Cove-Edged Chiral Graphene Nanoribbons with Chirality-Dependent Bandgap and Carrier Mobility.

Graphene nanoribbons (GNRs) have garnered significant interest due to their highly customizable physicochemical properties and potential utility in nanoelectronics. Besides controlling widths and edge structures, the inclusion of chirality in GNRs brings another dimension for fine-tuning their optoelectronic properties, but related studies remain elusive owing to the absence of feasible synthetic strategies. Here, we demonstrate a novel class of cove-edged chiral GNRs (CcGNRs) with a tunable chiral vector (n,m). Notably, the bandgap and effective mass of (n,2)-CcGNR show a distinct positive correlation with the increasing value of n, as indicated by theory. Within this GNR family, two representative members, namely, (4,2)-CcGNR and (6,2)-CcGNR, are successfully synthesized. Both CcGNRs exhibit prominently curved geometries arising from the incorporated [4]helicene motifs along their peripheries, as also evidenced by the single-crystal structures of the two respective model compounds (1 and 2). The chemical identities and optoelectronic properties of (4,2)- and (6,2)-CcGNRs are comprehensively investigated via a combination of IR, Raman, solid-state NMR, UV-vis, and THz spectroscopies as well as theoretical calculations. In line with theoretical expectation, the obtained (6,2)-CcGNR possesses a low optical bandgap of 1.37 eV along with charge carrier mobility of ∼8 cm2 V-1 s-1, whereas (4,2)-CcGNR exhibits a narrower bandgap of 1.26 eV with increased mobility of ∼14 cm2 V-1 s-1. This work opens up a new avenue to precisely engineer the bandgap and carrier mobility of GNRs by manipulating their chiral vector.

Abnormal phosphorylation / dephosphorylation and Ca2+ dysfunction in heart failure.

Heart failure (HF) can be caused by a variety of causes characterized by abnormal myocardial systole and diastole. Ca2+ current through the L-type calcium channel (LTCC) on the membrane is the initial trigger signal for a cardiac cycle. Declined systole and diastole in HF are associated with dysfunction of myocardial Ca2+ function. This disorder can be correlated with unbalanced levels of phosphorylation / dephosphorylation of LTCC, endoplasmic reticulum (ER), and myofilament. Kinase and phosphatase activity changes along with HF progress, resulting in phased changes in the degree of phosphorylation / dephosphorylation. It is important to realize the phosphorylation / dephosphorylation differences between a normal and a failing heart. This review focuses on phosphorylation / dephosphorylation changes in the progression of HF and summarizes the effects of phosphorylation / dephosphorylation of LTCC, ER function, and myofilament function in normal conditions and HF based on previous experiments and clinical research. Also, we summarize current therapeutic methods based on abnormal phosphorylation / dephosphorylation and clarify potential therapeutic directions.

A novel image deep learning-based sub-centimeter pulmonary nodule management algorithm to expedite resection of the malignant and avoid over-diagnosis of the benign.

OBJECTIVES: With the popularization of chest computed tomography (CT) screening, there are more sub-centimeter (≤ 1 cm) pulmonary nodules (SCPNs) requiring further diagnostic workup. This area represents an important opportunity to optimize the SCPN management algorithm avoiding "one-size fits all" approach. One critical problem is how to learn the discriminative multi-view characteristics and the unique context of each SCPN. METHODS: Here, we propose a multi-view coupled self-attention module (MVCS) to capture the global spatial context of the CT image through modeling the association order of space and dimension. Compared with existing self-attention methods, MVCS uses less memory consumption and computational complexity, unearths dimension correlations that previous methods have not found, and is easy to integrate with other frameworks. RESULTS: In total, a public dataset LUNA16 from LIDC-IDRI, 1319 SCPNs from 1069 patients presenting to a major referral center, and 160 SCPNs from 137 patients from three other major centers were analyzed to pre-train, train, and validate the model. Experimental results showed that performance outperforms the state-of-the-art models in terms of accuracy and stability and is comparable to that of human experts in classifying precancerous lesions and invasive adenocarcinoma. We also provide a fusion MVCS network (MVCSN) by combining the CT image with the clinical characteristics and radiographic features of patients. CONCLUSION: This tool may ultimately aid in expediting resection of the malignant SCPNs and avoid over-diagnosis of the benign ones, resulting in improved management outcomes. CLINICAL RELEVANCE STATEMENT: In the diagnosis of sub-centimeter lung adenocarcinoma, fusion MVCSN can help doctors improve work efficiency and guide their treatment decisions to a certain extent. KEY POINTS: • Advances in computed tomography (CT) not only increase the number of nodules detected, but also the nodules that are identified are smaller, such as sub-centimeter pulmonary nodules (SCPNs). • We propose a multi-view coupled self-attention module (MVCS), which could model spatial and dimensional correlations sequentially for learning global spatial contexts, which is better than other attention mechanisms. • MVCS uses fewer huge memory consumption and computational complexity than the existing self-attention methods when dealing with 3D medical image data. Additionally, it reaches promising accuracy for SCPNs' malignancy evaluation and has lower training cost than other models.

