Phosphonic acid anchored tripodal molecular films on indium tin oxide.

Whereas monopodal self-assembling monolayers (SAMs) are most frequently used for surface and interface engineering, tripodal SAMs are less popular due to the difficulty in achieving a reliable and homogeneous bonding configuration. In this context, in the present study, the potential of phosphonic acid (PA) decorated triptycene (TripPA) for formation of SAMs on oxide substrates was studied, using indium tin oxide (ITO) as a representative and application-relevant test support. A combination of several complementary experimental techniques was applied and a suitable monopodal reference system, benzylphosphonic acid (PPA), was used. The resulting data consistently show that TripPA forms well-defined, densely packed, and nearly contamination-free tripodal SAMs on ITO, with the similar parameters and properties as the monopodal reference system. Modification of wetting properties and work function of ITO by non-substituted and cyano-decorated TripPA SAMs was demonstrated, showing a potential of this tripodal system for surface engineering of oxide substrates.

Thoracoscopic McKeown esophagectomy in a patient with an azygos lobe.

BACKGROUND: The azygos lobe is a relatively rare anatomical variation, and there have been no reports, until date, of thoracoscopic McKeown esophagectomy for esophageal cancer in a patient with an azygos lobe. The azygos lobe can be diagnosed by chest X-ray or CT, and is usually not associated with any symptoms. However, surgeons should be aware that transthoracic surgical procedures in patients with an azygos lobe could be associated with a high risk of complications. CASE PRESENTATION: An 83-years-old man was brought to our emergency room with fever, severe headache, and difficulty in moving. MRI revealed a brain abscess, which was treated by abscess drainage and systemic antibiotic treatment. Further examinations to determine the cause of the brain abscess revealed esophageal cancer. In addition, CT revealed an azygos lobe in the right thoracic cavity. Although intrathoracic adhesions were anticipated on account of a previous history of bacterial pyothorax, we decided to perform esophagectomy via a thoracoscopic approach. Despite the difficulty in dissecting the intrathoracic adhesions, we were able to obtain the surgical field thoracoscopically. Then, we found the azygos lobe, as diagnosed preoperatively, and the azygos vein was supported by the mesentery draining into the superior vena cava. After dividing the mesentery, we clipped and cut the vessel, and both ends were further ligated. After these procedures, we safely performed esophagectomy with 3-field lymph node dissection. The postoperative course was uneventful, and the patient was discharged on the 21st postoperative day. CONCLUSIONS: Although there was a firm adhesion in the thoracic cavity, preoperative recognition of the azygos lobe could help in preventing intraoperative injury. Especially, esophageal surgeons are required to deal with the azygos lobe safely to avoid serious intraoperative injury.

Triple Isomerism in 3D Covalent Organic Frameworks.

Isomerism in covalent organic frameworks (COFs) has scarcely been known. Here, for the first time we show 3D COFs with three framework isomers or polymorphs constructed from the same building blocks. All isomers were obtained as large (>10 µm) crystals; although their crystal shapes were distinctly different, they showed identical FT-IR and solid-state NMR spectra. Our structural analyses revealed unprecedented triple isomerism in 3D COFs (noninterpenetrated dia, qtz, and 3-fold interpenetrated dia-c3 nets). Furthermore, this Communication reports the first known COF with qtz topology for which the structure determination was based on Rietveld analysis. We achieved triple framework isomerism by reticulating a tetrahedral building block with a flexible junction and a linear building block with PEO side chains and by varying solution compositions. Our energy calculations, along with the discovery of interisomer transition, revealed that the isomer with qtz topology was a kinetic isomer. Thus, this simple yet little-explored concept of reticulating only flexible building blocks is an effective pathway to significantly broaden the diversity of 3D COFs, which have been proposed for a myriad of applications.

MiR-181a targets STING to drive PARP inhibitor resistance in BRCA- mutated triple-negative breast cancer and ovarian cancer.

