Left ventricular global longitudinal strain using a novel fully automated method: A head-to-head comparison with a manual layer-specific strain and establishment of normal reference ranges.

BACKGROUND: A novel automated method for measuring left ventricular (LV) global longitudinal strain (GLS) along the endocardium has advantages in terms of its rapid application and excellent reproducibility. However, it remains unclear whether the available normal range for conventional GLS using the manual method is applicable to the automated GLS method. This study aimed to compare automated GLS head-to-head with manual layer-specific GLS, and to identify whether a specialized normal reference range for automated GLS is needed and explore the main determinants. METHODS: In total, 1683 healthy volunteers (men, 43%; age, 18-80 years) were prospectively enrolled from 55 collaborating laboratories. LV GLS was measured using both manual layer-specific and automated methods. RESULTS: Automated GLS was higher than endocardial, mid-myocardial, and epicardial GLS. Women had a higher automated GLS than men. GLS had no significant age dependency in men, but first increased and then decreased with age in women. Accordingly, sex- and age-specific normal ranges for automated GLS were proposed. Moreover, GLS appeared to have different burdens in relation to dominant determinants between the sexes. GLS in men showed no dominant determinants; however, GLS in women correlated with age, body mass index, and heart rate. CONCLUSIONS: Using the novel automated method, was LV GLS higher than when using the manual GLS method. The normal ranges of automated GLS stratified according to sex and age were provided, with dominant determinants showing sex disparities that require full consideration in clinical practice.

Rh(III)-Catalyzed C7-Alkylation of Isatogens with Malonic Acid Diazoesters.

Rh(III)-catalyzed C7-alkylation of isatogens (indolin-3-one N-oxides) with malonic acid diazoesters has been developed. This strategy utilizes oxygen anion on the N-oxide group of isatogens as a directing group and successfully achieves the synthesis of a series of C7-alkylated isatogens with moderate to good yields (48-86% yields). Moreover, the N-oxides of isatogens can not only serve as the simple directing group for C7-H bond cleavage but also be deoxidized for easy removal.

Structure-Guided Design, Synthesis, and Antivirulence Assessment of Covalent Staphylococcus aureus Sortase A Inhibitors.

Sortase A (SrtA) is a membrane-associated cysteine transpeptidase required for bacterial virulence regulation and anchors surface proteins to cell wall, thereby assisting biofilm formation. SrtA is targeted in antivirulence treatments against Gram-positive bacterial infections. However, the development of potent small-molecule SrtA inhibitors is constrained owing to the limited understanding of the mode of action of inhibitors in the SrtA binding pocket. Herein, we designed and synthesized a novel class of covalent SrtA inhibitors based on the binding mode detailed in the X-ray crystal structure of the ML346/Streptococcus pyogenes SrtA complex. ML346 analog Y40 exhibited 2-fold increased inhibitory activity on Staphylococcus aureus SrtA and showed superior inhibitory effects on biofilm formation in vitro. Y40 protected Galleria mellonella larvae fromS. aureusinfections in vivo while minimally attenuating staphylococcal growth in vitro. Our study indicates that the covalent SrtA inhibitor Y40 is an antivirulence agent that is effective againstS. aureusinfections.

Clinical practice of sepsis-induced immunosuppression: Current immunotherapy and future options.

Sepsis is a potentially fatal condition characterized by the failure of one or more organs due to a disordered host response to infection. The development of sepsis is closely linked to immune dysfunction. As a result, immunotherapy has gained traction as a promising approach to sepsis treatment, as it holds the potential to reverse immunosuppression and restore immune balance, thereby improving the prognosis of septic patients. However, due to the highly heterogeneous nature of sepsis, it is crucial to carefully select the appropriate patient population for immunotherapy. This review summarizes the current and evolved treatments for sepsis-induced immunosuppression to enhance clinicians' understanding and practical application of immunotherapy in the management of sepsis.

Brucella abortus Rough-Type Mutant Induces Ferroptosis and More Oxidative Stress in Infected Macrophages.

