TDO2-overexpressed Dendritic Cells Possess Tolerogenicity and Ameliorate Collagen-induced Arthritis by Modulating the Th17/Regulatory T Cell Balance.

Tolerogenic dendritic cells are promising for restoring immune homeostasis and may be an alternative therapy for autoimmune diseases such as rheumatoid arthritis. The kynurenine pathway is a vital mechanism that induces tolerance in dendritic cells (DCs). Tryptophan 2,3-dioxygenase (TDO2) is an important rate-limiting enzyme in the kynurenine pathway and participates in immune regulation. However, the role of TDO2 in shaping the tolerogenic phenotypes of DCs remains unclear. In this study, we investigated the effects and mechanisms of TDO2-overexpressed DCs in regulating the T cell balance both in vivo and in vitro. TDO2-overexpressed DC2.4 and TDO2-/- mouse bone marrow-derived DCs (BMDCs) were generated to verify the role of TDO2 in DC maturation and functionality. TDO2 overexpression in BMDCs via PGE2 treatment exhibited an immature phenotype and tolerogenic state, whereas TDO2-/- BMDCs exhibited a mature phenotype and a proinflammatory state. Furthermore, transplant of TDO2-overexpressed BMDCs alleviated collagen-induced arthritis severity in mice, which was correlated with a reduction in Th17 populations and an increase in regulatory T cells. Collectively, these results indicate that TDO2 plays an important role in the tolerogenic phenotype and may be a promising target for the generation tolerogenic DCs for rheumatoid arthritis treatment.

Wafer-Scale Patterning Integration of Chiral 3D Perovskite Single Crystals toward High-Performance Full-Stokes Polarimeter.

Chiral three-dimensional (3D) perovskites exhibit exceptional optoelectronic characteristics and inherent chiroptical activity, which may overcome the limitations of low-dimensional chiral optoelectronic devices and achieve superior performance. The integrated chip of high-performance arbitrary polarized light detection is one of the aims of chiral optoelectronic devices and may be achieved by chiral 3D perovskites. Herein, we first fabricate the wafer-scale integrated full-Stokes polarimeter by the synergy of unprecedented chiral 3D perovskites (R/S-PyEA)Pb2Br6 and one-step capillary-bridge assembly technology. Compared with the chiral low-dimensional perovskites, chiral 3D perovskites present smaller exciton binding energies of 57.3 meV and excellent circular dichroism (CD) absorption properties, yielding excellent circularly polarized light (CPL) photodetectors with an ultrahigh responsivity of 86.7 A W-1, an unprecedented detectivity exceeding 4.84 × 1013 Jones, a high anisotropy factor of 0.42, and high-fidelity CPL imaging with 256 pixels. Moreover, the anisotropic crystal structure also enables chiral 3D perovskites to have a large linear-polarization response with a polarized ratio of 1.52. The combination of linear-polarization and circular-polarization discrimination capabilities guarantees the achievement of a full-Stokes polarimeter. Our study provides new research insights for the large-scale patterning wafer integration of high-performance chiroptical devices.

Unveiling the therapeutic prospects of IFNW1 and IFNA21: insights into glioma pathogenesis and clinical significance.

Glioma, a type of brain tumor, poses significant challenges due to its heterogeneous nature and limited treatment options. Interferon-related genes (IRGs) have emerged as potential players in glioma pathogenesis, yet their expression patterns and clinical implications remain to be fully elucidated. We conducted a comprehensive analysis to investigate the expression patterns and functional enrichment of IRGs in glioma. This involved constructing protein-protein interaction networks, heatmap analysis, survival curve plotting, diagnostic and prognostic assessments, differential expression analysis across glioma subgroups, GSVA, immune infiltration analysis, and drug sensitivity analysis. Our analysis revealed distinct expression patterns and functional enrichment of IRGs in glioma. Notably, IFNW1 and IFNA21 were markedly downregulated in glioma tissues compared to normal tissues, and higher expression levels were associated with improved overall survival and disease-specific survival. Furthermore, these genes showed diagnostic capabilities in distinguishing glioma tissues from normal tissues and were significantly downregulated in higher-grade and more aggressive gliomas. Differential expression analysis across glioma subgroups highlighted the association of IFNW1 and IFNA21 expression with key pathways and biological processes, including metabolic reprogramming and immune regulation. Immune infiltration analysis revealed their influence on immune cell composition in the tumor microenvironment. Additionally, elevated expression levels were associated with increased resistance to chemotherapeutic agents. Our findings underscore the potential of IFNW1 and IFNA21 as diagnostic biomarkers and prognostic indicators in glioma. Their roles in modulating glioma progression, immune response, and drug sensitivity highlight their significance as potential therapeutic targets. These results contribute to a deeper understanding of glioma biology and may inform the development of personalized treatment strategies for glioma patients.

