Leveraging Electron Push-Pull Effect for Catalytic Polymerization and Degradation of a Cyclobutane Monomer System.

Ring-opening polymerization (ROP) offers a striking solution to solve problems encountered in step-growth condensation polymerization, including precise control over molecular weight, molecular weight distribution, and topology. This has inspired our interest in ROP of cycloalkanes with an ultimate goal to rethink polyolefins, which clearly poses a number of challenges. Practicality of ROP of cycloalkanes is actually limited by their low polymerizability and elusive mechanisms which arise from significantly varied ring size and non-polar C-C bonds in monomers. In this work, by using Lewis acid/Brønsted base/C(sp3)-H initiator system previously developed in our laboratory, we focus on cyclobutanes and explore the positional and electronic effects of substituents on the ring, namely electron push-pull effect, in promoting controlled polymerization to afford densely functionalized poly(cyclobutanes), as well as catalytic degradation of obtained polymers for upcycling. More importantly, experiments and DFT calculations unveil considerable population of Lewis-acid-induced thermostabilized 1,4-zwitterions, which distinguish cyclobutanes from cyclopropanes and others. All these findings would shed light on catalytic synthesis and degradation of saturated all-carbon main-chain polymers, as well as small molecule transformations of cyclobutanes.

Design and preparation of fluorescent covalent organic frameworks for biological sensing.

Covalent organic frameworks (COFs) are a new class of functional solids featuring several fantastic structural characteristics, including a great diversity of building units and cross-linking patterns, precise integration of building blocks, and adjustable topology of porous architecture. In addition to the above features, some COF samples are constructed with high-density conjugated fragments, which have unique potential advantages in fluorescence imaging, and thus may have great potential applications in bioimaging. Herein, this article summarizes the recent progress in the design and preparation of fluorescent covalent organic frameworks. We investigate the systemic correlation between the structural qualities of COF networks and biological sensors. Finally, the significant advantages, major challenges, and future opportunities of fluorescent covalent organic frameworks are discussed for the development of next-generation porous materials for sensing applications.

Endoscopic therapy versus esophagectomy for T1bN0M0 esophageal cancer: A population-based study using propensity score matching.

Background: Endoscopic therapy is an optional strategy for the treatment of esophageal cancer (EC) under an early stage, especially stage T1a. However, its efficacy in the treatment of T1b EC has not been thoroughly assessed. We investigated the efficacy of esophagectomy, endoscopic therapy, as well as chemoradiotherapy in patients with T1bN0M0 EC. Methods: The Surveillance, Epidemiology, and End Results database (SEER) was employed to identify patients diagnosed with T1bN0M0 EC. Patient demographics were compared among the endoscopic therapy, esophagectomy, and chemoradiotherapy groups. Our study employed Kaplan-Meier analysis and Cox regression model to evaluate patient outcomes and long-term survival rates. The overall survival (OS) and cancer-specific survival (CSS) rates were compared among patients with EC who underwent endoscopic therapy or esophagectomy, employing propensity score matching (PSM). Results: A total of 820 patients diagnosed with T1bN0M0 EC were identified. The number of patients who received endoscopic therapy, esophagectomy, and chemoradiotherapy was 173, 556, and 91, respectively. Patients subjected to endoscopic therapy and esophagectomy had greatly longer OS and CSS than those who underwent chemoradiotherapy. Patients treated with esophagectomy had longer OS than endoscopic therapy patients, but there were no differences in CSS between the two groups. PSM generated 153 patient pairs among T1bN0M0 patients, demonstrating that both the esophagectomy and endoscopic therapy groups exhibited comparable OS and CSS rates. Conclusion: Endoscopic therapy and esophagectomy were associated with a significant survival advantage compared with chemoradiotherapy in patients with T1bN0M0 EC. In contrast, after PSM, among the EC patients with stage T1bN0M0, OS and CSS did not differ after endoscopic therapy or esophagectomy. These results indicate that endoscopic therapy could be a viable alternative to esophagectomy in patients diagnosed with T1bN0M0 EC.

