Nitrogen-doped amorphous monolayer carbon.

Monoatomic-layered carbon materials, such as graphene1 and amorphous monolayer carbon2,3, have stimulated intense fundamental and applied research owing to their unprecedented physical properties and a wide range of promising applications4,5. So far, such materials have mainly been produced by chemical vapour deposition, which typically requires stringent reaction conditions compared to solution-phase synthesis. Herein, we demonstrate the solution preparation of free-standing nitrogen-doped amorphous monolayer carbon with mixed five-, six- and seven-membered (5-6-7-membered) rings through the polymerization of pyrrole within the confined interlayer cavity of a removable layered-double-hydroxide template. Structural characterizations and first-principles calculations suggest that the nitrogen-doped amorphous monolayer carbon was formed by radical polymerization of pyrrole at the α, ß and N sites subjected to confinement of the reaction space, which enables bond rearrangements through the Stone-Wales transformation. The spatial confinement inhibits the C-C bond rotation and chain entanglement during polymerization, resulting in an atom-thick continuous amorphous layer with an in-plane π-conjugation electronic structure. The spatially confined radical polymerization using solid templates and ion exchange strategy demonstrates potential as a universal synthesis approach for obtaining two-dimensional covalent networks, as exemplified by the successful synthesis of monolayers of polythiophene and polycarbazole.

Quaternary-centre-guided synthesis of complex polycyclic terpenes.

The presence of a quaternary centre-a carbon with four other carbons bonded to it-in any given molecule can have a substantial chemical and biological impact. In many cases, it can enable otherwise challenging chemistry. For example, quaternary centres induce large rate enhancements in cyclization reactions-known as the Thorpe-Ingold effect-which has application in drug delivery for molecules with modest bioavailability1. Similarly, the addition of quaternary centres to a drug candidate can enhance both its activity and its metabolic stability2. When present in chiral ligands3, catalysts4 and auxiliaries5, quaternary centres can guide reactions toward both improved and unique regio-, stereo- and/or enantioselectivity. However, owing to their distinct steric congestion and conformational restriction, the formation of quaternary centres can be achieved reliably by only a few chemical transformations6,7. For particularly challenging cases-for example, the vicinal all-carbon8, oxa- and aza-quaternary centres9 in molecules such as azadirachtin10,11, scopadulcic acid A12,13 and acutumine14-the development of target-specific approaches as well as multiple functional-group and redox manipulations is often necessary. It is therefore desirable to establish alternative ways in which quaternary centres can positively affect and guide synthetic planning. Here we show that if a synthesis is designed such that each quaternary centre is deliberately leveraged to simplify the construction of the next-either through rate acceleration or blocking effects-then highly efficient, scalable and modular syntheses can result. This approach is illustrated using the conidiogenone family of terpenes as a representative case; however, this framework provides a distinct planning logic that is applicable to other targets of similar synthetic complexity that contain multiple quaternary centres.

Divergent Synthesis of Scabrolide A and Havellockate via an exo-exo-endo Radical Cascade.

Here we report a concise and divergent synthesis of scabrolide A and havellockate, representative members of polycyclic marine natural product furano(nor)cembranoids. The synthesis features a highly efficient exo-exo-endo radical cascade. Through the generation of two rings, three C-C bonds, and three contiguous stereocenters in one step, this remarkable transformation not only assembles the bowl-shaped, common 6-5-5 fused ring system from simple building blocks but also precisely installs the functionalities at desired positions and sets the stage for further divergent preparation of both target molecules. Further studies reveal that the robust and unusual 6-endo radical addition in the cascade is likely facilitated by the rigidity of the substrate.

