Catalytic Asymmetric Synthesis of Sulfinamides via Cu-Catalyzed Asymmetric Addition of Aryl Boroxines to Sulfinylamines.

The application of sulfinamides has been witnessed in medicinal and agrochemistry with employment in asymmetric transformations. However, methods for their asymmetric catalytic synthesis have rarely been explored. Herein, the catalytic enantioselective addition of aryl boroxines to sulfinylamines via Cu catalyst and the newly developed Xuphos ligand were reported. A series of chiral aryl sulfinamides can be readily accessed in one step. This protocol enables the stereospecific transformation of sulfinamides to sulfonimidoyl fluorides, sulfonimidamides, and sulfonimidate esters. DFT calculations have revealed the reaction pathway, and the migratory insertion is the enantio-determining step. The noncovalent interaction between the oxygen atom of sulfinylamines and the C-H bonds in the ligand is crucial for enantioselectivity control.

A 5-hydroxymethylcytosine-based non-invasive model for early detection of colorectal carcinomas and advanced adenomas: the METHOD-2 study.

PURPOSE: Detection of colorectal carcinomas (CRC) at a time when there are more treatment options is associated with better outcomes. This prospective case-control study assessed the 5-hydroxymethylcytosine (5hmC) biomarkers in circulating cell-free DNA (cfDNA) for early detection of CRC and advanced adenomas (AA) Experimental Design: Plasma cfDNA samples from 2,576 study participants from the multi-center METHOD-2 study (NCT03676075) were collected, comprising patients with newly diagnosed CRC (n=1,074), AA (n=356), other solid tumors (n=80), and non-CRC/AA controls (n=1,066), followed by genome-wide 5hmC profiling using the 5hmC-Seal technique and the next-generation sequencing (NGS). A weighted diagnostic model for CRC (stage I-III) and AA was developed using the elastic net regularization in a discovery set and validated in independent samples. RESULTS: Distribution of 5hmC in cfDNA reflected gene regulatory relevance and tissue of origin. Besides being confirmed in internal validation, a 96-gene model achieved an area under the curve (AUC) of 90.7% for distinguishing stage I-III CRC from controls in 321 samples from multiple centers for external validation, regardless of primary location or mutation status. This model also showed cancer-type specificity as well as high capacity for distinguishing AA from controls with an AUC of 78.6%. Functionally, differential 5hmC features associated with CRC and AA demonstrated relevance to CRC biology, including pathways such as calcium and MAPK signaling. CONCLUSIONS: Genome-wide mapping of 5hmC in cfDNA shows the promise as a highly sensitive and specific non-invasive blood test to be integrated in screening programs for improving early detection of CRC and high-risk AA.

Water and Air Stable Copper(I) Complexes of Tetracationic Catenane Ligands for Oxidative C-C Cross-Coupling.

Aqueous soluble and stable Cu(I) molecular catalysts featuring a catenane ligand composed of two dicationic, mutually repelling but mechanically interlocked macrocycles are reported. The ligand interlocking not only fine-tunes the coordination sphere and kinetically stabilizes the Cu(I) against air oxidation and disproportionation, but also buries the hydrophobic portions of the ligands and prevents their dissociation which are necessary for their good water solubility and a sustained activity. These catenane Cu(I) complexes can catalyze the oxidative C-C coupling of indoles and tetrahydroisoquinolines in water, using H2O2 as a green oxidant with a good substrate scope. The successful use of catenane ligands in exploiting aqueous Cu(I) catalysis thus highlights the many unexplored potential of mechanical bond as a design element for exploring transition metal catalysis under challenging conditions.

Dynamic mechanostereochemical switching of a co-conformationally flexible [2]catenane controlled by specific ionic guests.

Responsive synthetic receptors for adaptive recognition of different ionic guests in a competitive environment are valuable molecular tools for not only ion sensing and transport, but also the development of ion-responsive smart materials and related technologies. By virtue of the mechanical chelation and ability to undergo large-amplitude co-conformational changes, described herein is the discovery of a chameleon-like [2]catenane that selectively binds copper(I) or sulfate ions and its associated co-conformational mechanostereochemical switching. This work highlights not only the advantages and versatility of catenane as a molecular skeleton in receptor design, but also its potential in constructing complex responsive systems with multiple inputs and outputs.