Simulation of thermal hazards risk in octogen based on non-isothermal DSC data.

To evaluate the possible thermal risks associated with the storage of octogen (HMX), non-isothermal differential scanning calorimetry (DSC) experiments were conducted in order to ascertain the kinetic model and parameters governing its thermal decomposition. DSC measurements indicate that HMX underwent a crystal transformation prior to thermal decomposition. A kinetic model for the autocatalytic thermal decomposition process was developed through the analysis of its primary exothermic peaks. Subsequently, numerical simulations were performed using the aforementioned kinetic model to assess the potential thermal explosion hazard of HMX under two distinct storage conditions. The comparison was made between the models of HMX autocatalytic decomposition temperature and thermal explosion critical temperature under two distinct storage conditions. The prediction of the influence of ambient temperature on the critical temperature of thermal explosion is conducted simultaneously. Finally, the thermal hazard parameters of HMX under different package quality are given.

ReaLigands: A Ligand Library Cultivated from Experiment and Intended for Molecular Computational Catalyst Design.

Computational catalyst design requires identification of a metal and ligand that together result in the desired reaction reactivity and/or selectivity. A major impediment to translating computational designs to experiments is evaluating ligands that are likely to be synthesized. Here, we provide a solution to this impediment with our ReaLigands library that contains >30,000 monodentate, bidentate (didentate), tridentate, and larger ligands cultivated by dismantling experimentally reported crystal structures. Individual ligands from mononuclear crystal structures were identified using a modified depth-first search algorithm and charge was assigned using a machine learning model based on quantum-chemical calculated features. In the library, ligands are sorted based on direct ligand-to-metal atomic connections and on denticity. Representative principal component analysis (PCA) and uniform manifold approximation and projection (UMAP) analyses were used to analyze several tridentate ligand categories, which revealed both the diversity of ligands and connections between ligand categories. We also demonstrated the utility of this library by implementing it with our building and optimization tools, which resulted in the very rapid generation of barriers for 750 bidentate ligands for Rh-hydride ethylene migratory insertion.

Skeleton engineering of rigid covalent organic frameworks to alter the number of binding sites for improved radionuclide extraction.

Crystalline porous covalent frameworks (COFs) have been considered as a platform for uranium extraction from seawater and nuclear waste. However, the role of rigid skeleton and atomically precise structures of COFs is often ignored in the design of defined binding configuration. Here, a COF with an optimized relative position of two bidentate ligands realizes full potential in uranium extraction. Compared with the para-chelating groups, the optimized ortho-chelating groups with oriented adjacent phenolic hydroxyl groups on the rigid skeleton endow an additional uranyl binding site, thereby increasing the total number of binding sites up to 150%. Experimental and theoretical results indicate that the uranyl capture is greatly improved via the energetically favored multi-site configuration and the adsorption capacity reaches up to 640 mg g-1, which exceeds that of most reported COF-based adsorbents with chemical coordination mechanism in uranium aqueous solution. This ligand engineering strategy can efficiently advance the fundamental understanding of designing the sorbent systems for extraction and remediation technology.

Glucose-activatable insulin delivery with charge-conversional polyelectrolyte multilayers for diabetes care.

One of the most effective treatments for diabetes is to design a glucose-regulated insulin (INS) delivery system that could adjust the INS release time and rate to reduce diabetes-related complications. Here, mixed multiple layer-by-layer (mmLbL)-INS microspheres were developed for glucose-mediated INS release and an enhanced hypoglycemic effect for diabetes care. To achieve ultrafast glucose-activated INS release, glucose oxidase (GOx) was assembled with a positively charged polymer and modified on INS LbL. The mmLbL-INS microspheres were constructed with one, two, and four layers of the polyelectrolyte LbL assembly at a ratio of 1:1:1. Under hyperglycemia, GOx converts a change in the hyperglycemic environment to a pH stimulus, thus providing sufficient hydrogen ion. The accumulated hydrogen ion starts LbL charge shifting, and anionic polymers are converted to cationic polymers through hydrolytic cleavage of amine-functionalized side chains. The results of in vitro INS release suggested that glucose can modulate the mmLbL-INS microspheres in a pulsatile profile. In vivo studies validated that this formulation enhanced the hypoglycemic effect in STZ-induced diabetic rats within 2 h of subcutaneous administration and facilitated stabilization of blood glucose levels for up to 2 days. This glucose-activatable LbL microsphere system could serve as a powerful tool for constructing a precisely controlled release system.

