour thrombosis versus conventional TACE. Patients and methods: Eighty-five patients who met the eligibility requirements were randomly assigned to receive the treatment of TACE combined with the endovascular implantation of an iodine-125 seed strand (43 cases) or conventional TACE (42 cases). The end points were survival time, complications related to the procedure and adverse events. Results: No significant differences in baseline characteristics were observed between groups. The mean and median survival times were 221.7 ± 16.3 days [95 % confidence interval (CI) 189.8-253.6 days] and 210.0 ± 17.5 days (95 % CI 175.8-244.2 days) in group A and 155.1 ± 7.9 days (95 % CI 139.6-170.5 days) and 154.0 ± 11.2 days (95 % CI 133.2-176.0 days) in group B ( P = 0.000). The 90-, 180- and 360-day cumulative survival rates were 97.6, 58.9 and 12.3 % in group A and 92.5, 30.7 and 0 % in group B ( P = 0.000). Conclusion: Transarterial chemoembolisation combined with the endovascular implantation of an iodine-125 seed strand is feasible, safe and effective in the treatment for hepatocellular carcinoma with PVTT. [ABSTRACT FROM AUTHOR]

In this work, a promising treatment strategy for triggering robust antitumor immune responses in transarterial chemoembolization of hepatocellular carcinoma (HCC) is presented. The zeolitic imidazolate framework nanoparticles loaded with hypoxia-activated prodrug tirapazamine and immune adjuvant resiquimod facilitated in situ generation of nanovaccine via a facile approach. The nanovaccine can strengthen the ability of killing the liver cancer cells under hypoxic environment, while was capable of improving immunogenic tumor microenvironment and triggering strong antitumor immune responses by increasing the primary and distant intratumoral infiltration of immune cells such as cytotoxic T cells. Moreover, a porous microcarrier, approved by FDA as pharmaceutical excipient, was designed to achieve safe and effective delivery of the nanovaccine via transarterial therapy in rabbit orthotopic VX2 liver cancer model. The microcarrier exhibited the characteristics of excellent drug loading and occlusion of peripheral artery. The collaborative delivery of the microcarrier and nanovaccine demonstrated an exciting inhibitory effect on solid tumors and tumor metastases, which provided a great potential as novel combination therapy for HCC interventional therapy. [Display omitted] • We successfully developed a cancer nanovaccine for in situ HCC chemoembolization therapy, which was shown to induce the apoptosis of cancer cells under hypoxic environment. • The nanovaccine exhibited strong local and systemic antitumor immune responses. • Functionalized embolic microcarrier loaded with nanovaccine was designed for transarterial interventional therapy of HCC. • The collaborative delivery of the microcarrier and nanovaccine demonstrated highly efficient inhibition to solid tumors and tumor metastases in rabbit orthotopic liver tumor model. [ABSTRACT FROM AUTHOR]

Purpose. The long noncoding RNAs (lncRNAs) play the important role in tumor occurrence and progression, and the epithelial to mesenchymal transition (EMT) is the critical process for tumor migration. However, the role of EMT-related lncRNA in hepatocellular carcinoma (HCC) has not been elucidated. Methods. In this study, we selected the EMT-related lncRNAs in HCC by using data from The Cancer Genome Atlas database (TCGA). Two prognostic models of the overall survival (OS) and relapse-free survival (RFS) were constructed and validated through Cox regression model, Kaplan-Meier analysis, and the receiver-operating characteristic (ROC) curves. The unsupervised clustering analysis was utilized to investigate the association between EMT-lncRNAs with tumor immune microenvironment. ESTIMATE algorithm and gene set enrichment analysis (GSEA) were used to estimate tumor microenvironment and associated KEGG pathways. Results. Two EMT-related lncRNA prognostic models of OS and RFS were constructed. Kaplan-Meier curves showed the dismal prognosis of OS and RFS in the group with high-risk score. The ROC curves and AUC values in two prognostic models indicated the discriminative value in the training set and validation set. Patients with HCC were clustered into two subgroups according the unsupervised clustering analysis. Lnc-CCNY-1 was selected as the key lncRNA. GSVA analysis showed that lnc-CCNY-1 was negatively associated with peroxisome proliferator-activated receptor (PPAR) signaling pathway and positively correlated with CELL cycle pathway. Conclusion. Two EMT-related lncRNA prognostic models of OS and RFS were constructed to discriminate patients and predict prognosis of HCC. EMT-related lncRNAs may play a role on prognosis of HCC by influencing the immune microenvironment. Lnc-CCNY-1 was selected as the key EMT-related lncRNA for further exploration. [ABSTRACT FROM AUTHOR]

