Single-cell transcriptome analysis reveals two subtypes of tumor cells of sclerosing pneumocytoma with distinct molecular features and clinical implications.

Pulmonary sclerosing pneumocytoma (PSP) is a rare, distinctive benign lung adenoma of pneumocyte origin. Despite its rarity, the tumor's unique cellular morphology has sparked ongoing debates regarding the origin of its constituent cells. This study aimed to elucidate the molecular features of PSP tumor cells and enhance our understanding of the cellular processes contributing to PSP formation and biological behavior. Tissue samples from PSP and corresponding normal lung tissues (n = 4) were collected. We employed single-cell RNA sequencing and microarray-based spatial transcriptomic analyses to identify cell types and investigate their transcriptomes, with a focus on transcription factors, enriched gene expression, and single-cell trajectory evaluations. Our analysis identified two types of tumor cells: mesenchymal epithelial dual phenotype cells (MEDPs) and a distinct subpopulation of type II alveolar epithelial cells exhibiting characteristics slightly reminiscent of type I alveolar epithelial cells (AT2Cs), corresponding to histological round stromal cells and surface cuboidal cells, respectively. MEDPs displayed weak alveolar epithelial differentiation but strong collagen production capabilities, as indicated by the expression of both TTF-1 and vimentin. These cells played a pivotal role in forming the solid and sclerotic areas of PSP. Moreover, MEDPs exhibited a pronounced propensity for epithelial-mesenchymal transition, suggesting a greater potential for metastasis compared to AT2Cs. The capillary endothelial cells of PSP displayed notable diversity. Overall, this study provides, for the first time, a comprehensive mapping of the single-cell transcriptome profile of PSP. Our findings delineate two distinct subtypes of tumor cells, MEDPs and AT2Cs, each with its own biological characteristics and spatial distribution. A deeper understanding of these cell types promises insights into the histology and biological behaviors of this rare tumor.

Reducing undesired solubility of squarephaneic tetraimide for use as an organic battery electrode material.

Locally aromatic alkyl-N-substituted squarephaneic tetraimide (SqTI) conjugated macrocycles are four-electron reducible, owing to global aromaticity and presumed global Baird aromaticity of the dianion and tetraanion states, respectively. However, their good solubility inhibits their application as a battery electrode material. By applying sidechain removal as a strategy to reduce SqTI solubility, we report the development of its unsubstituted derivative SqTI-H, which was obtained directly from squarephaneic tetraanhydride by facile treatment with hexamethyldisilazane and MeOH. Compared to alkyl-N-substituted SqTI-Rs, SqTI-H exhibited further improved thermal stability and low neutral state solubility in most common organic solvents, owing to computationally demonstrated hydrogen-bonding capabilities emanating from each imide position on SqTI-H. Reversible solid state electrochemical reduction of SqTI-H to the globally aromatic dianion state was also observed at -1.25 V vs. Fc/Fc+, which could be further reduced in two stages. Preliminary testing of SqTI-H in composite electrodes for lithium-organic half cells uncovered imperfect cycling performance, which may be explained by persistent solubility of reduced states, necessitating further optimisation of electrode fabrication procedures to attain maximum performance.

Machine-learning assisted scheduling optimization and its application in quantum chemical calculations.

Easy and effective usage of computational resources is crucial for scientific calculations, both from the perspectives of timeliness and economic efficiency. This work proposes a bi-level optimization framework to optimize the computational sequences. Machine-learning (ML) assisted static load-balancing, and different dynamic load-balancing algorithms can be integrated. Consequently, the computational and scheduling engine of the ParaEngine is developed to invoke optimized quantum chemical (QC) calculations. Illustrated benchmark calculations include high-throughput drug suit, solvent model, P38 protein, and SARS-CoV-2 systems. The results show that the usage rate of given computational resources for high throughput and large-scale fragmentation QC calculations can primarily profit, and faster accomplishing computational tasks can be expected when employing high-performance computing (HPC) clusters.

Squarephaneic Tetraanhydride: A Conjugated Square-Shaped Cyclophane for the Synthesis of Porous Organic Materials.