BACKGROUND: Poly (ADP-ribose) polymerase inhibitors (PARPi) are approved for the treatment of BRCA-mutated breast cancer (BC), including triple-negative BC (TNBC) and ovarian cancer (OvCa). A key challenge is to identify the factors associated with PARPi resistance; although, previous studies suggest that platinum-based agents and PARPi share similar resistance mechanisms. METHODS: Olaparib-resistant (OlaR) cell lines were analyzed using HTG EdgeSeq miRNA Whole Transcriptomic Analysis (WTA). Functional assays were performed in three BRCA-mutated TNBC cell lines. In-silico analysis were performed using multiple databases including The Cancer Genome Atlas, the Genotype-Tissue Expression, The Cancer Cell Line Encyclopedia, Genomics of Drug Sensitivity in Cancer, and Gene Omnibus Expression. RESULTS: High miR-181a levels were identified in OlaR TNBC cell lines (p = 0.001) as well as in tumor tissues from TNBC patients (p = 0.001). We hypothesized that miR-181a downregulates the stimulator of interferon genes (STING) and the downstream proinflammatory cytokines to mediate PARPi resistance. BRCA1 mutated TNBC cell lines with miR-181a-overexpression were more resistant to olaparib and showed downregulation in STING and the downstream genes controlled by STING. Extracellular vesicles derived from PARPi-resistant TNBC cell lines horizontally transferred miR-181a to parental cells which conferred PARPi-resistance and targeted STING. In clinical settings, STING levels were positively correlated with interferon gamma (IFNG) response scores (p = 0.01). In addition, low IFNG response scores were associated with worse response to neoadjuvant treatment including PARPi for high-risk HER2 negative BC patients (p = 0.001). OlaR TNBC cell lines showed resistance to platinum-based drugs. OvCa cell lines resistant to platinum showed resistance to olaparib. Knockout of miR-181a significantly improved olaparib sensitivity in OvCa cell lines (p = 0.001). CONCLUSION: miR-181a is a key factor controlling the STING pathway and driving PARPi and platinum-based drug resistance in TNBC and OvCa. The miR-181a-STING axis can be used as a potential marker for predicting PARPi responses in TNBC and OvCa tumors.

Skeletal rearrangement of a boron-containing annulenic molecule into a macrocycle bridged by an electronically stabilized boron cation.

An annulenic molecule containing a three-coordinate chloroborane moiety, which exhibits a borane-olefin proximity effect, undergoes a skeletal rearrangement upon chloride abstraction, to generate a three-dimensional macrocyclic molecule featuring a borocenium (η5-cyclopentadienyl-B+-R) structure.

Insights into Thermal Transport through Molecular π-Stacking.

π-Stacking, which is a ubiquitous structural motif in assemblies of aromatic compounds, is well-known to provide a transport pathway for charge carriers and excitons, while its contribution to thermal transport is still unclear. Herein, based on detailed experimental observations of the thermal diffusivity, thermal conductivity, and specific heat of a single-crystalline triphenylene featuring a one-dimensionally π-stacked structure, we describe the nature of thermal transport through the π-stacked columns. We reveal that acoustic phonons are responsible for thermal transport through the π-stacked columns, which exhibit crystal-like behavior. Importantly, the thermal energy stored as intramolecular vibrations can also be transported by coupling to the acoustic phonons. In contrast, in the direction perpendicular to the π-stacked columns, an amorphous-like thermal transport behavior dominates. The present finding offers deep insight into nanoscale thermal transport in organic materials, where the constituent molecules exist as discrete entities linked together by weak intermolecular interactions.

Effectiveness of computed tomography scoring for the early diagnosis of anastomotic leakage after esophagectomy.

PURPOSE: Anastomotic leakage after esophagectomy is associated with increased mortality; therefore, early diagnosis is highly important. This study aimed to identify the characteristic computed tomography (CT) findings of cervical anastomotic leakage after esophagectomy for esophageal cancer and evaluate the effectiveness of CT scoring in screening the anastomotic leakage. METHODS: Overall, 91 patients who underwent thoracoscopic esophagectomy with cervical esophago-gastric anastomosis were included. We investigated the correlation between anastomotic leakage and the presence of the microbubble sign, evident air retention, and fluid collection in the cervical and mediastinal regions. CT findings were scored, and the cutoff value was set to 2 points on the receiver operating characteristic curve. The patients were divided into two groups based on the CT score (≥ 2 points and ≤ 1 point). RESULTS: CT findings of the microbubble sign (p = 0.01; odds ratio [OR], 8.545; 95% confidence interval [CI], 1.596-45.73), cervical air retention (p < 0.01; OR, 12.43; 95% CI, 2.084-74.17), and cervical fluid collection (p < 0.01; OR, 9.359; 95% CI, 1.753-49.96) significantly correlated with anastomotic leakage. The ≥ 2-point CT score group showed a significantly higher incidence of anastomotic leakage than the ≤ 1-point group (p < 0.01; OR, 16.28; 95% CI [4.704-56.38]). A ≥ 2-point CT score had higher sensitivity (84.2%) than upper gastrointestinal series (36.8%). CONCLUSION: The presence of microbubble sign, air retention, and fluid collection in the cervical area correlated with anastomotic leakage after cervical anastomosis in thoracoscopic esophagectomy. CT scores are useful early anastomotic leakage detectors.