Beyond weight loss: the potential of glucagon-like peptide-1 receptor agonists for treating heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome with various phenotypes, and obesity is one of the most common and clinically relevant phenotypes of HFpEF. Obesity contributes to HFpEF through multiple mechanisms, including sodium retention, neurohormonal dysregulation, altered energy substrate metabolism, expansion of visceral adipose tissue, and low-grade systemic inflammation. Glucagon-like peptide-1 (GLP-1) is a hormone in the incretin family. It is produced by specialized cells called neuroendocrine L cells located in the distal ileum and colon. GLP-1 reduces blood glucose levels by promoting glucose-dependent insulin secretion from pancreatic ß cells, suppressing glucagon release from pancreatic α cells, and blocking hepatic gluconeogenesis. Recent evidence suggests that GLP-1 receptor agonists (GLP-1 RAs) can significantly improve physical activity limitations and exercise capacity in obese patients with HFpEF. The possible cardioprotective mechanisms of GLP-1 RAs include reducing epicardial fat tissue thickness, preventing activation of the renin-angiotensin-aldosterone system, improving myocardial energy metabolism, reducing systemic inflammation and cardiac oxidative stress, and delaying the progression of atherosclerosis. This review examines the impact of obesity on the underlying mechanisms of HFpEF, summarizes the trial data on cardiovascular outcomes of GLP-1 RAs in patients with type 2 diabetes mellitus, and highlights the potential cardioprotective mechanisms of GLP-1 RAs to give a pathophysiological and clinical rationale for using GLP-1 RAs in obese HFpEF patients.

Reciprocal negative feedback between Prrx1 and miR-140-3p regulates rapid chondrogenesis in the regenerating antler.

During growth phase, antlers exhibit a very rapid rate of chondrogenesis. The antler is formed from its growth center reserve mesenchyme (RM) cells, which have been found to be the derivatives of paired related homeobox 1 (Prrx1)-positive periosteal cells. However, the underlying mechanism that drives rapid chondrogenesis is not known. Herein, the miRNA expression profiles and chromatin states of three tissue layers (RM, precartilage, and cartilage) at different stages of differentiation within the antler growth center were analyzed by RNA-sequencing and ATAC-sequencing. We found that miR-140-3p was the miRNA that exhibited the greatest degree of upregulation in the rapidly growing antler, increasing from the RM to the cartilage layer. We also showed that Prrx1 was a key upstream regulator of miR-140-3p, which firmly confirmed by Prrx1 CUT&Tag sequencing of RM cells. Through multiple approaches (three-dimensional chondrogenic culture and xenogeneic antler model), we demonstrated that Prrx1 and miR-140-3p functioned as reciprocal negative feedback in the antler growth center, and downregulating PRRX1/upregulating miR-140-3p promoted rapid chondrogenesis of RM cells and xenogeneic antler. Thus, we conclude that the reciprocal negative feedback between Prrx1 and miR-140-3p is essential for balancing mesenchymal proliferation and chondrogenic differentiation in the regenerating antler. We further propose that the mechanism underlying chondrogenesis in the regenerating antler would provide a reference for helping understand the regulation of human cartilage regeneration and repair.

Multiomic meta-analysis suggests a correlation between steroid hormone-related genes and litter size in goats.

Litter size is a key indicator of production performance in livestock. However, its genetic basis in goats remains poorly understood. In this work, a genome-wide selection sweep analysis (GWSA) on 100 published goat genomes with different litter rates was performed for the first time to identify candidate genes related to kidding rate. This analysis was combined with the public RNA-sequencing data of ovary tissues (follicular phase) from high- and low-yielding goats. A total of 2278 genes were identified by GWSA. Most of these genes were enriched in signaling pathways related to ovarian follicle development and hormone secretion. Moreover, 208 differentially expressed genes between groups were obtained from the ovaries of goats with different litter sizes. These genes were substantially enriched in the cholesterol and steroid synthesis signaling pathways. Meanwhile, the weighted gene co-expression network was used to perform modular analysis of differentially expressed genes. The results showed that seven modules were reconstructed, of which one module showed a very strong correlation with litter size (r = -0.51 and p-value <0.001). There were 51 genes in this module, and 39 hub genes were screened by Pearson's correlation coefficient between core genes > 0.4, correlation coefficient between module members > 0.80 and intra-module connectivity ≥5. Finally, based on the results of GWSA and hub gene Venn analysis, seven key genes (ACSS2, HECW2, KDR, LHCGR, NAMPT, PTGFR and TFPI) were found to be associated with steroid synthesis and follicle growth development. This work contributes to understanding of the genetic basis of goat litter size and provides theoretical support for goat molecular breeding.

Electrochemical Azo-free Mitsunobu-type Reaction.

