Weak Interaction Activates Esters: Reconciling Catalytic Activity and Turnover Contradiction by Tailored Chalcogen Bonding.

The activation of esters by strong Lewis acids via the formation of covalent adducts is a classic strategy to give reactivity; however, this approach frequently incurs limited turnover due to the low efficiency in the dissociation of catalyst from a stable catalyst-product complex. While the use of some weak interaction catalysts that can easily dissociate from any bonding complexes in the reaction system would solve this catalyst turnover problem, the poor catalytic activity in the ester activation that can be provided by these noncovalent forces in turn sets up a formidable challenge. Herein, we describe the activation and catalytic transformation of esters by weak interactions, which provides a promising platform to reconcile the catalytic activity and turnover problems. Several tailored chalcogen-bonding catalysts were developed for the activation of esters, enabling achieving several inherently low reactive Diels-Alder reactions as well as the ring-opening polymerization of lactones through weak chalcogen bonding interactions. This supramolecular catalysis approach is particularly highlighted by its capability to promote some uncommon Diels-Alder reactions involving using dienes bearing electron-withdrawing groups coupled by α,ß-unsaturated ester as dienophiles and substrate incorporating competitive Lewis basic sites, in which typical strong Lewis acids showed low catalytic efficiency, while representative hydrogen and halogen bonding catalysts were inactive.

Nonplanar Rhombus and Kagome 2D Covalent Organic Frameworks from Distorted Aromatics for Electrical Conduction.

Two-dimensional (2D) covalent organic frameworks (COFs) are an emerging class of promising 2D materials with high crystallinity and tunable structures. However, the low electrical conductivity impedes their applications in electronics and optoelectronics. Integrating large π-conjugated building blocks into 2D lattices to enhance efficient π-stacking and chemical doping is an effective way to improve the conductivity of 2D COFs. Herein, two nonplanar 2D COFs with kagome (DHP-COF) and rhombus (c-HBC-COF) lattices have been designed and synthesized from distorted aromatics with different π-conjugated structures (flexible and rigid structure, respectively). DHP-COF shows a highly distorted 2D lattice that hampers stacking, consequently limiting its charge carrier transport properties. Conversely, c-HBC-COF, with distorted although concave-convex self-complementary nodes, shows a less distorted 2D lattice that does not interfere with interlayer π-stacking. Employing time- and frequency-resolved terahertz spectroscopy, we unveil a high charge-carrier mobility up to 44 cm2 V-1 s-1, among the highest reported for 2D COFs.

Enhancing the light extraction efficiency for AlGaN-based DUV LEDs with a laterally over-etched p-GaN layer at the top of truncated cones.

It is known that light extraction efficiency (LEE) for AlGaN-based deep ultraviolet light-emitting didoes (DUV LEDs) can be enhanced by using truncated cone arrays with inclined sidewalls. In this work, the air-cavity-shaped inclined sidewall is applied and the p-GaN layer at the top of the truncated cone is laterally over-etched so that more light escape paths are generated for AlGaN-based DUV LEDs. The experimental results manifest that when compared with DUV LEDs only having the air-cavity-shaped inclined sidewall, the optical power for the DUV LEDs with laterally over-etched p-GaN at the top of the truncated cone is enhanced by 30% without sacrificing the forward bias. It is because the over-etched p-GaN makes little effect on the carrier injection and does not affect the ohmic contact resistance. Moreover, the simulation results show that the truncated cone with laterally over-etched p-GaN layer can enhance the LEE because the reduced p-GaN area can suppress the optical absorption and supplies additional light paths for DUV photos. Then, more light will be reflected into escape cones at the sapphire side.

Donor-Acceptor Type Covalent Organic Frameworks.

