Enantioselective Cross-[4 + 2]-Cycloaddition/Decarboxylation of 2-Pyrones by Cooperative Catalysis of the Pd(0)/NHC Complex and Chiral Phosphoric Acid.

Here, we describe a cooperative Pd(0)/chiral phosphoric acid catalytic system that allows us to realize the first chemo-, regio-, and enantioselective sequential cross-[4 + 2]-cycloaddition/decarboxylation reaction between 2-pyrones and unactivated acyclic 1,3-dienes. The key to the success of this transformation is the utilization of an achiral N-heterocyclic carbene (NHC) as the ligand and a newly developed chiral phosphoric acid as the cocatalyst. Experimental investigations and computational studies support the idea that the Pd(0)/NHC complex acts as a π-Lewis base to increase the nucleophilicity of 1,3-dienes via η2 coordination, while the chiral phosphoric acid simultaneously increases the electrophilicity of 2-pyrones by hydrogen bonding. By this synergistic catalysis, the sequential cross-[4 + 2]-cycloaddition and decarboxylation reaction proceeds efficiently, enabling the preparation of a wide range of chiral vinyl-substituted 1,3-cyclohexadienes in good yields and enantioselectivities. The synthetic utility of this reaction is demonstrated by synthetic transformations of the product to various valuable chiral six-membered carbocycles.

Optical chaotic communication system based on time-delayed shift keying and common-signal-induced synchronization.

Aiming at the difficulty of traditional chaotic-shift-keying (CSK) systems in resisting return map attacks, we propose an optical chaotic communication system based on time-delayed shift keying and common-signal-induced synchronization. This scheme combines amplified spontaneous emission (ASE) noise, phase modulator (PM), and fiber Bragg grating (FBG) to achieve dual masking in both intensity and phase fields, achieving 10Gb/s information transmission. A common-signal-induced method is used to achieve the synchronization of the system. Moreover, by shifting the time delay as the message-feeding method, the return map attack is effectively resisted, to prevent the amplitude and frequency information of the chaotic attractor from being exposed. In terms of confidentiality and communication performance, this scheme demonstrates good performance of time delay signatures (TDSs) concealment and long-distance transmission capability. In addition, this scheme maintains high sensitivity to key parameters and achieves better confidentiality while increasing the key space.

Melatonin improves influenza virus infection-induced acute exacerbation of COPD by suppressing macrophage M1 polarization and apoptosis.

BACKGROUND: Influenza A viruses (IAV) are extremely common respiratory viruses for the acute exacerbation of chronic obstructive pulmonary disease (AECOPD), in which IAV infection may further evoke abnormal macrophage polarization, amplify cytokine storms. Melatonin exerts potential effects of anti-inflammation and anti-IAV infection, while its effects on IAV infection-induced AECOPD are poorly understood. METHODS: COPD mice models were established through cigarette smoke exposure for consecutive 24 weeks, evaluated by the detection of lung function. AECOPD mice models were established through the intratracheal atomization of influenza A/H3N2 stocks in COPD mice, and were injected intraperitoneally with melatonin (Mel). Then, The polarization of alveolar macrophages (AMs) was assayed by flow cytometry of bronchoalveolar lavage (BAL) cells. In vitro, the effects of melatonin on macrophage polarization were analyzed in IAV-infected Cigarette smoking extract (CSE)-stimulated Raw264.7 macrophages. Moreover, the roles of the melatonin receptors (MTs) in regulating macrophage polarization and apoptosis were determined using MTs antagonist luzindole. RESULTS: The present results demonstrated that IAV/H3N2 infection deteriorated lung function (reduced FEV20,50/FVC), exacerbated lung damages in COPD mice with higher dual polarization of AMs. Melatonin therapy improved airflow limitation and lung damages of AECOPD mice by decreasing IAV nucleoprotein (IAV-NP) protein levels and the M1 polarization of pulmonary macrophages. Furthermore, in CSE-stimulated Raw264.7 cells, IAV infection further promoted the dual polarization of macrophages accompanied with decreased MT1 expression. Melatonin decreased STAT1 phosphorylation, the levels of M1 markers and IAV-NP via MTs reflected by the addition of luzindole. Recombinant IL-1ß attenuated the inhibitory effects of melatonin on IAV infection and STAT1-driven M1 polarization, while its converting enzyme inhibitor VX765 potentiated the inhibitory effects of melatonin on them. Moreover, melatonin inhibited IAV infection-induced apoptosis by suppressing IL-1ß/STAT1 signaling via MTs. CONCLUSIONS: These findings suggested that melatonin inhibited IAV infection, improved lung function and lung damages of AECOPD via suppressing IL-1ß/STAT1-driven macrophage M1 polarization and apoptosis in a MTs-dependent manner. Melatonin may be considered as a potential therapeutic agent for influenza virus infection-induced AECOPD.