C-H Insertion in Dirhodium Tetracarboxylate-Catalyzed Reactions despite Dynamical Tendencies toward Fragmentation: Implications for Reaction Efficiency and Catalyst Design.

Rh-catalyzed C-H insertion reactions to form ß-lactones suffer from post-transition state bifurcations, with the same transition states leading to ketones and ketenes via fragmentation in addition to ß-lactones. In such a circumstance, traditional transition state theory cannot predict product selectivity, so we employed ab initio molecular dynamics simulations to do so and provide a framework for rationalizing the origins of said selectivity. Weak interactions between the catalyst and substrate were studied using energy decomposition and noncovalent interaction analyses, which unmasked an important role of the 2-bromophenyl substituent that has been used in multiple ß-lactone-forming C-H insertion reactions. Small and large catalysts were shown to behave differently, with the latter providing a means of overcoming dynamically preferred fragmentation by lowering the barrier for the recombination of the product fragments in the grip of the large catalyst active site cavity.

Cu(II) carboxylate arene C─H functionalization: Tuning for nonradical pathways.

We report carbon-hydrogen acetoxylation of nondirected arenes benzene and toluene, as well as related functionalization with pivalate and 2-ethylhexanoate ester groups, using simple copper(II) [Cu(II)] salts with over 80% yield. By changing the ratio of benzene and Cu(II) salts, 2.4% conversion of benzene can be reached. Combined experimental and computational studies results indicate that the arene carbon-hydrogen functionalization likely occurs by a nonradical Cu(II)-mediated organometallic pathway. The Cu(II) salts used in the reaction can be isolated, recycled, and reused with little change in reactivity. In addition, the Cu(II) salts can be regenerated in situ using oxygen and, after the removal of the generated water, the arene carbon-hydrogen acetoxylation and related esterification reactions can be continued, which leads to a process that enables recycling of Cu(II).

The influence of temperature environmental on performance of HNIW/FOX-7 based PBXs.

During application, energetic materials may suffer different temperature environmental stimulation. In order to study the influence of temperature environmental on performance of HNIW/FOX-7 based PBXs, HNIW/FOX-7 based PBX modeling powders and PBX columns were treated by LT (low temperature), HT (high temperature), HLC (high-low temperature cycle) and HLS (high-low temperature shock). Then scanning electron microscope (SEM), infrared spectra (IR), X-ray diffraction (XRD) and differential scanning calorimetry (DSC) were used to study the variation of PBX modeling powders after LT, HT, HLC and HLS treatments; in addition, the mass, size and mechanical properties of PBX columns were characterized after different temperature adaptability treatments as well. The results indicate that the change ratios of mass and size of HNIW/FOX-7 based PBX columns are less than 1%, illustrating that mass and size of PBX columns are at acceptable level after different temperature adaptability treatments. The unevenness degree of the surface of PBX modeling powders followed the order of HLC > HT > LT > HLS, which agrees well with mass loss order. Moreover, IR and XRD results indicated that the molecular structure and crystal form of HNIW and FOX-7 did not change after different temperature adaptability treatments. Additionally, thermal stabilities of PBX modeling powders are decreased after different temperature adaptability treatments, among which HLS has the largest influence on HNIW/FOX-based PBX modeling powders. The compression strengths and elastic moduli of HNIW/FOX-based PBX columns are enhanced after different temperature adaptability treatments, among which the strength of PBX columns after HLC has the maximum increase, indicating that HLC has more significant effect on mechanical property.

PD-L1 Expression and Intra-Tumoral CD8+ T Lymphocytes in Esophageal Carcinosarcoma.