Intermolecular charge transfer (ICT) effect has been widely studied in both small molecules and linear polymers. Covalently-bonded donor-acceptor pairs with tunable bandgaps and photoelectric properties endow these materials with potential applications in optoelectronics, fluorescent bioimaging, and sensors, etc. However, owing to the lack of charge transfer pathway or effective separation of charge carriers, unfavorable charge recombination gives rise to inevitable energy loss. Covalent organic frameworks (COFs) can be mediated with various geometry- and property-tailored building blocks, where donor (D) and acceptor (A) segments are connected by covalent bonds and can be finely arranged to form highly ordered networks (namely D-A COFs). The unique structural features of D-A COFs render the formation of segregated D-A stacks, thus provides pathways and channels for effective charge carriers transport. This review highlights the significant progress on D-A COFs over the past decade with emphasis on design principles, growing structural diversities, and promising application potentials.

Effect of Sacubitril/Valsartan vs Standard Medical Therapies on Plasma NT-proBNP Concentration and Submaximal Exercise Capacity in Patients With Heart Failure and Preserved Ejection Fraction: The PARALLAX Randomized Clinical Trial.

Importance: There is limited evidence on the benefits of sacubitril/valsartan vs broader renin angiotensin system inhibitor background therapy on surrogate outcome markers, 6-minute walk distance, and quality of life in patients with heart failure and mildly reduced or preserved left ventricular ejection fraction (LVEF >40%). Objective: To evaluate the effect of sacubitril/valsartan on N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, 6-minute walk distance, and quality of life vs background medication-based individualized comparators in patients with chronic heart failure and LVEF of more than 40%. Design, Setting, and Participants: A 24-week, randomized, double-blind, parallel group clinical trial (August 2017-October 2019). Of 4632 patients screened at 396 centers in 32 countries, 2572 patients with heart failure, LVEF of more than 40%, elevated NT-proBNP levels, structural heart disease, and reduced quality of life were enrolled (last follow-up, October 28, 2019). Interventions: Patients were randomized 1:1 either to sacubitril/valsartan (n = 1286) or to background medication-based individualized comparator (n = 1286), ie, enalapril, valsartan, or placebo stratified by prior use of a renin angiotensin system inhibitor. Main Outcomes and Measures: Primary end points were change from baseline in plasma NT-proBNP level at week 12 and in the 6-minute walk distance at week 24. Secondary end points were change from baseline in quality of life measures and New York Heart Association (NYHA) class at 24 weeks. Results: Among 2572 randomized patients (mean age, 72.6 years [SD, 8.5 years]; 1301 women [50.7%]), 2240 (87.1%) completed the trial. At baseline, the median NT-proBNP levels were 786 pg/mL in the sacubitril/valsartan group and 760 pg/mL in the comparator group. After 12 weeks, patients in the sacubitril/valsartan group (adjusted geometric mean ratio to baseline, 0.82 pg/mL) had a significantly greater reduction in NT-proBNP levels than did those in the comparator group (adjusted geometric mean ratio to baseline, 0.98 pg/mL) with an adjusted geometric mean ratio of 0.84 (95% CI, 0.80 to 0.88; P < .001). At week 24, there was no significant between-group difference in median change from baseline in the 6-minute walk distance with an increase of 9.7 m vs 12.2 m (adjusted mean difference, -2.5 m; 95% CI, -8.5 to 3.5; P = .42). There was no significant between-group difference in the mean change in the Kansas City Cardiomyopathy Questionnaire clinical summary score (12.3 vs 11.8; mean difference, 0.52; 95% CI, -0.93 to 1.97) or improvement in NYHA class (23.6% vs 24.0% of patients; adjusted odds ratio, 0.98; 95% CI, 0.81 to 1.18). The most frequent adverse events in the sacubitril/valsartan group vs the comparator group were hypotension (14.1% vs 5.5%), albuminuria (12.3% vs 7.6%), and hyperkalemia (11.6% vs 10.9%). Conclusions and Relevance: Among patients with heart failure and left ventricular ejection factor of higher than 40%, sacubitril/valsartan treatment compared with standard renin angiotensin system inhibitor treatment or placebo resulted in a significantly greater decrease in plasma N-terminal pro-brain natriuretic peptide levels at 12 weeks but did not significantly improve 6-minute walk distance at 24 weeks. Further research is warranted to evaluate potential clinical benefits of sacubitril/valsartan in these patients. Trial Registration: ClinicalTrials.gov Identifier: NCT03066804.