Aromatic carboxylic anhydrides are ubiquitous building blocks in organic materials chemistry and have received considerable attention in the synthesis of organic semiconductors, pigments, and battery electrode materials. Here we extend the family of aromatic carboxylic anhydrides with a unique new member, a conjugated cyclophane with four anhydride groups. The cyclophane is obtained in a three-step synthesis and can be functionalised efficiently, as shown by the conversion into tetraimides and an octacarboxylate. Crystal structures reveal the high degree of porosity achievable with the new building block. Excellent electrochemical properties and reversible reduction to the tetraanions are shown for the imides; NMR and EPR measurements confirm the global aromaticity of the dianions and evidence the global Baird aromaticity of the tetraanions. Considering the short synthesis and unique properties, we expect widespread use of the new building block in the development of organic materials.

Visible Light Stimulated Bistable Photo-Switching in Defect Engineered Metal-Organic Frameworks.

The incorporation of photoactive donor-acceptor Stenhouse adduct (DASA) moieties into Metal-Organic Frameworks (MOFs) provides a new route to the development of visible light switching materials. Herein, a DUT-5 mixed-linker defect series was exploited to produce a derivative group of DASA-modified materials via postsynthetic modification (PSM). The photoactive MOFs exhibited conversion stimulated by visible wavelengths and were stable following multiple cycles. Thermodynamic and metastable states persisted over an extended time period.

Influence of Backbone Curvature on the Organic Electrochemical Transistor Performance of Glycolated Donor-Acceptor Conjugated Polymers.

Two new glycolated semiconducting polymers PgBT(F)2gT and PgBT(F)2gTT of differing backbone curvatures were designed and synthesised for application as p-type accumulation mode organic electrochemical transistor (OECT) materials. Both polymers demonstrated stable and reversible oxidation, accessible within the aqueous electrochemical window, to generate polaronic charge carriers. OECTs fabricated from PgBT(F)2gT featuring a curved backbone geometry attained a higher volumetric capacitance of 170 F cm-3 . However, PgBT(F)2gTT with a linear backbone displayed overall superior OECT performance with a normalised peak transconductance of 3.00×104  mS cm-1 , owing to its enhanced order, expediting the charge mobility to 0.931 cm2 V-1 s-1 .

Mesoporous Silica-Coated Silver Nanoframes as Drug-Delivery Vehicles for Chemo/Starvation/Metal Ion Multimodality Therapy.

Cutting off the energy supply by glucose oxidase (GOx) to starve cancer cells has been a feasible and efficient oncotherapy strategy. The employment of GOx can effectively starve tumor cells by aerobic hydrolysis of glucose hopefully strengthening the abnormality (including the decrease in pH, the increase of hypoxia, and toxic hydrogen peroxide) in the tumor microenvironment (TME). On this basis, we designed and fabricated a GOx-conjugated yolk-shell Ag@mSiO2 nanoframe with Ag NPs and GOx-conjugated mesoporous silica as the yolk and the shell, respectively, to make full use of changes the GOx induces in TME. Specifically, lower pH and H2O2 could accelerate the transformation of Ag nanoparticles to poisonous Ag ions. At the same time, the anabatic hypoxia condition in turn activated chemotherapy drug tirapazamine (TPZ) to exert a chemotherapeutic effect, thereby achieving effective chemo/starvation and metal ion multimodality therapy. The drug release experiment in vitro demonstrated that the GOx is the key to the nanocarriers, which can activate the whole system. The excellent cellular uptake performances of nanocarriers were corroborated by a confocal laser scanning microscope (CLSM). In addition, its superb cancer-killing effect has been confirmed by cytotoxicity and apoptosis experiments. These results indicated that the drug-delivery system achieved the cascade cancer-killing process in situ and synergistic chemo/starvation/metal ion therapy, which has a bright prospect for treating cancer.

Chemi- and Bioluminescence of Cyclic Peroxides.