Perovskite light-emitting diodes based on spontaneously formed submicrometre-scale structures.

Light-emitting diodes (LEDs), which convert electricity to light, are widely used in modern society-for example, in lighting, flat-panel displays, medical devices and many other situations. Generally, the efficiency of LEDs is limited by nonradiative recombination (whereby charge carriers recombine without releasing photons) and light trapping1-3. In planar LEDs, such as organic LEDs, around 70 to 80 per cent of the light generated from the emitters is trapped in the device4,5, leaving considerable opportunity for improvements in efficiency. Many methods, including the use of diffraction gratings, low-index grids and buckling patterns, have been used to extract the light trapped in LEDs6-9. However, these methods usually involve complicated fabrication processes and can distort the light-output spectrum and directionality6,7. Here we demonstrate efficient and high-brightness electroluminescence from solution-processed perovskites that spontaneously form submicrometre-scale structures, which can efficiently extract light from the device and retain wavelength- and viewing-angle-independent electroluminescence. These perovskites are formed simply by introducing amino-acid additives into the perovskite precursor solutions. Moreover, the additives can effectively passivate perovskite surface defects and reduce nonradiative recombination. Perovskite LEDs with a peak external quantum efficiency of 20.7 per cent (at a current density of 18 milliamperes per square centimetre) and an energy-conversion efficiency of 12 per cent (at a high current density of 100 milliamperes per square centimetre) can be achieved-values that approach those of the best-performing organic LEDs.

The application of phenylboronic acid pinacol ester functionalized ROS-responsive multifunctional nanoparticles in the treatment of Periodontitis.

Periodontitis is an inflammatory disease induced by the complex interactions between the host immune system and the microbiota of dental plaque. Oxidative stress and the inflammatory microenvironment resulting from periodontitis are among the primary factors contributing to the progression of the disease. Additionally, the presence of dental plaque microbiota plays a significant role in affecting the condition. Consequently, treatment strategies for periodontitis should be multi-faceted. In this study, a reactive oxygen species (ROS)-responsive drug delivery system was developed by structurally modifying hyaluronic acid (HA) with phenylboronic acid pinacol ester (PBAP). Curcumin (CUR) was encapsulated in this drug delivery system to form curcumin-loaded nanoparticles (HA@CUR NPs). The release results indicate that CUR can be rapidly released in a ROS environment to reach the concentration required for treatment. In terms of uptake, HA can effectively enhance cellular uptake of NPs because it specifically recognizes CD44 expressed by normal cells. Moreover, HA@CUR NPs not only retained the antimicrobial efficacy of CUR, but also exhibited more pronounced anti-inflammatory and anti-oxidative stress functions both in vivo and in vitro. This provides a good potential drug delivery system for the treatment of periodontitis, and could offer valuable insights for dental therapeutics targeting periodontal diseases.

Exosome lncRNA IFNG-AS1 derived from mesenchymal stem cells of human adipose ameliorates neurogenesis and ASD-like behavior in BTBR mice.

BACKGROUND: The transplantation of exosomes derived from human adipose-derived mesenchymal stem cells (hADSCs) has emerged as a prospective cellular-free therapeutic intervention for the treatment of neurodevelopmental disorders (NDDs), as well as autism spectrum disorder (ASD). Nevertheless, the efficacy of hADSC exosome transplantation for ASD treatment remains to be verified, and the underlying mechanism of action remains unclear. RESULTS: The exosomal long non-coding RNAs (lncRNAs) from hADSC and human umbilical cord mesenchymal stem cells (hUCMSC) were sequenced and 13,915 and 729 lncRNAs were obtained, respectively. The lncRNAs present in hADSC-Exos encompass those found in hUCMSC-Exos and are associated with neurogenesis. The biodistribution of hADSC-Exos in mouse brain ventricles and organoids was tracked, and the cellular uptake of hADSC-Exos was evaluated both in vivo and in vitro. hADSC-Exos promote neurogenesis in brain organoid and ameliorate social deficits in ASD mouse model BTBR T + tf/J (BTBR). Fluorescence in situ hybridization (FISH) confirmed lncRNA Ifngas1 significantly increased in the prefrontal cortex (PFC) of adult mice after hADSC-Exos intraventricular injection. The lncRNA Ifngas1 can act as a molecular sponge for miR-21a-3p to play a regulatory role and promote neurogenesis through the miR-21a-3p/PI3K/AKT axis. CONCLUSION: We demonstrated hADSC-Exos have the ability to confer neuroprotection through functional restoration, attenuation of neuroinflammation, inhibition of neuronal apoptosis, and promotion of neurogenesis both in vitro and in vivo. The hADSC-Exos-derived lncRNA IFNG-AS1 acts as a molecular sponge and facilitates neurogenesis via the miR-21a-3p/PI3K/AKT signaling pathway, thereby exerting a regulatory effect. Our findings suggest a potential therapeutic avenue for individuals with ASD.