Polymorphism of 2D Imine Covalent Organic Frameworks.

We designed and synthesized A2 B2 type tetraphenyl benzene monomers (p-, m-, and o-TetPB) which have the para-, meta, and ortho-substituted isomeric structures, for the direct construction of isomeric frameworks. Interestingly, both kagome (kgm) and monoclinic square (sql) framework isomers are produced from either p-TetPB (C2h symmetry) or m-TetPB (C2v symmetry) by changing reaction solvents, while their isomeric structures are characterized by X-ray diffraction, computational simulation, microscopy, and sorption isotherm measurements. Only sql frameworks was formed for o-TetPB (C2v symmetry), irrespective of reaction solvents. These results disclose a unique feature in the framework structural formation, that is, the geometry of monomers directs and dominates the lattice growth process while the solvent plays a role in the perturbation of chain growth pattern. The isomeric frameworks exhibit highly selective adsorption of vitamin B12 owing to pore shape and size differences.

Docking Site Modulation of Isostructural Covalent Organic Frameworks for CO2 Fixation.

Three isostructural covalent organic frameworks (COFs) with either methoxyl, hydroxyl, or both groups on the channel wall, are synthesized and served as metal-free heterogeneous catalysts for chemical fixation of CO2 . Among them, the COF decorated with both hydroxyl and methoxyl groups named OMe-OH-TPBP-COF exhibits the highest catalytic activity and efficiency for CO2 cycloaddition under mild conditions.

Asymmetric synthesis of dihydrocoumarins via catalytic sequential 1,6-addition/transesterification of α-isocyanoacetates with para-quinone methides.

A catalytic asymmetric synthesis of 3,4-dihydrocoumarins with adjacent tertiary-quaternary stereocenters by 1,6-addition/transesterification cascade reaction of α-isocyanoacetates with ortho-hydroxyphenyl-substituted para-quinone methides (p-QMs) has been developed. Using a combination of dihydroquinidine-derived aminophosphine and silver nitrate as a binary catalytic system, moderate to good yields, excellent diastereoselectivities (>20 : 1 dr) and good to excellent enantioselectivities (up to 94% ee) were achieved for a wide range of isocyanoacetates and p-QMs.

Cinchona Alkaloid Squaramide-Catalyzed Asymmetric Ugi-Type Reaction of Isocyanoacetates with C,N-Cyclic Azomethine Imines: Access to Chiral Oxazole-Substituted Tetrahydroisoquinolines.

We reported herein an unexpected cinchona alkaloid-derived squaramide-catalyzed asymmetric two-component Ugi-type reaction of α-aryl-substituted isocyanoacetates with C,N-cyclic azomethine imines, which provides concise access to optically active C1-oxazole-substituted tetrahydroisoquinolines in good yields (86-93%) and high enantioselectivities (up to 98% enantiomeric excess) under mild conditions.

Deep Tumor Penetrating Bioparticulates Inspired Burst Intracellular Drug Release for Precision Chemo-Phototherapy.