The classic chemical Mitsunobu reaction suffers from the need of excess alcohol activation reagents and the generation of significant by-products. Efforts to overcome these limitations have resulted in numerous creative solutions, but the substrate scope of these catalytic processes remains limited. Here we report an electrochemical Mitsunobu-type reaction, which features azo-free alcohol activation and broad substrate scope. This user-friendly technology allows a vast collection of heterocycles as the nucleophile, which can couple with a series of chiral cyclic and acyclic alcohols in moderate to high yields and excellent ee's. This practical reaction is scalable, chemoselective, uses simple Electrasyn setup with inexpensive electrodes and requires no precaution to exclude air and moisture. The synthetic utility is further demonstrated on the structural modification of diverse bioactive natural products and pharmaceutical derivatives and its straightforward application in a multiple-step synthesis of a drug candidate.

Polyoxometalates-Mediated Selectivity in Pt Single-Atoms on Ceria for Environmental Catalysis.

Optimizing the reactivity and selectivity of single-atom catalysts (SACs) remains a crucial yet challenging issue in heterogeneous catalysis. This study demonstrates selective catalysis facilitated by a polyoxometalates-mediated electronic interaction (PMEI) in a Pt single-atom catalyst supported on CeO2 modified with Keggin-type phosphotungstate acid (HPW), labeled as Pt1/CeO2-HPW. The PMEI effect originates from the unique arrangement of isolated Pt atoms and HPW clusters on CeO2 surface. Electrons are transferred from ceria support to the electrophilic tungsten in HPW clusters, and subsequently, Pt atoms donate electrons to the now electron-deficient ceria. This phenomenon enhances the positive charge of Pt atoms, moderating O2 activation and limiting lattice oxygen mobility compared to the conventional Pt1/CeO2 catalyst. The resulting electronic structure of Pt combined with the strong and local acidic environment of HPW on Pt1/CeO2-HPW leads to improved degradation of NH3, N2 selectivity in the NO conversion, and CO2 yield when inputting volatile organic compounds. This study sheds the light on the design of SACs with balanced reactivity and selectivity for environmental catalysis applications.

Hybrid Lamellar Superlattices with Monoatomic Platinum Layers and Programmable Organic Ligands.

Compared with layered materials such as graphite and transitional metal dichalcogenides with highly anisotropic in-plane covalent bonds, freestanding metallic two-dimensional (2D) films with atomic thickness are intrinsically more difficult to achieve. The omnidirectional nature of typical metallic bonds prevents the formation of highly anisotropic atomically thin metallic layers. Herein, we report a ligand regulation strategy to stabilize monoatomic platinum layers by forming a unique lamellar superlattice structure with self-assembled organic ligand layers. We show that the interlayer spacings and coordination environments could be systematically tuned by varying programmable molecular ligands with the designed length and structural motifs, which further modulate the electronic states and catalytic performances. The strategy can be extended for preparing lamellar superlattices with monoatomic metallic layers from silver and gold. Such general and delicate synthetic control provides an exciting model system for systematic investigation of the intriguing structure-property correlation of monoatomic layers and promises a molecular design pathway for heterogeneous catalysts.

Study on Clinicopathological Features and Risk Factors of Patients with Multiple Primary Breast Cancers and Thyroid Disease.