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a tissue perfusion imaging technique. Some versatile free-breathing DCE-MRI techniques combining compressed sensing (CS) and parallel imaging with golden-angle radial sampling have been developed to improve motion robustness with high spatial and temporal resolution. These methods have demonstrated good diagnostic performance in clinical setting, but the reconstruction quality will degrade at high acceleration rates and overall reconstruction time remains long. In this paper, we proposed a new parallel CS reconstruction model for DCE-MRI that enforces flexible weighted sparse constraint along both spatial and temporal dimensions. Weights were introduced to flexibly adjust the importance of time and space sparsity, and we derived a fast-thresholding algorithm which was proven to be simple and efficient for solving the proposed reconstruction model. Results on both the brain tumor DCE and liver DCE show that, at relatively high acceleration factor of fast sampling, lowest reconstruction error and highest image structural similarity are obtained by the proposed method. Besides, the proposed method achieves faster reconstruction for liver datasets and better physiological measures are also obtained on tumor images. [ABSTRACT FROM AUTHOR]

Microwave ablation is a first-line treatment of small hepatocellular carcinoma (HCC), while incomplete ablation induces recurrence and metastasis. However, its underlying mechanism remains largely unexplored. Here we reported that sublethal heat treatment (46 °C) strongly promoted migration and EMT transition in HCC cells. Mechanistic investigation revealed that compared with 37 °C, HCC cells treated with 46 °C expressed higher level of CD47. Knockdown of CD47 significantly attenuated sublethal heat treatment stimulated migration and EMT transition. In addition, METTL3 which is the key enzyme of m6A modification was also induced by 46 °C treatment and triggered CD47 expression in HCC cells. Moreover, CD47 mRNA degradation was further proved to be stabled in the IGF2BP1-dependent manner. Importantly, sublethal heat treatment stimulated CD47 expression and EMT transition were also confirmed in patient-derived organoid. Taken together, our study suggests that METTL3/IGF2BP1/CD47 mediated EMT transition contributes to the incomplete ablation induced metastasis in HCC cells. Moreover, these findings identify the METTL3/IGF2BP1/CD47 axis as a potential therapeutic target for the microwave ablation and shed new lights on the crosstalk between incomplete heat ablation and RNA methylation. • Sublethal heat treatment stimulates CD47 and METTL3 expression in HCC. • METTL3/IGF2BP1 positively regulates CD47 expression in an m6A-dependent manner. • CD47 mediated EMT contributes to the microwave ablation induced metastasis in HCC. [ABSTRACT FROM AUTHOR]

Hepatic ischemia/reperfusion (I/R) injury is an unavoidable complication of liver hepatectomy, transplantation, and systemic shock. Pectolinarigenin (Pec) is a flavonoid with many biological activities, which include anti-inflammatory, anti-apoptotic, and antioxidant stress. This study explored whether Pec pretreatment could reduce hepatic I/R injury and the potential mechanisms at play. After pretreatment of mice and AML12 cells with Pec, I/R and hypoxia/reoxygenation (H/R) models were established. By examining markers related to liver injury, cell viability, oxidative stress, inflammatory response, and apoptosis, the effect of Pec on important processes involved in hepatic I/R injury was assessed. Protein levels associated with the PI3K/AKT/Nrf2 pathway were analyzed by relative quantification to investigate possible pathways through which Pec plays a role in the I/R process. Pec treatment corrected abnormal transaminase levels resulting from I/R injury, improved liver injury, and increased AML12 cell viability. Moreover, Pec treatment inhibited oxidative stress, inflammation and apoptosis and could activate the PI3K/AKT/Nrf2 pathway during I/R and H/R. Further studies found that LY294002 (PI3K inhibitor) suppressed the protective effect of Pec on hepatic I/R injury. In summary, our results show that Pec inhibits oxidative stress, inflammatory responses, and apoptosis, thereby attenuating I/R-induced liver injury and H/R-induced cell damage via activation of the PI3K/AKT/Nrf2 pathway. • Pectolinarigenin pretreatment can attenuate hepatic ischemia/reperfusion injury. • Pectolinarigenin reduces hypoxia/reoxygenation-induced AML12 cell damage. • Pectolinarigenin inhibits oxidative stress, inflammation and apoptosis during ischemia/reperfusion. • Pectolinarigenin exerts protective effects through activation of the PI3K/AKT/Nrf2 pathway. [ABSTRACT FROM AUTHOR]

