Robust ring-opening reaction via asymmetrically coordinated Fe single atoms scaffolded by spoke-like mesoporous carbon nanospheres.

The ability to construct metal single-atom catalysts (SACs) asymmetrically coordinated with organic heteroatoms represents an important endeavor toward developing high-performance catalysts over symmetrically coordinated counterparts. Moreover, it is of key importance in creating supporting matrix with porous architecture for situating SACs as it greatly impacts the mass diffusion and transport of electrolyte. Herein, we report the crafting of Fe single atoms with asymmetrically coordinated nitrogen (N) and phosphorus (P) atoms scaffolded by rationally designed mesoporous carbon nanospheres (MCNs) with spoke-like nanochannels for boosting ring-opening reaction of epoxide to produce an array of pharmacologically important ß-amino alcohols. Notably, interfacial defects in MCN derived from the use of sacrificial template create abundant unpaired electrons, thereby stably anchoring N and P atoms and in turn Fe atoms on MCN. Importantly, the introduction of P atom promotes the symmetry-breaking of common four N-coordinated Fe sites, resulting in the Fe-N3P sites on MCN (denoted Fe-N3P-MCN) with an asymmetric electronic configuration and thus superior catalytic capability. As such, the Fe-N3P-MCN catalysts manifest a high catalytic activity for ring-opening reaction of epoxide (97% yield) over the Fe-N3P docked on nonporous carbon surface (91%) as well as the sole Fe-N4 SACs grounded on the same MCN support (89%). Density functional theory calculations reveal that Fe-N3P SAC lowers the activation barrier for the C-O bond cleavage and the C-N bond formation, thus accelerating the ring-opening of epoxide. Our study provides fundamental and practical insights into developing advanced catalysts in a simple and controllable manner for multistep organic reactions.

Rapid production of kilogram-scale graphene nanoribbons with tunable interlayer spacing for an array of renewable energy.

Graphene nanoribbons (GNRs) are widely recognized as intriguing building blocks for high-performance electronics and catalysis owing to their unique width-dependent bandgap and ample lone pair electrons on both sides of GNR, respectively, over the graphene nanosheet counterpart. However, it remains challenging to mass-produce kilogram-scale GNRs to render their practical applications. More importantly, the ability to intercalate nanofillers of interest within GNR enables in-situ large-scale dispersion and retains structural stability and properties of nanofillers for enhanced energy conversion and storage. This, however, has yet to be largely explored. Herein, we report a rapid, low-cost freezing-rolling-capillary compression strategy to yield GNRs at a kilogram scale with tunable interlayer spacing for situating a set of functional nanomaterials for electrochemical energy conversion and storage. Specifically, GNRs are created by sequential freezing, rolling, and capillary compression of large-sized graphene oxide nanosheets in liquid nitrogen, followed by pyrolysis. The interlayer spacing of GNRs can be conveniently regulated by tuning the amount of nanofillers of different dimensions added. As such, heteroatoms; metal single atoms; and 0D, 1D, and 2D nanomaterials can be readily in-situ intercalated into the GNR matrix, producing a rich variety of functional nanofiller-dispersed GNR nanocomposites. They manifest promising performance in electrocatalysis, battery, and supercapacitor due to excellent electronic conductivity, catalytic activity, and structural stability of the resulting GNR nanocomposites. The freezing-rolling-capillary compression strategy is facile, robust, and generalizable. It renders the creation of versatile GNR-derived nanocomposites with adjustable interlay spacing of GNR, thereby underpinning future advances in electronics and clean energy applications.

Electrostatic tweezer for droplet manipulation.

Various physical tweezers for manipulating liquid droplets based on optical, electrical, magnetic, acoustic, or other external fields have emerged and revolutionized research and application in medical, biological, and environmental fields. Despite notable progress, the existing modalities for droplet control and manipulation are still limited by the extra responsive additives and relatively poor controllability in terms of droplet motion behaviors, such as distance, velocity, and direction. Herein, we report a versatile droplet electrostatic tweezer (DEST) for remotely and programmatically trapping or guiding the liquid droplets under diverse conditions, such as in open and closed spaces and on flat and tilted surfaces as well as in oil medium. DEST, leveraging on the coulomb attraction force resulting from its electrostatic induction to a droplet, could manipulate droplets of various compositions, volumes, and arrays on various substrates, offering a potential platform for a series of applications, such as high-throughput surface-enhanced Raman spectroscopy detection with single measuring time less than 20 s.