The relevance of personalized medicine has inspired research for individually concerted diagnosis and therapy. Numerous efforts are devoted to designing drug particulates with capabilities of tumor penetrating and subcellular trafficking to concurrently discharge theranostics in response to multistimulations. In this study, a bioinspired particulate, formulated with whole components of native high-density lipoproteins (HDLs) and decorated with the tumor-penetrating peptide iRGD, is proposed to promote tumor penetration of HDLs (pHDLs) together with payloads. Specifically, paclitaxel (PTX), and the NIR fluorescent probe indocyanine green (ICG) are integrated into pHDLs (pHDL/PTX-ICG) for synergetic chemo-phototherapy. Inspired by lipoproteins, pHDLs are not only restored from naturally occurring materials but also possessed artificially endowed functions, leading to an enhanced cellular uptake, higher accumulation, and deep penetration into tumors without causing appreciable adverse effects, compared to reconstituted HDLs or lipid-based nanoparticles. After intravenous administration, pHDL/PTX-ICG performs a burst of intracellular drug release and imaging-guided precision chemo-phototherapy upon NIR irradiation that completely eradicates xenograft tumors. Neither recurrence nor significant toxicity is observed due to maneuvered regional photodynamic and photothermal therapy. Taken together, pHDL/PTX-ICG is proven to be a promising platform to achieve deep tumor penetration and imaging-guided chemo-phototherapy.

Mid-infrared high-Q germanium microring resonator.

Germanium is a promising material for mid-infrared (MIR) integrated photonics due to its CMOS compatibility and wide transparency window covering the fingerprint spectral region (2-15 µm). However, due to the limited quality and structural configurations of conventional germanium-based integration platforms, the realization of high-Q on-chip germanium resonators in the MIR spectral range remains challenging to date. Here we experimentally demonstrate an air-cladding MIR germanium microring resonator with, to the best of our knowledge, the highest loaded Q-factor of ∼57,000 across all germanium-based integration platforms to date. A propagation loss of 5.4 dB/cm and a high extinction ratio of 22 dB approaching the critical coupling condition are experimentally realized. These are enabled by our smart-cut methods for developing high-quality germanium-on-insulator wafers and by implementing our suspended-membrane structure. Our high-Q germanium microring resonator is a promising step towards a number of on-chip applications in the MIR spectral range.

A 3D Organically Synthesized Porous Carbon Material for Lithium-Ion Batteries.

We report the first organically synthesized sp-sp3 hybridized porous carbon, OSPC-1. This new carbon shows electron conductivity, high porosity, the highest uptake of lithium ions of any carbon material to-date, and the ability to inhibit dangerous lithium dendrite formation. The new carbon exhibits exceptional potential as anode material for lithium-ion batteries (LIBs) with high capacity, excellent rate capability, long cycle life, and potential for improved safety performance.

Design for the sacubitril/valsartan (LCZ696) compared with enalapril study of pediatric patients with heart failure due to systemic left ventricle systolic dysfunction (PANORAMA-HF study).

BACKGROUND: Sacubitril/valsartan (LCZ696) is an angiotensin receptor neprilysin inhibitor approved for the treatment of adult heart failure (HF); however, the benefit of sacubitril/valsartan in pediatric HF patients is unknown. STUDY DESIGN: This global multi-center study will use an adaptive, seamless two-part design. Part 1 will assess the pharmacokinetics/pharmacodynamics of single ascending doses of sacubitril/valsartan in pediatric (1 month to <18 years) HF patients with systemic left ventricle and reduced left ventricular systolic function stratified into 3 age groups (Group 1: 6 to <18 years; Group 2: 1 to <6 years; Group 3: 1 month to <1 year). Part 2 is a 52-week, efficacy and safety study where 360 eligible patients will be randomized to sacubitril/valsartan or enalapril. A novel global rank primary endpoint derived by ranking patients (worst-to-best outcome) based on clinical events such as death, initiation of mechanical life support, listing for urgent heart transplant, worsening HF, measures of functional capacity (NYHA/Ross scores), and patient-reported HF symptoms will be used to assess efficacy. CONCLUSION: The PANORAMA-HF study, which will be the largest prospective pediatric HF trial conducted to date and the first to use a global rank primary endpoint, will determine whether sacubitril/valsartan is superior to enalapril for treatment of pediatric HF patients with reduced systemic left ventricular systolic function.

Mid-infrared germanium photonic crystal cavity.