Exosome-derived circKIF20B suppresses gefitinib resistance and cell proliferation in non-small cell lung cancer.

BACKGROUND: The gefitinib resistance mechanism in non-small cell lung cancer (NSCLC) remains unclear, albeit exosomal circular RNA (circRNA) is known to possibly play a vital role in it. METHODS: We employed high-throughput sequencing techniques to detect the expressions of exosomal circRNA both in gefitinib-resistant and gefitinib-sensitive cells in this study. The circKIF20B expression was determined in serum exosomes and tissues of patients by qRT-PCR. The structure, stability, and intracellular localization of circKIF20B were verified by Sanger sequencing, Ribonuclease R (RNase R)/actinomycin D (ACTD) treatments, and Fluorescence in situ hybridization (FISH). The functions of circKIF20B were investigated by 5-Ethynyl-20-deoxyuridine (EdU), flow cytometry, Cell Counting Kit-8 (CCK-8), oxygen consumption rate (OCR), and xenograft model. Co-culture experiments were performed to explore the potential ability of exosomal circKIF20B in treating gefitinib resistance. The downstream targets of circKIF20B were determined by luciferase assay, RNA pulldown, and RNA immunoprecipitation (RIP). RESULTS: We found that circKIF20B was poorly expressed in the serum exosomes of gefitinib-resistant patients (n = 24) and the tumor tissues of patients with NSCLC (n = 85). CircKIF20B was negatively correlated with tumor size and tumor stage. Decreasing circKIF20B was found to promote gefitinib resistance by accelerating the cell cycle, inhibiting apoptosis, and enhancing mitochondrial oxidative phosphorylation (OXPHOS), whereas increasing circKIF20B was found to restore gefitinib sensitivity. Mechanistically, circKIF20B is bound to miR-615-3p for regulating the MEF2A and then altering the cell cycle, apoptosis, and mitochondrial OXPHOS. Overexpressing circKIF20B parental cells can restore sensitivity to gefitinib in the recipient cells by upregulating the exosomal circKIF20B expression. CONCLUSIONS: This study revealed a novel mechanism of circKIF20B/miR-615-3p/MEF2A signaling axis involving progression of gefitinib resistance in NSCLC. Exosomal circKIF20B is expected to be an easily accessible and alternative liquid biopsy candidate and potential therapeutic target in gefitinib-resistant NSCLC. The schematic diagram of mechanism in this study. Exosomal circKIF20B inhibits gefitinib resistance and cell proliferation by arresting the cell cycle, promoting apoptosis, and reducing OXPHOS via circKIF20B/miR-615-3p/MEF2A axis in NSCLC.

De novo disruptive heterozygous MMP21 variants are potential predisposing genetic risk factors in Chinese Han heterotaxy children.

