Comprehensive analysis of full-length transcripts reveals novel splicing abnormalities and oncogenic transcripts in liver cancer.

Genes generate transcripts of various functions by alternative splicing. However, in most transcriptome studies, short-reads sequencing technologies (next-generation sequencers) have been used, leaving full-length transcripts unobserved directly. Although long-reads sequencing technologies would enable the sequencing of full-length transcripts, the data analysis is difficult. In this study, we developed an analysis pipeline named SPLICE and analyzed cDNA sequences from 42 pairs of hepatocellular carcinoma (HCC) and matched non-cancerous livers with an Oxford Nanopore sequencer. Our analysis detected 46,663 transcripts from the protein-coding genes in the HCCs and the matched non-cancerous livers, of which 5,366 (11.5%) were novel. A comparison of expression levels identified 9,933 differentially expressed transcripts (DETs) in 4,744 genes. Interestingly, 746 genes with DETs, including the LINE1-MET transcript, were not found by a gene-level analysis. We also found that fusion transcripts of transposable elements and hepatitis B virus (HBV) were overexpressed in HCCs. In vitro experiments on DETs showed that LINE1-MET and HBV-human transposable elements promoted cell growth. Furthermore, fusion gene detection showed novel recurrent fusion events that were not detected in the short-reads. These results suggest the efficiency of full-length transcriptome studies and the importance of splicing variants in carcinogenesis.

Assembling Smallest Prussian Blue Analogs Using Chiral Hydrogen Bond-Donating Unit toward Complete Phase Transition.

Exploring methods for assembling functional materials at the molecular level may yield functional expressions derived from the assembly method. This study developed novel switchable molecular assemblies characterized by abrupt, complete phase transitions promoted via hydrogen bonding with a chiral carboxylic acid. These assemblies were prepared by aggregating discrete molecules that are unresponsive to external stimuli. Furthermore, enantiopure hydrogen-bond donor (HBD) molecules provide switchable compounds with cooperative and abrupt phase transitions, whereas the racemic mixture of the HBD provides a hydrogen-bonded one-dimensional compound with a broad and incomplete phase transition when structural disordering is observed. This study presents a novel strategy for observing metal-to-metal electron-transfer-coupled spin transitions via hydrogen-bond formation.

Strongly Enhanced Polarization in a Ferroelectric Crystal by Conduction-Proton Flow.

Ion conductors comprising noncentrosymmetric frameworks have emerged as new functional materials. However, strongly correlated polarity functionality and ion transport have not been achieved. Herein, we report a ferroelectric proton conductor, K2MnN(CN)4·H2O (1·H2O), exhibiting the strong correlation between its polar skeleton and conductive ions that generate anomalous ferroelectricity via the proton-bias phenomenon. The application of an electric field of ±1 kV/cm (0.1 Hz) on 1·H2O at 298 K produced the ferroelectricity (polarization = 1.5 × 104 µC/cm2), which was enhanced by the ferroelectric-skeleton-trapped conductive protons. Furthermore, the strong polarity-proton transport coupling of 1·H2O induced a proton-rectification-like directional ion-conductive behavior that could be adjusted by the magnitude and direction of DC electric fields. Moreover, 1·H2O exhibited reversible polarity switching between the polar 1·H2O and its dehydrated form, 1, with a centrosymmetric structure comprising an order-disorder-type transition of the nitrido-bridged chains.