Current status and future perspectives for the treatment of resectable locally advanced esophagogastric junction cancer: A narrative review.

Incidence rates for esophagogastric junction cancer are rising rapidly worldwide possibly due to the economic development and demographic changes. Therefore, increased attention has been paid to the prevention, diagnosis, and the treatment of esophagogastric junction cancer. Although there are discrepancies in the treatment strategy between Asian and Western countries, surgery remains the mainstay of treatment for esophagogastric junction cancer. Recent developments of perioperative multidisciplinary treatment may lead to better therapeutic effect, higher complete resection rate, and better control of the residual diseases, thus result in prolonged prognosis. In this review, we will focus on the treatment of locally advanced resectable esophagogastric junction cancer, and discuss the current status and future perspectives of the perioperative treatment including chemotherapy, radiation therapy, and immunotherapy, as well as the surgical strategy. Better understanding of the latest treatment strategy and future overlook may enable to standardize and individualize the treatment for esophagogastric junction cancer, thus leading to better prognosis for those patients.

Effective Postoperative Surveillance Protocol after Thoracoscopic Esophagectomy Focusing on Symptoms in Patients with Esophageal Cancer.

BACKGROUND: The optimal postoperative surveillance protocol after esophagectomy for patients with esophageal cancer has still not been established. We investigated the risk factors for recurrence of esophageal cancer to devise an appropriate surveillance protocol. We focused on the appearance and worsening of symptoms to determine if additional imaging examinations should be performed. STUDY DESIGN: We enrolled 416 patients with esophageal and esophagogastric junctional cancer who had undergone thoracoscopic esophagectomy at Tokai University Hospital. Outpatient visits for the patients are usually scheduled at least 4 times per year with CT imaging and blood biochemical examination. We evaluated the time to recurrence after esophagectomy, especially the correlation of this parameter with the appearance and worsening of symptoms during the postoperative outpatient follow-up. RESULTS: Of the 416 patients, recurrence occurred in 127 patients (30.5%). The median time to recurrence was 6 months after esophagectomy; recurrence occurred within 24 months in 112 patients (88%), and 51 of these patients (40%) developed some new symptom(s) (symptomatic group) before the diagnosis of recurrence. The number of patients who developed recurrence within 6 months was significantly higher in the symptomatic group compared with that in the asymptomatic group (66.7% vs 46.0%, p = 0.02). The overall survival in the symptomatic group was significantly shorter than that in the asymptomatic group (p < 0.001). CONCLUSIONS: We advocate an effective surveillance protocol depending on the appearance and worsening of symptoms to diagnose recurrence of esophageal cancer; we recommend routine imaging examinations every 6 months and clinical outpatient follow-up at even shorter intervals for the first 24 months after esophagectomy.

Usefulness of three-dimensional thoracoscope for prone position thoracoscopic esophagectomy improves mediastinal lymph node dissection and prognosis for esophageal cancer.

OBJECTIVES: This study aimed to assess the superiority of 3D flexible thoracoscope against 2D thoracoscope for lymph node dissection (LND) and prognosis for prone-position thoracoscopic esophagectomy (TE) in esophageal cancer. METHODS: Three hundred and sixty-seven esophageal cancer patients who underwent prone-position TE with 3-field LND between 2009 and 2018 were evaluated. 2D and 3D thoracoscope was used in 182 (2D group) and 185 cases (3D group), respectively. Short-term surgical outcomes, numbers of retrieved mediastinal lymph node (LN), and rates of LN recurrence were compared. Risk factors for mediastinal LN recurrence and long-time prognosis were also evaluated. RESULTS: No differences in postoperative complications were observed between the groups. The numbers of retrieved mediastinal LN were significantly higher, and the rates of LN recurrence were significantly lower in the 3D group compared to 2D group. Use of 2D thoracoscope was a significant independent factor of middle mediastinal LN recurrence by multivariable analysis. Survival was compared by cox regression analysis, and the 3D group had a significantly better prognosis than the 2D group. CONCLUSIONS: Prone position TE using 3D thoracoscope may improve the accuracy of mediastinal LND and prognosis without increasing postoperative complications for esophageal cancer.

Collective bending motion of a two-dimensionally correlated bowl-stacked columnar liquid crystalline assembly under a shear force.