A Highly Sensitive and Specific Non-Invasive Test through Genome-Wide 5-Hydroxymethylation Mapping for Early Detection of Lung Cancer.

Low-dose computed tomography screening can increase the detection for non-small-cell lung cancer (NSCLC). To improve the diagnostic accuracy of early-stage NSCLC detection, ultrasensitive methods are used to detect cell-free DNA (cfDNA) 5-hydroxymethylcytosine (5hmC) in plasma. Genome-wide 5hmC is profiled in 1990 cfDNA samples collected from patients with non-small cell lung cancer (NSCLC, n = 727), healthy controls (HEA, n = 1,092), as well as patients with small cell lung cancer (SCLC, n = 41), followed by sample randomization, differential analysis, feature selection, and modeling using a machine learning approach. Differentially modified features reflecting tissue origin. A weighted diagnostic model comprised of 105 features is developed to compute a detection score for each individual, which showed an area under the curve (AUC) range of 86.4%-93.1% in the internal and external validation sets for distinguishing lung cancer from HEA controls, significantly outperforming serum biomarkers (p < 0.001). The 5hmC-based model detected high-risk pulmonary nodules (AUC: 82%)and lung cancer of different subtypes with high accuracy as well. A highly sensitive and specific blood-based test is developed for detecting lung cancer. The 5hmC biomarkers in cfDNA offer a promising blood-based test for lung cancer.

PETCH-DB: a Portal for Exploring Tissue-specific and Complex disease-associated 5-Hydroxymethylcytosines.

Epigenetic modifications play critical roles in gene regulation and disease pathobiology. Highly sensitive enabling technologies, including microarray- and sequencing-based approaches have allowed genome-wide profiling of cytosine modifications in DNAs in clinical samples to facilitate discovery of epigenetic biomarkers for disease diagnosis and prognosis. Historically, many previous studies, however, did not distinguish the most investigated 5-methylcytosines (5mC) from other modified cytosines, especially the biochemically stable 5-hydroxymethylcytosines (5hmC), which have been shown to have a distinct genomic distribution and regulatory role from 5mC. Notably, during the past several years, the 5hmC-Seal, a highly sensitive chemical labeling technique, has been demonstrated to be a powerful tool for genome-wide profiling of 5hmC in clinically feasible biospecimens (e.g. a few milliliter of plasma or serum). The 5hmC-Seal technique has been utilized by our team in biomarker discovery for human cancers and other complex diseases using circulating cell-free DNA (cfDNA), as well as the characterization of the first 5hmC Human Tissue Map. Convenient access to the accumulating 5hmC-Seal data will allow the research community to validate and re-use these results, potentially providing novel insights into epigenetic contribution to a range of human diseases. Here we introduce the PETCH-DB, an integrated database that was implemented to provide 5hmC-related results generated using the 5hmC-Seal technique. We aim the PETCH-DB to be a central portal, which will be available to the scientific community with regularly updated 5hmC data in clinical samples to reflect current advances in this field. Database URL http://petch-db.org/.

PETCH-DB: a Portal for Exploring Tissue-specific and Complex disease-associated 5-Hydroxymethylcytosines.