Histone methyltransferase SUV420H1/KMT5B contributes to poor prognosis in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) has a high rate of recurrence and poor prognosis, even after curative surgery. Multikinase inhibitors have been applied for HCC patients, but their effect has been restricted. This study aims to clarify the clinical impact of SUV420H1/KMT5B, one of the methyltransferases for histone H4 at lysine 20, and elucidate the novel mechanisms of HCC progression. We retrospectively investigated SUV420H1 expression using HCC clinical tissue samples employing immunohistochemical analysis (n = 350). We then performed loss-of-function analysis of SUV420H1 with cell cycle analysis, migration assay, invasion assay and RNA sequence for Gene Ontology (GO) pathway analysis in vitro, and animal experiments with xenograft mice in vivo. The SUV420H1-high-score group (n = 154) had significantly poorer prognosis for both 5-year overall and 2-year/5-year disease-free survival than the SUV420H1-low-score group (n = 196) (p < 0.001 and p < 0.05, respectively). The SUV420H1-high-score group had pathologically larger tumor size, more tumors, poorer differentiation, and more positive vascular invasion than the SUV420H1-low-score group. Multivariate analysis demonstrated that SUV420H1 high score was the poorest independent factor for overall survival. SUV420H1 knockdown could suppress cell cycle from G1 to S phase and cell invasion. GO pathway analysis showed that SUV420H1 contributed to cell proliferation, cell invasion, and/or metastasis. Overexpression of SUV420H1 clinically contributed to poor prognosis in HCC, and the inhibition of SUV420H1 could repress tumor progression and invasion both in vitro and in vivo; thus, further analyses of SUV420H1 are necessary for the discovery of future molecularly targeted drugs.

Laparoscopic and open minor liver resection for hepatocellular carcinoma with clinically significant portal hypertension: a multicenter study using inverse probability weighting approach.

BACKGROUND: Liver resection offers substantial advantages over open liver resection (OLR) for patients with hepatocellular carcinoma (HCC) in terms of reduced intraoperative blood loss and morbidity. However, there is limited evidence comparing the indications and perioperative outcomes with the open versus laparoscopic approach for resection. This study aimed to compare postoperative outcomes between patients undergoing laparoscopic liver resection (LLR) and OLR for HCC with clinically significant portal hypertension (CSPH). METHODS: A total of 316 HCC patients with CSPH (the presence of gastroesophageal varices or platelet count < 100,000/ml and spleen diameter > 12 cm) undergoing minor liver resection at eight centers were included in this study. To adjust for confounding factors between the LLR and OLR groups, an inverse probability weighting method analysis was performed. RESULTS: Overall, 193 patients underwent LLR and 123 underwent OLR. After weighting, LLR was associated with a lower volume of intraoperative blood loss and the incidence of postoperative complications (including pulmonary complications, incisional surgical site infection, and paralytic ileus) compared to the OLR group. The 3-, 5-, and 7-year postoperative recurrence-free survival rates were 39%, 26%, and 22% in the LLR group and 49%, 18%, and 18% in the OLR group, respectively (p = 0.18). And, the 3-, 5-, and 7-year postoperative overall survival rates were 71%, 56%, and 44% in the LLR group and 76%, 51%, 44% in the OLR group, respectively (p = 0.87). CONCLUSIONS: LLR for HCC patients with CSPH is clinically advantageous by lowering the volume of intraoperative blood loss and incidence of postoperative complications, thereby offering feasible long-term survival.

Adhesion States Greatly Affect Cellular Susceptibility to Graphene Oxide: Therapeutic Implications for Cancer Metastasis.

Graphene oxide (GO) has received increasing attention in the life sciences because of its potential for various applications. Although GO is generally considered biocompatible, it can negatively impact cell physiology under some circumstances. Here, we demonstrate that the cytotoxicity of GO greatly varies depending on the cell adhesion states. Human HCT-116 cells in a non-adhered state were more susceptible to GO than those in an adherent state. Apoptosis was partially induced by GO in both adhered and non-adhered cells to a similar extent, suggesting that apoptosis induction does not account for the selective effects of GO on non-adhered cells. GO treatment rapidly decreased intracellular ATP levels in non-adhered cells but not in adhered ones, suggesting ATP depletion as the primary cause of GO-induced cell death. Concurrently, autophagy induction, a cellular response for energy homeostasis, was more evident in non-adhered cells than in adhered cells. Collectively, our observations provide novel insights into GO's action with regard to cell adhesion states. Because the elimination of non-adhered cells is important in preventing cancer metastasis, the selective detrimental effects of GO on non-adhered cells suggest its therapeutic potential for use in cancer metastasis.

Response Prediction Model of Atezolizumab plus Bevacizumab in Patients with Unresectable Hepatocellular Carcinoma: Multicenter Retrospective Study.