Enhancing Chiroptical Responses in Helical Nanographenes via Geometric Engineering of Double [7]Helicenes.

Helical nanographenes with high quantum yields and strong chiroptical responses are pivotal for developing circularly polarized luminescence (CPL) materials. Here, we present the successful synthesis of novel π-extended double [7]helicenes (ED7Hs) where two helicene units are fused at the meta- or para-position of the middle benzene ring, respectively, as the structural isomers of the reported ortho-fused ED7H. The structural geometry of these ED7Hs is clearly characterized by single-crystal X-ray analysis. Notably, this class of ED7Hs exhibits bright luminescence with high quantum yields exceeding 40 %. Through geometric regulation of two embedded [7]helicene units from ortho-, meta- to para-position, these ED7Hs display exceptional amplification in chiroptical responses. This enhancement is evident in a remarkable approximate fivefold increase in the absorbance and luminescence dissymmetry factors (gabs and glum), respectively, along with a boosted CPL brightness up to 176 M-1 cm-1, surpassing the performance of most helicene-based chiral NGs. Furthermore, DFT calculations elucidate that the geometric adjustment of two [7]helicene units allows the precise alignment of electric and magnetic transition dipole moments, leading to the observed enhancement of their chiroptical responses. This study offers an effective strategy for magnifying the CPL performance in chiral NGs, promoting their expanded application as CPL emitters.

Synthesis and Interlayer Assembly of a Graphenic Bowl with Peripheral Selenium Annulation.

Pentagonal cyclization at the bay positions of armchair-edged graphenic cores can build molecular bowls without the destruction of hexagonal lattices. However, this synthesis remains challenging due to unfavorable strain and the multiple reactions required. Here, we show that a new type of graphenic molecular bowl with a depth of 1.7 Å and a diameter of 1.2 nm is constructed by sextuple Se annulation at the bay positions of armchair-edged hexa-peri-hexabenzocoronene. This graphenic bowl is functionalized with phenylseleno groups that stack into a discrete bilayer dimer in solution. Such a dimer exhibits high stability and survives in the gas phase after laser ablation. Strikingly, the asymmetric one-dimensional supramolecular columns of graphenic bowl with coherent stacking configuration are observed in the solid state, which results in a strong second harmonic generation with prominent polarization dependence. Our findings present a concise synthesis of a giant molecular bowl with a graphenic core and demonstrate the unique supramolecular assembly of extended graphenic bowls.

Helical Trilayer Nanographenes with Tunable Interlayer Overlaps.

The synthesis of well-defined nanocarbon multilayers, beyond the bilayer structure, is still a challenging goal. Herein, two trilayer nanographenes were synthesized by covalently linking nanographene layers through helicene bridges. The structural characterization of the trilayer nanographenes revealed a compact trilayer-stacked architecture. The introduction of a furan ring into the helicene linker modulates the interlayer overlap and π-conjugation of the trilayer nanographenes, enabling the tuning of the interlayer coupling, as demonstrated by optical, electrochemical, and theoretical analyses. Both synthesized trilayer nanographenes are rigid chiral nanocarbons and show a chirality transfer from the helicene moiety to the stacked nanographene layers. These helical trilayer nanographenes reported here represent the covalently linked multilayer nanographenes rather than bilayer ones, showing the tunable multilayer stacking structure.

π-Extended Helical Multilayer Nanographenes with Layer-Dependent Chiroptical Properties.