Brucella is an intracellular parasitic bacterium that uses multiple strategies to evade the host's defense mechanisms. However, how Brucella manipulates the host-induced oxidative stress and relevant biological processes are still poorly understood. In this study, a comparative transcriptome assay of macrophages infected with Brucella abortus S2308 and its rough mutant RB14 was performed to investigate the differentially expressed genes which might be associated with the pathogenic mechanism of Brucella. Our results showed that numerous host pro-oxidative and antioxidative stress genes were differentially expressed in macrophages infected with B. abortus S2308 and mutant RB14 at 4, 8, 24, and 48 h post-infection. Interestingly, we found that several ferroptosis-associated genes were differentially expressed during B. abortus RB14 infection. Moreover, we found that the rough mutant RB14-induced macrophage death was associated with reduced levels of host glutathione and glutathione peroxidase 4, together with increased free iron, lipid peroxidation, and ROS, all of which are important hallmarks of ferroptosis. The ferroptosis occurring during infection with RB14 was reduced by treatment with the inhibitor ferrostatin-1. However, B. abortus S2308 infection did not induce these hallmarks of ferroptosis. Taken together, our results demonstrate that ferroptosis is involved in rough B. abortus infection. Investigating how Brucella manipulates oxidative stress and ferroptosis in its host will be helpful to clarify the pathogenicity of B. abortus.

Normal reference values for mitral annular plane systolic excursion by motion-mode and speckle tracking echocardiography: a prospective, multicentre, population-based study.

AIMS: Mitral annular plane systolic excursion (MAPSE) is a simple and reliable index for evaluating left ventricular (LV) systolic function, particularly in patients with poor image quality; however, the lack of reference values limits its widespread use. This study aimed to establish the normal ranges for MAPSE measured using motion-mode (M-mode) and two-dimensional speckle tracking echocardiography (2D-STE) and to explore its principal determinants. METHODS AND RESULTS: This multicentre, prospective, cross-sectional study included 1952 healthy participants [840 men (43%); age range, 18-80 years] from 55 centres. MAPSE was measured using M-mode echocardiography and 2D-STE. The results showed that women had a higher MAPSE than men and MAPSE decreased with age. The age- and sex-specific reference values for MAPSE were established for these two methods. Multiple linear regression analyses revealed that MAPSE on M-mode echocardiography correlated with age and MAPSE on 2D-STE with age, blood pressure (BP), heart rate, and LV volume. Moreover, MAPSE measured by 2D-STE correlated more strongly with global longitudinal strain compared with that measured using M-mode echocardiography. CONCLUSION: Normal MAPSE reference values were established based on age and sex. BP, heart rate, and LV volume are potential factors that influence MAPSE and should be considered in clinical practice. Normal values are useful for evaluating LV longitudinal systolic function, especially in patients with poor image quality, and may further facilitate the use of MAPSE in routine assessments.

Synthesis of diarylmethyl thioethers via a DABCO-catalyzed 1,6-conjugate addition reaction of p-quinone methides with organosulfur reagents.

A rapid and simple method was developed for the synthesis of diarylmethyl thioethers via a DABCO-catalyzed 1,6-conjugate addition reaction of para-quinone methides (p-QMs) with organosulfur reagents. A series of diarylmethyl thioethers were synthesized at 13-85% yields by this method. After that, the antibacterial activities of synthesized diarylmethyl thioethers and their derivatives were evaluated. The MIC range (µg mL-1) against Staphylococcus aureus ATCC 25923 and clinically isolated methicillin-resistant S. aureus was 8-128 and 64-128, respectively.

On the Imaginary Wings: Text-Assisted Complex-Valued Fusion Network for Fine-Grained Visual Classification.