BACKGROUND: Heterotaxy syndrome (HTX) is caused by aberrant left-right patterning early in embryonic development, which results in abnormal positioning and morphology of the thoracic and abdominal organs. Currently, genetic testing discerns the underlying genetic cause in less than 20% of sporadic HTX cases, indicating that genetic pathogenesis remains poorly understood. In this study, we aim to garner a deeper understanding of the genetic factors of this disease by documenting the effect of different matrix metalloproteinase 21 (MMP21) variants on disease occurrence and pathogenesis. METHODS: Eighty-one HTX patients with complex congenital heart defects and 89 healthy children were enrolled, and we investigated the pathogenetic variants related to patients with HTX by exome sequencing. Zebrafish splice-blocking Morpholino oligo-mediated transient suppression assays were performed to confirm the potential pathogenicity of missense variants found in these patients with HTX. RESULTS: Three MMP21 heterozygous non-synonymous variants (c.731G > A (p.G244E), c.829C > T (p.L277F), and c.1459A > G (p.K487E)) were identified in three unrelated Chinese Han patients with HTX and complex congenital heart defects. Sanger sequencing confirmed that all variants were de novo. Cell transfection assay showed that none of the variants affect mRNA and protein expression levels of MMP21. Knockdown expression of mmp21 by splice-blocking Morpholino oligo in zebrafish embryos revealed a heart looping disorder, and mutant human MMP21 mRNA (c.731G > A, c.1459A > G, heterozygous mRNA (wild-type&c.731G > A), as well as heterozygous mRNA (wild-type& c.1459A > G) could not effectively rescue the heart looping defects. A patient with the MMP21 p.G244E variant was identified with other potential HTX-causing missense mutations, whereas the patient with the MMP21 p.K487E variant had no genetic mutations in other causative genes related to HTX. CONCLUSION: Our study highlights the role of the disruptive heterozygous MMP21 variant (p.K487E) in the etiology of HTX with complex cardiac malformations and expands the current mutation spectrum of MMP21 in HTX.

Multi-Stimuli-Responsive Nanoparticles Formed of POSS-PEG for the Delivery of Boronic Acid-Containing Therapeutics.

Polymeric vehicles often exhibit batch-to-batch variations due to polydispersity, limiting their reproducibility for biomedical applications. In contrast, polyhedral oligomeric silsesquioxane (POSS) has emerged as an attractive candidate for drug delivery due to its precise chemical structure and rigid molecular shape. A promising strategy to enhance drug efficacy while reducing systemic toxicity is the development of multi-stimuli-responsive delivery systems capable of targeted drug release at a disease site. Herein, we developed a drug delivery platform based on POSS-polymer conjugates. By functionalizing the POSS with amino groups and establishing B-N coordination with boronic acids, the nanoparticles (NPs) exhibit responsive behavior to stimuli, including adenosine-5'-triphosphate (ATP), acidic pH, and nucleophilic reagents. We successfully encapsulated two boronic acid-containing molecules: tetraphenylethylene (TPE), serving as a fluorescent probe, and bortezomib (BTZ), an anticancer drug. The TPE@NPs were employed to visualize the cellular uptake of NPs by tumor cells, while the BTZ@NPs exhibited increased cytotoxicity in tumor cells compared with normal cells. This POSS-PEG conjugate offers a nanoparticle platform for encapsulating versatile boronic acid-containing molecules, thereby enhancing drug efficacy while minimizing systemic toxicity. Given the wide-ranging applications of boronic acid-containing molecules in biomedicine, our platform holds significant promise for the development of intelligent drug delivery systems for diagnostics and therapeutics.

Dynamic hippocampal functional connectivity responses to varying working memory loads following total sleep deprivation.

Sleep loss with work overload can impact human cognitive performance. However, the brain's response to an increased working memory load following total sleep deprivation (TSD) remains unclear. In the present study, we focussed on the dynamic response of the hippocampus to increased working memory load before and after total sleep deprivation of 36 h. A total of 16 male participants completed a verbal working memory task under functional magnetic resonance imaging. After whole-brain activation analysis and region of interest analysis of the hippocampus, the generalised form of context-dependent psychophysiological interactions (gPPI) was used to analyse the hippocampal functional connectivity with the whole brain. The results revealed that as the working memory load increased within a small range, from 0-back to 1-back task, the left hippocampal functional connectivity decreased with the left supplementary motor area, left pars opercularis, left rolandic operculum, right superior frontal gyrus, bilateral precentral gyrus, and left middle cingulate cortex following total sleep deprivation compared with that observed in resting wakefulness. When the working memory load further increased from 1-back to 2-back task, the connectivity increased between the left hippocampus and the left superior parietal lobule as well as between the left hippocampus and right lingual gyrus after total sleep deprivation compared with that observed in resting wakefulness. Moreover, the left hippocampus gPPI effect on the left middle cingulate cortex and left superior parietal lobule could predict the behavioural test accuracy in 1-back and 2-back task, respectively, following total sleep deprivation. These findings indicated that increased working memory load after total sleep deprivation disrupts working memory processes. The brain reacts to these disruptions in a dynamic and flexible manner, involving not only brain activation but also hippocampus-related functional network connections.