Helical nanographenes (NGs) have attracted increasing attention recently because of their intrinsic chirality and exotic chiroptical properties. However, the efficient synthesis of extended helical NGs featuring a multilayer topology is still underdeveloped, and their layer-dependent chiroptical properties remain elusive. In this study, we demonstrate a modular synthetic strategy to construct a series of novel helical NGs (1-3) with a multilayer topology through a consecutive Diels-Alder reaction and regioselective cyclodehydrogenation from the readily accessible phenanthrene-based precursors bearing ethynyl groups. The resultant NGs exhibit bilayer, trilayer, and tetralayer structures with elongated π extension and rigid helical backbones, as unambiguously confirmed by single-crystal X-ray or electron diffraction analysis. We find that the photophysical properties of these helical NGs are notably influenced by the degree of π extension, which varies with the number of layers, leading to obvious redshifted absorption, a fast rising molar extinction coefficient (ε), and markedly boosted fluorescence quantum yield (Φf). Moreover, the embedded [7]helicene subunits in these NGs result in stable chirality, enabling both chiral resolution and exploration of their layer-dependent chiroptical properties. Profiting from the good alignment of electric and magnetic dipole moments determined by the multilayer structure, the resultant NGs exhibit excellent circular dichroism and circularly polarized luminescence response with unprecedented high CPL brightness up to 168 M-1 cm-1, rendering them promising candidates for CPL emitters.

Expression Changes in Programmed Death Ligand 1 from Precancerous Lesions to Invasive Adenocarcinoma in Subcentimeter Pulmonary Nodules: A Large Study of 2022 Cases in China.

PURPOSE: This large-scale, multicenter, retrospective observational study aimed to evaluate the clinicopathological and molecular profiles associated with programmed death-ligand 1 (PD-L1) expression in precancerous lesions and invasive adenocarcinoma in subcentimeter pulmonary nodules. PATIENTS AND METHODS: Patients with histologically confirmed atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma (ADC) were included. PD-L1 expression was evaluated at each center using a PD-L1 immunohistochemistry 22C3 pharmDx kit (Agilent, Santa Clara, CA, USA). The tumor proportion score (TPS) cutoff values were set at ≥ 1% and ≥ 50%. RESULTS: A total of 2022 nodules from 1844 patients were analyzed. Of these, 9 (0.45%) nodules had PD-L1 TPS ≥ 50%, 187 (9.25%) had PD-L1 TPS 1-49%, and 1826 (90.30%) had PD-L1 TPS < 1%. A total of 378 (18.69%), 1016 (50.25%), and 628 (31.06%) nodules were diagnosed as AAH/AIS, MIA, and ADC, respectively, by pathology. A total of 1377 (68.10%), 591 (25.67%), and 54 (2.67%) nodules were diagnosed as pure ground-glass opacity (GGO), mixed GGO, and solid nodules, respectively, by computed tomography. There was a significant difference between PD-L1 expression and anaplastic lymphoma kinase (ALK) mutation status (P < 0.001). PD-L1 expression levels were significantly different from those determined using the International Association for the Study of Lung Cancer (IASLC) grading system (P < 0.001). CONCLUSIONS: PD-L1 expression was significantly associated with radiological and pathological invasiveness and driver mutation status in subcentimeter pulmonary nodules. The significance of PD-L1 expression in the evolution of early-stage lung adenocarcinoma requires further investigation.

The Role of P53 in Myocardial Ischemia-Reperfusion Injury.

PURPOSE: P53 is one of the key tumor suppressors. In normal cells, p53 is maintained at low levels by the ubiquitination of the ubiquitinated ligase MDM2. In contrast, under stress conditions such as DNA damage and ischemia, the interaction between p53 and MDM2 is blocked and activated by phosphorylation and acetylation, thereby mediating the trans-activation of p53 through its target genes to regulate a variety of cellular responses. Previous studies have shown that the expression of p53 is negligible in normal myocardium, tends to increase in myocardial ischemia and is maximally induced in ischemia-reperfused myocardium, demonstrating a possible key role of p53 in the development of MIRI. In this review, we detail and summarize recent studies on the mechanism of action of p53 in MIRI and describe the therapeutic agents targeting the relevant targets to provide new strategies for the prevention and treatment of MIRI. METHODS: We collected 161 relevant papers mainly from Pubmed and Web of Science (search terms "p53" and "myocardial ischemia-reperfusion injury"). After that, we selected pathway studies related to p53 and classified them according to their contents. We eventually analyzed and summarized them. RESULTS AND CONCLUSION: In this review, we detail and summarize recent studies on the mechanism of action of p53 in MIRI and validate its status as an important intermediate affecting MIRI. On the one hand, p53 is regulated and modified by multiple factors, especially non-coding RNAs; on the other hand, p53 regulates apoptosis, programmed necrosis, autophagy, iron death and oxidative stress in MIRI through multiple pathways. More importantly, several studies have reported medications targeting p53-related therapeutic targets. These medications are expected to be effective options for the alleviation of MIRI, but further safety and clinical studies are needed to convert them into clinical applications.