We detected PD-L1 and intra-tumoral CD8+ T lymphocytes (CD8+ TIL) in 19 patients with esophageal carcinosarcoma (ECS). The median follow-up period of these patients was 43 months, and the three- and five-year survival rates were 78.9 and 63.2%, respectively. No statistically significant correlation was observed between PD-L1 and CD8+ TIL in sarcomatous components(SC) (r = -0.262, p = 0.279) and epithelial carcinomatous (EC) (r = 0.055, p = 0.824). This study examined the immunological markers in ECS for the first time. PD-L1 is highly expressed in the SC and is associated with a poorer prognosis.

Theory and Experiment Demonstrate that Sb(V)-Promoted Methane C-H Activation and Functionalization Outcompete Superacid Protonolysis in Sulfuric Acid.

Sb(V) in strong Brønsted acid solvents is traditionally assumed to react with light alkanes through superacid protonolysis, which results in carbocation intermediates, H2, and carbon oligomerization. In contrast to this general assumption, our density functional theory (DFT) calculations revealed an accessible barrier for C-H activation between methane and Sb(V) in sulfuric acid that could potentially outcompete superacid protonolysis. This prompted us to experimentally examine this reaction in sulfuric acid with oleum, which has never been reported because of presumed superacid reactivity. Reaction of methane at 180 °C for 3 h resulted in very high yields of methyl bisulfate without significant overoxidation. Our DFT calculations show that a C-H activation and Sb-Me bond functionalization mechanism to give methyl bisulfate outcompetes methane protonolysis and many other possible reaction mechanisms, such as electron transfer, proton-coupled electron transfer, and hydride abstraction. Our DFT calculations also explain experimental hydrogen-deuterium exchange studies and the absence of methane carbo-functionalization/oligomerization products. Overall, this work demonstrates that in very strong Brønsted acid solvent, Sb(V) can induce innersphere reaction mechanisms akin to transition metals and outcompete superacid reactivity.

Rapid Removal of Mercury from Water by Novel MOF/PP Hybrid Membrane.

Mercury is one of the most toxic heavy metals that can cause terrible disease for human beings. Among different absorption materials, MOF (metal-organic framework) materials show potential as very attractive materials for the rapid removal of mercury. However, the instability and difficulty for regeneration of MOF crystals limit their applications. Here, a continuous sulfur-modified MOF (UiO-66-NHC(S)NHMe) layer was synthesized in situ on polymeric membranes (PP non-woven fabrics) by post-synthetic modification and used for rapid mercury removal. The MOF-based membrane (US-N) showed high selectivity for mercury in different aqueous systems, which is better than sulfur-modified MOF powders. A thinner MOF layer on US-N showed a much better mercury ion removal performance. US-N with a 59.3 nm MOF layer could remove more than 85% of mercury in 20 min from an aqueous solution. In addition, the US-N can simply regenerate several times for mercury removal and maintain the initial performance (removal ratio > 98%), exhibiting excellent durability and stability. This work promotes the application of MOF materials in the rapid removal of hazardous heavy metal ions from practical environments.

Esophageal Carcinosarcoma: Analysis of Clinical Features and Prognosis of 24 Cases and a Literature Review.

OBJECTIVE: Esophageal carcinosarcoma (ECS) is a rare malignant tumor that accounts for only 0.5%-2.8% of all esophageal malignancies. As most current studies are case reports, the relationship between clinical features and prognosis remains controversial. METHODS: We investigated the clinical features and prognosis of 24 patients with ECS in a single center from 2006 to 2018. There were 18 male and 6 female patients aged 52-82 years with a median age of 62.5 years. In addition, we included 9 studies on ECS from PubMed and a literature review. RESULTS: The median follow-up time of the 24 patients was 70.5 (range, 10-156)months. The 3-year and 5-year survival rates were 83.3% and 70.8%, respectively. Among the 24 patients, none of the 10 (41.7%) stage T1 cancer patients had lymph node metastasis; however, lymph node metastasis was noted in 8 (57.1%) stage T2-4 cancer patients. The literature review revealed that 211 patients had a 5-year survival rate of 11.8%-68.2%, and 54.5%-95.8% study participants had early stage ECS. Although the information provided in the literature review is limited, it appears to be a characteristic of the early stage of the disease and predicts better prognosis when ECS is diagnosed, which is similar to the result of the current study. CONCLUSION: Our results indicate that ECS has a favorable prognosis, even among patients with early stage ECS who undergo radical esophagectomy with lymph node dissection. Because of the low incidence of ECS, further studies with more cases need to investigate this rare malignancy.