Epigenetic modifications play critical roles in gene regulation and disease pathobiology. Highly sensitive enabling technologies, including microarray- and sequencing-based approaches have allowed genome-wide profiling of cytosine modifications in DNAs in clinical samples to facilitate discovery of epigenetic biomarkers for disease diagnosis and prognosis. Historically, many previous studies, however, did not distinguish the most investigated 5-methylcytosines (5mC) from other modified cytosines, especially the biochemically stable 5-hydroxymethylcytosines (5hmC), which have been shown to have a distinct genomic distribution and regulatory role from 5mC. Notably, during the past several years, the 5hmC-Seal, a highly sensitive chemical labeling technique, has been demonstrated to be a powerful tool for genome-wide profiling of 5hmC in clinically feasible biospecimens (e.g. a few milliliter of plasma or serum). The 5hmC-Seal technique has been utilized by our team in biomarker discovery for human cancers and other complex diseases using circulating cell-free DNA (cfDNA), as well as the characterization of the first 5hmC Human Tissue Map. Convenient access to the accumulating 5hmC-Seal data will allow the research community to validate and re-use these results, potentially providing novel insights into epigenetic contribution to a range of human diseases. Here we introduce the PETCH-DB, an integrated database that was implemented to provide 5hmC-related results generated using the 5hmC-Seal technique. We aim the PETCH-DB to be a central portal, which will be available to the scientific community with regularly updated 5hmC data in clinical samples to reflect current advances in this field. Database URL http://petch-db.org/.

Fast and High-Performance Self-Powered Photodetector Based on the ZnO/Metal-Organic Framework Heterojunction.

Electrical conductive metal-organic frameworks (EC-MOFs) are emerging as an appealing class of highly tailorable electrically conducting materials with potential applications in optoelectronics. Here, we in situ grew nickel hexahydroxytriphenylene (Ni-CAT) on the surface of ZnO nanorods (NRs). The self-powered photodetectors (PDs) were fabricated with heterojunctions formed at the interface of ZnO NRs and Ni-CAT. With this, the built-in electric field (BEF) can effectively separate the photogenerated electron-hole pairs and enhance the photoresponse. We observe that the PDs based on hybrid ZnO/Ni-CAT with 3 h of growth time (ZnO/Ni-CAT-3) show good photoresponse (137 µA/W) with the fast rise (3 ms) and decay time (50 ms) under 450 nm light illumination without biased voltage. This work provides a facile and controllable method for the growth of the ZnO/Ni-CAT heterojunction with an effective BEF zone, which will benefit their optoelectronic applications.

Water Electrolysis toward Elevated Temperature: Advances, Challenges and Frontiers.

Since severe global warming and related climate issues have been caused by the extensive utilization of fossil fuels, the vigorous development of renewable resources is needed, and transformation into stable chemical energy is required to overcome the detriment of their fluctuations as energy sources. As an environmentally friendly and efficient energy carrier, hydrogen can be employed in various industries and produced directly by renewable energy (called green hydrogen). Nevertheless, large-scale green hydrogen production by water electrolysis is prohibited by its uncompetitive cost caused by a high specific energy demand and electricity expenses, which can be overcome by enhancing the corresponding thermodynamics and kinetics at elevated working temperatures. In the present review, the effects of temperature variation are primarily introduced from the perspective of electrolysis cells. Following an increasing order of working temperature, multidimensional evaluations considering materials and structures, performance, degradation mechanisms and mitigation strategies as well as electrolysis in stacks and systems are presented based on elevated temperature alkaline electrolysis cells and polymer electrolyte membrane electrolysis cells (ET-AECs and ET-PEMECs), elevated temperature ionic conductors (ET-ICs), protonic ceramic electrolysis cells (PCECs) and solid oxide electrolysis cells (SOECs).

Rapid Gas-Phase Synthesis of the Perovskite-Type BaCe0.7Zr0.1Y0.1Yb0.1O3-δ Proton-Conducting Nanocrystalline Electrolyte for Intermediate-Temperature Solid Oxide Fuel Cells.