INTRODUCTION: Atezolizumab plus bevacizumab (ATZ+BV) treatment has become the first-line regimen for unresectable hepatocellular carcinoma (u-HCC). Prediction of response to it might be clinically beneficial. Using peripheral blood parameters, we aimed to construct a prediction model for ATZ+BV treatment. METHODS: Clinical records of 119 patients with u-HCC treated by ATZ+BV were retrospectively analyzed. The primary outcome measurement was defined as any-size reduction at the initial image evaluation. Using baseline values of peripheral blood parameters, a prediction model was constructed by univariate and multivariate logistic regression analysis. Validation was performed internally by bootstrap method. RESULTS: The primary outcome was achieved in 46 patients. Univariate analysis showed that C-reactive protein (CRP), alpha-fetoprotein (AFP), des-gamma-carboxy prothrombin (DCP), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were possible predictors. CRP and DCP, and NLR and PLR had correlation (correlation coefficient >0.3), so we used CRP and NLR as representative factors, respectively. Multivariate analysis constructed the following prediction model: Logit = 1.62-0.61×[CRP] -0.38×[Log10AFP] -0.37×[NLR]. Bootstrapped median (95% confidence interval) of coefficients of CRP, Log10AFP, NLR were -0.64 (-1.46 ∼ -0.11), -0.40 (-0.82 ∼ -0.03), and -0.38 (-0.74 ∼ -0.05), respectively. The area under the receiver operating characteristic curve (95% confidence interval) was 0.73 (0.60-0.80). Median overall survival of the favorably and unfavorably predicted groups were 17.0 and 11.0 months (p = 0.03), respectively. DISCUSSION: In patients with u-HCC treated by ATZ+BEV, a prediction model constructed using baseline values of CRP, AFP, and NLR had impact on any-size reduction at the initial image evaluation and on prognosis.

Spin Crossover Induced by Changing the Identity of the Secondary Metal Ion from PdII to NiII in a Face-Centered FeII 8 MII 6 Cubic Cage.

Discrete spin crossover (SCO) heteronuclear cages are a rare class of materials which have potential use in next-generation molecular transport and catalysis. Previous investigations of cubic cage [Fe8 Pd6 L8 ]28+ constructed using semi-rigid metalloligands, found that FeII centers of the cage did not undergo spin transition. In this work, substitution of the secondary metal center at the face of the cage resulted in SCO behavior, evidenced by magnetic susceptibility, Mössbauer spectroscopy and single crystal X-ray diffraction. Structural comparisons of these two cages shed light on the possible interplay of inter- and intramolecular interactions associated with SCO in the NiII analogue, 1 ([Fe8 Ni6 L8 (CH3 CN)12 ]28+ ). The distorted octahedral coordination environment, as well as the occupation of the CH3 CN in the NiII axial positions of 1, prevented close packing of cages observed in the PdII analogue. This led to offset, distant packing arrangements whereby important areas within the cage underwent dramatic structural changes with the exhibition of SCO.

Flexible Aliphatic Diammonioacetates as Zwitterionic Ligands in UO22+ Complexes: Diverse Topologies and Interpenetrated Structures.