Objective: To explore the clinicopathological features and risk factors of patients with multiple primary breast cancers and thyroid disease. Method: An analytic approach of the reviewing method was adopted to analyze the clinical data of 80 breast cancer patients who were admitted to our hospital from January 2020 to January 2022. They were divided into an observation group (breast cancer with thyroid lesions) and a control group (simple breast cancer) according to whether the clinical data were accompanied with thyroid lesions to compare the clinical characteristics, pathological types, staging characteristics, and molecular biological characteristics of the two groups and to research the risk factors of the two groups. Result: (1) In the comparison of clinical data, the number of people aged ≥60 in the observation group was higher than that in the control group, and there was significant difference between the groups in the menopausal status data (P < 0.05). There was no statistical difference between the observation group and the control group in the comparison of clinical data of the body mass index, pregnancy frequency, labor frequency, and abortion history (P > 0.05). (2) In the comparison of pathological type and staging data, there was no statistical difference in the comparison of data on the pathological type, histological grade, T staging, N staging, and TNM staging between the observation group and the control group (P > 0.05). (3) In the comparison of data on molecular biology characteristics, there was a statistical difference in the nuclear proliferation antigen data between the observation group and the control group (P < 0.05). There was no statistical difference in the comparison of data on the estrogen receptor, progesterone receptor, human epidermal growth factor receptor-2, and molecular typing between the observation group and the control group (P > 0.05). (4) Logistic regression analysis showed that age, menopausal status, and nuclear proliferation antigen index were the high-risk inflammatory factors for combined thyroid lesions (P < 0.05). Conclusion: For patients with simple breast cancer, age, menopausal status, and nuclear proliferation antigen index are risk factors for combined thyroid lesions. Therefore, clinical attention should be paid to the above factors in the process of clinical treatment, and early-risk screening should be performed to achieve the purpose of improving the prognosis to the greatest extent.

Naringenin facilitates M2 macrophage polarization after myocardial ischemia-reperfusion by promoting nuclear translocation of transcription factor EB and inhibiting the NLRP3 inflammasome pathway.

Myocardial ischemia-reperfusion injury (MIRI) remains an unsolved puzzle in medical circles. Naringenin (NAR) is a flavonoid with cardioprotective potential. The purpose of this article was to discuss the protective mechanism of NAR in MIRI by regulating macrophage polarization. The MIRI mouse model was established and perfused with NAR before surgery. In the in vitro experiment, macrophages RAW264.7 were treated with lipopolysaccharide to induce M1 polarization after pretreatment with NAR. Rescue experiments were carried out to validate the functions of transcription factor EB (TFEB), the NLR pyrin domain containing 3 (NLRP3) inflammasome, and autophagy in macrophage polarization. NAR reduced histopathological injury and infarction of myocardial tissues in MIRI mice, inhibited M1 polarization and promoted M2 polarization of macrophages, diminished levels of pro-inflammatory factors, and augmented levels of anti-inflammatory factors. NAR facilitated TFEB nuclear translocation and inhibited the NLRP3 inflammasome pathway. Silencing TFEB or Nigericin partly nullified the effect of NAR on macrophage polarization. NAR increased autophagosome formation, autophagy flux, and autophagy level. Autophagy inhibitor 3-methyladenine partly invalidated the inhibition of NAR on the NLRP3 inflammasome pathway. In animal experiments, NAR protected MIRI mice through the TFEB-autophagy-NLRP3 inflammasome pathway. Collectively, NAR inhibited NLRP3 inflammasome activation and facilitated M2 macrophage polarization by stimulating TFEB nuclear translocation, thus protecting against MIRI.

Smart Grid Outlier Detection Based on the Minorization-Maximization Algorithm.

Outliers can be generated in the power system due to aging system equipment, faulty sensors, incorrect line connections, etc. The existence of these outliers will pose a threat to the safe operation of the power system, reduce the quality of the data, affect the completeness and accuracy of the data, and thus affect the monitoring analysis and control of the power system. Therefore, timely identification and treatment of outliers are essential to ensure stable and reliable operation of the power system. In this paper, we consider the problem of detecting and localizing outliers in power systems. The paper proposes a Minorization-Maximization (MM) algorithm for outlier detection and localization and an estimation of unknown parameters of the Gaussian mixture model (GMM). To verify the performance of the method, we conduct simulation experiments by simulating different test scenarios in the IEEE 14-bus system. Numerical examples show that in the presence of outliers, the MM algorithm can detect outliers better than the traditional algorithm and can accurately locate outliers with a probability of more than 95%. Therefore, the algorithm provides an effective method for the handling of outliers in the power system, which helps to improve the monitoring analyzing and controlling ability of the power system and to ensure the stable and reliable operation of the power system.

Detection of False Data Injection Attacks in Smart Grids Based on Expectation Maximization.