Bioluminescence is a phenomenon that has fascinated mankind for centuries. Today the phenomenon and its sibling, chemiluminescence, have impacted society with a number of useful applications in fields like analytical chemistry and medicine, just to mention two. In this review, a molecular-orbital perspective is adopted to explain the chemistry behind chemiexcitation in both chemi- and bioluminescence. First, the uncatalyzed thermal dissociation of 1,2-dioxetane is presented and analyzed to explain, for example, the preference for triplet excited product states and increased yield with larger nonreactive substituents. The catalyzed fragmentation reaction and related details are then exemplified with substituted 1,2-dioxetanone species. In particular, the preference for singlet excited product states in that case is explained. The review also examines the diversity of specific solutions both in Nature and in artificial systems and the difficulties in identifying the emitting species and unraveling the color modulation process. The related subject of excited-state chemistry without light absorption is finally discussed. The content of this review should be an inspiration to human design of new molecular systems expressing unique light-emitting properties. An appendix describing the state-of-the-art experimental and theoretical methods used to study the phenomena serves as a complement.

Benchmark study of popular density functionals for calculating binding energies of three-center two-electron bonds.

Density functional theory (DFT) can be used to study the three-center two-electron (3c2e) bonding mode, which is universal in catalysts containing alkaline-earth (Ae) and boron-group (Bg) elements. However, because of the delocalization pattern of the 3c2e bond, the wavefunction cannot be accurately described by DFT methods. The calculated energies of Ae and Bg catalysts therefore fluctuate greatly when different functionals are used, largely because of inconsistent DFT-calculated binding energies of 3c2e bonds. Nevertheless, with the development of supercomputers and theoretical calculation software, the DFT method is becoming increasingly popular for studying Ae and Bg catalysts. In this study, we compared the performances of 21 functionals with the high-level composite G3B3 method in calculations for the binding energies of 3c2e bonds. Several frequently used post-Hartree-Fock methods were also tested. The calculation results indicate that the M06-2X, MN12-L, and MN15 functionals give consistent and reliable binding energies for common 3c2e bonds. © 2018 Wiley Periodicals, Inc.

Tuning the fluorescence of calcium-discharged photoprotein obelin via mutating at the His22-Phe88-Trp92 triad - a QM/MM study.

The fluorescence (FL) of calcium-discharged photoprotein (CaDP) can be altered by easily mutating CaDP without modifying coelenteramide (CLM), which is the decarboxylation product of coelenterazine in calcium-regulated photoprotein. The His22-Phe88-Trp92 triad (the ordering numbers of three amino acids are sorted by a crystal structure (PDB: 2F8P) of calcium-discharged obelin, i.e., CaDP-obelin) is closely related to CaDP-obelin FL, since it exists in close proximity to the 5-p-hydroxyphenyl of CLM. Therefore, it is important to thoroughly investigate how the mutations of this triad affect the emission color of CaDP-obelin FL. In this study, by mutating wild-type CaDP-obelin (WT) at the His22-Phe88-Trp92 triad, we theoretically constructed its nine mutants of separable FL colors. Through combined quantum mechanics and molecular mechanics (QM/MM) calculations and molecular dynamics (MD) simulations, the influence of the mutations of this triad on the CaDP-obelin FL was analyzed considering the H-bond effect and the charge effect. This study demonstrated that the mutations at the His22-Phe88-Trp92 triad redistribute the charges on the D-π-A molecule, CLM, change the charge transfer from the D to the (π + A) moiety, and thereby alter the FL emission. Appending more negative charges on the phenolate moiety of CLM benefits the FL redshift.

Prospects for electroactive and conducting framework materials.

Electroactive and conducting framework materials, encompassing coordination polymers and metal-organic frameworks, have captured the imagination of the scientific community owing to their highly designable nanoporous structures and their potential applications in electrochromic devices, electrocatalysts, porous conductors, batteries and solar energy harvesting systems, among many others. While they are now considered integral members of the broader field of inorganic materials, it is timely to reflect upon their strengths and challenges compared with 'traditional' solid-state materials such as minerals, pigments and zeolites. Indeed, the latter have been known since ancient times and have been prized for centuries in fields as diverse as art, archaeology and industrial catalysis. This opinion piece considers a brief historical perspective of traditional electroactive and conducting inorganic materials, with a view towards very recent experimental progress and new directions for future progress in the burgeoning area of coordination polymers and metal-organic frameworks. Overall, this article bears testament to the rich history of electroactive solids and looks at the challenges inspiring a new generation of scientists. This article is part of the theme issue 'Mineralomimesis: natural and synthetic frameworks in science and technology'.