[Clinical centralized safety monitoring and evaluation of traditional Chinese medicine formula granules].

Traditional Chinese medicine(TCM) formula granules are highly praised for the advanced, convenient, and modern use of Chinese medicinal materials. The safety of TCM formula granules has long been a concern of regulatory authorities and the medical industry. A multi-center, prospective, open, non-interventional, and centralized monitoring was carried out for the patients treated with TCM formula granules in 252 medical institutions from February 5, 2020 to April 19, 2022. All the case data and the incidence of adverse drug reactions/events were recorded. This study evaluated the safety of TCM formula granules, aiming to provide a reference for the clinically use. A total of 20 547 patients were included in this study. Four adverse events were recorded, including 3 adverse drug reactions with an adverse drug reaction rate of 0.015%, all of which occurred in the digestive system. There was no serious adverse event, and no factors related to adverse drug reactions/events were identified. The incidence of adverse drug reactions/events associated with China Resources Sanjiu Medical & Pharmaceutical Co., Ltd. TCM formula granules was rare, which proved their safety in clinical use. A comprehensive data mining and objective analysis was carried out for the medicines with high frequency in TCM formula granules, the commonly used medicine pairs and combinations, and departmental medication. The drug use characteristics, prescription rules, and departmental use of TCM formula granules were summarized, which can shed light on the prescription compatibility and clinical application.

[Guideline for clinical comprehensive evaluation of Chinese patent medicine (2022 version)].

Currently,the research or publications related to the clinical comprehensive evaluation of Chinese patent medicine are increasing,which attracts the broad attention of all circles. According to the completed clinical evaluation report on Chinese patent medicine,there are still practical problems and technical difficulties such as unclear responsibility of the evaluation organization,unclear evaluation subject,miscellaneous evaluation objects,and incomplete and nonstandard evaluation process. In terms of evaluation standards and specifications,there are different types of specifications or guidelines with different emphases issued by different academic groups or relevant institutions. The professional guideline is required to guide the standardized and efficient clinical comprehensive evaluation of Chinese patent medicine and further improve the authority and quality of evaluation. In combination with the characteristics of Chinese patent medicine and the latest research achievement at home and abroad,the detailed specifications were formulated from six aspects including design,theme selection,content and index,outcome,application and appraisal,and quality control. The guideline was developed based on the guideline development requirements of China Assoication of Chinese medicine. After several rounds of expert consensus and public consultation,the current version of the guideline has been developed.

Step-Assisted On-Surface Synthesis of Graphene Nanoribbons Embedded with Periodic Divacancies.

The bottom-up approach through on-surface synthesis of porous graphene nanoribbons (GNRs) presents a controllable manner for implanting periodic nanostructures to tune the electronic properties of GNRs in addition to bandgap engineering by width and edge configurations. However, owing to the existing steric hindrance in small pores like divacancies, it is still difficult to embed periodic divacancies with a nonplanar configuration into GNRs. Here, we demonstrate the on-surface synthesis of atomically precise eight-carbon-wide armchair GNRs embedded with periodic divacancies (DV8-aGNRs) by utilizing the monatomic step edges on the Au(111) surface. From a single molecular precursor correspondingly following a trans- and cis-coupling, the DV8-aGNR and another porous nanographene are respectively formed at step edges and on terraces at 720 and 570 K. Combining scanning tunneling microscopy/spectroscopy, atomic force microscopy, and first-principles calculations, we determine the out-of-plane conformation, wide bandgap (∼3.36 eV), and wiggly shaped frontier orbitals of the DV8-aGNR. Nudged elastic band calculations further quantitatively reveal that the additional steric hindrance effect in the cyclodehydrogenative reactions has a higher barrier of 1.3 eV than that in the planar porous nanographene, which also unveils the important role played by the monatomic Au step and adatoms in reducing the energy barriers and enhancing the thermodynamic preference of the oxidative cyclodehydrogenation. Our results provide the first case of GNRs containing periodic pores as small as divacancies with a nonplanar configuration and demonstrate the strategy by utilizing the chemical heterogeneity of a substrate to promote the formation of novel carbon nanomaterials.