Dynamic and Asymmetrical Ion Concentration Polarization in Dual Nanopipettes.

Dual nanopipettes with two channels have been receiving great attention due to the convenient experimental setup and multiple measuring channels in sensing applications at nanoscale, while the involved dynamic and asymmetrical ion transport processes have not been fully elucidated. In this paper, both experimental and simulation methods are used to investigate the dynamic mass transport processes inside dual nanopipettes with two well-separated channels. The results present that the ion transport resistance through the two channels (R12) is always the add-up of the individual ones (R13 + R23) with respect to the bulk solutions, at various ionic strengths and scan rates. A constant zero-current potential is obtained when loading an asymmetrical electrolyte concentration in the two channels, and the zero-potential current displays a good linear relationship with the bulk concentration outside the pipet. Besides revealing the dynamic and asymmetrical concentration polarization in the dual nanopipettes, these results would also further promote the better usage of dual nanopipettes in electrochemical sensing and imaging applications.

Phase Engineering Reinforced Energy Transfer for High-Performance Blue Perovskite Light-Emitting Diodes.

Layered metal-halide perovskites, a category of self-assembled quantum wells, are of paramount importance in emerging photonic sources, such as lasers and light-emitting diodes (LEDs). Despite high trap density in two-dimensional (2D) perovskites, efficient non-radiative energy funneling from wide- to narrow-bandgap components, sustained by the Förster resonance energy transfer (FRET) mechanism, contributes to efficient luminescence by light or electrical injection. Herein, it is demonstrated that bandgap extension of layered perovskites to the blue-emitting regime will cause sluggish and inefficient FRET, stemming from the tiny spectral overlap between different phases. Motivated by the importance of blue LEDs and inefficient energy transfer in materials with phase polydispersity, wide-bandgap quasi-2D perovskites with narrow phase distribution, improved crystallinity, and the pure crystal orientation perpendicular to the charge transport layer are developed. Based on this emitter, high-performance blue perovskite LEDs with improved electroluminescence (EL) external quantum efficiency (EQE) of 7.9% at 478 nm, a narrow full width at half-maximum (FWHM) of 22 nm and a more stable EL spectra are achieved. These results provide an important insight into spectrally stable and efficient blue emitters and EL devices based on perovskites.

The microRNA ppe-miR393 mediates auxin-induced peach fruit softening by promoting ethylene production.