Unexpected electro-catalytic activity of the CO reduction reaction on Cr-embedded poly-phthalocyanine realized by strain engineering: a computational study.

The electrochemical conversion of carbon monoxide (CO) into value-added products is highly promising for carbon utilization and CO removal. Based on previous theoretical studies, we computationally explored the effect of strain engineering on electrocatalysis of the CO reduction reaction (CORR) by two-dimensional (2D) transition metal embedded polyphthalocyanines (MPPcs). By calculating the adsorption energy of CO and the free energies of key intermediates on the MPPcs under uniaxial and biaxial strains, it was revealed that only CrPPc under biaxial strain has the potential to exhibit significant enhancement of the catalytic performance. The free energy diagrams of the CORR catalyzed by CrPPc were plotted under specific biaxial strains, where both the optimal reaction pathway and rate-determining step are found to be evidently changed. What's more, the 5% compressive strain imposed on CrPPc results in an ultra-low limiting potential (UL = -0.09 V) with high selectivity on CH4 as the final product, indicating unexpected electro-catalytic activity. Our study clearly elucidates that moderate strain could greatly enhance the electrocatalytic performance of 2D materials in the CORR.

Muscle cytotoxicity and immuno-reactivity analysis of the porous carbon nanospheres fabricated by high temperature calcination.

Carbon-based nanomaterials have a high specific surface area, biocompatibility, and controlled mesopore structures. These characteristics make carbon nanospheres excellent carriers for drugs, biological dyes, photosensitizers, etc. Nevertheless, little is known about the impact of topological features on the surface of carbon nanomaterials on their in vivo immunoreactivity. In this study, we fabricated mesoporous carbon nanoparticles (MCNs) and solvent-processable carbon vesicles (CVs) by high-temperature calcination. The hematoxylin and eosin (H&E) staining suggested CVs' relatively poor dispersion capacity compared to MCNs and carbon precursors (CPs), leading to more severe muscle inflammation and necrosis. Immunostaining and Fluorescence Activated Cell Sorter (FACS) analysis further showed that both MCNs and CVs triggered a transient immune response in transplanted muscle and muscle-draining lymph nodes, but did not alter muscle resistance to exogenous viruses. In conclusion, this study provides insights into how carbon nanoparticles modulate the activation of immune responses in vivo.

Aquaporins in Nervous System.

Aquaporins (AQPs) mediate water flux between the four distinct water compartments in the central nervous system (CNS). In the present chapter, we mainly focus on the expression and function of the nine AQPs expressed in the CNS, which include five members of aquaporin subfamily: AQP1, AQP4, AQP5, AQP6, and AQP8; three members of aquaglyceroporin subfamily: AQP3, AQP7, and AQP9; and one member of superaquaporin subfamily: AQP11. In addition, AQP1, AQP2, and AQP4 expressed in the peripheral nervous system are also reviewed. AQP4, the predominant water channel in the CNS, is involved both in the astrocyte swelling of cytotoxic edema and the resolution of vasogenic edema and is of pivotal importance in the pathology of brain disorders such as neuromyelitis optica, brain tumors, and neurodegenerative disorders. Moreover, AQP4 has been demonstrated as a functional regulator of recently discovered glymphatic system that is a main contributor to clearance of toxic macromolecule from the brain. Other AQPs are also involved in a variety of important physiological and pathological process in the brain. It has been suggested that AQPs could represent an important target in treatment of brain disorders like cerebral edema. Future investigations are necessary to elucidate the pathological significance of AQPs in the CNS.

Deciphering molecular mechanisms of phase separation in RNA biology by single-molecule biophysical technologies.

Ribonucleic acid (RNA) biology has emerged as one of the most important areas in modern biology and biomedicine. RNA and RNA-binding proteins (RBPs) are involved in forming biomolecular condensates, which are crucial for RNA metabolism. To quantitively decipher the molecular mechanisms of RNP granules, researchers have turned to single-molecule biophysical techniques, such as single-molecule Förster resonance energy transfer (smFRET), in vivo single-molecule imaging technique with single particle tracking (SPT), DNA Curtains, optical tweezers, and atomic force microscopy (AFM). These methods are used to investigate the molecular biophysical properties within RNP granules, as well as the molecular interactions between RNA and RBPs and RBPs themselves, which are challenging to study using traditional experimental methods of the liquid-liquid phase separation (LLPS) field, such as fluorescence recovery after photobleaching (FRAP). In this work, we summarize the applications of single-molecule biophysical techniques in RNP granule studies and highlight how these methods can be used to reveal the molecular mechanisms of RNP granules.

