Molecular copper(I)-sensitized photoanodes for alcohol oxidation under ambient conditions.

Dye-sensitized photoelectrochemical cells can enable the production of molecules currently accessible through energetically demanding syntheses. Copper(I)-based dyes represent electronically tunable charge transfer and separation systems. Herein, we report a Cu(I)-bisdiimine donor-chromophore-acceptor dye with an absorbance in the visible part of the solar spectrum composed of a phenothiazine electron donor, and dipyrido[3,2-a:2',3'-c]phenazine electron acceptor. This complex is incorporated onto a zinc oxide nanowire semiconductor surface effectively forming a photoanode that is characterized spectroscopically and electrochemically. We investigate the photo-oxidation of hydroquinone, and the photosensitization of 2,2,6,6-tetramethylpiperidine-1-oxyl and N-hydroxyphthalimide for the oxidation of furfuryl alcohol to furfuraldehyde, resulting in near quantitative conversions, with poor selectivity to the alcohol.

A Modular and Catalytic Methodology To Access 2,5-Furan-Based Phenylene/Thiophene Oligomers through a One-Pot Decarboxylative Cross-Coupling from 5-Bromofurfural.

A library of 2,5-furan-based phenylene/thiophene oligomers were synthesized starting from 5-bromofurfural, a derivative of biomass-derived furfural. Varied electronic groups are coupled onto the furan motif, followed by the installation of a phenylene or thiophene central linker through a one-pot Pd-catalyzed decarboxylative cross-coupling reaction. Resulting oligomers containing the furan-phenylene-furan core possess high photoluminescent quantum yields in solution (83-98%), which are crucial for optoelectronic devices. Absorbance and photoluminescence maxima are tuned by changing peripheral functional groups and the center linker coupled onto the furan backbone.

Effects of increasing ligand conjugation in Cu(I) photosensitizers on NiO semiconductor surfaces.

Dye-sensitized photoelectrodes may be used as heterogeneous components for fuel-forming reactions in photoelectrochemical cells. There has been increasing interest in developing Earth-abundant cheaper photosensitizers based on first-row transition metals. We describe here the synthesis, characterization, and study of the ground and excited state properties of three Cu(I) complexes bearing ligands with varying electron-accepting capacities and conjugation that may act as photosensitizers for wide bandgap semiconductors. Femtosecond transient absorption studies indicate that the nature of the final excited state is dictated by the extent of conjugation in the electron-accepting ligand, where shorter conjugation leads to the formation of a singly reduced ligand and longer conjugation leads to the formation of a ligand-centered final excited state. These complexes were surface anchored onto nanostructured NiO on conductive fluorine-doped tin oxide glass to fabricate photocathodes. It was found that even though the ligands with increasing conjugation have an effect on the formation of the final excited state in solution, all complexes exhibit similar photocurrents upon white light illumination, suggesting that charge transfer to NiO happens in advance of the formation of the final excited state.

Long live(d) CsPbBr3 superlattices: colloidal atomic layer deposition for structural stability.

Superlattice formation afforded by metal halide perovskite nanocrystals has been a phenomenon of interest due to the high structural order induced in these self-assemblies, an order that is influenced by the surface chemistry and particle morphology of the starting building block material. In this work, we report on the formation of superlattices from aluminum oxide shelled CsPbBr3 perovskite nanocrystals where the oxide shell is grown by colloidal atomic layer deposition. We demonstrate that the structural stability of these superlattices is preserved over 25 days in an inert atmosphere and that colloidal atomic layer deposition on colloidal perovskite nanocrystals yields structural protection and an enhancement in photoluminescence quantum yields and radiative lifetimes as opposed to gas phase atomic layer deposition on pre-assembled superlattices or excess capping group addition. Structural analyses found that shelling resulted in smaller nanocrystals that form uniform supercrystals. These effects are in addition to the increasingly static capping group chemistry initiated where oleic acid is installed as a capping ligand directly on aluminum oxide. Together, these factors lead to fundamental observations that may influence future superlattice assembly design.