Stacked teacups inspired the idea that columnar assemblies of stacked bowl-shaped molecules may exhibit a unique dynamic behavior, unlike usual assemblies of planar disc- and rod-shaped molecules. On the basis of the molecular design concept for creating higher-order discotic liquid crystals, found in our group, we synthesized a sumanene derivative with octyloxycarbonyl side chains. This molecule forms an ordered hexagonal columnar mesophase, but unexpectedly, the columnar assembly is very soft, similar to sugar syrup. It displays, upon application of a shear force on solid substrates, a flexible bending motion with continuous angle variations of bowl-stacked columns while preserving the two-dimensional hexagonal order. In general, alignment control of higher-order liquid crystals is difficult to achieve due to their high viscosity. The present system that brings together higher structural order and mechanical softness will spark interest in bowl-shaped molecules as a component for developing higher-order liquid crystals with unique mechanical and stimuli-responsive properties.

Synthesis and Properties of B4 N4 -Heteropentalenes Fused with Polycyclic Hydrocarbons.

Hybrid molecules of π-conjugated carbon rings and BN-heterocyclic rings (h-CBNs) fused with each other have been a rare class of compounds due to the limited availability of their synthetic methods. Here we report the synthesis of new h-CBNs featuring a B4 N4 -heteropentalene core and polycyclic aromatic hydrocarbon wings. Using 1,2-azaborinine derivatives as a building block, we developed a rational synthetic protocol that allows the formation of a B4 N4 ring in a stepwise manner, resulting in the fully fused ABA-type triblock molecules. Thus, three derivatives of 1 bearing naphthalene (1Naph ), anthracene (1Anth ), or phenanthrene (1Phen ) wings fused with the B4 N4 core were synthesized and characterized. Among them, 1Phen , which displays the highest triplet-state energy, was found to serve a host material for phosphorescent OLED devices, for which a maximum external quantum efficiency of 13.7 % was recorded. These findings may promote the synthesis of various types of h-CBNs aiming at new properties arising from the synergy of two different π-electronic systems.

Thoracoscopic esophagectomy for stenosis of thoracic esophagus due to acute esophageal necrosis associated with alcoholic ketoacidosis.

Acute esophageal necrosis (AEN) is a rare disease characterized by the appearance of diffuse black mucosa on upper gastrointestinal endoscopy; the condition often progresses to esophageal stenosis in the chronic phase. A 70-year-old man was admitted to a neighborhood hospital with the diagnosis of alcoholic ketoacidosis and an upper gastrointestinal endoscopy performed to investigate the symptom of esophageal tightness revealed AEN. The patient developed esophageal stenosis with scarring in the chronic phase and was referred to our hospital for surgery 6 months after the diagnosis of AEN. We performed thoracoscopic esophagectomy with the patient in the prone position. Although the esophagus was thickened and strong adhesions were present around the esophagus due to inflammation, we were able to complete the surgical procedure thoracoscopically. In patients presenting with benign esophageal stenosis developing after AEN, thoracoscopic esophagectomy may be a useful treatment option, even in the presence of severe fibrosis.

Genomic Amplification of UBQLN4 Is a Prognostic and Treatment Resistance Factor.

Ubiquilin-4 (UBQLN4) is a proteasomal shuttle factor that directly binds to ubiquitylated proteins and delivers its cargo to the 26S proteasome for degradation. We previously showed that upregulated UBQLN4 determines the DNA damage response (DDR) through the degradation of MRE11A. However, the regulatory mechanism at DNA level, transcriptionally and post-transcriptional levels that control UBQLN4 mRNA levels remains unknown. In this study, we screened 32 solid tumor types and validated our findings by immunohistochemistry analysis. UBQLN4 is upregulated at both mRNA and protein levels and the most significant values were observed in liver, breast, ovarian, lung, and esophageal cancers. Patients with high UBQLN4 mRNA levels had significantly poor prognoses in 20 of 32 cancer types. DNA amplification was identified as the main mechanism promoting UBQLN4 upregulation in multiple cancers, even in the early phases of tumor development. Using CRISPR screen datasets, UBQLN4 was identified as a common essential gene for tumor cell viability in 81.1% (860/1,060) of the solid tumor derived cell lines. Ovarian cancer cell lines with high UBQLN4 mRNA levels were platinum-based chemotherapy resistant, while they were more sensitive to poly (adenosine diphosphate-ribose) polymerase inhibitors (PARPi). Our findings highlight the utilities of UBQLN4 as a significant pan-cancer theranostic factor and a precision oncology biomarker for DDR-related drug resistance.

Design of discotic liquid crystal enabling complete switching along with memory of homeotropic and homogeneous alignment over a large area.