Through-Space Intervalence Charge Transfer as a Mechanism for Charge Delocalization in Metal-Organic Frameworks.

Understanding the nature of charge transfer mechanisms in 3-dimensional metal-organic frameworks (MOFs) is an important goal owing to the possibility of harnessing this knowledge to design electroactive and conductive frameworks. These materials have been proposed as the basis for the next generation of technological devices for applications in energy storage and conversion, including electrochromic devices, electrocatalysts, and battery materials. After nearly two decades of intense research into MOFs, the mechanisms of charge transfer remain relatively poorly understood, and new strategies to achieve charge mobility remain elusive and challenging to experimentally explore, validate, and model. We now demonstrate that aromatic stacking interactions in Zn(II) frameworks containing cofacial thiazolo[5,4- d]thiazole (TzTz) units lead to a mixed-valence state upon electrochemical or chemical reduction. This through-space intervalence charge transfer (IVCT) phenomenon represents a new mechanism for charge transfer in MOFs. Computational modeling of the optical data combined with application of Marcus-Hush theory to the IVCT bands for the mixed-valence framework has enabled quantification of the degree of charge transfer using both in situ and ex situ electro- and spectro-electrochemical methods. A distance dependence for the through-space electron transfer has also been identified on the basis of experimental studies and computational calculations. This work provides a new window into electron transfer phenomena in 3-dimensional coordination space, of relevance to electroactive MOFs where new mechanisms for charge transfer are highly sought after, and to understanding biological light-harvesting systems where through-space mixed-valence interactions are operative.

[Application of Rectal Prolapse Constipation Balloon in Single Auxiliary Defecation].

OBJECTIVE: To explore the application value of rectal prolapse constipation balloon in single auxiliary defecation. METHODS: Forty-one patients with moderate or severe rectocele were treated with a rectocele constipation balloon through the vagina. The defecography and VAS scores were compared before and after implantation. RESULTS: There was a significant difference between the anorectal angle, rectocele, and VAS scores before and after intervention in defecography (P<0.01). CONCLUSIONS: A single assisted defecation of the rectocelicular constipation balloon is feasible.

Bioluminescence of Firefly Squid via Mechanism of Single Electron-Transfer Oxygenation and Charge-Transfer-Induced Luminescence.

Watasenia scintillans (W. scintillans) is a deep-sea luminescent squid with a popular name of firefly squid. It produces flashes of blue light via a series of complicated luciferin-luciferase reactions involving ATP, Mg2+, and molecular oxygen. Tsuji has proposed a hypothetical scheme for this mysterious bioluminescence (BL) process, but the proposal is short of strong evidence experimentally or theoretically, especially for two key steps. They are the addition of molecular oxygen to luciferin and the formation of light emitter. For the first time, the present study investigates the two steps by reliable density functional theory (DFT) and time-dependent DFT. The results of calculated energetics, charge transfer process, electronic structures, and molecular dynamics give convincing support for Tsuji's proposal. The oxygenation reaction occurs with a single electron-transfer (SET) mechanism, and the light emitter is produced via the mechanism of gradually reversible charge-transfer-induced luminescence (GRCTIL). The simulation of nonadiabatic molecular dynamics further confirms the GRCTIL mechanisms and evaluates the quantum yield of the light emitter to be 43%. The knowledge obtained in the current study will help to understand a large amount of BL systems in nature, since the core structure of W. scintillans luciferin, imidazopyrazinone, is common in the luciferins of about eight phyla of luminescent organisms.

Photoactive Poly-L-Lysine gel with resveratrol-magnesium metal polyphenol network: A promising strategy for preventing tracheal anastomotic complications following surgery.