Auxin can inhibit or promote fruit ripening, depending on the species. Melting flesh (MF) peach fruit (Prunus persica L. Batsch) cultivars produce high levels of ethylene caused by high concentrations of indole-3-acetic acid (IAA), which leads to rapid fruit softening at the late stage of development. In contrast, due to the low concentrations of IAA, the fruit of stony hard (SH) peach cultivars does not soften and produces little ethylene. Auxin seems necessary to trigger the biosynthesis of ethylene in peach fruit; however, the mechanism is not well understood. In this study, we identified miRNA gene family members ppe-miR393a and ppe-miR393b that are differentially expressed in SH and MF fruits. RNA ligase-mediated 5' rapid amplification of cDNA ends and transient transformation of Nicotiana benthamiana revealed TRANSPORT INHIBITOR RESPONSE 1 (PpTIR1), part of the auxin perception and response system, as a target of ppe-miR393a and b. Yeast 2-hybrid assay and bimolecular fluorescence complementation assay revealed that PpTIR1 physically interacts with an Aux/IAA protein PpIAA13. The results of yeast 1-hybrid assay, electrophoretic mobility shift assay, and dual-luciferase assay indicated that PpIAA13 could directly bind to and trans-activate the promoter of 1-aminocyclopropane-1-carboxylic acid synthase 1 (PpACS1), required for ethylene biosynthesis. Transient overexpression and suppression of ppe-miR393a and PpIAA13 in peach fruit induced and repressed the expression of PpACS1, confirming their regulatory role in ethylene synthesis. Gene expression analysis in developing MF and SH fruits, combined with postharvest α-naphthalene acetic acid (NAA) treatment, supports a role for a ppe-miR393-PpTIR1-PpIAA13-PpACS1 module in regulating auxin-related differences in ethylene production and softening extent in different types of peach.

Macrocycle-Based Hierarchically Porous Hydrogen-Bonded Organic Frameworks.

Hydrogen-bonded organic frameworks (HOFs) are porous crystalline materials. The pores in HOFs are usually non-covalent extrinsic pores constructed through the formation of the framework. Supramolecular macrocycles with intrinsic pores in their structures are good candidates for constructing HOFs with intrinsic pores from the macrocycles themselves, thus leading to hierarchically porous structures. Combining the macrocycle and HOFs will endow these hierarchically porous materials with enhanced properties and special functionalities. This review summarizes recent advances in macrocycle-based HOFs, including the macrocycles used for constructing HOFs, the hierarchically porous structures of the HOFs, and the applications induced by the hierarchically HOFs porous structures. This review provides insights for future research on macrocycle-based hierarchically porous HOFs and the appropriate applications of the unique structures.

Donor-Acceptor Interactions Enhanced Colorimetric Sensors for Both Acid and Base Vapor Based on Two-Dimensional Covalent Organic Frameworks.

Due to the high surface area and uniform porosity of covalent organic frameworks (COFs), they exhibit superior properties in capturing and detecting even trace amounts of gases in the air. However, the COFs materials that possess dual detected functionality are still less reported. Here, an imine-based COF containing thiophene as a donor and triazine as an acceptor to form spatial-distribution-defined D-A structures was prepared. D-A system between thiophene and triazine facilitates the charge transfer process during the protonation process of the imine and the triazine units. The obtained COF exhibits simultaneous sensing ability toward both acidic and alkaline vapors with obvious colorimetric sensing functionality.

Rare coding variants as risk modifiers of the 22q11.2 deletion implicate postnatal cortical development in syndromic schizophrenia.

22q11.2 deletion is one of the strongest known genetic risk factors for schizophrenia. Recent whole-genome sequencing of schizophrenia cases and controls with this deletion provided an unprecedented opportunity to identify risk modifying genetic variants and investigate their contribution to the pathogenesis of schizophrenia in 22q11.2 deletion syndrome. Here, we apply a novel analytic framework that integrates gene network and phenotype data to investigate the aggregate effects of rare coding variants and identified modifier genes in this etiologically homogenous cohort (223 schizophrenia cases and 233 controls of European descent). Our analyses revealed significant additive genetic components of rare nonsynonymous variants in 110 modifier genes (adjusted P = 9.4E-04) that overall accounted for 4.6% of the variance in schizophrenia status in this cohort, of which 4.0% was independent of the common polygenic risk for schizophrenia. The modifier genes affected by rare coding variants were enriched with genes involved in synaptic function and developmental disorders. Spatiotemporal transcriptomic analyses identified an enrichment of coexpression between modifier and 22q11.2 genes in cortical brain regions from late infancy to young adulthood. Corresponding gene coexpression modules are enriched with brain-specific protein-protein interactions of SLC25A1, COMT, and PI4KA in the 22q11.2 deletion region. Overall, our study highlights the contribution of rare coding variants to the SCZ risk. They not only complement common variants in disease genetics but also pinpoint brain regions and developmental stages critical to the etiology of syndromic schizophrenia.