Fine-grained visual classification (FGVC) is challenging due to the interclass similarity and intraclass variation in datasets. In this work, we explore the great merit of complex values in introducing an imaginary part for modeling data uncertainty (e.g., different points on the complex plane can describe the same state) and graph convolutional networks (GCNs) in learning interdependently among classes to simultaneously tackle the above two major challenges. To the end, we propose a novel approach, termed text-assisted complex-valued fusion network (TA-CFN). Specifically, we expand each feature from 1-D real values to 2-D complex value by disassembling feature maps, thereby enabling the extension of traditional deep convolutional neural networks over the complex domain. Then, we fuse the real and imaginary parts of complex features through complex projection and modulus operation. Finally, we build an undirected graph over the object labels with the assistance of a text corpus, and a GCN is learned to map this graph into a set of classifiers. The benefits are in two folds: 1) complex features allow for a richer algebraic structure to better model the large variation within the same category and 2) leveraging the interclass dependencies brought by the GCN to capture key factors of the slight variation among different categories. We conduct extensive experiments to verify that our proposed model can achieve the state-of-the-art performance on two widely used FGVC datasets.

Expert consensus on the monitoring and treatment of sepsis-induced immunosuppression.

Emerged evidence has indicated that immunosuppression is involved in the occurrence and development of sepsis. To provide clinical practice recommendations on the immune function in sepsis, an expert consensus focusing on the monitoring and treatment of sepsis-induced immunosuppression was developed. Literature related to the immune monitoring and treatment of sepsis were retrieved from PubMed, Web of Science, and Chinese National Knowledge Infrastructure to design items and expert opinions were collected through an online questionnaire. Then, the Delphi method was used to form consensus opinions, and RAND appropriateness method was developed to provide consistency evaluation and recommendation levels for consensus opinions. This consensus achieved satisfactory results through two rounds of questionnaire survey, with 2 statements rated as perfect consistency, 13 as very good consistency, and 9 as good consistency. After summarizing the results, a total of 14 strong recommended opinions, 8 weak recommended opinions and 2 non-recommended opinions were produced. Finally, a face-to-face discussion of the consensus opinions was performed through an online meeting, and all judges unanimously agreed on the content of this consensus. In summary, this expert consensus provides a preliminary guidance for the monitoring and treatment of immunosuppression in patients with sepsis.

Differentially expressed long noncoding RNAs in RAW264.7 macrophages during Brucella infection and functional analysis on the bacterial intracellular replication.

Long noncoding RNAs (lncRNAs) are a group of functional RNA molecules without protein-coding potential and play vital roles in majority of biological processes. To date, the expression profiles of lncRNAs and their influence on Brucella replication in RAW264.7 cells are poorly understood. In this study, we performed high-throughput transcriptome analysis to investigate the differentially expressed lncRNAs associated with Brucella abortus S2308 infection. Of these, 8, 6, 130 and 94 cellular lncRNAs were differentially expressed at 4, 8, 24 and 48 h post-infection, respectively. Moreover, 1918 protein-coding genes are predicted as potential cis target genes of differentially expressed lncRNAs by searching protein-coding genes located at upstream and downstream of lncRNA loci on the chromosome DNA of Mus musculus. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses indicated that majority of lncRNA target genes were associated with B. abortus infection. Fourteen lncRNAs from transcriptome data were selected for qRT-PCR verification, confirming 13 were differentially expressed. Animal experiments revealed three were differentially expressed in vivo by qRT-PCR analysis. Furthermore, knockdown of LNC_000428 by CRISPR/dCas9 inhibition or Locked Nucleic Acids transfection downregulated Tnfrsf8 expression at mRNA level and increased Brucella intracellular replication. Thus, we provide a novel evidence that lncRNAs induced by Brucella-infection function on Brucella intracellular replication.

Genome-Wide Association Studies Revealed Significant QTLs and Candidate Genes Associated with Backfat and Loin Muscle Area in Pigs Using Imputation-Based Whole Genome Sequencing Data.