Highly enantio- and diastereoselective construction of spirocyclic oxindoles via a palladium-catalyzed decarboxylative asymmetric [4 + 2] annulation strategy.

A palladium-catalyzed decarboxylative asymmetric [4 + 2] annulation of methyleneindolinones with a zwitterionic oxo-1,4-dipole intermediate was successfully developed to access spirocyclic oxindoles bearing two vicinal stereocenters in good yields with high diastereoselectivities and enantioselectivities. This strategy features a broad substrate scope (28 examples), allowing for efficient scale-up. Further selective transformation of the product and preliminary mechanistic studies were conducted.

Divergent Chemo- and Biocatalytic Route to 16ß-Methylcorticoids: Asymmetric Synthesis of Betamethasone Dipropionate, Clobetasol Propionate, and Beclomethasone Dipropionate.

16ß-Methylcorticoids are among the most important glucocorticoid steroids for the treatment of various dermatological disorders, respiratory infections, and other allergic reactions elicited during inflammatory responses of the human body. Betamethasone dipropionate, clobetasol propionate, and beclomethasone dipropionate are particularly noteworthy for their synthetic intractability. Despite five decades of research, these 16ß-methylcorticoids have remained challenging synthetic targets owing to insurmountable issues of reactivity, selectivity, and cost efficiency associated with all previously explored strategies. We herein report our practicability-oriented strategy toward the unified stereoselective synthesis of 16ß-methylcorticoids in 12.6-14.0 % overall yield from commercially available 9α-hydroxyandrost-4-ene-3,17-dione (9α-OH-AD). In this approach, the chiral C16ß-Me and C17α-OH groups of the corticosteroid D ring were installed via a substrate-controlled diastereo- and enantioselective Mn-catalyzed oxidation-reduction hydration of Δ4,9(11),16 -triene-3,20-dione. The C1-C2 double bond of the corticosteroid A ring was constructed using an unprecedented engineered 3-ketosteroid-Δ1 -dehydrogenase (MK4-KstD)-catalyzed regioselective Δ1 -dehydrogenation of Δ4,9(11) -diene-3,21-dione. This strategy provides a general method and a key precursor for the divergent synthesis of a variety of glucocorticoids and related steroidal drugs.

Cascade Synthesis of Fe-N2-Fe Dual-Atom Catalysts for Superior Oxygen Catalysis.

Dual-atom catalysts (DACs) have been proposed to break the limitation of single-atom catalysts (SACs) in the synergistic activation of multiple molecules and intermediates, offering an additional degree of freedom for catalytic regulation. However, it remains a challenge to synthesize DACs with high uniformity, atomic accuracy, and satisfactory loadings. Herein, we report a facile cascade synthetic strategy for DAC via precise electrostatic interaction control and neighboring vacancy construction. We synthesized well-defined, uniformly dispersed dual Fe sites which were connected by two nitrogen bonds (denoted as Fe-N2-Fe). The as-synthesized DAC exhibited superior catalytic performances towards oxygen reduction reaction, including good half-wave potential (0.91 V), high kinetic current density (21.66 mA cm-2), and perfect durability. Theoretical calculation revealed that the DAC structure effectively tunes the oxygen adsorption configuration and decreases the cleavage barrier, thereby improving the catalytic kinetics. The DAC-based zinc-air batteries exhibited impressive power densities of 169.8 and 52.18 mW cm-2 at 25 oC and -40 oC, which is 1.7 and 2.0 times higher than those based on Pt/C+Ir/C, respectively. We also demonstrated the universality of our strategy in synthesizing other M-N2-M DACs (M= Co, Cu, Ru, Pd, Pt, and Au), facilitating the construction of a DAC library for different catalytic applications.

