Synthesis and characterization of Craig-type antiaromatic species with [4n + 2] π electrons.

Antiaromaticity is extended from aromaticity as a complement to describe the unsaturated cyclic molecules with antiaromatic destabilization. To prepare antiaromatic species is a particularly challenging goal in synthetic chemistry because of the thermodynamic instability of such molecules. Among that, both Hückel and Möbius antiaromatic species have been reported, whereas the Craig one has not been realized to date. Here, we report the first example of planar Craig antiaromatic species. Eight Craig antiaromatic compounds were synthesized by deprotonation-induced reduction process and were fully characterized as follows. Single-crystal X-ray crystallography showed that these complexes have planar structures composed of fused five-membered rings with clearly alternating carbon-carbon bond lengths. In addition, proton NMR (1H NMR) spectroscopy in these structures showed distinctive upfield shifts of the proton peaks to the range of antiaromatic peripheral hydrogens. Experimental spectroscopy observations, along with density-functional theory (DFT) calculations, provided evidence for the Craig antiaromaticity of these complexes. Further study experimentally and theoretically revealed that the strong exothermicity of the acid-base neutralization process was the driving force for this challenging transformation forming Craig antiaromatic species. Our findings complete a full cycle of aromatic chemistry, opening an avenue for the development of new class of antiaromatic systems.

Simultaneous Photocatalytic Tetracycline Oxidation and Cr(VI) Reduction by Z-Scheme Multiple Layer TiO2/SnIn4S8.

Wastewater pollutants are a major threat to natural resources, with antibiotics and heavy metals being common water contaminants. By harnessing clean, renewable solar energy, photocatalysis facilitates the synergistic removal of heavy metals and antibiotics. In this paper, MXene was both a template and raw material, and MXene-derived oxide (TiO2) and SnIn4S8 Z-scheme composite materials were synthesized and characterized. The synergistic mode of photocatalytic reduction and oxidation leads to the enhanced utilization of e-/h+ pairs. The TiO2/SnIn4S8 exhibited a higher photocatalytic capacity for the simultaneous removal of tetracycline (TC) (20 mg·L-1) and Cr(VI) (15 mg·L-1). The main active substances of TC degradation and Cr(VI) reduction were identified via free radical scavengers and electron paramagnetic resonance (EPR). Additionally, the potential photocatalytic degradation route of TC was thoroughly elucidated through liquid chromatography-mass spectrometry (LC-MS).

Electrophilic aromatic substitution reactions of compounds with Craig-Möbius aromaticity.

Electrophilic aromatic substitution (EAS) reactions are widely regarded as characteristic reactions of aromatic species, but no comparable reaction has been reported for molecules with Craig-Möbius aromaticity. Here, we demonstrate successful EAS reactions of Craig-Möbius aromatics, osmapentalenes, and fused osmapentalenes. The highly reactive nature of osmapentalene makes it susceptible to electrophilic attack by halogens, thus osmapentalene, osmafuran-fused osmapentalene, and osmabenzene-fused osmapentalene can undergo typical EAS reactions. In addition, the selective formation of a series of halogen substituted metalla-aromatics via EAS reactions has revealed an unprecedented approach to otherwise elusive compounds such as the unsaturated cyclic chlorirenium ions. Density functional theory calculations were conducted to study the electronic effect on the regioselectivity of the EAS reactions.

Inorganic Nanosheet-Shielded Probiotics: A Self-Adaptable Oral Delivery System for Intestinal Disease Treatment.

The oral delivery of probiotics is commonly adopted for intestinal disease treatments in clinical settings; however, the probiotics suffer from a strong acidic attack in the gastric area and the low-efficiency intestinal colonization of naked probiotics. Coating living probiotics with synthetic materials has proven effective in enabling the adaption of bacteria to gastrointestinal environments, which, unfortunately, may shield the probiotics from initiating therapeutic responses. In this study, we report a copolymer-modified two-dimensional H-silicene nanomaterial (termed SiH@TPGS-PEI) that can facilitate probiotics to adapt to diverse gastrointestinal microenvironments on-demand. Briefly, SiH@TPGS-PEI electrostatically coated on the surface of probiotic bacteria helps to resist erosive destruction in the acidic stomach and spontaneously degrades by reacting with water to generate hydrogen, an anti-inflammatory gas in response to the neutral/weakly alkaline intestinal environment, thus exposing the probiotic bacteria for colitis amelioration. This strategy may shed new light on the development of intelligent self-adaptive materials.