The secure operation of smart grids is closely linked to state estimates that accurately reflect the physical characteristics of the grid. However, well-designed false data injection attacks (FDIAs) can manipulate the process of state estimation by injecting malicious data into the measurement data while bypassing the detection of the security system, ultimately causing the results of state estimation to deviate from secure values. Since FDIAs tampering with the measurement data of some buses will lead to error offset, this paper proposes an attack-detection algorithm based on statistical learning according to the different characteristic parameters of measurement error before and after tampering. In order to detect and classify false data from the measurement data, in this paper, we report the model establishment and estimation of error parameters for the tampered measurement data by combining the the k-means++ algorithm with the expectation maximization (EM) algorithm. At the same time, we located and recorded the bus that the attacker attempted to tamper with. In order to verify the feasibility of the algorithm proposed in this paper, the IEEE 5-bus standard test system and the IEEE 14-bus standard test system were used for simulation analysis. Numerical examples demonstrate that the combined use of the two algorithms can decrease the detection time to less than 0.011883 s and correctly locate the false data with a probability of more than 95%.

Joint multiscale cloud detection algorithm for ground-based lidar.

A ground-based lidar is a powerful tool for studying the vertical structure and optical properties of clouds. A layer detection algorithm is important to determine the presence and spatial position of clouds from vast lidar signals. However, current detection algorithms for ground-based lidar still involve substantial missing and false detections for tenuous layers and layer edges. Here, a joint multiscale cloud layer detection algorithm is proposed. The algorithm can effectively capture the tenuous layers and layer edges by using joint multiscale detection methods based on a trend function and the Bernoulli distribution assumption. Results show that the proposed algorithm detects 10.45% more cloud layers than the official cloud product of Micro Pulse Lidar Network (MPLNET) does. Specifically, 7.93% and 12.57% more cloud layers are detected at daytime and nighttime, respectively. The evaluation based on depolarization properties proves that the additional cloud layers detected by the joint multiscale algorithm are reliable. These additional detected clouds have important implications for cloud climatology and climate change research. The new algorithm remarkably enhances the cloud detection capability of ground-based lidar and potentially be widely used by the community.

Effect of Surface Heterogeneities on Interactions between Air Bubbles and Heterogeneous Surfaces.

The effects of surface heterogeneities on bubble-particle interactions have received little attention although heterogeneities are common for varieties of substance surfaces. In this work, heterogeneous surfaces consisting of discrete hydrophilic dots on a hydrophobic background were fabricated. The interactions between air bubbles and heterogeneous surfaces with different hydrophilic area fractions were investigated using a high-sensitivity microbalance coupled with a high-speed video camera. It was found that the snap-in, maximum adhesion, and pull-off forces increased as the hydrophilic area fraction decreased. These experimental results were compared with the calculated interaction forces. The comparison between experimental results and the calculated interaction forces showed that the normalized contact line length (δ) should be considered in the calculation of the snap-in force, and its value was between 1 and the δ value corresponding to the maximum pinning strength. In contrast, δ = 1 is more appropriate for the calculation of maximum adhesion force, indicating that the corrugations in the three-phase contact line could be neglected. These findings demonstrate that discrete hydrophilic defects make bubble-surface attachment difficult but have nearly no effect on bubble-surface detachment. Better understanding of the interactions between air bubbles and heterogeneous surfaces potential offers a new thought to control the bubble-particle interactions using appropriately design of particle surfaces.

N-Ammonium Ylide Mediators for Electrochemical C-H Oxidation.

The site-specific oxidation of strong C(sp3)-H bonds is of uncontested utility in organic synthesis. From simplifying access to metabolites and late-stage diversification of lead compounds to truncating retrosynthetic plans, there is a growing need for new reagents and methods for achieving such a transformation in both academic and industrial circles. One main drawback of current chemical reagents is the lack of diversity with regard to structure and reactivity that prevents a combinatorial approach for rapid screening to be employed. In that regard, directed evolution still holds the greatest promise for achieving complex C-H oxidations in a variety of complex settings. Herein we present a rationally designed platform that provides a step toward this challenge using N-ammonium ylides as electrochemically driven oxidants for site-specific, chemoselective C(sp3)-H oxidation. By taking a first-principles approach guided by computation, these new mediators were identified and rapidly expanded into a library using ubiquitous building blocks and trivial synthesis techniques. The ylide-based approach to C-H oxidation exhibits tunable selectivity that is often exclusive to this class of oxidants and can be applied to real-world problems in the agricultural and pharmaceutical sectors.