The mid-infrared (MIR) spectral range holds significant potential for spectroscopic and sensing applications because it encompasses the fingerprint region that unveils the vibrational and rotational signatures of molecules. CMOS-compatible on-chip devices that can achieve strong light-matter interaction in the entire fingerprint region are considered a promising way for such applications, but remain unprecedented. Here we present an on-chip MIR germanium photonic crystal cavity that covers the entire fingerprint region. This is made possible by harnessing a homemade air-cladding germanium platform. Our MIR device creates a new avenue toward integrated nonlinear optics and on-chip biochemical sensing in the fingerprint region.

Natural Particulates Inspired Specific-Targeted Codelivery of siRNA and Paclitaxel for Collaborative Antitumor Therapy.

The effective combination of drugs promoting antiangiogenesis and apoptosis effects has proven to be a promising collaborative tumor antidote; and the codelivery of small interfering RNA (siRNA) and chemotherapy agents within one efficient vehicle has gained more attention over single regimen administration. Herein, vascular endothelial growth factor specific siRNA (siVEGF) and paclitaxel (PTX) were introduced as therapeutic companions and coencapsulated into naturally mimic high-density lipoproteins (rHDL/siVEGF-PTX), so that various mechanisms of treatment can occur simultaneously. The terminal nanoparticles share capacity of specific-targeting to tumor cells overexpressed scavenger receptor class B type I (SR-BI) and deliver siVEGF and PTX into cytoplasm by a nonendocytosis mechanism. By exchanging HDL core lipids with hydrophobic therapeutics, rHDL/siVEGF-PTX possessed particle size of ∼160 nm, surface potential of ∼-20 mV, and desirable long-term storage stability. In vitro results confirmed that the parallel activity of siVEGF and PTX displayed enhanced anticancer efficacy. The half-maximal inhibitory concentration (IC50) of rHDL/siVEGF-PTX toward human breast cancer MCF-7 cell is 0.26 µg/mL (PTX concentration), which presents a 14.96-fold increase in cytotoxicity by taking Taxol as comparison. Moreover, in vivo results further demonstrated that rHDL/siVEGF-PTX performed enhanced tumor growth inhibition via natural targeting pathway, accompanied by remarkable inhibition of neovascularization in situ caused by siVEGF silencing in down-regulation of VEGF proteins. On the premise of effective drug codelivery, rHDL/siVEGF-PTX demonstrated high tumor targeting for collaborative antitumor efficacy without side effects after systemic administration, and this bioinspired strategy could open an avenue for exploration of combined anticancer therapy.

Fabrication and Thermophysical Properties of La(2-x)Zr(2-y)O7 Nanocrystal by a Sol-Gel Method.

Non-Stoichiometric La2Zr2O7 (La(2-x)Zr(2-y)O7) Nanocrystal was synthesized by a simple sol-gel method. The crystalline structure, oxygen vacancy concentration, thermal expansion coefficient, as well as the fracture toughness of as-prepared materials were charactered by XRD, TG-DSC, PL spectra, dilatometer, and electronic universal testing machine respectively. The crystal structure of La2Zr2O7 is of the cubic type while lattice parameter increases with the deviatation of Zr4+ and La3+ from Stoichiometric La2Zr2O7 increasing. The average linear thermal expansion coefficient of non-stoichiometric La2Zr2O7 is obviously bigger than that of La2Zr2O7 in the temperature range between 150 degrees C and 950 degrees C. The fracture toughness of La(2-x)Zr(2-y)O7 increases with x and y increasing up to x = 0.3 and y = 0.25.

Estimating the survival function based on the semi-Markov model for dependent censoring.

In this paper, we study a nonparametric maximum likelihood estimator (NPMLE) of the survival function based on a semi-Markov model under dependent censoring. We show that the NPMLE is asymptotically normal and achieves asymptotic nonparametric efficiency. We also provide a uniformly consistent estimator of the corresponding asymptotic covariance function based on an information operator. The finite-sample performance of the proposed NPMLE is examined with simulation studies, which show that the NPMLE has smaller mean squared error than the existing estimators and its corresponding pointwise confidence intervals have reasonable coverages. A real example is also presented.