[Progress in Surgical Treatment of Upper Urinary Tract Stones in Children].

The incidence of urinary calculi in children has been increasing annually,and most of the cases are upper urinary tract stones.At present,surgery is the main way to treat upper urinary tract stones in children.With the gradual development of minimally invasive techniques in surgery,percutaneous nephrolithotomy,retrograde intrarenal surgery,and extracorporeal shock wave lithotripsy have become the main methods for treating upper urinary tract stones in children.We reviewed the current progress in surgical treatment of upper urinary tract stones in children and provided prospects for future treatment options.

Connections to the Electrodes Control the Transport Mechanism in Single-Molecule Transistors.

When designing a molecular electronic device for a specific function, it is necessary to control whether the charge-transport mechanism is phase-coherent transmission or particle-like hopping. Here we report a systematic study of charge transport through single zinc-porphyrin molecules embedded in graphene nanogaps to form transistors, and show that the transport mechanism depends on the chemistry of the molecule-electrode interfaces. We show that van der Waals interactions between molecular anchoring groups and graphene yield transport characteristic of Coulomb blockade with incoherent sequential hopping, whereas covalent molecule-electrode amide bonds give intermediately or strongly coupled single-molecule devices that display coherent transmission. These findings demonstrate the importance of interfacial engineering in molecular electronic circuits.

Iodinene Nanosheet-to-Iodine Molecule Allotropic Transformation for Antibiosis.

Iodine, as a typical haloid element in group VIIA, has been extensively applied as antiseptics clinically, thanks to its effective and wide-spectrum antimicrobial activity against bacteria, fungi, and viruses. Nevertheless, current iodic sterilizing agents are still limited to topical applications such as instrument sterilization and treatments of skin or mucous membrane infection due to its unsatisfactory stability and biocompatibility. Here, we propose an emerging two-dimensional iodine nanomaterial (noted as iodinene) for the treatment of infection diseases in vivo. Iodinene nanosheets were fabricated by a facile and environmentally friendly approach via sonication-assisted liquid exfoliation, which present an intriguing layered structure and negligible toxicity. The as-synthesized iodinene would experience an in situ allotropic transformation spontaneously to release active HIO and I2 molecules by reacting with H2O2 in the infectious microenvironment. By the in situ production of active HIO and I2 molecules via allotropic transformation, iodinene presents enhanced antibacterial efficacy against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. In vivo outcome demonstrates the desirable antibacterial efficacy of iodinene in treating bacterial wound infection and pneumonia. This study thus offers an alternative to conventional sterilizing agents against hard-to-treat bacterial infections.

Phase-Coherent Charge Transport through a Porphyrin Nanoribbon.

Since the early days of quantum mechanics, it has been known that electrons behave simultaneously as particles and waves, and now quantum electronic devices can harness this duality. When devices are shrunk to the molecular scale, it is unclear under what conditions does electron transmission remain phase-coherent, as molecules are usually treated as either scattering or redox centers, without considering the wave-particle duality of the charge carrier. Here, we demonstrate that electron transmission remains phase-coherent in molecular porphyrin nanoribbons connected to graphene electrodes. The devices act as graphene Fabry-Pérot interferometers and allow for direct probing of the transport mechanisms throughout several regimes. Through electrostatic gating, we observe electronic interference fringes in transmission that are strongly correlated to molecular conductance across multiple oxidation states. These results demonstrate a platform for the use of interferometric effects in single-molecule junctions, opening up new avenues for studying quantum coherence in molecular electronic and spintronic devices.