Clinicopathological characteristics and survival outcomes in neuroendocrine prostate cancer: A population-based study.

OBJECTIVE: This study aimed to investigate the clinicopathological features and the survival outcomes of neuroendocrine prostate cancer (NEPC). METHODS: Within the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute, we identified a total of 510 patients with NEPC between 2006 and 2015. Age-adjusted incidence rates were evaluated in the study by the SEER∗Stat Software version 8.3.6. Kaplan-Meier analysed assessed overall survival (OS) after stratification according to marital status, age, histologic subtype, metastatic status, and treatment. The significant differences were assessed in a log-rank test. Univariate and multivariate cox hazard regression analysis were performed to determine independent predictors of OS. RESULTS: From a total of 560,124 patients with prostate cancer diagnosed between 2006 and 2015, we identified 510 cases of de novo NEPC. Regarding histology, among all the NEPC, 329 (64.5%) patients were diagnosed as small cell carcinoma, 181 (39.8%) were nonsmall cell carcinoma. The overall age-adjusted incidence of NEPC statistically significantly increased from 0.321/1,000,000 person-years in 2006 to 0.587/1,000,000 person-years in 2015. The median OS in our study cohort was 9 months (95% CI, 8-10 months). Multivariate cox regression analysis showed that age, histologic subtype, and stage were independent prognostic factors for NEPC patients. The majority of NEPC (78.2%) were metastatic at diagnosis. In terms of treatment, for metastatic tumor patients, chemotherapy was the most effective therapy. Chemotherapy increased the OS of patients with regional (distant) metastases from 8 months (5 months) to 13.5 months (9 months). CONCLUSION: NEPC is extremely rare but the incidence of NEPC has been increasing in the past years. The prognosis of NEPC is poor because most cases are diagnosed at metastatic stage. The patients with metastases are typically treated with chemotherapy and chemotherapy shows survival benefits in both regional and distant metastatic tumor patients.

Chiral-Anion-Mediated Asymmetric Heck-Matsuda Reaction of Acyclic Alkenyl Alcohols.

Acyclic internal alkenes are a class of challenging substrates in asymmetric Heck-type reactions due to difficulties related to both reactivity and selectivity control. Employing acyclic alkenyl alcohols, an asymmetric Heck-Matsuda reaction is developed through the strategy of chiral anion phase transfer. Various chiral ketones could be obtained in high levels of enantioselectivity. A catalytic amount of dimethyl sulfoxide (DMSO) as an additive is crucial for the reaction to suppress the palladium-hydride-mediated side reactions.

Effects of electrostatic drag on the velocity of hydrogen migration - pre- and post-transition state enthalpy/entropy compensation.

Ab initio molecular dynamics calculations were used to explore the underlying factors that modulate the velocity of hydrogen migration for 1,2 hydrogen shifts in carbocations in which different groups interact noncovalently with the migrating hydrogen. Our results indicate that stronger electrostatic interactions between the migrating hydrogen and nearby π-systems lead to slower hydrogen migration, an effect tied to entropic contributions from the hydrogen + neighboring group substructures.

Potential for Ladderane (Bio)synthesis from Oligo-Cyclopropane Precursors.

Quantum chemical calculations were used to determine the energetic viability of several mechanisms for formation of ladderanes from oligocyclopropanes. Pathways involving radical cations, diradicals, and carbocations were considered, and a hybrid of carbocation and radical cation pathways was predicted to have the lowest overall barrier.