Perovskite-type proton-conducting materials, such as BaCe0.7Zr0.1Y0.1Yb0.1O3-δ (BCZYYb), are very attractive for the next-generation equipment of electrochemical energy conversion and storage owing to their excellent conductivity in the intermediate-temperature range (300-750 °C), as well as good thermo-chemical stability, coking resistance, and sulfur tolerance. However, the lack of a reliable and cost-effective synthesis method for such multi-component co-doping oxides limits their large-scale application. In this study, for the first time, we successfully synthesize BCZYYb electrolyte nanopowders by using a rapid, scalable flame-based gas-phase synthesis method with two different barium precursors Ba(NO3)2 and Ba(CH3COO)2, named as BCZYYb (N) and BCZYYb (CA). The as-synthesized nanoparticles exhibit good crystallinity of the pure orthorhombic perovskite BCZYYb phase. BCZYYb (CA) shows more uniform doping with the element ratio of 1:0.74:0.12:0.08:0.1, which is very close to the theoretical value. The shrinkage and surface SEM (scanning electron microscope) results indicate that the flame-made powders have superior sinterability compared to the sol-gel-made powders because of the smaller primary particle size (∼20 nm). Electrochemical impedance spectroscopy tests show that BCZYYb (CA) sintered at 1450 °C has the highest protonic conductivity of 1.31 × 10-2 S cm-1 in wet H2 when operating at 600 °C and still maintains a high-level conductivity of 1.19 × 10-2 S cm-1 even when the sintering temperature is reduced to 1350 °C, which is mainly attributed to uniform doping and good sinterability. The activation energy for the conductivity of BCZYYb (CA) is also significantly lower than that of conventional electrolytes, which suggests much better conductivity in the intermediate (∼600 °C) and even lower operating temperature. The excellent conductivity performance combined with the high-throughput production capability makes the swirling spray flame a promising synthesis method for promoting the BCZYYb electrolytes from lab to industrial-scale solid oxide fuel cells.

The negative impact of increasing temperatures on rice yields in southern China.

China is the main producer and consumer of rice in the world, and rice is a major staple food grain for more than half of the world's population. Reduced rice yields caused by climate factors not only affect the food security of China, but also has global repercussions. Thus, it is vital to assess the potential impact of climate warming on rice production. Using daily temperature and phenology records of double-cropping rice from agro-meteorological stations in southern China, the influence of increased temperatures on rice yields during the last several decades was investigated. Associated with an increase in average daily mean temperatures by 0.7 °C during 2009-2018 relative to 1961-1970, Killing Degree Days (KDD), an indicator for damaging high temperature, for early and late rice increased by 110% and 88.6% respectively. However, the negative influence of KDDs on yields was mainly evident for early rice, because high temperatures occurred frequently during the sensitive grain-filling period; early-rice yields showed a decrease of 8% per 1 °C increase in mean growing season air temperature. Late rice yields, on the other hand, were not as negatively influenced by increasing temperatures as early rice, because high temperature usually occurred during the vegetative growth stage, which was not so sensitive to high temperature.

Stable epidermal electronic device with strain isolation induced by in situ Joule heating.

Epidermal electronics play increasingly important roles in human-machine interfaces. However, their efficient fabrication while maintaining device stability and reliability remains an unresolved challenge. Here, a facile in situ Joule heating method is proposed for fabricating stable epidermal electronics on a polyvinyl alcohol (PVA) substrate. Benefitting from the precise control of heating locations, the crystallization and enhanced rigidity of PVA are restricted to desired areas, leading to strain isolation of the active regions. As a result, the electronic device can be conformably attached to skin while showing negligible degradation in device performance during deformation. Based on this method, a flexible surface electromyography (sEMG) sensor with outstanding stability and highly comfortable wearability is demonstrated, showing high accuracy (91.83%) for human hand gesture recognition. These results imply that the fabrication method proposed in this research is a facile and reliable approach for the fabrication of epidermal electronics.

Corrigendum to "Comparative analysis of Phytophthora genomes reveals oomycete pathogenesis in crops" [Heliyon 7 (2) (February 2021) e06317].

[This corrects the article DOI: 10.1016/j.heliyon.2021.e06317.].

Comparative analysis of Phytophthora genomes reveals oomycete pathogenesis in crops.