How Toll-like Receptor 9 Plays a Key Role in the Development of Gastric Cancer and Is Linked to Epstein-Barr Virus Infection.

The relationship between Toll-like receptor 9 (TLR-9) signaling and its involvement with Epstein-Barr virus (EBV) in gastric cancer (GC) is complex and currently under study. This research intended to understand TLR-9's role in certain T and B lymphocytes and the serum levels of TLR-9 in GC patients versus healthy subjects. The team explored links between these immune markers and various GC traits, such as histological grade, tumor progression stages, cancer types, and survival rates. Additionally, the research sought to find if EBV genetic material influences these immune reactions. Using flow cytometry, TLR-9 levels in different immune cells were analyzed. At the same time, the amount of TLR-9 in the serum was determined. The results showed GC patients had varied TLR-9 levels compared to healthy subjects, with specific cells showing noticeable changes. When grouped by GC attributes, key relationships emerged between TLR-9 amounts, the histological grade, progression stages, and cancer types. A notable finding was the connection between TLR-9 levels and EBV genetic presence, suggesting possible interactions between TLR-9 responses and EBV-related GC processes. Survival data also hinted at TLR-9's potential as a predictor linked to clinical traits. Overall, this research emphasizes TLR-9's complex role in GC's immune responses, pinpointing its interactions with particular cells, clinical features, and EBV. The study unveils a complex web affecting GC and paves the way for new treatment avenues targeting TLR-9 pathways.

Photonic enhancement in photoluminescent metal halide perovskite-photonic crystal bead hybrids.

We report two photonic crystal-perovskite nanocrystal microbead hybrids with photoluminescence matching that of the parent nanocrystals but with increased photoluminescence quantum yields. Time-resolved photoluminescence spectroscopy quantifies the radiative enhancement afforded by the photonic environment of the microbeads. The reported hybrids also demonstrate markedly better resistance to degradation in water over 30 days of immersion.

Could Toll-like Receptor 2 Serve as Biomarker to Detect Advanced Gastric Cancer?

Gastric cancer is one of the five most common types of cancer worldwide. Due to the heterogeneous course and the involvement of many risk factors, its treatment and diagnosis is an important challenge for modern medicine. Recent studies have emphasized the i role of Toll-like receptors (TLRs) expressed on selected cells of the immune system in the pathogenesis of gastric cancer. The aim of this study was to determine the prevalence of TLR2 on T lymphocytes, B lymphocytes, monocytes, and dendritic cells in patients diagnosed with gastric cancer, with particular emphasis on the stage of the disease. Based on the obtained results, we have shown that patients with gastric cancer are characterized by a higher percentage of all tested populations of peripheral blood immune cells expressing TLR2 in relation to patients from the control group. Moreover, a detailed analysis of the collected results showed a significant link between TLR2 and the stage of the disease.

Microbiota and the Immune System-Actors in the Gastric Cancer Story.

Gastric cancer remains one of the most commonly diagnosed cancers in the world, with a relatively high mortality rate. Due to the heterogeneous course of the disease, its diagnosis and treatment are limited and difficult, and it is associated with a reduced prognosis for patients. That is why it is so important to understand the mechanisms underlying the development and progression of this cancer, with particular emphasis on the role of risk factors. According to the literature data, risk factors include: changes in the composition of the stomach and intestinal microbiota (microbiological dysbiosis and the participation of Helicobacter pylori), improper diet, environmental and genetic factors, and disorders of the body's immune homeostasis. Therefore, the aim of this review is to systematize the knowledge on the influence of human microbiota dysbiosis on the development and progression of gastric cancer, with particular emphasis on the role of the immune system in this process.

Binary Cu2-xS Templates Direct the Formation of Quaternary Cu2ZnSnS4 (Kesterite, Wurtzite) Nanocrystals.