Sex differences in comorbidities and mortality risk among patients with chronic obstructive pulmonary disease: a study based on NHANES data.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) commonly have coexisting comorbidities that contribute to higher exacerbation frequency, poorer health status, and increased all-cause mortality; however, there are only a few studies available on the sex discrepancy in the comorbidity distribution and outcomes among COPD patients, and there is limited information about the discrepancy in all-cause mortality between men and women. METHODS: Based on data from the U.S. National Health and Nutrition Examination Survey conducted between 2007 and 2012, we compared participants aged 40-79 years with spirometry-defined COPD to compare the prevalence of comorbidities between men and women. The survival of the subjects was documented, and the sex discrepancy was determined using Kaplan-Meier analysis. Comorbidities and all-cause mortality were analyzed by using a Cox proportional hazards model to determine their strength of association in different sex groups. RESULTS: Compared to men, women had a significantly higher prevalence of asthma (OR 1.93, 95% CI 1.46 to 2.57, p < 0.001) and arthritis (OR 1.77, 95% CI 1.39 to 2.24, p < 0.001). Women had a significantly lower prevalence of coronary heart disease (OR 0.48, 95% CI 0.27 to 0.87, p = 0.015) and gout (OR 0.42, 95% CI 0.25 to 0.67, p = 0.001). Kaplan-Meier analysis revealed that compared with that of the female group, the survival rate of the male group was significantly lower (p < 0.001). Among men, the presence of anemia (HR 2.38, [95% CI 1.52-3.73], p < 0.001), gout (HR 1.55, [95% CI 1.04-2.30], p = 0.029) and congestive heart failure comorbidities (HR 1.85, [95% CI 1.12-3.04] p = 0.016) was associated with a higher risk of mortality; among women, the presence of anemia (HR 2.21, [95% CI 1.17-4.20], p = 0.015) and stroke (HR 2.04, [95% CI 1.07-3.88], p = 0.031) comorbidities was associated with a higher risk of mortality after adjusting for age, race/Hispanic status, BMI, smoking status, FEV1% predicted and prevalent comorbidities. CONCLUSIONS: COPD-related comorbidities and all-cause mortality were discrepant between men and women, and men had poorer survival than women in the nationally representative data that were analyzed.

Effect of zearalenone on aflatoxin B1-induced intestinal and ovarian toxicity in pregnant and lactating rats.

Aflatoxin B1 (AFB1) and zearalenone (ZEN) cause serious damage to mammals, but few studies have investigated the impacts of these toxins on pregnant and lactating mammals. This study investigated the effects of ZEN on AFB1-induced intestinal and ovarian toxicity in pregnant and lactating rats. Based on the results, AFB1 reduces the digestion, absorption, and antioxidant capacity in the intestine, increases intestinal mucosal permeability, destroys intestinal mechanical barriers, and increases pathogenic bacteria' relative abundances. Simultaneously, ZEN can exacerbate the intestinal injury caused by AFB1. The intestines of the offspring were also damaged, but the damage was less severe than that observed for the dams. While AFB1 activates various signalling pathways in the ovary and affects genes related to endoplasmic reticulum stress, apoptosis, and inflammation, ZEN may exacerbate or antagonize the AFB1 toxicity on gene expression in the ovary through key node genes and abnormally expressed genes. Our study found that mycotoxins can not only directly damage the ovaries and affect gene expression in the ovaries but can also impact ovarian health by disrupting intestinal microbes. Mycotoxins are an important environmental pathogenic factor for intestinal and ovarian disease in pregnancy and lactation mammals.

Six-Step Continuous Flow Synthesis of Diclofenac Sodium via Cascade Etherification/Smiles Rearrangement Strategy: Tackling the Issues of Batch Processing.

Diclofenac sodium is a widely used nonsteroidal anti-inflammatory drug (NSAID) as over-the-counter (OTC) medication for the treatment of inflammatory diseases. Herein, the development of an intensified six-step continuous flow synthesis of diclofenac sodium from commercially available aniline and chloroacetic acid is described. A challenging and unprecedented etherification/Smiles rearrangement cascade of 2-chloro-N-phenylacetamide and 2,6-dichlorophenol into hydroxyacetyldiphenylamine operated with the precise control of reaction conditions in continuous flow was realized as the key step in this multistep synthetic chemistry. The undesired amide hydrolysis in Smiles rearrangement was addressed and the extra installation of N-chloroacetyl group in current industrial batch mode was avoided. Diclofenac sodium was obtained in 63 % isolated yield with an average yield of above 90 % for each step in a total residence time of 205 min.