N,N,N',N'-Tetramethylethane-1,2-diammonioacetate (L1) and N,N,N',N'-tetramethylpropane-1,3-diammonioacetate (L2) are two flexible zwitterionic dicarboxylates which have been used as ligands for the uranyl ion, 12 complexes having been obtained from their coupling to diverse anions, mostly anionic polycarboxylates, or oxo, hydroxo and chlorido donors. The protonated zwitterion is a simple counterion in [H2L1][UO2(2,6-pydc)2] (1), where 2,6-pydc2- is 2,6-pyridinedicarboxylate, but it is deprotonated and coordinated in all the other complexes. [(UO2)2(L2)(2,4-pydcH)4] (2), where 2,4-pydc2- is 2,4-pyridinedicarboxylate, is a discrete, binuclear complex due to the terminal nature of the partially deprotonated anionic ligands. [(UO2)2(L1)(ipht)2]·4H2O (3) and [(UO2)2(L1)(pda)2] (4), where ipht2- and pda2- are isophthalate and 1,4-phenylenediacetate, are monoperiodic coordination polymers in which central L1 bridges connect two lateral strands. Oxalate anions (ox2-) generated in situ give [(UO2)2(L1)(ox)2] (5) a diperiodic network with the hcb topology. [(UO2)2(L2)(ipht)2]·H2O (6) differs from 3 in being a diperiodic network with the V2O5 topological type. [(UO2)2(L1)(2,5-pydc)2]·4H2O (7), where 2,5-pydc2- is 2,5-pyridinedicarboxylate, is a hcb network with a square-wave profile, while [(UO2)2(L1)(dnhpa)2] (8), where dnhpa2- is 3,5-dinitro-2-hydroxyphenoxyacetate, formed in situ from 1,2-phenylenedioxydiacetic acid, has the same topology but a strongly corrugated shape leading to interdigitation of layers. (2R,3R,4S,5S)-Tetrahydrofurantetracarboxylic acid (thftcH4) is only partially deprotonated in [(UO2)3(L1)(thftcH)2(H2O)] (9), which crystallizes as a diperiodic polymer with the fes topology. [(UO2)2Cl2(L1)3][(UO2Cl3)2(L1)] (10) is an ionic compound in which discrete, binuclear anions cross the cells of the cationic hcb network. 2,5-Thiophenediacetate (tdc2-) is peculiar in promoting self-sorting of the ligands in the ionic complex [(UO2)5(L1)7(tdc)(H2O)][(UO2)2(tdc)3]4·CH3CN·12H2O (11), which is the first example of heterointerpenetration in uranyl chemistry, involving a triperiodic, cationic framework and diperiodic, anionic hcb networks. Finally, [(UO2)7(O)3(OH)4.3Cl2.7(L2)2]Cl·7H2O (12) crystallizes as a 2-fold interpenetrated, triperiodic framework in which chlorouranate undulating monoperiodic subunits are bridged by the L2 ligands. Complexes 1, 2, 3, and 7 are emissive with photoluminescence quantum yields in the range of 8-24%, and their solid-state emission spectra show the usual dependence on number and nature of donor atoms.

Cooperative Spin-State Switching and Vapochromism of Mononuclear Ni(II) Complexes by Pyridine Coordination/Decoordination.

Two mononuclear Ni(II) complexes (1 and 2) have been found to display color changes upon coordination/decoordination of pyridine, resulting in their structural transformation between square-planar and octahedral geometries as well as a change in their spin state. Compound 1 changes between red (1r) and yellow (1y) upon exposure to or elimination of pyridine, while 2 undergoes a two-step transformation, changing orange 2o (S = 0) ⇄ gray 2g' (S = 1) → yellow 2y' (S = 1) depending on the reaction time. The first step (2o → 2g') takes less than 45 min, which is significantly faster than the previously reported reaction time of 1 day for a Ni(II) complex/pyridine vapor system. Compound 2o reacting with pyridine can be easily prepared by dispersing 2g in methanol instead of annealing at high temperatures (130 °C), which can be applied to develop chemical sensors for pyridine utilizing color changes and/or magnetic switching.

Quinoid-Based Three-Dimensional Metal-Organic Framework Fe2(dhbq)3: Porosity, Electrical Conductivity, and Solid-State Redox Properties.

We report the synthesis, characterization, and electronic properties of the quinoid-based three-dimensional metal-organic framework [Fe2(dhbq)3]. The MOF was synthesized without using cations as a template, unlike other reported X2dhbq3-based coordination polymers, and the crystal structure was determined by using single-crystal X-ray diffraction. The crystal structure was entirely different from the other reported [Fe2(X2dhbq3)]2-; three independent 3D polymers were interpenetrated to give the overall structure. The absence of cations led to a microporous structure, investigated by N2 adsorption isotherms. Temperature dependence of electrical conductivity data revealed that it exhibited a relatively high electrical conductivity of 1.2 × 10-2 S cm-1 (Ea = 212 meV) due to extended d-π conjugation in a three-dimensional network. Thermoelectromotive force measurement revealed that it is an n-type semiconductor with electrons as the majority of charge carriers. Structural characterization and spectroscopic analyses, including SXRD, Mössbauer, UV-vis-NIR, IR, and XANES measurements, evidenced the occurrence of no mixed valency based on the metal and the ligand. [Fe2(dhbq)3] upon incorporating as a cathode material for lithium-ion batteries engendered an initial discharge capacity of 322 mAh/g.