Kesterite Cu2ZnSnS4 (k-CZTS) nanocrystals have received attention for their tunable optoelectronic properties, as well as the earth abundance of their constituent atoms. However, the phase-pure synthesis of these quaternary NCs is challenging due to their polymorphism, as well as the undesired formation of related binary and ternary impurities. A general synthetic route to tackle this complexity is to pass through intermediate template nanocrystals that direct subsequent cation exchange toward the desired quaternary crystalline phase, particularly those that are thermodynamically disfavored or otherwise synthetically challenging. Here, working within this model multinary system, we achieve control over the formation of three binary copper sulfide polymorphs, cubic digenite (Cu1.8S), hexagonal covellite (CuS), and monoclinic djurleite (Cu1.94S). Controlled experiments with Cu0 seeds show that selected binary phases can be favored by the identity and stoichiometry of the sulfur precursor alone under otherwise comparable reaction conditions. We then demonstrate that the nature of the Cu2-xS template dictates the final polymorph of the CZTS nanocrystal products. Through digenite, the cation exchange reaction readily yields the k-CZTS phase due to its highly similar anion sublattice. Covellite nanocrystals template the k-CZTS phase but via major structural rearrangement to digenite that requires elevated temperatures in the absence of a strong reducing agent. In contrast, we show that independently synthesized djurleite nanorods template the formation of the wurtzite polymorph (w-CZTS) but with prominent stacking faults in the final product. Applying this refined understanding to the standard one-pot syntheses of k- and w-CZTS nanocrystals, we identify that these reactions are each effectively templated by binary intermediates formed in situ, harnessing their properties to guide the overall synthesis of phase-pure quaternary materials. Our results provide tools for the careful development of tailored nanocrystal syntheses in complex polymorphic systems.

Initial Results of Antegrade Laser Fenestrations Using Image Fusion Guidance and Company Manufactured Stent Grafts in Complex Aortic Aneurysm Repair.

OBJECTIVE: The aim was to describe initial outcomes of physician modified stent grafts using antegrade laser fenestrations and image fusion guidance (LEVAR) and company manufactured custom made (CM) stent grafts for the treatment of complex abdominal aortic aneurysms (CAAAs), thoraco-abdominal aortic aneurysms (TAAAs) and type I endoleaks (T1ELs). METHODS: This was a retrospective single centre study. All LEVAR and Zenith (Cook) CM stent graft procedures between 1 January 2012 and 31 December 2018 were reviewed. Endpoints included intra-operative adverse events (IOAEs), in hospital mortality, re-interventions, target vessel patency, and 12 month outcomes (overall survival, freedom from re-intervention, target vessel patency). Outcomes at 12 months were estimated using the Kaplan-Meier method. RESULTS: A hundred patients were identified and included in the study. All patients were deemed unfit for open repair. The cohort included 22 LEVAR and 78 CM stent grafts. LEVAR cases included painful aneurysms (n = 5), > 65 mm aneurysms (n = 10), anatomical constrains and/or presence of previous renal stents (n = 7) or cases declined by the manufacturer planning centre (n = 2). IOAEs were recorded in 41% of cases (n = 9) in the LEVAR group vs. 10% (n = 8, p = .002) in the CM group. The in hospital mortality rate in the LEVAR group was 9% (n = 2) vs. 4% (n = 3, p = .30) in the CM group. The median follow up duration was 22 months (7 - 38) in the LEVAR group and 28 months (11 - 78) in the CM group. The estimate of overall survival at one year was 91% in both groups. The freedom from re-intervention rate at one year was 58% in the LEVAR group vs. 87% in the CM group. The target vessel patency rates at one year were 95% in both groups. CONCLUSION: In high risk patients deemed unfit for open repair, LEVAR may provide satisfactory 12 month overall survival and target vessel patency rates, though reported IOAE, mortality, and re-interventions rates were high thus requiring close and extensive follow up.

A historical perspective on porphyrin-based metal-organic frameworks and their applications.