Global prediction for mpox epidemic.

The mpox epidemic had spread worldwide and become an epidemic of international concern. Before the emergence of targeted vaccines and specific drugs, it is necessary to numerically simulate and predict the epidemic. In order to better understand and grasp its transmission situation, and take some countermeasures accordingly when necessary, we predicted and simulated mpox transmission, vaccination and control scenarios using model developed for COVID-19 predictions. The results show that the prediction model can also achieve good results in predicting the mpox epidemic based on modified SEIR model. The total number of people infected with mpox on Dec 31, 2022 reached 83878, while the prediction of the model was 96456 with a relative error of 15%. The United States, Brazil, Spain, France, the United Kingdom and Germany are six countries with serve mpox epidemic. The predictions of their epidemic are 30543, 11191, 7447, 5945, 5606 and 4291 cases respectively, with an average relative error of 20%. If 30% of the population is vaccinated using a vaccine that is 78% effective, the number of infected people will drop by 29%. This shows that the system can be practically applied to the prediction of mpox epidemic and provide corresponding decision-making reference.

Toll-like receptor 2, hyaluronan, and neutrophils play a key role in plaque erosion: the OPTICO-ACS study.

BACKGROUND AND AIMS: In one-third of patients with acute coronary syndrome (ACS), thrombosis occurs despite an intact fibrous cap (IFC) (IFC-ACS, 'plaque erosion'). Recent studies emphasize neutrophils as the immediate inflammatory response in this pathology, but their exact molecular activation patterns are still poorly understood and may represent future therapeutic targets. METHODS AND RESULTS: Thirty-two patients with IFC-ACS and matched patients with ACS with ruptured fibrous cap (RFC) (RFC-ACS) from the OPTICO-ACS study were included, and blood samples were collected from the local site of the culprit lesion and the systemic circulation. Neutrophil surface marker expression was quantified by flow cytometry. Neutrophil cytotoxicity towards endothelial cells was examined in an ex vivo co-culture assay. Secretion of active matrix metalloproteinase 9 (MMP9) by neutrophils was evaluated using zymography in supernatants and in plasma samples. Optical coherence tomography (OCT)-embedded thrombi were used for immunofluorescence analysis. Toll-like receptor 2 (TLR2) expression was higher on neutrophils from IFC-ACS than RFC-ACS patients. TLR2 stimulation increased the release of active MMP9 from local IFC-ACS-derived neutrophils, which also aggravated endothelial cell death independently of TLR2. Thrombi of IFC-ACS patients exhibited more hyaluronidase 2 with concomitant increase in local plasma levels of the TLR2 ligand: hyaluronic acid. CONCLUSION: The current study provides first in-human evidence for distinct TLR2-mediated neutrophil activation in IFC-ACS, presumably triggered by elevated soluble hyaluronic acid. Together with disturbed flow conditions, neutrophil-released MMP9 might be promoting endothelial cell loss-triggered thrombosis and therefore providing a potential future target for a phenotype-specific secondary therapeutic approach in IFC-ACS.

Single-crystal polymers (SCPs): from 1D to 3D architectures.

Single-crystal polymers (SCPs) with unambiguous chemical structures at atomic-level resolutions have attracted great attention. Obtaining precise structural information of these materials is critical as it enables a deeper understanding of the potential driving forces for specific packing and long-range order, secondary interactions, and kinetic and thermodynamic factors. Such information can ultimately lead to success in controlling the synthesis or engineering of their crystal structures for targeted applications, which could have far-reaching impact. Successful synthesis of SCPs with atomic level control of the structures, especially for those with 2D and 3D architectures, is rare. In this review, we summarize the recent progress in the synthesis of SCPs, including 1D, 2D, and 3D architectures. Solution synthesis, topochemical synthesis, and extreme condition synthesis are summarized and compared. Around 70 examples of SCPs with unambiguous structure information are presented, and their synthesis methods and structural analysis are discussed. This review offers critical insights into the structure-property relationships, providing guidance for the future rational design and bottom-up synthesis of a variety of highly ordered polymers with unprecedented functions and properties.