Structural-transformation-induced Drastic Luminescence Changes in an Organic-Inorganic Hybrid [ReN(CN)4 ]2- Salt Triggered by Chemical Stimuli.

We synthesized a (1-propylpyridinium)2 [ReN(CN)4 ]-type organic-inorganic hybrid exhibiting water-vapor-induced drastic structural changes of the [ReN(CN)4 ]2- assemblies. Specifically, upon exposure to water vapor, dehydrated nitrido-bridged chains were converted to hydrated cyanido-bridged tetranuclear clusters via rearrangements of large molecular building units in the crystals. These switchable assembly forms display substantially different photo-physical properties, although in both cases the emission is caused by a metal-centered d-d transition. The nitrido-bridged chain exhibited a near-infrared (749 nm) emission, which blue-shifted as the temperature increased, while a visible (561 nm) emission and its red shift was demonstrated by the cyanido-bridged cluster.

Circulating Tumor DNA as a Potential Prognostic Marker in Patients with Borderline-Resectable Pancreatic Cancer Undergoing Neoadjuvant Chemotherapy Followed by Pancreatectomy.

BACKGROUND: Circulating tumor DNA (ctDNA) might be a promising biomarker for pancreatic cancer in liquid biopsy. This study aimed to evaluate the usefulness of liquid biopsy for patients with borderline-resectable pancreatic cancer (BR-PC). METHODS: Patients with BR-PC according to the National Comprehensive Cancer Network guidelines (2017) and eligible for neoadjuvant chemotherapy (NAC) followed by pancreatectomy were recruited at Wakayama Medical University Hospital (UMIN000026647) between March 2017 and April 2020. The study enrolled 55 patients with locally advanced PC, and each patient consented to inclusion in the study. The study investigated the relationship between KRAS status in ctDNA and clinicopathologic features, analyzing ctDNA at three time points: pretreatment, post-NAC, and post-operation. RESULTS: Of the 55 enrolled patients with a diagnosis of BR-PC, 34 were scheduled to undergo pancreatectomy. From 27 patients with resected BR-PC, 81 blood samples were analyzed in triplicate for ctDNA. The patients with positive pretreatment and post-NAC ctDNA status had no significant decrease in median relapse-free survival (RFS) or overall survival (OS). However, the patients with positive postoperation ctDNA status had a significantly shorter median OS (723 days) than the patients with negative ctDNA results (not reached; P = 0.0148). A combined analysis of postoperative ctDNA and CA19-9 values showed the cumulative effect on both RFS (P = 0.0066) and OS (P = 0.0046). The adjusted hazard ratio for risk of survival computed for the patients carrying risk factors (either detectable ctDNA or CA19-9 > 37 U/ml) increased from 4.13-fold to 17.71-fold (both P = 0.0055) compared with the patients who had no risk factors. CONCLUSION: Positive ctDNA predicts poor survival for patients with BR-PC who undergo NAC followed by pancreatectomy.

A Ferroelectric Metallomesogen Exhibiting Field-Induced Slow Magnetic Relaxation.

Magnetoelectric (ME) materials exhibiting coupled electric and magnetic properties are of significant interest because of their potential use in memory storage devices, new sensors, or low-consumption devices. Herein, we report a new category of ME material that shows liquid crystal (LC), ferroelectric (FE), and field-induced single molecule magnet (SMM) behaviors. Co(II) complex incorporating alkyl chains of type [Co(3C16 -bzimpy)2 ](BF4 )2 (1; 3C16 -bzimpy=2,2'-(4-hexadecyloxy-2,6-diyl)bis(1-hexadecyl-1H-benzo[d]imidazole)) displayed a chiral smectic C mesophase in the temperature range 321 K-458 K, in which distinct FE behavior was observed, with a remnant polarization (88.3 nC cm-2 ). Complex 1 also exhibited field-induced slow magnetic relaxation behavior that reflects the large magnetic anisotropy of the Co(II) center. Furthermore, the dielectric property of 1 was able to be tuned by an external magnetic field occurring from both spin-lattice coupling and molecular orientational variation. Clearly, this multifunctional compound, combining LC, FE, and SMM properties, represents an entry to the development of a range of next-generation ME materials.