Nanoarchitectonics of RGO-Wrapped CNF/GO Aerogels with Controlled Pore Structures by PVA-Assisted Freeze-Casting Approach for Efficient Sound and Microwave Absorption.

Acoustic absorption materials play an important role in eliminating the negative effects of noise. Herein, a polyvinyl alcohol (PVA)-assisted freeze-casting was developed for controllably fabricating reduced graphene oxide wrapped carbon nanofiber (RGO@CNF)/graphene oxide composite aerogel. During the freeze-casting, PVA was used as an icing inhibitor to control the size of ice crystals. While the concentration of PVA increased from 0 to 15 mg ⋅ ml-1 , the average pore size of the aerogel was reduced from 154 to 45 µm. Due to the modulation of the pore size and composition, the propagation path and friction loss for sound were optimized, especially at low frequency. For instance, the normalized sound absorption coefficient of RGO@CNF/GO-10 achieves 0.79 (250-6300 Hz). The sample also exhibits a desirable microwave absorbing property whose maximum reflection loss is -47.3 dB (9.44 GHz, d=3.0 mm). Prospectively, this synthetic strategy can be extended to develop other forms of elastic aerogel with a controlled pore size.

Rational design of a turn-on near-infrared fluorescence probe for the highly sensitive and selective monitoring of carboxylesterase 2 in living systems.

In vivo selective fluorescence imaging of carboxylesterase 2 (CES2) remains a great challenge because existing fluorescence probes can potentially suffer from interference by other hydrolases. In addition, some fluorescent probes that have been separately reported for measuring CES2 activity in vitro are affected by autofluorescence and absorption of the biological matrix due to their limited emission wavelength or short Stokes shift. Herein, based on the substrate preference and catalytic performance of CES2, a novel and NIR fluorescent probe was developed, in which a hemi-cyanine dye ester derivative was used as the basic fluorescent group. In the presence of CES2, the probe was hydrolyzed to expose the fluorophore CZX-OH (λabs ∼ 675 nm, λem ∼ 850 nm), which led to a notable red-shift in the fluorescence (∼175 nm) spectrum. Confocal imaging of cells and live mice demonstrated that the fluorescent signal of this probe was related to the real activities of CES2 in cancer cells. All these results will powerfully promote the screening of CES2 regulators and the analysis of CES2-related physiological and pathological processes.

Interleukin 10 inhibits oxidative stress-induced autophagosome formation in hepatic stellate cells by activating the mTOR-STAT3 pathway.

Autophagy is involved in the activation of hepatic stellate cells (HSCs) and liver fibrosis. Previous studies have shown that interleukin 10 (IL-10) has a marked therapeutic effect against liver fibrosis. However, few studies have evaluated the effect of IL-10 on autophagy in HSCs and fibrotic livers. The aim of this study was to assess the effect of IL-10 on the autophagy of HSCs in vitro and in vivo and then to explore the underlying pathway. In vitro, The results revealed that IL-10 had inhibitory effects on hydrogen peroxide (H2O2)-induced autophagy, as evidenced by the decreased LC3II/I ratio and Beclin1 expression, increased p62 expression, reduced numbers of autophagosomes, and blocked autophagy initiation in HSCs. Mechanistically, IL-10 significantly promoted the phosphorylation of the signal transducer and activator of transcription 3(STAT3) and mammalian target of rapamycin (mTOR), leading to the activation of STAT3 and mTOR, which in turn inhibited autophagy. In vivo, the increased expression of IL-10 in fibrotic livers inhibited significantly liver fibrosis and decreased the autophagic activity in fibrotic livers and HSCs. Overall, our results indicate that IL-10 suppressed H2O2-induced autophagy in HSCs by activating the STAT3-mTOR signaling pathway. Present study provides a new theoretical basis for the anti-fibrotic effects of IL-10.

The use of high-sensitivity cardiac troponin T and creatinine kinase-MB as a prognostic markers in patients with acute myocardial infarction and chronic kidney disease.