Cognitive appraisal of health and its influencing factors among pregnant women with gestational diabetes mellitus: A cross-sectional study.

AIM: To investigate the status quo of cognitive appraisal of health and its influencing factors among pregnant women with gestational diabetes mellitus. METHODS: A cross-sectional survey was conducted from June 2020 to November 2020. Participants were recruited from a tertiary hospital by a convenient sample method. A total of 300 pregnant women with gestational diabetes mellitus completed the survey, including self-compiled individual information questionnaire, Cognitive Appraisal of Health Scale, Pregnancy Stress Rating Scale and General Self-Efficacy Scale. RESULTS: For cognitive appraisal of health, the median score of challenge dimension was 3.75 (3.50, 4.00), benign/irrelevant was 2.75 (2.00, 3.50), harm/loss was 2.38 (2.00, 3.00) and threat was 2.40 (2.00, 2.80), respectively. Regression analyses showed that gestational age, mode of conception, history of abortion, insulin usage, pregnancy stress and self-efficacy were the predictors of cognitive appraisal of health. CONCLUSIONS: This study revealed that pregnant women with gestational diabetes mellitus tended to make positive cognitive appraisal of health. And healthcare providers need to make full use of their predictors of cognitive appraisal of health to improve cognitive appraisal to manage stress and ameliorate pregnancy outcomes.

Effects of decision aids on breast reconstruction: A systematic review and meta-analysis of randomised controlled trials.

AIMS AND OBJECTIVES: To systematically evaluate the effects of decision aids for women facing breast reconstruction decision on decision conflict, decision regret, knowledge, satisfaction, anxiety and depression. BACKGROUND: Breast reconstruction decision is not good or bad and should be guided by clinical evidence and patient preferences. Decision aids can increase the patient's decision-making enthusiasm and ability, improve the quality of decision and promote shared decision-making between patients and medical staff. DESIGN: Systematic review and meta-analysis. METHODS: Eight databases were conducted from the establishment of the database until October 2021. The PRISMA checklist was selected for analysis in this paper. The meta-analysis was conducted in Review Manager 5.3. The quality of the studies was assessed using the Cochrane risk-of-bias tool. The result is decision conflict, decision regret, knowledge and other secondary outcomes. Sensitivity analysis and subgroup analysis were also conducted. RESULTS: A total of twelve randomised controlled trials (RCTs) were included in the systematic review and meta-analysis. Meta-analysis revealed that decision aids could significantly reduce decision conflict and decision regret, improve knowledge, satisfaction and depression and had no influence on anxiety. CONCLUSIONS: The results of the systematic review and meta-analysis reviewed the positive effect of decision aids on the decision-making of women facing postmastectomy breast reconstruction. In the future, more well-designed RCTs are needed to confirm the effects of decision aids on the decision-making of breast reconstruction and nurses should be encouraged to take part in the development of decision aids in accordance with strict standards and apply them to breast cancer patients considering postmastectomy breast reconstruction. RELEVANCE TO CLINICAL PRACTICE: Our study provides evidence for the effectiveness of decision aids on breast reconstruction and points to the important role of healthcare providers in the use of decision aids and in facilitating shared decision-making.

Cardiac-Specific Expression of Cre Recombinase Leads to Age-Related Cardiac Dysfunction Associated with Tumor-like Growth of Atrial Cardiomyocyte and Ventricular Fibrosis and Ferroptosis.