Electroreductive Olefin-Ketone Coupling.

A user-friendly approach is presented to sidestep the venerable Grignard addition to unactivated ketones to access tertiary alcohols by reversing the polarity of the disconnection. In this work a ketone instead acts as a nucleophile when adding to simple unactivated olefins to accomplish the same overall transformation. The scope of this coupling is broad as enabled using an electrochemical approach, and the reaction is scalable, chemoselective, and requires no precaution to exclude air or water. Multiple applications demonstrate the simplifying nature of the reaction on multistep synthesis, and mechanistic studies point to an intuitive mechanism reminiscent of other chemical reductants such as SmI2 (which cannot accomplish the same reaction).

lncRNA PVT1 aggravates doxorubicin-induced cardiomyocyte apoptosis by targeting the miR-187-3p/AGO1 axis.

OBJECTIVES: To investigate the effect of long non-coding (lnc) RNA PVT1 on apoptosis induced by doxorubicin-induced cardiotoxicity. METHODS: We analyzed the expression levels of lncRNA PVT1, miR-187-3p, using reverse transcription real-time quantitative PCR (RT-qPCR) in doxorubicin-treated cardiomyocytes. The mechanism of lncRNA PVT1 in cardiotoxicity was investigated using cell transfection, CCK-8, flow cytometry, Western blot, and dual-luciferase reporter assays. RESULTS: Doxorubicin promotes H9c2 apoptosis and increased PVT1 expression in cardiomyocytes. Knockdown of PVT1 attenuated doxorubicin-induced cardiomyocyte apoptosis. We found that miR-187-3p is a direct target of PVT1, and that lncRNA PVT1 adsorbs miR-187-3p by sponge action, reducing miR-187-3p levels. miR-187-3p negatively regulates AGO1, and PVT1 regulates AGO1 expression by targeting miR-187-3p, thereby regulating apoptosis. In addition, we knocked down AGO1 in H9c2 cells transfected with the miR-187-3p inhibitor, and found that it inhibited apoptosis. CONCLUSION: In doxorubicin-induced cardiomyocyte toxicity, the highly expressed lncRNA PVT1 enhances the expression of AGO1 by sponge adsorption of miR-187-3p. Decreasing the expression of lncRNA PVT1 inhibits the adsorption of miR-187-3p through competing endogenous (ce) RNA, thereby reducing the expression of AGO1 and decreasing the apoptosis of cardiomyocytes.

Laparoscopic pancreaticoduodenectomy in elderly patients.

OBJECTIVE: The objective of the study is to evaluate the safety and feasibility of laparoscopic pancreaticoduodenectomy (LPD) in elderly patients by short-term surgical effects. METHODS: We retrospectively collected clinical data of 55 non-elderly patients (< 70 years), 27 elderly patients (≥ 70 years) underwent LPD, and 19 elderly patients underwent open pancreaticoduodenectomy (OPD) in biliopancreatic surgery department of Huadong Hospital, affiliated to Fudan University, from Jan 2015 to Jan 2018. Patients were divided into 3 groups: LPD aged < 70 years, LPD aged ≥ 70 years, and OPD aged ≥ 70 years, according to their age at admission and surgical approach in order to compare baseline characteristics and short-term surgical outcomes. RESULTS: Totally 101 patients were included in this study; 59 cases were male; 42 cases were female; mean age was 66 years old. Elderly LPD patients seemed to have higher overall morbidity (41% vs. 20%, P = 0.05) compared to non-elderly patients. This difference is even more significant in our multivariable analysis model with an odds ratio of 4.48 (95% CI 1.31-17.87, P = 0.018). The 90-days mortality, operative time, estimated blood loss (EBL), and post-operative hospital stay (POHS) were similar in two groups. Elderly LPD patients had less EBL and shorter POHS than elderly OPD patients. However, the mortality and morbidity rate were comparable in these two groups. CONCLUSIONS: Aging patients have higher overall morbidity than younger patients in LPD. However, for aging population who need to undergo pancreaticoduodenectomy, LPD might have some advantages over OPD.