Background: High-sensitivity cardiac troponin T (hs-cTnT) and creatine kinase (CK)-MB are the most commonly used biomarkers for the diagnosis and prognosis of acute myocardial infarction (AMI). Chronic kidney disease (CKD) often leads to elevated hs-cTnT levels in non-AMI patients. However, studies comparing the prognostic value of both hs-cTnT and CK-MB in patients with AMI and CKD are lacking.Methods: We conducted a retrospective study on AMI patients diagnosed between January 2015 and October 2020. Patients were categorized based on renal function as normal or CKD. Peak hs-cTnT and CK-MB levels during hospitalization were collected, and their diagnostic value was evaluated using receiver operating characteristic (ROC) curves. The impact on in-hospital mortality was analyzed using multivariate logistic regression. The relationship between the hs-cTnT/CK-MB ratio and in-hospital death was examined using a restricted cubic spline (RCS) curve.Results: The study included 5022 AMI patients, of whom 797 (15.9%) had CKD. The AUCs of Hs-cTnT and CK-MB were higher in the CKD group [0.842 (95% CI: 0.789-0.894) and 0.821 (95% CI: 0.760-0.882)] than in the normal renal function group [0.695 (95% CI: 0.604-0.790) and 0.708 (95% CI: 0.624-0.793)]. After full adjustment for all risk factors, hs-cTnT (OR, 2.82; 95% CI, 1.03-9.86; p = 0.038) and CK-MB (OR, 4.91; 95% CI, 1.54-14.68; p = 0.007) above the cutoff values were independent predictors of in-hospital mortality in patients with CKD. However, in patients with normal renal function, only CK-MB above the cutoff (OR, 2.45; 95% CI, 1.02-8.24; p = 0.046) was a predictor of in-hospital mortality, whereas hs-cTnT was not. There was an inverted V-shaped relationship between the hs-cTnT/CK-MB ratio and in-hospital mortality, with an inflection point of 19.61. The ratio within the second quartile (9.63-19.6) was an independent predictor of in-hospital mortality in patients with CKD (OR 5.3, 95% CI 1.66-16.86, p = 0.005).Conclusions: Hs-cTnT independently predicted in-hospital mortality in AMI patients with CKD, whereas its predictive value was not observed in patients with normal renal function. CK-MB was an independent predictor of in-hospital mortality regardless of renal function. Moreover, the hs-cTnT/CK-MB ratio may aid in risk stratification of AMI patients with CKD.

Bandgap-Engineered Germanene Nanosheets as an Efficient Photodynamic Agent for Cancer Therapy.

Two-dimensional (2D) monoelemental materials (Xenes) show considerable potential in bioapplications owing to their unique 2D physicochemical features and the favored biosafety resulting from their monoelemental composition. However, the narrow band gaps of Xenes prevent their broad applications in biosensors, bioimaging and phototherapeutics. In this study, it is demonstrated that 2D germanene terminated with -H via surface chemical engineering, shows a much broadened direct band gap of 1.65 eV, which enables the material to be used as a novel inorganic photosensitizer for the photodynamic therapy of singlet oxygen. Through theoretical analysis and in vitro studies, H-germanene nanosheets demonstrate a substantially enlarged band gap and favorable biodegradability, demonstrating a substantial cancer treatment capacity. This study demonstrates the feasibility of constructing novel therapeutic photodynamic agents by surface covalent engineering for catalytic tumor therapy.

Water-Enabled H2 Generation from Hydrogenated Silicon Nanosheets for Efficient Anti-Inflammation.

As an emerging therapeutic gas, hydrogen (H2) is gifted with excellent biosafety, high tissue permeability, and radical-trapping capacity and is extensively considered as a highly promising antioxidant in clinics. However, a facile and effective strategy of H2 production for major inflammatory disease treatments is still lacking. In this study, by a facile wet-chemical exfoliation synthesis, a hydrogen-terminated silicon nanosheet (H-silicene) has been synthesized, which can favorably react with environmental water to generate H2 rapidly and continuously without any external energy input. Furthermore, theoretical calculations were employed to reveal the mechanism of enhanced H2 generation efficacy of H-silicene nanosheets. The as-synthesized H-silicene has been explored as a flexible hydrogen gas generator for efficient antioxidative stress application for the first time, which highlights a promising prospect of this two-dimensional H-silicene nanomaterial for acute inflammatory treatments by on-demand H2 production-enabled reactive oxygen species scavenging. This study provides a novel and efficient modality for nanomaterial-mediated H2 therapy.