Benzoin is one of the most commonly used photoinitiators to induce free radical polymerization. Here, improved benzoin properties could be accomplished by the introduction of two methoxy substituents, leading to the formation of 3',5'-dimethoxybenzoin (DMB) which has a higher photo-cleavage quantum yield (0.54) than benzoin (0.35). To elucidate the underlying reaction mechanisms of DMB and obtain direct information of the transient species involved, femtosecond transient absorption (fs-TA) and nanosecond transient absorption (ns-TA) spectroscopic experiments in conjunction with density functional theory/time-dependent density functional theory (DFT/TD-DFT) calculations were performed. It was found that the photo-induced α-cleavage (Norrish Type I reaction) of DMB occurred from the nπ* triplet state after a rapid intersystem crossing (ISC) process (7.6 ps), leading to the generation of phenyl radicals on the picosecond time scale. Compared with Benzoin, DMB possesses two methoxy groups which are able to stabilize the alcohol radical and thus result in a stronger driving force for cleavage and a higher quantum yield of photodissociation. Two stable conformations (cis-DMB and trans-DMB) at ground state were found via DFT calculations. The influence of the intramolecular hydrogen bond on the α-cleavage of DMB was elaborated. [ABSTRACT FROM AUTHOR]

Background: Gastroesophageal variceal hemorrhage is the most severe complication of portal hypertension, with a high mortality rate. The current recommendations for gastroesophageal varices include pharmacological treatment, endoscopic treatment, transjugular intrahepatic portosystemic shunt (TIPS) placement, and splenectomy with devascularization surgery. Multidisciplinary team (MDT) comprises of a group of medical experts and specialists across a range of disciplines, providing personalized and targeted patient care tailored to each individual's condition, circumstances, and expectations.Methods: Patients referred to the MDT clinic since its establishment in September 2014 were prospectively enrolled and followed-up for at least 12 months. Patient baseline characteristics, treatment methods, outcome and survival were compared to non-MDT patients retrieved from a prospectively maintained database with propensity score matching.Results: Propensity-score matching (PSM) was carried out to balance available covariates, resulting in 58 MDT patients vs. 111 non-MDT patients. Overall survival and variceal rebleed was compared between the two groups. The rate of variceal rebleed was significantly higher in the non-MDT group, while no difference in overall survival was observed.Conclusions: This study is the first to investigate the role of a multidisciplinary team in the management of gastroesophageal varices secondary to portal hypertension. Patients treated based on MDT clinic recommendations had a significantly lower risk for variceal rebleed. [ABSTRACT FROM AUTHOR]

Although anti-angiogenic therapies (AATs) have some effects against multiple malignancies, they are limited by subsequent tumor vasculogenesis and progression. To investigate the mechanisms by which tumor vasculogenesis and progression following AATs, we transfected microRNA (miR)-9 into human umbilical vein endothelial cells (HUVECs) to mimic the tumor-associated endothelial cells in hepatocellular carcinoma and simulated the AATs in vitro and in vivo. We found that administration of the angiogenesis inhibitor vandetanib completely abolished miR-9-induced angiogenesis and promoted autophagy in HUVECs, but induced the release of vascular endothelial growth factor (VEGF)-enriched exosomes. These VEGF-enriched exosomes significantly promoted the formation of endothelial vessels and vasculogenic mimicry in hepatocellular carcinoma and its progression in mice. Anti-autophagic therapy is proposed to improve the efficacy of AATs. However, similar effects by AATs were observed with the application of anti-autophagy by 3-methyladenine. Our results revealed that tumor vasculogenesis and progression after AATs and anti-autophagic therapies were due to the cross-talk between endothelial and tumor cells via VEGF-enriched exosomes. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to compare the efficacy and safety of radiofrequency ablation (RFA) and microwave ablation (MWA) for the treatment of benign thyroid nodules (BTNs).Methods: Patients with BTNs were treated in our hospital, including 72 patients treated with RFA and 100 patients treated with MWA from June 2016 to March 2019. The volume reduction rates (VRRs), thyroid function, clinical status, and complications were compared at each postoperative duration to evaluate the efficacy and safety of the two modalities.Results: The mean VRRs of the RFA group vs. the MWA group at 1, 3, 6, and 12 months were 22.7±13.4% vs. 24.0±16.1% (P = 0.681), 56.1±19.5% vs. 54.8±22.8% (P = 0.788), 77.9±21.0% vs. 68.7±19.1% (P = 0.038), and 85.4±18.9% vs. 75.8±19.4% (P = 0.029), respectively. There was no significant difference in the VRRs between the two treatments at 1 and 3 months and the RFA group achieved higher VRRs than MWA group at 6 and 12 months. Moreover, the symptom and cosmetic scores decreased significantly in both groups and all patients succeeded in preserving thyroid function. Of the total patients, 2.8% in the RFA group and 4% in the MWA group experienced voice changes after undergoing thyroid ablation, and one patient in the RFA group had intraoperative hemorrhage of about 10 mL.Conclusions: RFA and MWA are both effective and safe techniques for treating BTNs. Higher VRRs were observed at the 6- and 12-month follow-ups in the RFA group. [ABSTRACT FROM AUTHOR]