Six-Step Continuous Flow Synthesis of Diclofenac Sodium via Cascade Etherification/Smiles Rearrangement Strategy: Tackling the Issues of Batch Processing.

Invited for the cover of this issue are Dang Cheng, Fener Chen and co-workers at Fudan University. The image depicts six-step continuous-flow synthesis of diclofenac sodium from commercially available aniline and chloroacetic acid in a desktop microchemical plant. Read the full text of the article at 10.1002/chem.202201420.

Development of a Fully Continuous-Flow Approach Towards Asymmetric Total Synthesis of Tetrahydroprotoberberine Natural Alkaloids.

Continuous flow synthetic technologies had been widely applied in the total synthesis in the past few decades. Fully continuous flow synthesis is still extremely focused on multi-step synthesis of complex natural pharmaceutical molecules. Thus, the development of fully continuous flow total synthesis of natural products is in demand but challenging. Herein, we demonstrated the first fully continuous flow approach towards asymmetric total synthesis of natural tetrahydroprotoberberine alkaloids, (-)-isocanadine, (-)-tetrahydropseudocoptisine, (-)-stylopine and (-)-nandinine. This method features a concise linear sequence involving four chemical transformations and three on-line work-up processing in an integrated flow platform, without any intermediate purification. The overall yield and enantioselectivity of this four-step continuous flow chemistry were up to 50 % and 92 %ee, respectively, in a total residence time of 32.5 min, corresponding to a throughput of 145 mg/h.

MicroRNA-494-3p Exacerbates Renal Epithelial Cell Dysfunction by Targeting SOCS6 under High Glucose Treatment.

BACKGROUND: Diabetic nephropathy is a common complication of the kidneys induced by diabetes and is the main cause of end-stage renal disease. MicroRNA-494-3p was reported to be upregulated in renal tissues collected from db/db mice, but its specific role in diabetic nephropathy was still unclear. This study aimed to explore the effect of miR-494-3p on renal fibrosis using an in vitro cell model of diabetic nephropathy. METHODS: After human renal tubular epithelial cells (HK-2) were treated with high glucose (HG), the viability and apoptosis of cells were examined by CCK-8 assays and flow cytometry analyses. Additionally, protein levels of fibronectin, collagen I, collagen III, collagen IV, and epithelial-mesenchymal transition (EMT) markers in HG-induced HK-2 cells were quantified by Western blotting. miR-494-3p expression in HK-2 cells was detected by reverse-transcription quantitative polymerase chain reaction. The binding relation between miR-494-3p and the messenger RNA suppressor of cytokine signaling 6 (SOCS6) was detected by luciferase reporter assays. RESULTS: HG reduced cell viability and enhanced cell apoptosis in a time- or concentration-dependent manner. Additionally, HG induced collagen accumulation and triggered the EMT process. miR-494-3p was upregulated in HG-treated HK-2 cells. miR-494-3p inhibition alleviated HG-induced cell dysfunction. Mechanistically, miR-494-3p bound with SOCS6 and negatively regulated SOCS6 expression. Moreover, silencing SOCS6 rescued the suppressive effect of miR-499-5p inhibition on HG-induced cell dysfunction. CONCLUSION: miR-494-3p aggravates renal fibrosis, EMT process, and cell apoptosis by targeting SOCS6, suggesting that the miR-494-3p/SOCS6 axis may become a potential strategy for the treatment of diabetic nephropathy.

Dual effects of zearalenone on aflatoxin B1-induced liver and mammary gland toxicity in pregnant and lactating rats.