The KDM6A-SPARCL1 axis blocks metastasis and regulates the tumour microenvironment of gastrointestinal stromal tumours by inhibiting the nuclear translocation of p65.

BACKGROUND: It is urgent to explore the pathogenic mechanism of gastrointestinal stromal tumours (GISTs). KDM6A, a histone demethylase, can activate gene transcription and has not been reported in GISTs. SPARCL1 may serve as a metastasis marker in GIST, but the molecular mechanism remains to be further explored. This study aimed to explore the biological function and molecular mechanism of KDM6A and SPARCL1 in GIST. METHODS: CCK-8, live cell count, colony formation, wound-healing and Transwell migration and invasion assays were employed to detect the cell proliferation, migration and invasion. A xenograft model and hepatic metastasis model were used to assess the role of KDM6A and SPARCL1 in vivo. RESULTS: KDM6A inhibited the proliferation, migration and invasion of GIST cells. Mechanistically, KDM6A promotes the transcription of SPARCL1 by demethylating histone H3 lysine trimethylation and consequently leads to the inactivation of p65. SPARCL1 affected the metastasis of GIST cells in a mesenchymal-epithelial transition- and matrix-metalloproteinase-dependent manner. SPARCL1 knockdown promoted angiogenesis, M2 polarisation and macrophage recruitment by inhibiting the phosphorylation of p65. Moreover, KDM6A and SPARCL1 inhibited hepatic metastasis and macrophage infiltration in vivo. CONCLUSIONS: Our findings establish the critical role of the KDM6A-SPARCL1-p65 axis in restraining the malignancy of GIST.

Single-Molecule Tunneling Sensors for Nitrobenzene Explosives.

The tunneling current through the single-molecule junctions principally offers the ultimate solution for chemical and biochemical sensing via the interactions between probes and target analytes at the single-molecule level. However, it remains unexplored to achieve the sensitive and selective detection of targeted analytes using single-molecule junction techniques due to the challenge in quantitative evaluation of sensing sensitivity and selectivity. Herein, we demonstrate a single-molecule tunneling sensor for the highly sensitive and selective detection of nitrobenzene explosives using scanning tunneling microscope break junction (STM-BJ). Taking advantage of π-π stacking interactions between the molecular probes and nitrobenzene explosives, we use a spectral clustering algorithm to assign the signal of probes and π-stacked probes for sensitively detecting the targeted analytes and the distinguishable conductance change of probes when interacting with different nitroaromatic explosive compounds for selective detection. We find that pronounced conductance changes up to 0.8 orders of magnitude when the probes interact with TNT. Also, we obtain a sensitivity of up to ∼10 pM for TNT and high sensitivity for eight TNT analogues. Combined with theoretical calculations, we discover that the harness of the destructive quantum interference of the probe M1OH after interacting with TNT leads to high selectivity in sensing with TNT. Our work demonstrates the great potential of the single-molecule tunneling current for environmental sensing molecules with high selectivity and sensitivity.

Charge-State Dependent Vibrational Relaxation in a Single-Molecule Junction.

The outcome of an electron-transfer process is determined by the quantum-mechanical interplay between electronic and vibrational degrees of freedom. Nonequilibrium vibrational dynamics are known to direct electron-transfer mechanisms in molecular systems; however, the structural features of a molecule that lead to certain modes being pushed out of equilibrium are not well understood. Herein, we report on electron transport through a porphyrin dimer molecule, weakly coupled to graphene electrodes, that displays sequential tunneling within the Coulomb-blockade regime. The sequential transport is initiated by current-induced phonon absorption and proceeds by rapid sequential transport via a nonequilibrium vibrational distribution of low-energy modes, likely related to torsional molecular motions. We demonstrate that this is an experimental signature of slow vibrational dissipation, and obtain a lower bound for the vibrational relaxation time of 8 ns, a value dependent on the molecular charge state.