Improvement of carcass features is an essential goal in pig genetic breeding programs. Backfat (BF) and loin muscle area (LMA) are important carcass production metrics and useful indicators of pig production performance and lean meat rate. However, the genetic architecture of BF and LMA traits remains elusive. To identify quantitative trait loci (QTLs) and genes associated with these traits, we performed a genome-wide association study (GWAS) using imputation-based whole genome sequencing data for four phenotypes (adjusted 100 kg BF and LMA, adjusted 100 kg BF EBV and LMA EBV) in 1131 pigs from 3 breeds (French Yorkshire, Landrace, and Duroc). After genotype imputation and quality control, 14,163,315 single nucleotide polymorphisms (SNPs) were retained for further analysis. For the adjusted 100 kg BF trait, using the 2-LOD drop method, a QTL with a 13.4 Kb interval (2.91 to 2.93 Mb on SSC2) and containing a SHANK2 gene was defined. In addition, two QTLs with 135.40 Kb (from 66.10 to 66.23 Mb) and 3.12 Kb (from 66.886 to 66.889 Mb) intervals containing CCND2 and TSPAN11 genes, respectively, were found on SSC5. For the BF-EBV trait, two QTLs (128.77 Kb from 66.10 to 66.23 Mb on SSC5 and 42.10 Kb from 2.89 to 2.93 Mb on SSC2) were identified. Notably, CCND2 and SHANK2 were the only candidate genes in their respective QTL interval. Furthermore, we detected a 3.33 Kb (66.106 to 66.110 Mb on SSC2) haplotype block which was detected as affecting the BF_EBV trait, which only contained the CCND2 gene. Thus, we suggested CCND2 and SHANK2 as strong candidate genes for regulating the BF trait for pigs. The empirical confidence intervals of the QTLs were 1.14 Mb (165.65 to 166.79 Mb on SSC6) for adjusted 100 kg LMA and 1.49 Mb (165.26-166.74 Mb on SSC6) for LMA-EBV. These two confidence intervals contained 13 and 28 annotated genes, respectively. Our results provide a deeper understanding of the genetic basis of pig carcass traits. The identified molecular markers will be useful for selecting breeding lines for breeding pigs with superior carcass traits.

Composite Electrolytes Prepared by Improving the Interfacial Compatibility of Organic-Inorganic Electrolytes for Dendrite-Free, Long-Life All-Solid Lithium Metal Batteries.

Compared with simplex ceramic or polymer solid electrolytes, composite solid electrolyte (CSE) is more promising for its better interfacial compatibility to electrode and high ionic conductivity simultaneously. Further, the interfacial compatibility within ceramic and polymer is considered to be more and more critical to the overall performance of solid-state batteries. Avoiding the agglomeration of ceramic particles at high loadings can improve the whole intrinsic characteristic and electrochemical performance of CSEs. Herein, we designed a CSE (EO@LLZTO-PEO), which consists of composite particles (EO@LLZTO) as a filler and polyethylene oxide (PEO) as polymer matrix. EO@LLZTO was prepared by chemically grafting polyethylene glycol monomethyl ether methacrylate (MPEG-MAA) on the micro-sized Li6.4La3Zr1.4Ta0.6O12 (LLZTO) particles. By introducing of polymer containing EO segments onto LLZTO, the interfacial compatibility between LLZTO and PEO matrix is highly enhanced, and the intrinsic Li+ complexation capability of MPEG-MAA is improved, even at the high loading of garnet. EO@LLZTO-PEO shows a high ionic conductivity (1.91 mS cm-1), a broad electrochemical window (∼5.2 V vs Li/Li+), and a high lithium ion transference number (0.72). The Li/EO@LLZTO-PEO/Li battery also exhibits a long cycle stability (over 1200 h of cycling). Moreover, all-solid-state batteries with LiFePO4 and LiNi0.8Co0.1Mn0.1O2 (NCM811) cathodes exhibit excellent cycling stability and rate performance. Consequently, enhancing the interfacial compatibility between organic and inorganic electrolytes is identified to be one of the crucial strategies for commercial solid-state lithium batteries.

Synthesis and antibacterial activity studies in vitro of indirubin-3'-monoximes.