Food and feed are frequently co-contaminated with aflatoxin B1 (AFB1) and zearalenone (ZEN). This study investigated the effects of ZEN on the AFB1-induced liver and mammary gland toxicity in pregnant and lactating rats. AFB1 and ZEN co-exposure inhibited the growth of rats and caused oxidative stress and inflammatory responses in the liver and mammary gland. Compared with the AFB1-only group, damage was aggravated in the AFB1 + 10 mg/kg ZEN group, and the AFB1 + 1 mg/kg ZEN group showed a reduction in some metrics. The metabolomic results of the mammary gland showed that metabolite changes were mainly in lipid, amino acid, and glucose metabolism. Compared with the AFB1 + 0 mg/kg ZEN group, the AFB1 + 1 mg/kg ZEN group had the most metabolite changes. Moreover, AFB1 and ZEN co-exposure reduced the levels of sex hormones and RNA m6A methylation in the mammary gland. We speculate that ZEN affects the toxicity of AFB1 to the liver and mammary gland by interfering with the function of sex hormones, regulating cell proliferation and metabolic processes.

Rapid and Persistent Suction Condensation on Hydrophilic Surfaces for High-Efficiency Water Collection.

Water collection by dew condensation emerges as a sustainable solution to water scarcity. However, the transient condensation process that involves droplet nucleation, growth, and transport imposes conflicting requirements on surface properties. It is challenging to satisfy all benefits for different condensation stages simultaneously. By mimicking the structures and functions of moss Rhacocarpus, here, we report the attainment of dropwise condensation for efficient water collection even on a hydrophilic surface gated by a liquid suction mechanism. The Rhacocarpus-inspired porous surface (RIPS), which possesses a three-level wettability gradient, facilitates a rapid, directional, and persistent droplet suction. Such suction condensation enables a low nucleation barrier, frequent surface refreshing, and well-defined maximum droplet shedding radius simultaneously. Thus, a maximum ∼160% enhancement in water collection performance compared to the hydrophobic surface is achieved. Our work provides new insights and a design route for developing engineered materials for a wide range of water-harvesting and phase-change heat-transfer applications.

Catalytic Syn-Selective Nitroaldol Approach to Amphenicol Antibiotics: Evolution of a Unified Asymmetric Synthesis of (-)-Chloramphenicol, (-)-Azidamphenicol, (+)-Thiamphenicol, and (+)-Florfenicol.

A unified strategy for an efficient and high diastereo- and enantioselective synthesis of (-)-chloramphenicol, (-)-azidamphenicol, (+)-thiamphenicol, and (+)-florfenicol based on a key catalytic syn-selective Henry reaction is reported. The stereochemistry of the ligand-enabled copper(II)-catalyzed aryl aldehyde Henry reaction of nitroethanol was first explored to forge a challenging syn-2-amino-1,3-diol structure unit with vicinal stereocenters with excellent stereocontrol. Multistep continuous flow manipulations were carried out to achieve the efficient asymmetric synthesis of this family of amphenicol antibiotics.

TfOH-Catalyzed Cascade C-H Activation/Lactonization of Phenols with α-Aryl-α-diazoesters: Rapid Access to α-Aryl Benzofuranones.

Aryl benzofuranones are privileged structural units present in natural products and pharmaceutically relevant compounds with high bioactivity and therapeutic value; synthetic access to these scaffolds remains an area of intensive interest. A new and efficient TfOH-catalyzed cascade ortho C-H activation/lactonization of phenols with α-aryl-α-diazoacetates is reported. This metal-free protocol provides an operationally simple and rapid method for the one-pot assembly of diverse α-aryl benzofuranones in high yields with broad substrate scope, a readily starting material, good chemo-regioselectivity, and excellent functional group compatibility.

Unified Strategy to Amphenicol Antibiotics: Asymmetric Synthesis of (-)-Chloramphenicol, (-)-Azidamphenicol, and (+)-Thiamphenicol and Its (+)-3-Floride.

The asymmetric synthesis of (-)-chloramphenicol, (-)-azidamphenicol, and (+)-thiamphenicol and its (+)-3-floride, (+)-florfenicol, is reported. This approach toward the amphenicol antibiotic family features two key steps: (1) a cinchona alkaloid derived urea-catalyzed aldol reaction allows highly enantioselective access to oxazolidinone gem-diesters and (2) a continuous flow diastereoselective decarboxylation of thermally stable oxazolidinone gem-diesters to form the desired trans-oxazolidinone monoesters with two adjacent stereocenters that provide the desired privileged scaffolds of syn-vicinal amino alcohols in the amphenicol family.