Graphene-Based Nanomaterials for Solar-Driven Overall Water Splitting.

Water splitting through photocatalysis and photoelectrochemical methods is a promising strategy for solar energy utilization. Graphene is widely used in solar-driven overall water splitting because of its versatile properties. This review summarizes the preparation of graphene-based photocatalysts and photoelectrodes and the functions of graphene, and highlights the challenges and prospects of the future applications of graphene in solar-driven water splitting.

Ticagrelor versus Clopidogrel in Patients with Severe Renal Insufficiency Undergoing PCI for Acute Coronary Syndrome.

Background: Current guidelines recommend the use of potent antiplatelet agents in patients undergoing percutaneous coronary intervention (PCI) following an acute coronary syndrome (ACS). However, data about optimal platelet inhibition in severe renal insufficiency patients are scarce. The purpose of this study is to determine if ticagrelor is more effective than clopidogrel in patients with ACS and severe renal insufficiency treated with PCI. Methods: We retrospectively enrolled patients with ACS and severe renal insufficiency (eGFR ≤ 30 ml/min·1.73 m2 or dialysis) who underwent PCI at our hospital between January 2015 and March 2020. We used the adjusted Cox proportional hazards models to analyze the 1-year outcome endpoints, including the primary endpoint (the composite of cardiovascular death, recurrence of MI, or nonfatal ischemic stroke), death from any cause, and bleeding events (Bleeding Academic Research Consortium, BARC criteria). Results: A total of 276 patients with ACS and severe renal insufficiency who were treated with PCI with ticagrelor (n = 108) or clopidogrel (n = 168) were included in the study. After adjustment, there was no statistical difference in risk of the primary endpoint (HR, 0.78; 95% CI, 0.46-1.33; P=0.367) and death from any cause (HR, 0.86; 95% CI, 0.38-1.89; P=0.708) in the ticagrelor group against the clopidogrel group. However, the risk of total bleeding was significantly higher in the ticagrelor group (HR, 3.01; 95% CI, 1.81-5.62; P=0.01). Subgroup analysis according to the confounders did not identify any significant subgroup heterogeneity. Conclusion: Ticagrelor did not improve the major adverse cardiovascular events and all-cause mortality when compared to clopidogrel, but significantly increased the risk of bleeding in Chinese patients with ACS and severe renal insufficiency undergoing PCI.

Magnetostrictive-Piezoelectric-Triggered Nanocatalytic Tumor Therapy.

Magnetic-based theranostics feature a high efficiency, excellent tissue penetration, and minimal damage to normal tissues, are noninvasive, and are widely used in the diagnosis and therapy of clinical diseases. Herein, a conceptually novel magnetostrictive-piezoelectric nanocatalytic medicine (MPE-NCM) for tumor therapy is proposed by initiating an intratumoral magneto-driven and piezoelectric-catalyzed reaction using core-shell structured CoFe2O4-BiFeO3 magnetostrictive-piezoelectric nanoparticles (CFO-BFO NPs) under an alternating magnetic field. The CFO-BFO NPs catalyze the generation of cytotoxic reactive oxygen species (ROS): superoxide radicals (•O2-) and hydroxyl radicals (•OH). The simulation calculation demonstrates the highly controllable electric polarization, facilitating the above catalytic reactions under the magnetic stimulation. Both a detailed cell-level assessment and the tumor xenograft evaluation evidence the significant tumor eradication efficacy of MPE-NCM. This study proposes an original and novel magneto-responsive nanocatalytic modality for cancer therapy, which displays promising prospects for the future clinic translation owing to its excellent catalytic dynamic responsiveness, high therapeutic efficacy, and biosafety in vivo.