Risk Factors and Hazards of Recipient-Area Perifollicular Erythema After Hair Transplantation: A Multicenter Retrospective Cohort Study.

BACKGROUND: Recipient-area perifollicular erythema (RPE) may delay graft growth after hair transplantation. However, there is currently a lack of observational clinical studies of RPE. OBJECTIVE: To study the clinical features and risk factors associated with RPE while analyzing its correlation with graft growth. METHODS: We conducted a multicenter retrospective cohort study between June 2020 and January 2023. RESULTS: A total of 1090 participants were included, 178 (16.33%) showed mild RPE, 56 (5.14%) showed moderate RPE, and 10 (0.92%) showed severe RPE. Patients with RPE had severe hair shaft shedding (P < 0.001) and a lower survival rate (P < 0.001) of grafts. Logistic regression analysis showed that folliculitis is a significant risk factor for mild RPE (OR 6.061, 95% CI 3.343-10.991, P < 0.001) and moderate RPE (OR 3.397, 95% CI 1.299-8.882, P = 0.013). Besides, untimely first postoperative hair washing was associated with the development of moderate RPE (OR 0.724, 95% CI 0.553-0.947, P = 0.018) and severe RPE (OR 1.553, 95% CI 1.156-2.086, P = 0.003). CONCLUSION: RPE is a postoperative complication closely related to high hair shaft shedding proportion and low graft survival rate. Both postoperative folliculitis and untimely first postoperative hair washing may induce the occurrence of RPE. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Precise Preparation of Triarylboron-Based Graphdiyne Analogues for Gas Separation.

A series of triarylboron-based graphdiyne analogues (TAB-GDYs) with tunable pore size were prepared through copper mediated coupling reaction. The elemental composition, chemical bond, morphology of TAB-GDYs were well characterized. The crystallinity was confirmed by selected area electron diffraction (SAED) and stacking modes were studied in combination with high resolution transmission electron microscope (HRTEM) and structure simulation. The absorption and desorption isotherm revealed relatively high specific surface area of these TAB-GDYs up to 788 m2 g-1 for TMTAB-GDY, which decreased as pore size enlarged. TAB-GDYs exhibit certain selectivity for CO2 /N2 (21.9), CO2 /CH4 (5.3), CO2 /H2 (41.8) and C2 H2 /CO2 (2.3). This work has developed a series of boron containing two-dimensional frameworks with clear structures and good stability, and their tunable pore sizes have laid the foundation for future applications in the gas separation field.

Bipolar Molecular Torque Wrench Modulates the Stacking of Two-Dimensional Metal-Organic Framework Nanosheets.

The precise modulation of nanosheet stacking modes introduces unforeseen properties and creates momentous applications but remains a challenge. Herein, we proposed a strategy using bipolar molecules as torque wrenches to control the stacking modes of 2-D Zr-1,3,5-(4-carboxylphenyl)-benzene metal-organic framework (2-D Zr-BTB MOF) nanosheets. The bipolar phenyl-alkanes, phenylmethane (P-C1) and phenyl ethane (P-C2), predominantly instigated the rotational stacking of Zr-BTB-P-C1 and Zr-BTB-P-C2, displaying a wide angular distribution. This included Zr-BTB-P-C1 orientations at 0, 12, 18, and 24° and Zr-BTB-P-C2 orientations at 0, 6, 12, 15, 24, and 30°. With reduced polarity, phenyl propane (P-C3) and phenyl pentane (P-C5) introduced steric hindrance and facilitated alkyl hydrophobic interactions with the nanosheets, primarily resulting in the modulation of eclipsed stacking for Zr-BTB-P-C3 (64.8%) and Zr-BTB-P-C5 (93.3%) nanosheets. The precise angle distributions of four Zr-BTB-P species were in agreement with theoretical calculations. The alkyl induction mechanism was confirmed by the sequential guest replacement and 2-D 13C-1H heteronuclear correlation (HETCOR). In addition, at the single-particle level, we first observed that rotational stacked pores exhibited similar desorption rates for xylene isomers, while eclipsed stacked pores showed significant discrepancy for xylenes. Moreover, the eclipsed nanosheets as stationary phases exhibited high resolution, selectivity, repeatability, and durability for isomer separation. The universality was proven by another series of bipolar acetate-alkanes. This bipolar molecular torque wrench strategy provides an opportunity to precisely control the stacking modes of porous nanosheets.