Porphyrins are important molecules widely found in nature in the form of enzyme active sites and visible light absorption units. Recent interest in using these functional molecules as building blocks for the construction of metal-organic frameworks (MOFs) have rapidly increased due to the ease in which the locations of, and the distances between, the porphyrin units can be controlled in these porous crystalline materials. Porphyrin-based MOFs with atomically precise structures provide an ideal platform for the investigation of their structure-function relationships in the solid state without compromising accessibility to the inherent properties of the porphyrin building blocks. This review will provide a historical overview of the development and applications of porphyrin-based MOFs from early studies focused on design and structures, to recent efforts on their utilization in biomimetic catalysis, photocatalysis, electrocatalysis, sensing, and biomedical applications.

Loss of Optineurin Drives Cancer Immune Evasion via Palmitoylation-Dependent IFNGR1 Lysosomal Sorting and Degradation.

Mutations in IFN and MHC signaling genes endow immunotherapy resistance. Patients with colorectal cancer infrequently exhibit IFN and MHC signaling gene mutations and are generally resistant to immunotherapy. In exploring the integrity of IFN and MHC signaling in colorectal cancer, we found that optineurin was a shared node between the two pathways and predicted colorectal cancer patient outcome. Loss of optineurin occurs in early-stage human colorectal cancer. Immunologically, optineurin deficiency was shown to attenuate IFNGR1 and MHC-I expression, impair T-cell immunity, and diminish immunotherapy efficacy in murine cancer models and patients with cancer. Mechanistically, we observed that IFNGR1 was S-palmitoylated on Cys122, and AP3D1 bound with and sorted palmitoylated IFNGR1 to lysosome for degradation. Unexpectedly, optineurin interacted with AP3D1 to prevent palmitoylated IFNGR1 lysosomal sorting and degradation, thereby maintaining IFNγ and MHC-I signaling integrity. Furthermore, pharmacologically targeting IFNGR1 palmitoylation stabilized IFNGR1, augmented tumor immunity, and sensitized checkpoint therapy. Thus, loss of optineurin drives immune evasion and intrinsic immunotherapy resistance in colorectal cancer. SIGNIFICANCE: Loss of optineurin impairs the integrity of both IFNγ and MHC-I signaling pathways via palmitoylation-dependent IFNGR1 lysosomal sorting and degradation, thereby driving immune evasion and intrinsic immunotherapy resistance in colorectal cancer. Our work suggests that pharmacologically targeting IFNGR1 palmitoylation can stabilize IFNGR1, enhance T-cell immunity, and sensitize checkpoint therapy in colorectal cancer.See related commentary by Salvagno and Cubillos-Ruiz, p. 1623.This article is highlighted in the In This Issue feature, p. 1601.

Combination of Quadruple Antegrade and Retrograde In Situ Stent-Graft Laser Fenestration in the Management of a Complex Abdominal Aortic Aneurysm.

BACKGROUND: We report a case of juxtarenal abdominal aortic aneurysm-anatomically unsuitable for conventional endovascular repair because of narrow distal aorta-successfully treated by endovascular repair facilitated by in situ laser fenestration. METHODS AND RESULTS: An aortic stent graft was inserted to exclude a juxtarenal aneurysm: under image fusion guidance, antegrade in situ laser fenestration allowed to perfuse superior mesenteric artery and both renal arteries. After complementary insertion of an extended aortouni-iliac stent graft, retrograde in situ laser fenestration was performed to perfuse the contralateral left iliac artery, in order to overcome a narrow distal aorta. Postoperative course was uneventful. Six month's CT showed an excluded aneurysm, patency of the inserted stents and the absence of endoleak. CONCLUSIONS: In situ laser fenestration seems to be an effective solution for endovascular therapy of complex juxtarenal aneurysms. In this case of narrow distal aorta it was a suitable alternative to overcome endovascular aneurysm repair anatomical restrictions and to prevent other additional open surgical interventions.

Molecular Copper(I)-Copper(II) Photosensitizer-Catalyst Photoelectrode for Water Oxidation.