Multi-drug-resistant microbial pathogens are a serious global health problem. New compounds with antibacterial activity serve as good candidates for developing novel antibacterial drugs which is very urgent and important. In this work, based on the unique scaffold of indirubin, an active ingredient of traditional Chinese medicine formulation Danggui Luhui Wan, we synthesized 29 indirubin-3'-monoximes and preliminarily evaluated their antibacterial activities. The antibacterial activity results demonstrated that the synthesized indirubin-3'-monoximes 5a-5z and 5aa-5ad displayed good potency against S. aureus ATCC25923 (MIC = 0.4-25.6 µg mL-1). Among them, we found that the 5-F, 5-Cl and 7-CF3 substituted indirubin-3'-monoximes 5r, 5s and 5aa also showed better antibacterial efficiency for S. aureus (MICs up to 0.4 µg mL-1) than the prototype natural product indirubin (MIC = 32 µg mL-1). More importantly, indirubin-3'-monoxime 5aa has certain synergistic effect with levofloxacin against clinic multidrug-resistant S. aureus (fractional inhibitory concentration index: 0.375). In addition, relevant experiments including electron microscopy observations, PI staining and the leakage of extracellular potassium ions and nucleic acid (260 nm) have been performed after treating S. aureus with indirubin-3'-monoxime 5aa, and the results revealed that indirubin-3'-monoximes could increase the cell membrane permeability of S. aureus. Although indirubin-3'-monoxime 5aa showed some cytotoxicity toward SH-SY5Y cells relative to compounds 5r and 5s, the skin irritation test of male mice after shaving showed that compound 5aa at a concentration of 12.8 µg mL-1 had no toxicity to mouse skin, and it could be used as a leading compound for skin antibacterial drugs.

[Research Hotspots and Trends of Multimorbidity].

Objective To clarify the hotspots and trends of multimorbidity research and to provide evidence for further research in China. Methods Papers on multimorbidity were retrieved from PubMed and Web of Science (from inception to August 11,2021).BICOMB and gCLUTO were used for bibliometric and clustering analysis,and CiteSpace was employed for analysis of authors and citations,and burst detection of keywords. Results The research on multimorbidity has been on the rise.Among the authors,Mercer SW published the most papers on this topic and Fortin M was the most cited author.Karolinska Institute topped the institutions in the number of published papers,and the paper published in Lancet by Barnett K in 2012 was the most cited.A total of 75 high-frequency keywords were extracted,on the basis of which seven research hotspots were summarized:epidemiology (including the prevalence and trend),medication (involving polypharmacy,medication compliance,etc.),medical expenditure (including cost and medical services),aging (such as elderly patients,frailty,and disability),psychology (involving mental health,social support,etc.),multimorbidity management (such as the treatment,primary health care,and integrated care),and comorbidity of cardiovascular and metabolic diseases (involving obesity,stroke,diabetes,etc.). Conclusions Multimorbidity is concerned as a major health threat and public health problem worldwide.The management of multimorbidity is more complex than that of one disease,which thus faces more challenges.Therefore,researchers,health care providers,and policy-makers should underscore it.

Covalent sortase A inhibitor ML346 prevents Staphylococcus aureus infection of Galleria mellonella.

The housekeeping sortase A (SrtA), a membrane-associated cysteine transpeptidase, is responsible for anchoring surface proteins to the cell wall peptidoglycan in Gram-positive bacteria. This process is essential for the regulation of bacterial virulence and pathogenicity. Therefore, SrtA is considered to be an ideal target for antivirulence therapy. In this study, we report that ML346, a compound with a barbituric acid and cinnamaldehyde scaffold, functions as an irreversible inhibitor of Staphylococcus aureus SrtA (SaSrtA) and Streptococcus pyogenes SrtA (SpSrtA) in vitro at low micromolar concentrations. According to our X-ray crystal structure of the SpSrtAΔN81/ML346 complex (Protein Data Bank ID: 7V6K), ML346 covalently modifies the thiol group of Cys208 in the active site of SpSrtA. Importantly, ML346 significantly attenuated the virulence phenotypes of S. aureus and exhibited inhibitory effects on Galleria mellonella larva infection caused by S. aureus. Collectively, our results indicate that ML346 has potential for development as a covalent antivirulence agent for treating S. aureus infections, including methicillin-resistant S. aureus.