Characterization of Chromium Waste Form Based on Biocementation by Microbacterium sp. GM-1.

This paper demonstrated a biocementation technology for chromium slag by strain GM-1, a calcifying ureolytic bacterium identified as Microbacterium, based on microbially induced calcium carbonate. The characterization of Microbacterium sp. GM-1 was assessed to know the growth curve in different concentrations of Cr(VI). Microbacterium sp. GM-1 was tolerant to a concentration of 120 mg/L Cr(VI). Chromium waste forms were prepared using chromium, sand, soil and bacterial culture. There we had three quality ratios (8:2:1; 8:1:1; 8:2:0.5) of material (chromium, sand and soil, respectively). Bacterial and control chromium waste forms were analyzed by thermal gravimetric analyzer. All bacterial forms (8:2:1; 8:1:1; 8:2:0.5 J) showed sharp weight loss near the decomposition temperature of calcium carbonate between 600 and 700 °C. It indicated that the efficient bacterial strain GM-1 had induced calcium carbonate precipitate during bioremediation process. A five step Cr(VI) sequential extraction was performed to evaluate its distribution pattern in chromium waste forms. The percentage of Cr(VI) was found to significantly be decreased in the exchangeable fraction of chromium waste forms and subsequently, that was markedly increased in carbonated fraction after biocementation by GM-1. Further, compressive strength test and leaching test were carried out. The results showed that chromium waste forms after biocementation had higher compressive strength and lower leaching toxicity. Additionally, the samples made of 8:1:1 (m/m/m) chromium + sand + soil were found to develop the highest compressive strength and stand the lowest concentration of Cr(VI) released into the environment.

Multi-source information fusion-driven corn yield prediction using the Random Forest from the perspective of Agricultural and Forestry Economic Management.

The objective of this study is to promptly and accurately allocate resources, scientifically guide grain distribution, and enhance the precision of crop yield prediction (CYP), particularly for corn, along with ensuring application stability. The digital camera is selected to capture the digital image of a 60 m × 10 m experimental cornfield. Subsequently, the obtained data on corn yield and statistical growth serve as inputs for the multi-source information fusion (MSIF). The study proposes an MSIF-based CYP Random Forest model by amalgamating the fluctuating corn yield dataset. In relation to the spatial variability of the experimental cornfield, the fitting degree and prediction ability of the proposed MSIF-based CYP Random Forest are analyzed, with statistics collected from 1-hectare, 10-hectare, 20-hectare, 30-hectare, and 50-hectare experimental cornfields. Results indicate that the proposed MSIF-based CYP Random Forest model outperforms control models such as support vector machine (SVM) and Long Short-Term Memory (LSTM), achieving the highest prediction accuracy of 89.30%, surpassing SVM and LSTM by approximately 13.44%. Meanwhile, as the experimental field size increases, the proposed model demonstrates higher prediction accuracy, reaching a maximum of 98.71%. This study is anticipated to offer early warnings of potential factors affecting crop yields and to further advocate for the adoption of MSIF-based CYP. These findings hold significant research implications for personnel involved in Agricultural and Forestry Economic Management within the context of developing agricultural economy.

Supramolecular catalysis with ethers enabled by dual chalcogen bonding activation.

The activation of ethers by weak interactions is a long-standing objective in supramolecular catalysis, but yet it remains an underdeveloped topic. The obstacles towards solving this problem are prominent since it is difficult for a weak interaction to cleave a relatively strong C-O σ-bond and moreover, the ionic intermediate composing of an alkoxide ion and an electrophilic carbocation would deactivate weak interaction donors. Herein, we describe a distinctive activation mode, dual Se···π and Se···O bonding, that could activate benzylic as well as allylic ether C-O σ-bonds to achieve cyclization, coupling and elimination reactions. This dual Se···π and Se···O bonding catalysis approach could tolerate various alkoxide leaving groups, while the other representative weak interaction donors showed no catalytic activity.