Zwitterionic and Anionic Polycarboxylates as Coligands in Uranyl Ion Complexes, and Their Influence on Periodicity and Topology.

The three zwitterionic di- and tricarboxylate ligands 1,1'-[(2,3,5,6-tetramethylbenzene-1,4-diyl)bis(methylene)]bis(pyridin-1-ium-4-carboxylate) (pL1), 1,1'-[(2,3,5,6-tetramethylbenzene-1,4-diyl)bis(methylene)]bis(pyridin-1-ium-3-carboxylate) (mL1), and 1,1',1″-[(2,4,6-trimethylbenzene-1,3,5-triyl)tris(methylene)]tris(pyridin-1-ium-4-carboxylate) (L2) have been used as ligands to synthesize a series of 15 uranyl ion complexes involving various anionic coligands, in most cases polycarboxylates. [(UO2)2(pL1)2(cbtc)(H2O)2]·10H2O (1, cbtc4- = cis,trans,cis-1,2,3,4-cyclobutanetetracarboxylate) is a discrete, dinuclear ring-shaped complex with a central cbtc4- pillar. While [UO2(pL1)(NO3)2] (2), [UO2(pL1)(OAc)2] (3), and [UO2(pL1)(HCOO)2] (4) are simple chains, [(UO2)2(mL1)(1,3-pda)2] (5, 1,3-pda2- = 1,3-phenylenediacetate) is a daisy chain and [UO2(pL1)(pdda)]3·10H2O (6, pdda2- = 1,2-phenylenedioxydiacetate) is a double-stranded, ribbon-like chain. Both [UO2(pL1)(pht)]·5H2O (7, pht2- = phthalate) and [(UO2)3(mL1)(pht)2(OH)2] (8) crystallize as diperiodic networks with the sql topology, the latter involving hydroxo-bridged trinuclear nodes. [(UO2)2(pL1)(c/t-1,3-chdc)2] (9, c/t-1,3-chdc2- = cis/trans-1,3-cyclohexanedicarboxylate) and [UO2(pL1)(t-1,4-chdc)]·1.5H2O (10, t-1,4-chdc2- = trans-1,4-cyclohexanedicarboxylate) are also diperiodic, with the V2O5 and sql topologies, respectively. Both [(UO2)2(mL1)(c/t-1,4-chdc)2] (11) and [(UO2)2(pL1)(1,2-pda)2] (12, 1,2-pda2- = 1,2-phenylenediacetate) crystallize as diperiodic networks with hcb topology, and they display threefold parallel interpenetration. [HL2][(UO2)3(L2)(adc)3]Br (13, adc2- = 1,3-adamantanedicarboxylate) contains a very corrugated hcb network with two different kinds of cells, and the uncoordinated HL2+ molecule associates with the coordinated L2 to form a capsule containing the bromide anion. [(UO2)2(pL1)(kpim)2] (14, kpim2- = 4-ketopimelate) is a three-periodic framework with pL1 molecules pillaring fes diperiodic subunits, whereas [(UO2)2(L2)2(t-1,4-chdc)](NO3)1.7Br0.3·6H2O (15), the only cationic complex in the series, is a triperiodic framework with dmc topology and t-1,4-chdc2- anions pillaring fes diperiodic subunits. Solid-state emission spectra and photoluminescence quantum yields are reported for all complexes.

A pentanuclear iron catalyst designed for water oxidation.