The oomycete genus Phytophthora includes devastating plant pathogens that are found in almost all ecosystems. We sequenced the genomes of two quarantined Phytophthora species-P. fragariae and P. rubi. Comparing these Phytophthora species and related genera allowed reconstruction of the phylogenetic relationships within the genus Phytophthora and revealed Phytophthora genomic features associated with infection and pathogenicity. We found that several hundred Phytophthora genes are putatively inherited from red algae, but Phytophthora does not have vestigial plastids originating from phototrophs. The horizontally-transferred Phytophthora genes are abundant transposons that "transmit" exogenous gene to Phytophthora species thus bring about the gene recombination possibility. Several expansion events of Phytophthora gene families associated with cell wall biogenesis can be used as mutational targets to elucidate gene function in pathogenic interactions with host plants. This work enhanced the understanding of Phytophthora evolution and will also be helpful for the design of phytopathological control strategies.

Soft Electrochemical Actuators with a Two-Dimensional Conductive Metal-Organic Framework Nanowire Array.

Electrically activated soft actuators capable of large deformation are powerful and broadly applicable in multiple fields. However, designing soft actuators that can withstand a high strain, provide a large actuation displacement, and exhibit stable reversibility are still the main challenges toward their practical application. Here, for the first time, we report a two-dimensional (2D) conductive metal-organic framework (MOF) based electrochemical actuator, which consists of vertically oriented and hierarchical Ni-CAT NWAs/CNF electrodes through the use of a facile one-step in situ hydrothermal growth method. The soft actuator prepared in this study demonstrated improvements in actuation performance and benefits from both the intrinsically ordered porous architecture and efficient transfer pathways for fast ion and electron transport; furthermore, this actuator facilitated a considerably high diffusion rate and low interfacial resistance. In particular, the actuator demonstrated a rapid response (<19 s) at a 3 V DC input, large actuation displacement (12.1 mm), and a correspondingly high strain of 0.36% under a square-wave AC voltage of ±3 V. Specifically, the actuator achieved a broad-band frequency response (0.1-20 Hz) and long-term cyclability in air (10000 cycles) with a negligible degradation in actuation performance. Our work demonstrates new opportunities for bioinspired artificial actuators and overcomes current limitations in electrode materials for soft robotics and bionics.

An Effective Method to Facilitate Personalized and Precise Medicine for Schizophrenia Treatment Based on Pharmacogenomics.

Background: Schizophrenia is a serious mental illness affecting 0.3-0.7% of the world's population. It is a classic quantitative genetic disease and is affected by a variety of common and rare genetic variants. Methods: To facilitate personalized and precise medicine for schizophrenia treatment, we designed a program by genotyping a panel of related genes for schizophrenic patients using MassARRAY time-of-flight mass spectrometry. The program was tested in an observational clinical study conducted at the Hulunbuir Mental Health Center of China. In the study, a total of 254 patients diagnosed with schizophrenia were recruited and genotyped. The genotyping results were used to generate reports listing where the 16 included antipsychotics should be placed: "Use as directed," "Use with caution," or "Use with caution and with frequent blood concentration monitoring" categories. Seventy-two of the patients completed the 24-week follow-up observation, during which their PANSS scores were assessed at eight time points. Results: For all of the subjects who completed the study, the PANSS scores dropped significantly, showing the effectiveness of the treatment. During the 24-week study, PANSS scores of patients whose medications were consistent (N = 48) with their genetic test results dropped from 84.3 (SD = 12.4) to 58.8 (SD = 15.3), and average PANSS change rate reached 56.1% after 24 weeks. In contrast, PANSS scores of patients with genetic tests reported as "Use with caution" or "Use with caution and with frequent blood concentration monitoring" (N = 24) dropped from 81.1 (SD = 10.5) to 63.8 (SD = 10.1), and their average PANSS change rate was 37.6%. Conclusions: This research indicates that our pharmacogenomic-based program could be a suitable and effective tool to facilitate precise medication in schizophrenia treatment.

Photoinduced Nonlinear Contraction Behavior in Metal-Organic Frameworks.