Copper(II)-based electrocatalysts for water oxidation in aqueous solution have been studied previously, but photodriving these systems still remains a challenge. In this work, a bis(diimine)copper(I)-based donor-chromophore-acceptor system is synthesized and applied as the light-harvesting component of a photoanode. This molecular assembly was integrated onto a zinc oxide nanowire surface, and upon photoexcitation, chronoamperometric studies reveal that the integrated triad can inject electrons directly into the conduction band of zinc oxide, generating oxidizing equivalents that are then transferred to a copper(II) water oxidation catalyst in aqueous solution, yielding O2 from water with a Faradaic efficiency of 76%.

Response to lubiprostone in chronic constipation is associated with increased mucus and mucin output: a randomized clinical trial.

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Peripheral blood T lymphocytes are downregulated by the PD-1/PD-L1 axis in advanced gastric cancer.

INTRODUCTION: Programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) function as an immune checkpoint pathway that can be exploited by tumor cells to evade immuno-surveillance. The precise role of PD-1/PD-L1 inhibition of the immune response in GC is unknown. The study investigated PD-1 and PD-L1 expression on peripheral T-cells and its potential association with clinicopathological features in gastric cancer (GC) patients. MATERIAL AND METHODS: PD-1/PD-L1 expression on CD4(+) and CD8(+) T-cells from peripheral blood of 40 patients primarily diagnosed with advanced GC was evaluated by multicolor flow cytometry. RESULTS: The frequency of CD4(+)PD-1(+) and CD8(+)PD-1(+) cells in GC patients was higher than in the control group (p < 0.0001 and p < 0.01, respectively). Expression of PD-1 on CD8(+) cells in GC was higher than in the control group (p < 0.0001). The frequency of CD4(+)PD-L1(+) and CD8(+)PD-L1(+) cells was higher than in the control group (p < 0.0001). Expression of PD-L1 on CD4(+) and CD8(+) cells in GC was higher than in the control group (p < 0.0001). A higher frequency of CD4(+)PD-1(+) cells was found in diffuse-type compared to intestinal tumors (p < 0.029). A higher frequency of CD8(+)PD-1(+) cells was found in patients with poorly differentiated compared to well/moderately differentiated tumors (p < 0.019). CONCLUSIONS: Downregulation of peripheral blood CD4(+) and CD8(+) lymphocytes can be associated with PD-1/PD-L1 expression. This can lead to attenuation of the general immune response in GC.

Image Fusion Guidance for In Situ Laser Fenestration of Aortic Stent graft for Endovascular Repair of Complex Aortic Aneurysm: Feasibility, Efficacy and Overall Functional Success.

OBJECTIVE: To evaluate feasibility, efficacy and overall functional success of image fusion guidance during laser-assisted in situ fenestration of aortic stent graft (LISFAS) for endovascular repair of complex aortic aneurysm (complex-EVAR) in a prospective study. METHODS: Between September 2016 and July 2018, 20 patients were included and treated with LISFAS for complex-EVAR. Aortic aneurysms were either para-renal (n = 15) or thoraco-abdominal (n = 5) with 57 mm [first quartile: 54; third quartile: 68] median aneurysm diameter in 69 years [68;78] patients. All interventions were performed using the same angiographic system and 3D image fusion software for overlying pre-intervention CTA on per-intervention 2D fluoroscopy with cone-beam CT images to display target vessels ostia. RESULTS: LISFAS for complex-EVAR with image fusion was performed in all patients, and no endovascular intervention required conversion to an open aortic repair. LISFAS of all target vessels was feasible in 18 patients (90%); 48 fenestrations out of 50 were performed successfully. Two fenestrations failed for renal arteries in two patients. Median ischemic times were as follows: 34 min [25;43] for superior mesenteric artery; 69 min [56;83] for left renal artery; 73 min [36;102] for right renal artery; and 93 min [89;96] for the celiac trunk. Median intervention and fluoroscopy times, iodinated contrast volume and X-ray exposure were 180 min [150;180], 74 min [64;87], 80 mL [59;113] and 338 Gy.cm2 [259;495], respectively. Efficacy was found in 17 patients (85%) on one-week follow-up CTA: Two patients had type 1 and 3 endoleaks, respectively, that were successfully embolized. Overall functional success was 90%. Median hospitalization stay was 9 days [8, 17]. The 30-day safety analysis was 90% (n = 2 deaths) owing to an undetermined cause and to bowel ischemia after low flow in intensive care unit. CONCLUSIONS: LISFAS using image fusion was feasible, efficient and overall functionally successful for complex-EVAR in this preliminary study.