The alignment control of discotic columnar liquid crystals (LCs), featuring a low motility of the constituent molecules and thus having a large viscosity, is a challenging task. Here we show that triphenylene hexacarboxylic ester, when functionalized with hybrid side chains consisting of alkyl and perfluoroalkyl groups in an appropriate ratio, gives a hexagonal columnar (Colh) LC capable of selectively forming large-area uniform homeotropic or homogeneous alignments, upon cooling from its isotropic melt or upon application of a shear force at its LC temperature, respectively. In addition to the alignment switching ability, each alignment state remains persistent unless the LC is heated to its melting temperature. In situ X-ray diffraction analysis under the application of a shear force, together with polarized optical microscopy observations, revealed how the columnar assembly is changed during the alignment-switching process. The remarkable behavior of the discotic LC is discussed in terms of its rheological properties.

A carbon-functionality-appended diborylacetylene available for a component of organic synthesis and OLEDs.

We present new 1,2-diborylacetylene derivatives with planar 9-oxa-10-boraanthracene termini, which display excellent stability to allow usual handling and even thermal evaporation for the preparation of thin films for OLEDs, and also undergo typical reactions of alkynes such as the Diels-Alder reaction.

Bringing out the potential of organoboron compounds by designing the chemical bonds and spaces around boron.

Since the structures, reactivity and properties of organoboron compounds stem from the electron deficiency and low electronegativity of boron, the design of the chemical bonds attached to boron as well as the space provided by substituents around boron leads to particular reactivity and functions of organoboron compounds. Based on the concept of vacant boron p-orbital engineering in combination with peripheral space design for boron, we have developed new organoboron compounds, which exhibit exotic reactivity and properties and boron-mediated organic transformations capable of constructing large π-conjugated systems. Here we describe our recent study by focusing on three topics: (i) the synthesis and its derivatization, small-molecule activation and application to materials science of a two-coordinate boron cation (borinium ion), (ii) a 9-borafluorene-mediated benzannulation reaction of alkyne derivatives and (iii) BN-substituted molecules featuring a 4nπ heterocycle exhibiting unique electronic and emission properties. The molecules and reactions appearing in this article are unprecedented, yet feature very simple systems, and therefore clearly demonstrate intrinsic and new potential of organoboron compounds.

Capturing the Trajectory of Metal-Ion-Cluster Formation: Stepwise Accumulation of Zn(II) Ions in a Robust Coordination Space Formed by a Rigid Tridentate Carboxylate Ligand.

Organic ligand-directed synthesis of metal-ion clusters with a well-defined number and arrangement of metal ions is an important subject toward the development of functional inorganic-organic nanohybrids. Here we report the synthesis of multinuclear Zn-oxo clusters using a triptycene-based rigid ligand (H3L) featuring three metal-coordination sites arranged in a triangular shape. Upon complexation of H3L with zinc acetate dihydrate, a decanuclear Zn-oxo cluster and multinuclear Zn-oxo clusters with a smaller number of Zn(II) ions were formed as the final product and its intermediates, respectively. A comparison of the X-ray structure of the final product with those of the intermediates revealed the cluster-formation process, where four triptycene ligands preorganize to form a robust coordination space to which Zn(II) ions accumulate in a stepwise manner. This stepwise metal-ion accumulation, along with the formation of a large tetrahedral decanuclear Zn-oxo cluster, highlights the potential of ligand design using 1,8,13-substituted triptycenes for the development of various metal-ion clusters.

Recent Developments of Circulating Tumor Cell Analysis for Monitoring Cutaneous Melanoma Patients.

Circulating tumor cells (CTCs) have been studied using multiple technical approaches for interrogating various cancers, as they allow for the real-time assessment of tumor progression, disease recurrence, treatment response, and tumor molecular profiling without the need for a tumor tissue biopsy. Here, we will review studies from the last 15 years on the assessment of CTCs in cutaneous melanoma patients in relation to different clinical outcomes. The focus will be on CTC detection in blood samples obtained from cutaneous melanoma patients of different clinical stages and treatments utilizing multiple platforms. Assessment of multiple molecular melanoma-associated antigen (MAA) markers by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was the most common assay allowing for the improvement of assay sensitivity, tumor heterogeneity, and to predict patient outcomes. Multicenter studies demonstrate the utility of CTC assays reducing the bias observed in single- center trials. The recent development of CTC enrichment platforms has provided reproducible methods. CTC assessment enables both multiple mRNAs and DNAs genomic aberration profiling. CTC provides specific important translational information on tumor progression, prediction of treatment response, and survival outcomes for cutaneous melanoma patients. The molecular studies on melanoma CTCs have provided and may set standards for other solid tumor CTC analyses.