Digital Gonioscopy Based on Three-dimensional Anterior-Segment OCT: An International Multicenter Study.

PURPOSE: To develop and evaluate the performance of a 3-dimensional (3D) deep-learning-based automated digital gonioscopy system (DGS) in detecting 2 major characteristics in eyes with suspected primary angle-closure glaucoma (PACG): (1) narrow iridocorneal angles (static gonioscopy, Task I) and (2) peripheral anterior synechiae (PAS) (dynamic gonioscopy, Task II) on OCT scans. DESIGN: International, cross-sectional, multicenter study. PARTICIPANTS: A total of 1.112 million images of 8694 volume scans (2294 patients) from 3 centers were included in this study (Task I, training/internal validation/external testing: 4515, 1101, and 2222 volume scans, respectively; Task II, training/internal validation/external testing: 378, 376, and 102 volume scans, respectively). METHODS: For Task I, a narrow angle was defined as an eye in which the posterior pigmented trabecular meshwork was not visible in more than 180° without indentation in the primary position captured in the dark room from the scans. For Task II, PAS was defined as the adhesion of the iris to the trabecular meshwork. The diagnostic performance of the 3D DGS was evaluated in both tasks with gonioscopic records as reference. MAIN OUTCOME MEASURES: The area under the curve (AUC), sensitivity, and specificity of the 3D DGS were calculated. RESULTS: In Task I, 29.4% of patients had a narrow angle. The AUC, sensitivity, and specificity of 3D DGS on the external testing datasets were 0.943 (0.933-0.953), 0.867 (0.838-0.895), and 0.878 (0.859-0.896), respectively. For Task II, 13.8% of patients had PAS. The AUC, sensitivity, and specificity of 3D DGS were 0.902 (0.818-0.985), 0.900 (0.714-1.000), and 0.890 (0.841-0.938), respectively, on the external testing set at quadrant level following normal clinical practice; and 0.885 (0.836-0.933), 0.912 (0.816-1.000), and 0.700 (0.660-0.741), respectively, on the external testing set at clock-hour level. CONCLUSIONS: The 3D DGS is effective in detecting eyes with suspected PACG. It has the potential to be used widely in the primary eye care community for screening of subjects at high risk of developing PACG.

Serum immunoglobulin profiles in Chinese children with Henoch-Schönlein purpura.

The present study focuses on the associations of serum immunoglobulin with disease activity, relapse/recurrence and renal involvement in Henoch-Schönlein purpura (HSP) children. 1683 Chinese children with HSP were recruited from January 2015 to January 2021. Laboratory data of blood samples and urine tests were collected. Renal biopsy was performed by the percutaneous technique. Patients' histories associated with HSP onset were obtained by interviews and questionnaires. (1) IgA and IgE were dramatically elevated in HSP patients as compared to their normal values and subject to a 1.75-3.09 fold and a 1.97-2.61 fold increase, respectively. (2) No significant correlation of the disease activity with IgA and IgE was determined, respectively. (3) The serum IgA levels were significantly lower in patients with relapse/recurrence than that in patients without relapse/recurrence, which may be attributed to the transmission of IgA-mediated immune complexes from blood to vessel walls. (4) No significant correlation was found between serum IgA, IgE levels and the pathological classification. HSP children have marked disorders of serum immunoglobulin profiles, characterized by significant increases in IgA and IgE. The detection of serum IgA may be applicable to predict relapse/recurrence of HSP whereas not associated with disease activity and renal involvement.

A new scoring system for coronary artery abnormalities in Kawasaki disease.