Although the oxidation of water is efficiently catalysed by the oxygen-evolving complex in photosystem II (refs 1 and 2), it remains one of the main bottlenecks when aiming for synthetic chemical fuel production powered by sunlight or electricity. Consequently, the development of active and stable water oxidation catalysts is crucial, with heterogeneous systems considered more suitable for practical use and their homogeneous counterparts more suitable for targeted, molecular-level design guided by mechanistic understanding. Research into the mechanism of water oxidation has resulted in a range of synthetic molecular catalysts, yet there remains much interest in systems that use abundant, inexpensive and environmentally benign metals such as iron (the most abundant transition metal in the Earth's crust and found in natural and synthetic oxidation catalysts). Water oxidation catalysts based on mononuclear iron complexes have been explored, but they often deactivate rapidly and exhibit relatively low activities. Here we report a pentanuclear iron complex that efficiently and robustly catalyses water oxidation with a turnover frequency of 1,900 per second, which is about three orders of magnitude larger than that of other iron-based catalysts. Electrochemical analysis confirms the redox flexibility of the system, characterized by six different oxidation states between Fe(II)5 and Fe(III)5; the Fe(III)5 state is active for oxidizing water. Quantum chemistry calculations indicate that the presence of adjacent active sites facilitates O-O bond formation with a reaction barrier of less than ten kilocalories per mole. Although the need for a high overpotential and the inability to operate in water-rich solutions limit the practicality of the present system, our findings clearly indicate that efficient water oxidation catalysts based on iron complexes can be created by ensuring that the system has redox flexibility and contains adjacent water-activation sites.

Dorsal vs ventral approach to the middle hepatic vein during laparoscopic left hemihepatectomy: multicenter retrospective observational study.

BACKGROUND: Left hemihepatectomy requires exposure of the middle hepatic vein (MHV) at the cutting-surface. Two procedures are used to approach the MHV: a conventional ventral approach and a laparoscopy-specific dorsal approach. This multicenter retrospective observational study aimed to evaluate the perioperative outcomes of these two procedures. METHODS: Clinical records of 38 consecutive patients that underwent laparoscopic left hemihepatectomy in four university hospitals between 2016 and 2021 were retrospectively reviewed. Outcome measurements were operative blood loss, operating time, trend of postoperative laboratory data within 7 days after hepatectomy, and postoperative complications. Quality of MHV exposure was also evaluated and compared by three-grade evaluation (excellent/good/poor) using recorded still images of the cut-surface of the remnant liver (n = 35). RESULTS: Dorsal and ventral approaches were performed in 9 and 29 patients, respectively. Median operating time was 316 min (dorsal) and 314 min (ventral) (P = 0.71). Median operative blood loss was 45 ml (dorsal) and 105 ml (ventral) (P = 0.10). Two patients in the ventral approach group had bleeding in excess of 500 ml, which was not seen in the dorsal approach group. Excellent/good/poor MHV appearance on the cutting-surface was observed in 5/3/1 patients in the dorsal approach group, respectively, and in 7/8/11 patients in the ventral approach group, respectively (P = 0.03). In the ventral approach group, significant increases of aspartate aminotransferase (on postoperative day 1 and day 4/5) and of alanine aminotransferase (on postoperative day 2/3 and 4/5) were observed (P < 0.05). Postoperative complications were observed only in the ventral approach group (n = 3). CONCLUSIONS: The dorsal approach could achieve safe and precise anatomical left hemihepatectomy with operation time and operative blood loss comparable to the conventional ventral approach.

Treatment strategy for resectable colorectal cancer liver metastases from the viewpoint of time to surgical failure.

PURPOSE: The efficacy of pre or postoperative chemotherapy for resectable colorectal cancer liver metastases (CRLM) is disputed. This study aimed to examine the risk factors for time to surgical failure (TSF) and analyze the efficacy of pre or postoperative chemotherapy prior to liver resection for CRLM. METHODS: The clinicopathological factors of 567 patients who underwent initial hepatectomy for CRLM at 7 university hospitals between April 2007 and March 2013 were retrospectively analyzed. The prognostic factors were identified and then stratified into two groups according to the number of preoperative prognostic factors: the high-score group (H-group, score 2-4) and the low-score group (L-group, score 0 or 1). RESULTS: Patients who experienced unresectable recurrence within 12 months after initial treatment had a significantly shorter prognosis than other patients (p < 0.001). Multivariate analysis identified age ≥ 70 (p = 0.001), pT4 (p = 0.015), pN1 (p < 0.001), carbohydrate antigen 19-9 ≥ 37 U/ml (p = 0.002), Clavien-Dindo grade ≥ IIIa (p = 0.013), and postoperative chemotherapy (p = 0.006) as independent prognostic factors. In the H-group, patients who received chemotherapy had a better prognosis than those who did not (p = 0.001). CONCLUSION: Postoperative chemotherapy is beneficial in colorectal cancer patients with more than two of the following factors: age ≥ 70, carbohydrate antigen 19-9-positivity, pT4, and lymph node metastasis.