Background/aim: Percutaneous thermal ablation combined with transarterial chemoembolization (TACE) becomes a treatment option for unresectable hepatocellular carcinoma (HCC). This study aims to investigate the safety and feasibility of percutaneous thermal ablation combined with simultaneous TACE for patients with HCC ≤ 5 cm.Materials and Methods: From June 2010 to February 2017, a total of 280 patients with HCC ≤ 5 cm who underwent percutaneous thermal ablation combined with simultaneous TACE were included in our study. Their clinical data were collected and analyzed.Results: Major complications occurred in five cases (1.8%). The complete necrosis rate was 91.9%. The median overall survival (OS) was 66.5 months (95% confidence interval [CI] = 57.7-75.2). The OS rates in 1-, 3-, 5-, and 7-year were 96.7%, 76.0%, 59.7%, and 31.1%, respectively. Tumor size (hazard ratio = 1.826; 95% CI = 1.131-2.947; P = 0.014) was considered as independent prognostic factors of long-term survival.Conclusion: Percutaneous thermal ablation combined with simultaneous TACE is a safe and effective treatment for HCC ≤ 5 cm. [ABSTRACT FROM AUTHOR]

Nitrenium ions are important reactive intermediates in chemistry and biology. In this work, femtosecond and nanosecond transient absorption (fs-TA and ns-TA) along with nanosecond time-resolved resonance Raman (ns-TR3) experiments were employed to examine the photochemical pathways of N-(4,4′-dibromodiphenylamino)-2,4,6-trimethylpyridinium BF4− (salt (DN) from just absorption of a photon of light to the production of the important N,N-di(4-bromophenyl)nitrenium ion 2. In acetonitrile (MeCN), the formation of halogenated diarylnitrenium ion 2 was observed within 4 ps, showing the vibrational spectra with strong intensity. The nucleophilic adduct reaction of ion 2 with H2O was also examined in aqueous solutions. The direct detection of the unique ortho adduct intermediate 3 shows that there is an efficient and exclusive reaction pathway for 2 with H2O. The results shown in this paper give new characterization of 2, which can be used to design time-resolved spectroscopy investigations of covalent addition reactions of nitrenium ions with other molecules in future studies. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC), the most common primary tumor of the liver, has a poor prognosis, rapid progression. The aim of the current study was to establish a stable lentiviral expression vector for enhanced green fluorescent protein (EGFP) and to evaluate biological characteristics on HCC growth and migration following transfection of HCC cells with EGFP. McA-RH7777 cells were transfected with EGFP overexpression lentiviral vector. Cell activity and mobility were monitored with a Cell-IQ Analyzer. Transwell assays were performed to detect invasiveness and flow cytometry was performed for cell cycle analysis. A subcutaneous tumor rat model was established to analyze the stability of fluorescent protein expression. The result suggested no significant differences between wild-type and EGFP-overexpressing McA-RH7777 cells with regards to cell proliferation, activity, mobility, invasiveness and cell cycle. Green fluorescence was detected over 108 days of culturing. The subcutaneous tumor rat model demonstrated that EGFP expression had no influence on tumor growth and long-term expression was stable. The stable EGFP expression of the HCC transplanted tumor rat model may share biological characteristics with human liver cancer. The model established in the current study may be suitable for various applications, including research focusing on liver cancer metastasis and recurrence, interventional therapy, imaging diagnosis and drug screenings. [ABSTRACT FROM AUTHOR]