BACKGROUND: In China, coronary artery abnormalities (CAAs) secondary to Kawasaki disease (KD) tend to have an increased occurrence. We hypothesize that Chinese children with KD may possess several unique CAA risks, and the predictive efficacy of multiple scoring systems in Chinese patients are still to be further studied. METHODS: Two hundred and three KD patients were recruited. Using multivariable analysis, independent predictors of CAAs were combined into a scoring system. Subsequently, CAA risks of our patients were evaluated by the newly established scoring system and eight other published scoring systems. RESULTS: Seventeen (8.37%) KD patients were identified as CAAs. The newly established scoring system contained the following 5 independent predictors: days of illness at initial treatment ≥7, redness and swelling of extremities, hematocrit ≤33%, percentage of monocytes ≥8.89%, and procalcitonin ≥0.5 ng/mL. The AUC value of newly established scoring system was 0.685 with a sensitivity of 41.18% and a specificity of 84.41%, higher than Harada score, Egami score, Kobayashi score, Sato score, San Diego score, Formosa score, and Tang score, whereas lower than Hua score. CONCLUSIONS: Days of illness at initial treatment ≥7 and procalcitonin are unique predictors of CAAs in newly established scoring system. Taking into account different identification criteria and analytical methodologies, there is still some heterogeneity among different scoring systems. IMPACT: The newly established scoring system contains the five independent predictors. Days of illness at initial treatment ≥7 and PCT are unique predictors of CAAs in our study, compared with 8 other systems. The AUC value of newly established scoring system is 0.685, similar to Hua score. There is some heterogeneity among different scoring systems.

Selective Separation Catalysis Membrane for Highly Efficient Water and Soil Decontamination via a Persulfate-Based Advanced Oxidation Process.

The application of sulfate radical advanced oxidation for organic pollutant removal has been hindered by some shortages such as the recycling difficulty of a powered catalyst, the low utilization efficiency of oxidants, and the secondary pollution (including soil acidification) after reaction. Herein, we fabricate a selective separation catalysis membrane (SSCM) for a highly efficient and environment-friendly persulfate-based advanced oxidation process. The SSCM comprises a top polydimethylsiloxane layer which is selectively penetrable to hydrophobic organic pollutants, followed by a catalyst layer with a magnetic nitrogen-doped porous carbon material, targeting the advanced oxidation of the selected pollutants. Compared with the catalyst in powder form, such SSCM devices significantly reduced the dosage of peroxymonosulfate by more than 40% and the catalyst dosage by 97.8% to achieve 80% removal of phenol with the coexistence of 20 mg L-1 humic acid (HA). The SSCM can extract target pollutants while rejecting HA more than 91.43% for 100 h. The pH value in the receiving solution demonstrated a significant reduction from 7.01 to 3.00. In comparison, the pH value in the feed solution varied from 6.05 to a steady 4.59. The results can be ascribed to the specific functionality for the catalyst anchored, natural organic matter isolation, and reaction compartmentation provided by SSCMs. The developed SSCM technology is beneficial for catalysts reused in remediation practices, saving oxidant dosage, and avoiding acidification of soil and water, thus having tremendous application potential.

The Protective Role of Bmal1-Regulated Autophagy Mediated by HDAC3/SIRT1 Pathway in Myocardial Ischemia/Reperfusion Injury of Diabetic Rats.

PURPOSE: Histone deacetylase 3 (HDAC3) and silent information regulator 1 (SIRT1) are histone deacetylases that regulate important metabolic pathways and play important roles in diabetes and myocardial ischemia/reperfusion (IR) injury. In this study, we explored the protective mechanism of Bmal1-regulated autophagy mediated by the HDAC3/SIRT1 pathway in myocardial IR injury of diabetic rats. METHODS AND RESULTS: Type 1 diabetes was established by administering an intraperitoneal injection of streptozotocin. After 8 weeks, the left anterior descending coronary artery was ligated for 30 min and reperfused for 120 min to establish a myocardial IR injury model in diabetic rats. H9c2 cardiomyocytes were exposed to high glucose concentration (30 mM) and hypoxia/reoxygenation (H/R) stimulation in vitro. The myocardial infarct size and levels of serum cTn-I, CK-MB, and LDH in diabetic rats subjected to myocardial IR injury were significantly higher. Upregulated HDAC3 and downregulated SIRT1 expression were observed in diabetic and IR hearts, along with a lower Bmal1 level. Autophagy was rapidly increased in the hearts of diabetic or non-diabetic rats in the IR group compared with the sham group, but significantly attenuated in the hearts of diabetic rats compared with the hearts of non-diabetic rats after IR insult. Consistent with decreased autophagy, we observed increased HDAC3 expression and decreased SIRT1 and Bmal1 levels in the myocardial tissue of diabetic rats after IR. Inhibition of HDAC3 by the inhibitor RGFP966 and activation of SIRT1 by the agonist SRT1720 could significantly attenuate myocardial IR injury in diabetic rats by restoring Bmal1-regulated autophagy. CONCLUSION: Based on these findings, the disordered HDAC3/SIRT1 circuit (upregulated HDAC3 and downregulated SIRT1 levels) plays an important role in aggravating myocardial IR injury in diabetic rats by downregulating Bmal1-mediated autophagy. Treatments targeting HDAC3/SIRT1 to activate the autophagy may represent a novel strategy to alleviate myocardial IR injury in diabetes.