Complete Sequence of the 22q11.2 Allele in 1,053 Subjects with 22q11.2 Deletion Syndrome Reveals Modifiers of Conotruncal Heart Defects.

The 22q11.2 deletion syndrome (22q11.2DS) results from non-allelic homologous recombination between low-copy repeats termed LCR22. About 60%-70% of individuals with the typical 3 megabase (Mb) deletion from LCR22A-D have congenital heart disease, mostly of the conotruncal type (CTD), whereas others have normal cardiac anatomy. In this study, we tested whether variants in the hemizygous LCR22A-D region are associated with risk for CTDs on the basis of the sequence of the 22q11.2 region from 1,053 22q11.2DS individuals. We found a significant association (FDR p < 0.05) of the CTD subset with 62 common variants in a single linkage disequilibrium (LD) block in a 350 kb interval harboring CRKL. A total of 45 of the 62 variants were associated with increased risk for CTDs (odds ratio [OR) ranges: 1.64-4.75). Associations of four variants were replicated in a meta-analysis of three genome-wide association studies of CTDs in affected individuals without 22q11.2DS. One of the replicated variants, rs178252, is located in an open chromatin region and resides in the double-elite enhancer, GH22J020947, that is predicted to regulate CRKL (CRK-like proto-oncogene, cytoplasmic adaptor) expression. Approximately 23% of patients with nested LCR22C-D deletions have CTDs, and inactivation of Crkl in mice causes CTDs, thus implicating this gene as a modifier. Rs178252 and rs6004160 are expression quantitative trait loci (eQTLs) of CRKL. Furthermore, set-based tests identified an enhancer that is predicted to target CRKL and is significantly associated with CTD risk (GH22J020946, sequence kernal association test (SKAT) p = 7.21 × 10-5) in the 22q11.2DS cohort. These findings suggest that variance in CTD penetrance in the 22q11.2DS population can be explained in part by variants affecting CRKL expression.

Molecular subtypes identified by multiomics analysis based on cuproptosis-related genes precisely predict response to immunotherapy and chemotherapy in colorectal cancer.

Cuproptosis is a newly reported type of programmed cell death that is involved in the progression of various diseases. Some studies have reported its potential significance in multiple tumors. Colorectal cancer (CRC) is one of the malignant tumors with high incidence and mortality. The purpose of this study was to further explore the importance of cuproptosis in the CRC development and treatment. We analyzed the expression, alterations, and promoter methylation of cuproptosis-related genes (CRGs) in patients with CRC. Three machine learning methods was used to determine cuproptosis-related feature genes and a diagnostic model was built based on them. Using the unsupervised clustering, patients with CRC were classified into distinct clusters. Then, the LASSO method was used to establish a cuproptosis risk model. We analyzed the association of risk scores with outcomes, immune microenvironment, response to immunotherapy, and sensitivity to chemotherapeutic drugs. The results showed that the expression of CRGs was dysregulated in CRC. The diagnostic model based on cuproptosis-related feature genes showed great clinical value. The patients in two clusters displayed different prognosis and microenvironment. Furthermore, the risk score was correlated with clinical characteristics, immune infiltration and response to immunotherapy and chemotherapy. Above all, the present findings revealed the involvement of cuproptosis in CRC development and provided a diagnostic tool to evaluate CRC occurrence risk. The immune infiltration and drug sensitivity analysis results helped to predict the response of patients in different subtypes of CRC to immunotherapy and chemotherapy.

Heat waves accelerate the spread of infectious diseases.