Postoperative complications at the anastomosis site following tracheal resection are a prevalent and substantial concern. However, most existing solutions primarily focus on managing symptoms, with limited attention given to proactively preventing the underlying pathological processes. To address this challenge, we conducted a drug screening focusing on clinically-relevant polyphenolic compounds, given the growing interest in polyphenolic compounds for their potential role in tissue repair during wound healing. This screening led to the identification of resveratrol as the most promising candidate for mitigating tracheal complications, as it exhibited the most significant efficacy in enhancing the expression of vascular endothelial growth factor (VEGF) while concurrently suppressing the pivotal fibrosis factor: transforming growth factor-beta 1 (TGF-ß1), showcasing its robust potential in addressing these issues. Building upon this discovery, we further developed an innovative photosensitive poly-L-lysine gel integrated with a resveratrol-magnesium metal polyphenol network (MPN), named Res-Mg/PL-MA. This design allows for the enables sustained release of resveratrol and synergistically enhances the expression of VEGF and also promotes resistance to tensile forces, aided by magnesium ions, in an anastomotic tracheal fistula animal models. Moreover, the combination of resveratrol and poly-L-lysine hydrogel effectively inhibits bacteria, reduces local expression of key inflammatory factors, and induces polarization of macrophages toward an anti-inflammatory phenotype, as well as inhibits TGF-ß1, consequently decreasing collagen production levels in an animal model of post-tracheal resection. In summary, our novel Res-Mg/PL-MA hydrogel, through antibacterial, anti-inflammatory, and pro-vascularization mechanisms, effectively prevents complications at tracheal anastomosis, offering significant promise for translational applications in patients undergoing tracheal surgeries.

Clinicopathologic Features and Frozen Diagnostic Pitfalls of Bronchiolar Adenoma/Ciliated Muconodular Papillary Tumors (BA/CMPTs).

To describe the histologic features of bronchiolar adenoma/ciliated muconodular papillary tumors (BA/CMPTs) and analyze the pitfalls in diagnosis from frozen sections. A total of 208 frozen and permanent sections of BA/CMPTs from Shanghai Chest Hospital from July 2018 to July 2021 were retrospectively analyzed. The median age of BA/CMPT patients was 65 years (15 to 79 y), and women accounted for 61.62% (122/198). The median size of BA/CMPTs was 0.6 cm (range 0.2 to 2 cm), of which 88.94% were small (≤1 cm, 185/208). In terms of location, the right lower lobe accounted for 44.23% (92/208), and the left lower lobe accounted for 33.65% (70/208). In 10 patients with 2 independent BA/CMPTs, 5 lesions were located in the left lower lobe and 4 in the right lower lobe. A total of 86.06% of the CT images of BA/CMPT showed solid/subsolid nodules (179/208). Among 208 tumors, 68.75% were distal type (143/208), and 31.25% were proximal type (65/208). The qualitative error rate of frozen sections was 21.33% (32/150), of which the distal type accounted for 75% (24/32); most of them were misdiagnosed as invasive adenocarcinoma during frozen diagnosis. The frozen diagnosis of BA/CMPTs might result in misdiagnosis as invasive adenocarcinoma. A careful search for characteristics of BA/CMPT, such as bilayer epithelial cells with basal cells and a lack of cellular atypia and invasive growth patterns, may be helpful for frozen diagnosis.

Molecular, clinicopathological characteristics and surgical results of resectable SMARCA4-deficient thoracic tumors.

PURPOSE: SMARCA4-deficient thoracic tumors are rapid aggressive malignancies, often diagnosed at an advanced and inoperable stage. The value of pulmonary resection for resectable SMARCA4-deficient thoracic tumors is largely unknown. METHODS: In this observational study, we included 45 patients who received surgery for stage I-III SMARCA4-deficient tumors. We compared the molecular, clinicopathological characteristics and survival between SMARCA4-dNSCLC and SMARCA4-deficient undifferentiated tumor (SMARCA4-dUT) patients. RESULTS: Thirty-four SMARCA4-dNSCLC and 11 SMARCA4-dUT patients were included in this study. Molecular profiles were available in 33 out of 45 patients. The most common mutated gene was TP53 (21, 64%), and followed by STK11 (9, 27%), KRAS (5, 15%), FGFR1 (4, 12%) and ROS1 (4, 12%). There were 3 patients that harbored ALK mutation including 1 EML4-ALK rearrangement. There were 2 patients that harbored EGFR rare site missense mutation. SMARCA4-dUT patients had significance worse TTP (HR = 4.35 95% CI 1.77-10.71, p = 0.001) and OS (HR = 4.27, 95% CI 1.12-16.35, p = 0.022) compared to SMARCA4-dNSCLC patients. SMARCA4-dUT histologic type, stage II/III, R1/2 resection and lymphovascular invasion were independent poor prognostic predictors for both TTP and OS. There were 8 patients who received immunotherapy, the objective response rate was 50%. The SMARCA4-dNSCLC patient with ALK rearrangement was treated with crizotinib as second-line therapy, and achieved stable disease for 9.7 months. CONCLUSION: Patients with SMARCA4-deficient tumors have a high probability of early recurrence after surgery, except for stage I patients. Immunotherapy seems to be a valuable strategy to treat recurrence.