Green Synthesis of Indeno[1,2-b]quinoxalines Using ß-Cyclodextrin as Catalyst.

An efficient, mild, and green method was developed for the synthesis of indeno[1,2-b]quinoxaline derivatives via o-phenylenediamine (OPD) and 2-indanone derivatives utilizing ß-cyclodextrin (ß-CD) as the supramolecular catalyst. The reaction can be carried out in water and in a solid state at room temperature. ß-CD can also catalyze the reaction of indan-1,2-dione with OPD with a high degree of efficiency. Compared to the reported methods, this procedure is milder, simpler, and less toxic, making it an eco-friendly alternative. In addition, the ß-CD can be recovered and reused without the loss of activity.

[Evaluation for druggability of traditional Chinese medicine preparations in medical institutions based on human use experience].

Traditional Chinese medicine(TCM) preparations in medical institutions are an important source of research and development(R&D) of TCM new drug. With years of usage in therapy, these preparations' safety and effectiveness have generally been validated in clinic. However, there are still a few disadvantages in TCM new medicine development, such as similar prescriptions, excessive prescription ingredients, too broad clinical orientation, lack of solid clinical data, issue in pharmaceutical quality control, and intellectual property disputes. Nowadays, the Three-Combined Evaluation System has strengthened policy support for the new TCM R&D. In order to improve the success rate of TCM R&D, due to the difficulties within, this paper proposes the process of transforming TCM preparations in medical institutions into new TCM and advocates the evaluation for druggability based on Human Use Experience(HUE). The potencial preparations ought to follow traditional Chinese Medical theory, sufficient HUE data in indication, syndrome type of TCM, target population, usage, dosage, and course of treatment are required. Particular attention should be paid to the source, evolution, and improvement process of prescription, and evaluate the dosage, ingredients, and herb resources of prescription. To assess the feasibility of mass production, it is necessary to determine whether the pharmaceutical process is mostly consistent with the new drug and whether the dosage form is reasonable. By summarizing the clinical application of the preparations, the whole picture of its clinical application would be reveal as much as possible. It is beneficial to evaluate its clinical value and R&D prospect. In consideration of the lack of clinical safety data of preparations, safety profile needs to be collected according to the prescription. The quality of clinical data needs to be evaluated by focusing on the integrity and accuracy of data to reduce bias and confusion. Significant care should be paid to intellectual property protection to avoid legal disputes.

Nanographene with Multiple Embedded Heptagons: Cascade Radical Photocyclization.

Although heptagons are widely found in graphenic materials, the precise synthesis of nanocarbons containing heptagons remains a challenge, especially for the nanocarbons containing multiple-heptagons. Herein, we show that photo-induced radical cyclization (PIRC) can be used to synthesize multi-heptagon-embedded nanocarbons. Notably, a nanographene containing six heptagons (1) was obtained via a six-fold cascade PIRC reaction. The structure of 1 was clearly validated and showed a Monkey-saddle-shaped conformation. Experimental bond analysis and theoretical calculations indicated that the heptagons in 1 were non-aromatic, whereas the peripheral rings were highly aromatic. Compared to planar nanographene with the same number of π electrons, 1 had a similar optical gap due to a compromise between the decreased conjugation in the wrapped structure and enhanced electronic delocalization at the rim. Electrochemical studies showed that 1 had low-lying oxidation potentials, which was attributed to the nitrogen-doping.