The photoinduced dynamic behavior of flexible materials has received considerable attention for potential applications, such as in data storage or as smart optical devices and molecular mechanical actuators. Until now, precisely controlling expansion and contraction with light has remained a challenge. Unraveling the detailed mechanisms of photoinduced structural transformations remains a critical step necessary to understand the molecular architecture necessary for the design of sensitive photomechanical actuators. Herein, a two-dimensional flexible metal-organic framework [Zn2 (bdc)2 (3-CH3 -spy)2 ]⋅H2 O (Zn2 -1; H2 bdc=1,4-benzenedicaboxylic acid; 3-CH3 -spy=3-methylstyrylpyridine) with a positive volumetric thermal expansion coefficient of +78.78×10-6  K-1 is reported. Upon light irradiation at different wavelengths, the MOF underwent a [2+2] cycloaddition, which afforded a family of isomeric, three-dimensional MOFs (Zn2 -2 n, n=a-d) in a single-crystal-to-single-crystal (SCSC) manner. An unprecedented phenomenon, that is, photoinduced nonlinear contraction (PINC), was observed during this conversion. The PINC is caused by conformational changes in the 3-CH3 -spy and bdc2- ligands, the bending of metal-ligand bonds, and the local distortion of the paddle-wheel SBUs. The formation of a "wrinkle morphology" on the crystal surface after the photoreaction was observed by AFM. This PINC behavior can broaden the studies on materials expansion and offer a photodriven approach for the future design of supersensitive photomechanical actuators.

Fabrication of Photoactuators: Macroscopic Photomechanical Responses of Metal-Organic Frameworks to Irradiation by UV Light.

Photoreactive olefinic species are incorporated into a metal-organic framework (MOF), [Zn(bdc)(3-F-spy)] (1). Single crystals of 1 are shown to undergo three types of photomechanical macroscopic deformation upon illumination by UV light. To demonstrate the practical potential of this system, the inclusion of 1 in a PVA (polyvinyl alcohol) composite membrane, by exploiting hydrogen-bonding interactions, is presented. Using this composite membrane, the amplification of mechanical stress to achieve macroscopic actuation behavior is demonstrated. These results pave the way for the generation of MOF-based soft photoactuators that produce clearly defined mechanical responses upon irradiation with light. Such systems are anticipated to have considerable potential in photomechanical energy harvesting and conversion systems.

The dynamic changes of chemical components and microbiota during the natural fermentation process in Da-Jiang, a Chinese popular traditional fermented condiment.

There is limited information on the chemical components and microbiota changes involved in da-jiang, a Chinese popular traditional fermented soybean condiment. Therefore, dynamic changes both in physicochemical quality and microbial community diversity of 20 samples of naturally fermented da-jiang collected over 95 days were measured, and we classified the samples into 5 groups (each containing 4 time points) according to the results. Based on OTUs analysis, Group 2 and Group 3 might represent the shift-stage between bacteria and fungi. Also, our results demonstrated that the formation of flavour, nutrient and quality of the traditional da-jiang were actually related to all of microbial community, especially the increased bacteria, including Staphylococcus and Leuconostoc. Correspondingly, 'Membrane Transport', 'Carbohydrate Metabolism', 'Amino Acid Metabolism' and 'Replication and Repair' were the top 4 KEGG pathways based on bacterial genes. The findings are expected to be helpful for us not only to understand the formation of flavour, taste and quality of traditional fermented da-jiang, but also to improve the industrialised fermented da-jiang.

Guest-Induced Switchable Breathing Behavior in a Flexible Metal-Organic Framework with Pronounced Negative Gas Pressure.

Flexible metal-organic frameworks (MOFs) have attracted great interest for their dynamically structural transformability in response to external stimuli. Herein, we report a switchable "breathing" or "gate-opening" behavior associated with the phase transformation between a narrow pore (np) and a large pore (lp) in a flexible pillared-layered MOF, denoted as MOF-1 as, which is also confirmed by SCXRD and PXRD. The desolvated phase (MOF-1 des) features a unique stepwise adsorption isotherm for N2 coupled with a pronounced negative gas adsorption pressure. For comparison, however, no appreciable CO2 adsorption and gate-opening phenomenon with stepwise sorption can be observed. Furthermore, the polar micropore walls decorated with thiophene groups in MOF-1 des reveals the selective sorption of toluene over benzene and p-xylene associated with self-structural adjustment in spite of the markedly similar physicochemical properties of these vapor molecules.