COVID-19 pandemic appeared summer surge in 2022 worldwide and this contradicts its seasonal fluctuations. Even as high temperature and intense ultraviolet radiation can inhibit viral activity, the number of new cases worldwide has increased to >78% in only 1 month since the summer of 2022 under unchanged virus mutation influence and control policies. Using the attribution analysis based on the theoretical infectious diseases model simulation, we found the mechanism of the severe COVID-19 outbreak in the summer of 2022 and identified the amplification effect of heat wave events on its magnitude. The results suggest that approximately 69.3% of COVID-19 cases this summer could have been avoided if there is no heat waves. The collision between the pandemic and the heatwave is not an accident. Climate change is leading to more frequent extreme climate events and an increasing number of infectious diseases, posing an urgent threat to human health and life. Therefore, public health authorities must quickly develop coordinated management plans to deal with the simultaneous occurrence of extreme climate events and infectious diseases.

( ±)-Dibrevianamides Q1 and Q2, the key precursors of asperginulin A from a marine-derived fungus.

Two pairs of new dimeric diketopiperazine alkaloids, ( ±)-dibrevianamides Q1 and Q2 (( ±)-1 and ( ±)-2), together with seven previously reported analogues (( ±)-3, 4-6, and ( ±)-7) were obtained from a marine-derived fungus Aspergillus sp. The structures of ( ±)-1 and ( ±)-2 were clarified using comprehensive spectroscopic analyses, the calculated ECD, and DP4 + probability methods. Speculated from the biogenesis, ( ±)-dibrevianamides Q1 and Q2 (( ±)-1 and ( ±)-2) might be the key precursor of [2 + 2] diketopiperazine dimers (( ±)-3). Compounds ( +)-1 and ( -)-2 displayed anti-H1N1 virus activity with IC50 values of 12.6 and 19.5 µM. Compound ( +)-1 showed significant activity against Mycobacterium tuberculosis (MIC, 10.2 µg/mL). KEY POINTS: • Two pairs of new dimeric diketopiperazine alkaloids were obtained from the marine-derived fungus Aspergillus sp. • The structures of the new compounds were clarified using comprehensive spectroscopic analyses, the calculated ECD, and DP4 + probability methods. • ( ±)-Dibrevianamides Q1 and Q2 were speculated to be the key precursor of [2 + 2] diketopiperazine dimers ( ±)-asperginulin A.

The association between the body roundness index and the risk of colorectal cancer: a cross-sectional study.

BACKGROUND: Colorectal cancer (CRC), has a link between obesity, especially visceral fat. The body roundness index (BRI) can more accurately assess body fat and visceral fat levels. It is, however, unknown whether BRI is associated with CRC risk. METHODS: 53,766 participants were enrolled from the National Health and Nutrition Examination Survey (NHANES). Analysing the corelation between BRI and CRC risk was performed using logistic regression. Stratified analyses revealed the association based on the population type. Receiver operating characteristic curve (ROC) was performed for predicting CRC risk using different anthropometric indices. RESULTS: The risk of CRC mounting apparently with elevated BRI for participants with CRC compared to normal participants (P-trend < 0.001). The association persisted even after adjusting for all covariates (P-trend = 0.017). In stratified analyses, CRC risk increased with increasing BRI, especially among those who were inactive (OR (95% CI): Q3 3.761 (2.139, 6.610), P < 0.05, Q4 5.972 (3.347, 8.470), P < 0.01), overweight (OR (95% CI): Q3 2.573 (1.012, 7.431), P < 0.05, Q4 3.318 (1.221, 9.020), P < 0.05) or obese (OR (95% CI): Q3 3.889 (1.829, 8.266), P < 0.001, Q4 4.920 (2.349, 10.308), P < 0.001). ROC curve showed that BRI had a better ability in forecasting the risk of CRC than other anthropometric indices such as body weight etc. (all P < 0.05). CONCLUSIONS: CRC risk and BRI have a positive and significant relationship, particularly in inactive participants with BMI ≥ 25 kg/m2. It is hoped that these results will raise awareness of the importance of reducing visceral fat deposition.