Competition between Singlet Fission and Spin-Orbit-Induced Intersystem Crossing in Anthanthrene and Anthanthrone Derivatives.

Singlet and triplet excited-state dynamics of anthanthrene and anthanthrone derivatives in solution are studied. Triisopropylsilyl- (TIPS) or H-terminated ethynyl groups are used to tune the singlet and triplet energies to enable their potential applications in singlet fission and triplet fusion processes. Time-resolved optical and electron paramagnetic resonance (EPR) spectroscopies are used to obtain a mechanistic understanding of triplet formation. The anthanthrene derivatives form triplet states efficiently at a rate (ca. 107  s-1 ) comparable to radiative singlet fluorescence processes with approximately 30 % triplet yields, despite their large S1 -T1 energy gap (>1 eV) and the lack of carbonyl groups. In contrast, anthanthrone has a higher triplet yield (50±10 %) with a faster intersystem crossing rate (2.7 × 108  s-1 ) because of the n-π* character of the S1 ←S0 transition. Analysis of time-resolved spin-polarized EPR spectra of these compounds reveals that the triplet states are primarily generated by the spin-orbit-induced intersystem crossing mechanism. However, at high concentrations, the EPR spectrum of the 4,6,10,14-tetrakis(TIPS-ethynyl)anthanthrene triplet state shows a significant contribution from a non-Boltzmann population of the ms =0 spin sublevel, which is characteristic of triplet formation by singlet fission.

Surface CD200 and CD200R antigens on lymphocytes in advanced gastric cancer: a new potential target for immunotherapy.

INTRODUCTION: Gastric cancer (GC) is one of the leading causes of cancer death worldwide. The membrane glycoprotein CD200, widely expressed on multiple cells/tissues, uses a structurally similar receptor (CD200R), delivering immunoregulatory signals. There is evidence that CD200/CD200R signaling suppresses anti-tumor responses in different types of malignancies. Little is known about the CD200/CD200R pathway in GC. The aim of the study was to evaluate the frequencies of CD200+ and CD200R+ lymphocytes in patients with GC. MATERIAL AND METHODS: Forty patients primarily diagnosed with GC and 20 healthy volunteers (control group) were enrolled. The viable peripheral blood lymphocytes underwent labeling with fluorochrome-conjugated monoclonal antibodies and were analyzed using a flow cytometer. RESULTS: In the GC group, the percentages of T CD3+, CD3+/CD4+, and CD3+/CD8+ cells expressing CD200 antigen were higher than in the control group (p < 0.00013, p < 0.0004, and p < 0.0006, respectively). In the GC group, the frequencies of T CD3+, CD3+/CD4+ and CD3+/CD8+ cells expressing CD200R were lower than in the control group (p < 0.0009, p < 0.004, and p < 0.002, respectively). The percentage of B CD19+/CD200+ lymphocytes was higher in GC patients than in the control group (p < 0.00005). Lower frequency of B CD19+/CD200R+ cells was observed in GC patients compared to the control group (p < 0.0001). No differences in the frequencies of CD200+ and CD200R+ lymphocytes were found in relation to either UICC stage or histological grading of the tumors. CONCLUSIONS: For GC pathogenesis, deregulation of the CD200/CD200R axis is important. High percentages of lymphocytes with CD200 expression may contribute to the continuous T cell activation and development of chronic inflammation and influence gastric carcinogenesis.