Patterned Amyloid Materials Integrating Robustness and Genetically Programmable Functionality.

The precise manipulation, localization, and assembly of biological and bioinspired molecules into organized structures have greatly promoted material science and bionanotechnology. Further technological innovation calls for new patternable soft materials with the long-sought qualities of environmental tolerance and functional flexibility. Here, we report a patterned amyloid material (PAM) platform for producing hierarchically ordered structures that integrate these material attributes. This platform, combining soft lithography with generic amyloid monomer inks (consisting of genetically engineered biofilm proteins dissolved in hexafluoroisopropanol), along with methanol-assisted curing, enables the spatially controlled deposition and in situ reassembly of amyloid monomers. The resulting patterned structures exhibit spectacular chemical and thermal stability and mechanical robustness under harsh conditions. The PAMs can be programmed for a vast array of multilevel functionalities, including anchoring nanoparticles, enabling diverse fluorescent protein arrays, and serving as self-supporting porous sheets for cellular growth. This PAM platform will not only drive innovation in biomanufacturing but also broaden the applications of patterned soft architectures in optics, electronics, biocatalysis, analytical regents, cell engineering, medicine, and other areas.

Effects and Mechanisms of Transcutaneous Electrical Acustimulation on Postoperative Recovery After Elective Cesarean Section.

OBJECTIVES: To explore the effects and mechanisms of transcutaneous electrical acustimulation (TEA) on postoperative recovery after cesarean section (CS). MATERIALS AND METHODS: A total of 108 women who underwent CS were randomized to receive TEA or sham-TEA. Four hours after CS, electrogastrogram (EGG) and electrocardiogram (ECG) were recorded for 30 min to assess gastric slow waves and autonomic functions, respectively. TEA at ST36 or sham-TEA at non-acupoints was performed for one hour right after recording ECG and EGG and then twice daily from postoperative days (POD) 1 to 3. In the morning of POD4, the EGG and ECG were recorded again for 30 min. RESULTS: TEA enhanced postoperative recovery associated with lower GI motility, reflected as a reduction in time of first flatus (p = 0.002) and time of first defecation (p < 0.001), an increase in the Bristol stool score (p < 0.001) and the number of SBMs (p < 0.001) in comparison with sham-TEA. TEA reduced symptoms associated with upper GI motility, including a reduction in time to resume semifluid (p = 0.008), and the total score of loss of appetite (p = 0.003) and belching (p = 0.038) from POD1 to POD3. Physiologically, TEA but not sham-TEA increased the percentage of normal gastric slow waves on POD4 compared with POD0 (p = 0.001). TEA reduced the visual analogue scale (VAS) pain score from POD1 to POD3 (p < 0.001). TEA but not sham-TEA increased vagal activity (p = 0.013) and decreased sympathetic activity (p = 0.013) on POD4 compared with POD0. Two factors were found to be independent predictors of shortened time of the first defecation: the use of TEA and a shorter surgical duration. CONCLUSIONS: Needleless non-invasive TEA at ST36 is effective in promoting both lower and upper GI symptoms after CS by enhancing vagal and suppressing sympathetic activities [Correction added on 23 June 2020, after first online publication: The first word of the preceded sentence has been corrected.].

Access to a Key Building Block for the Prostaglandin Family via Stereocontrolled Organocatalytic Baeyer-Villiger Oxidation.

A new protocol for the construction of a crucial bicyclic lactone of prostaglandins using a stereocontrolled organocatalytic Baeyer-Villiger (B-V) oxidation was developed. The key B-V oxidation of a racemic cyclobutanone derivative with aqueous hydrogen peroxide has enabled an early-stage construction of a bicyclic lactone skeleton in high enantiomeric excess (up to 95 %). The generated bicyclic lactone is fully primed with two desired stereocenters and enabled the synthesis of the entire family of prostaglandins according to Corey's route. Furthermore, the reactivity and enantioselectivity of B-V oxidation of racemic bicyclic cyclobutanones were evaluated and 90-99 % ee was obtained, representing one of the most efficient routes to chiral lactones. This study further facilitates the synthesis of prostaglandins and chiral lactone-containing natural products to promote drug discovery.