Preoperative Risk Assessment for Loss of Independence Following Hepatic Resection in Elderly Patients: A Prospective Multicenter Study.

OBJECTIVE: To establish a preoperative risk assessment method for loss of independence after hepatic resection. SUMMARY BACKGROUND DATA: Hepatic resection often results in loss of independence in preoperatively self-sufficient elderly people. Elderly patients should therefore be carefully selected for surgery. METHODS: In this prospective, multicenter study, 347 independently-living patients aged ≥65 years, scheduled for hepatic resection, were divided into study (n = 232) and validation (n = 115) cohorts. We investigated the risk factors for postoperative loss of independence in the study cohort and verified our findings with the validation cohort. Loss of independence was defined as transfer to a rehabilitation facility, discharge to residence with home-based healthcare, 30-day readmission for poor functionality, and 90-day mortality (except for cancer-related deaths). RESULTS: In the study cohort, univariate and multivariate analyses indicated that frailty, age ≥ 76 years, and open surgery were independent risk factors for postoperative loss of independence. Proportions of patients with postoperative loss of independence in the study and validation cohorts were respectively 3.0% and 0% among those with no applicable risk factors, 8.1% and 12.5% among those with 1 applicable risk factor, 25.5% and 25.0% among those with 2 applicable risk factors, and 56.3% and 50.0% among those with all 3 factors applicable (P < 0.001 for both cohorts). Areas under the receiver operating characteristic curves for the study and validation groups were 0.777 and 0.783, respectively. CONCLUSIONS: Preoperative risk assessments using these 3 factors may be effective in predicting and planning for postoperative loss of independence after hepatic resection in elderly patients.

Radiographic Splenic Artery Involvement Is a Poor Prognostic Factor in Upfront Surgery for Patients with Resectable Pancreatic Body and Tail Cancer.

PURPOSE: The prognostic impact of radiographic splenic vessel involvement in pancreatic cancer remains unclear. We evaluate its oncological significance in resectable pancreatic body/tail cancer. PATIENTS AND METHODS: We retrospectively review 102 cases of resectable pancreatic cancer and 51 of borderline resectable pancreatic cancer (BRPC) who underwent pancreatectomy for pancreatic body/tail cancer. Resectable pancreatic body/tail cancer was classified into one of three categories based on radiographic splenic vessel involvement. RESULTS: Among 102 cases of resectable pancreatic cancer, 37 (36.3%), 35 (34.3%), and 30 cases (29.4%) were classified as no splenic vessel involvement (Rnone), splenic vein involvement (RV), and splenic artery involvement (RA), respectively. Disease-free survival (DFS) among patients with Rnone, RV, RA, and BRPC was 58.5, 18.4, 10.8, and 9.2 months, respectively. Patients with RV and RA had significantly poorer DFS than patients with Rnone (P = 0.010, P < 0.001, respectively). Median survival among Rnone, RV, RA, and BRPC was 80.6, 23.4, 15.1, and 21.3 months, respectively. Patients with RV and RA had significantly poorer survival than patients with Rnone (P = 0.001, P < 0.001, respectively) and had short survival similar to that of those with BRPC. Multivariate Cox proportional hazard analysis detected preoperative CA19-9 ≥ 37 IU/L, radiologic splenic vein involvement, radiologic splenic artery involvement, intraoperative bleeding ≥ 500 ml, transfusion, positive washing cytology, and noncompletion of adjuvant therapy as independent prognostic factors. CONCLUSIONS: Radiographic splenic artery involvement is a poor prognostic factor in resectable pancreatic body/tail cancer and may have a role in stratification of treatment strategy.