Transgenic expression of Cre recombinase driven by a specific promoter is normally used to conditionally knockout a gene in a tissue- or cell-type-specific manner. In αMHC-Cre transgenic mouse model, expression of Cre recombinase is controlled by the myocardial-specific α-myosin heavy chain (αMHC) promoter, which is commonly used to edit myocardial-specific genes. Toxic effects of Cre expression have been reported, including intro-chromosome rearrangements, micronuclei formation and other forms of DNA damage, and cardiomyopathy was observed in cardiac-specific Cre transgenic mice. However, mechanisms associated with Cardiotoxicity of Cre remain poorly understood. In our study, our data unveiled that αMHC-Cre mice developed arrhythmias and died after six months progressively, and none of them survived more than one year. Histopathological examination showed that αMHC-Cre mice had aberrant proliferation of tumor-like tissue in the atrial chamber extended from and vacuolation of ventricular myocytes. Furthermore, the αMHC-Cre mice developed severe cardiac interstitial and perivascular fibrosis, accompanied by significant increase of expression levels of MMP-2 and MMP-9 in the cardiac atrium and ventricular. Moreover, cardiac-specific expression of Cre led to disintegration of the intercalated disc, along with altered proteins expression of the disc and calcium-handling abnormality. Comprehensively, we identified that the ferroptosis signaling pathway is involved in heart failure caused by cardiac-specific expression of Cre, on which oxidative stress results in cytoplasmic vacuole accumulation of lipid peroxidation on the myocardial cell membrane. Taken together, these results revealed that cardiac-specific expression of Cre recombinase can lead to atrial mesenchymal tumor-like growth in the mice, which causes cardiac dysfunction, including cardiac fibrosis, reduction of the intercalated disc and cardiomyocytes ferroptosis at the age older than six months in mice. Our study suggests that αMHC-Cre mouse models are effective in young mice, but not in old mice. Researchers need to be particularly careful when using αMHC-Cre mouse model to interpret those phenotypic impacts of gene responses. As the Cre-associated cardiac pathology matched mostly to that of the patients, the model could also be employed for investigating age-related cardiac dysfunction.

Towards energy conservation by constructing more transportation infrastructure?: An endogenous stochastic frontier analysis framework.

Whether constructing more transportation infrastructure can be helpful for the achievement of energy conservation is a long-running and debatable issue. To answer this question, the relationship between transportation infrastructure and energy efficiency must first be clarified. Nonetheless, the existence of the endogeneity problem poses a challenge to defining the relationship. In this paper, an endogenous stochastic frontier analysis method is used to investigate the influence of transportation infrastructure on energy efficiency. Based on the prefecture-city level panel data in China, we find that after addressing the endogeneity problem, the impact of transportation infrastructure on energy efficiency increases dramatically. Moreover, this impact is more pronounced in small-scale cities compared to large and medium-scale cities. Regardless of the measurement of transportation infrastructure, instrumental variable, or production function form, we get the similar conclusions, demonstrating the robustness of our findings. Additional simulation analysis shows that the energy conservation potential would be 1222-2935 million kilowatt hours if the level of transportation infrastructure could be optimized. We recommend accelerating the transportation infrastructure construction, particularly in the small-scale cities so as to boost the energy efficiency and achieve energy conservation targets.

Piezocatalytic Techniques in Environmental Remediation.

As a consequence of rapid industrialization throughout the world, various environmental pollutants have begun to accumulate in water, air, and soil. This endangers the ecological environment of the earth, and environmental remediation has become an immediate priority. Among various environmental remediation techniques, piezocatalytic techniques, which uniquely take advantage of the piezoelectric effect, have attracted much attention. Piezoelectric effects allow pollutant degradation directly, while also enhancing photocatalysis by reducing the recombination of photogenerated carriers. In this Review, we provide a comprehensive summary of recent developments in piezocatalytic techniques for environmental remediation. The origin of the piezoelectric effect as well as classification of piezoelectric materials and their application in environmental remediation are systematically summarized. We also analyze the potential underlying mechanisms. Finally, urgent problems and the future development of piezocatalytic techniques are discussed.

Enantioselective Synthesis of cis-Decalins by Merging the Birch Reduction and Inverse-Electron-Demand Diels-Alder Reaction.

Herein, we show that the combination of the Birch reduction of readily available anisole derivatives and the catalytic asymmetric inverse-electron-demand Diels-Alder reaction of 2-pyrones can serve as a powerful platform for the diverse synthesis of synthetically important cis-decalin scaffolds. Enabled by a well-modified chiral bis(oxazoline) ligand/CuII complex, a wide range of polysubstituted cis-decalin scaffolds with up to six contiguous stereocenters were generated efficiently. The synthetic potential of this method is demonstrated by the concise synthesis of the sesquiterpene (+)-occidentalol and a key intermediate for seven triterpenes. Mechanistic studies suggest the 1,3-cyclohexadienes formed in situ are the key intermediates, and efficient kinetic resolution occurs when C2- and/or C3-substituted 1,4-cyclohexadienes are utilized as substrates. DFT calculations elucidated that the Diels-Alder reaction proceeds in a stepwise fashion and revealed the origins of the stereoselectivities.