Mind the Remainder: Taylor's Theorem View on Recurrent Neural Networks.

Recurrent neural networks (RNNs) have gained tremendous popularity in almost every sequence modeling task. Despite the effort, these kinds of discrete unstructured data, such as texts, audio, and videos, are still difficult to be embedded in the feature space. Studies in improving the neural networks have accelerated since the introduction of more complex or deeper architectures. The improvements of previous methods are highly dependent on the model at the expense of huge computational sources. However, few of them pay attention to the algorithm. In this article, we bridge the Taylor series with the construction of RNN. Training RNN can be considered as a parameter estimate for the Taylor series. However, we found that there is a discrete term called the remainder in the finite Taylor series that cannot be optimized using gradient descent, which is part of the reason for the truncation error and the model falling into the local optimal solution. To address this, we propose a training algorithm that estimates the range of remainder and introduces the remainder obtained by sampling in this continuous space into the RNN to assist in optimizing the parameters. Notably, the performance of RNN can be improved without changing the RNN architecture in the testing phase. We demonstrate that our approach is able to achieve state-of-the-art performance in action recognition and cross-modal retrieval tasks.

Brucella induces heme oxygenase-1 expression to promote its infection.

Brucellosis is a zoonotic and contagious infectious disease caused by Brucella spp, which causes substantial economic losses to animal husbandry and leads to severe public health problems. Brucella have evolved multiple strategies to escape host immunity and survive within host cells. Elucidating the immune evasion strategies during Brucella infection will facilitate the control of brucellosis. The host enzyme, heme oxygenase-1 (HO-1), is a multifunctional protein that functions during inflammatory diseases and microbial infections. However, how HO-1 functions during Brucella infection is rarely studied. In this study, we evaluated the role of HO-1 during Brucella infection. We found that Brucella infection induced HO-1 expression in macrophages. We further showed that HO-1 was regulated by PI3K, AMPK kinase, and nuclear erythroid-related factor 2 (Nrf2) in macrophages. Interestingly, knocking out HO-1 or inhibiting the activity of HO-1 significantly decreased Brucella intracellular growth. Inducing the expression of HO-1 by treatment with CoPP promoted Brucella intracellular growth. Mechanistic analyses indicated that the effect of HO-1 was not meditated by HO-1 metabolites, but by decreasing the production of reactive oxygen species (ROS), TNF-α, and IL-1ß. Moreover, Brucella induced HO-1 expression in bone marrow-derived macrophages (BMDMs) and mice. When the expression of HO-1 was knocked down in BMDMs, the intracellular survival of Brucella was reduced. Furthermore, the induction of HO-1 by CoPP significantly increased bacterial loads in vivo. Thus, we demonstrated that Brucella induced HO-1 expression to promote its survival and growth in vitro and in vivo. This study also identified HO-1 as a novel innate immune evasion factor during Brucella infection.

Retrospective Study of Critically Ill COVID-19 Patients With and Without Extracorporeal Membrane Oxygenation Support in Wuhan, China.