Novel nomograms for predicting survival for immediate breast reconstruction patients diagnosed with invasive breast cancer-a single-center 15-year experience.

Background: Immediate breast reconstruction is widely accepted following oncologic mastectomy. This study aimed to build a novel nomogram predicting the survival outcome for Chinese patients undergoing immediate reconstruction following mastectomy for invasive breast cancer. Methods: A retrospective review of all patients undergoing immediate reconstruction following treatment for invasive breast cancer was performed from May 2001 to March 2016. Eligible patients were assigned to a training set or a validation set. Univariate and multivariate Cox proportional hazard regression models were used to select associate variables. Two nomograms were developed based on the training cohort for breast cancer-specific survival (BCSS) and disease-free survival (DFS). Internal and external validations were performed, and the C-index and calibration plots were generated to evaluate the performance (discrimination and accuracy) of the models. Results: The 10-year estimated BCSS and DFS were 90.80% (95% CI: 87.30%-94.40%) and 78.40% (95% CI: 72.50%-84.70%), respectively, in the training cohort. In the validation cohort, they were and 85.60% (95% CI, 75.90%-96.50%) and 84.10% (95% CI, 77.80%-90.90%), respectively. Ten independent factors were used to build a nomogram for prediction of 1-, 5- and 10-year BCSS, while nine were used for DFS. The C-index was 0.841 for BCSS and 0.737 for DFS in internal validation, and the C-index was 0.782 for BCSS and 0.700 for DFS in external validation. The calibration curve for both BCSS and DFS demonstrated acceptable agreement between the predicted and actual observation in the training and the validation cohorts. Conclusion: The nomograms provided valuable visualization of factors predicting BCSS and DFS in invasive breast cancer patients with immediate breast reconstruction. The nomograms may have tremendous potential in guiding individualized decision-making for physicians and patients in choosing the optimized treatment methods.

Tunable control of the performance of aqueous-based electrochemical devices by post-polymerization functionalization.

Functionalized polymeric mixed ionic-electronic conductors (PMIECs) are highly desired for the development of electrochemical applications, yet are hindered by the limited conventional synthesis techniques. Here, we propose a "graft-onto-polymer" synthesis strategy by post-polymerization functionalization (GOP-PPF) to prepare a family of PMIECs sharing the same backbone while functionalized with varying ethylene glycol (EG) compositions (two, four, and six EG repeating units). Unlike the typical procedure, GOP-PPF uses a nucleophilic aromatic substitution reaction for the facile and versatile attachment of functional units to a pre-synthesized conjugated-polymer precursor. Importantly, these redox-active PMIECs are investigated as a platform for energy storage devices and organic electrochemical transistors (OECTs) in aqueous media. The ion diffusivity, charge mobility and charge-storage capacity can be significantly improved by optimizing the EG composition. Specifically, g2T2-gBT6 containing the highest EG density gives the highest charge-storage capacity exceeding 180 F g-1 among the polymer series, resulting from the improved ion diffusivity. Moreover, g2T2-gBT4 with four EG repeating units exhibits a superior performance compared to its two analogues in OECTs, associated with a high µC* up to 359 F V-1 cm-1 s-1, owing to the optimal balance between ionic-electronic coupling and charge mobility. Through the GOP-PPF, PMIECs can be tailored to access desirable performance metrics at the molecular level.