Background: Extracorporeal membrane oxygenation (ECMO) might benefit critically ill COVID-19 patients. But the considerations besides indications guiding ECMO initiation under extreme pressure during the COVID-19 epidemic was not clear. We aimed to analyze the clinical characteristics and in-hospital mortality of severe critically ill COVID-19 patients supported with ECMO and without ECMO, exploring potential parameters for guiding the initiation during the COVID-19 epidemic. Methods: Observational cohort study of all the critically ill patients indicated for ECMO support from January 1 to May 1, 2020, in all 62 authorized hospitals in Wuhan, China. Results: Among the 168 patients enrolled, 74 patients actually received ECMO support and 94 not were analyzed. The in-hospital mortality of the ECMO supported patients was significantly lower than non-ECMO ones (71.6 vs. 85.1%, P = 0.033), but the role of ECMO was affected by patients' age (Logistic regression OR 0.62, P = 0.24). As for the ECMO patients, the median age was 58 (47-66) years old and 62.2% (46/74) were male. The 28-day, 60-day, and 90-day mortality of these ECMO supported patients were 32.4, 68.9, and 74.3% respectively. Patients survived to discharge were younger (49 vs. 62 years, P = 0.042), demonstrated higher lymphocyte count (886 vs. 638 cells/uL, P = 0.022), and better CO2 removal (PaCO2 immediately after ECMO initiation 39.7 vs. 46.9 mmHg, P = 0.041). Age was an independent risk factor for in-hospital mortality of the ECMO supported patients, and a cutoff age of 51 years enabled prediction of in-hospital mortality with a sensitivity of 84.3% and specificity of 55%. The surviving ECMO supported patients had longer ICU and hospital stays (26 vs. 18 days, P = 0.018; 49 vs. 29 days, P = 0.001 respectively), and ECMO procedure was widely carried out after the supplement of medical resources after February 15 (67.6%, 50/74). Conclusions: ECMO might be a benefit for severe critically ill COVID-19 patients at the early stage of epidemic, although the in-hospital mortality was still high. To initiate ECMO therapy under tremendous pressure, patients' age, lymphocyte count, and adequacy of medical resources should be fully considered.

Dendritic CsSnI3 for Efficient and Flexible Near-Infrared Perovskite Light-Emitting Diodes.

All-inorganic and lead-free CsSnI3 is emerging as one of the most promising candidates for near-infrared perovskite light-emitting diodes (NIR Pero-LEDs), which find practical applications including facial recognition, biomedical apparatus, night vision camera, and Light Fidelity. However, in the CsSnI3 -based Pero-LEDs, the holes injection is significantly higher than that of electrons, resulting in unbalanced charge injection, undesired exciton dissipation, and poor device performance. Herein, it is proposed to manage charge injection and recombination behavior by tuning the interface area of perovskite and charge-transporter. A dendritic CsSnI3 structure is prepared on the hole-transporter, only making a bottom contact with the hole-transporter and exposing all other available crystal surfaces to the electron-transporter. In other words, the interface area of perovskite/electron-transporter is significantly higher than that of perovskite/hole-transporter. Moreover, the embedding interface of perovskite/electron-transporter can spatially confine holes and electrons, increasing the radiation recombination. By taking advantage of the dendritic structure, efficient lead-free NIR Pero-LEDs are achieved with a record external quantum efficiency (EQE) of 5.4%. More importantly, the dendritic structure shows great superiorities in flexible devices, for there is almost no morphology change after 2000-cycles of bends, and the fabricated Pero-LEDs can keep 93.4% of initial EQEs after 50-cycles of bends.

Roles of Nicotinamide N-Methyltransferase in Obesity and Type 2 Diabetes.

Type 2 diabetes (T2D) is thought to be a complication of metabolic syndrome caused by disorders of energy utilization and storage and characterized by insulin resistance or deficiency of insulin secretion. Though the mechanism linking obesity to the development of T2D is complex and unintelligible, it is known that abnormal lipid metabolism and adipose tissue accumulation possibly play important roles in this process. Recently, nicotinamide N-methyltransferase (NNMT) has been emerging as a new mechanism-of-action target in treating obesity and associated T2D. Evidence has shown that NNMT is associated with obesity and T2D. NNMT inhibition or NNMT knockdown significantly increases energy expenditure, reduces body weight and white adipose mass, improves insulin sensitivity, and normalizes glucose tolerance and fasting blood glucose levels. Additionally, trials of oligonucleotide therapeutics and experiments with some small-molecule NNMT inhibitors in vitro and in preclinical animal models have validated NNMT as a promising therapeutic target to prevent or treat obesity and associated T2D. However, the exact mechanisms underlying these phenomena are not yet fully understood and clinical trials targeting NNMT have not been reported until now. Therefore, more researches are necessary to reveal the acting mechanism of NNMT in obesity and T2D and to develop therapeutics targeting NNMT.