Ketogenesis supports hepatic polyunsaturated fatty acid homeostasis via fatty acid elongation.

Therapeutic interventions targeting hepatic lipid metabolism in metabolic dysfunction-associated steatotic liver disease (MASLD) and steatohepatitis (MASH) remain elusive. Using mass spectrometry-based stable isotope tracing and shotgun lipidomics, we established a novel link between ketogenesis and MASLD pathophysiology. Our findings show that mouse liver and primary hepatocytes consume ketone bodies to support fatty acid (FA) biosynthesis via both de novo lipogenesis (DNL) and FA elongation. Analysis of 13 C-labeled FAs in hepatocytes lacking mitochondrial D-ß-hydroxybutyrate dehydrogenase (BDH1) revealed a partial reliance on mitochondrial conversion of D-ßOHB to acetoacetate (AcAc) for cytoplasmic DNL contribution, whereas FA elongation from ketone bodies was fully dependent on cytosolic acetoacetyl-CoA synthetase (AACS). Ketone bodies were essential for polyunsaturated FA (PUFA) homeostasis in hepatocytes, as loss of AACS diminished both free and esterified PUFAs. Ketogenic insufficiency depleted liver PUFAs and increased triacylglycerols, mimicking human MASLD, suggesting that ketogenesis supports PUFA homeostasis, and may mitigate MASLD-MASH progression in humans.

Discovery of Oxidized p-Terphenyls as Phosphodiesterase 4 Inhibitors from Marine-Derived Fungi.

Four new p-terphenyl derivatives, talaroterphenyls A-D (1-4), together with three biosynthetically related known ones (5-7), were obtained from the mangrove sediment-derived Talaromyces sp. SCSIO 41412. Compounds 1-3 are rare p-terphenyls, which are completely substituted on the central benzene ring by oxygen atoms; this is the first report of their isolation from natural sources. Their structures were elucidated through NMR spectroscopy, HRESIMS, and X-ray diffraction. Genome sequence analysis revealed that 1-7 were biosynthesized from tyrosine and phenylalanine, involving four key biosynthetic genes (ttpB-ttpE). These p-terphenyls (1-7) and 36 marine-derived terphenyl analogues (8-43) were screened for phosphodiesterase 4 (PDE4) inhibitory activities, and 1-5, 14, 17, 23, and 26 showed notable activities with IC50 values of 0.40-16 µM. The binding pattern of p-terphenyl inhibitors 1-3 with PDE4 were explored by molecular docking analysis. Talaroterphenyl A (1), with a low cytotoxicity, showed obvious anti-inflammatory activity in LPS-stimulated RAW264.7 cells. Furthermore, in the TGF-ß1-induced medical research council cell strain-5 (MRC-5) pulmonary fibrosis model, 1 could down-regulate the expression levels of FN1, COL1, and α-SMA significantly at concentrations of 5-20 µM. This study suggests that the oxidized p-terphenyl 1, as a marine-derived PDE4 inhibitor, could be used as a promising antifibrotic agent.

Ergone Derivatives from the Deep-Sea-Derived Fungus Aspergillus terreus YPGA10 and 25,28-Dihydroxyergone-Induced Apoptosis in Human Colon Cancer SW620 Cells.

Ten new ergone derivatives (1-10) and five known analogues (11-15) were isolated from the deep-sea-derived fungus Aspergillus terreus YPGA10. The structures including the absolute configurations were established by detailed analysis of the NMR spectroscopic data, HRESIMS, ECD calculation, and coupling constant calculation. All the structures are characterized by a highly conjugated 25-hydroxyergosta-4,6,8(14),22-tetraen-3-one nucleus. Structurally, compound 2 bearing a 15-carbonyl group and compounds 5-7 possessing a 15ß-OH/OCH3 group are rarely encountered in ergone derivatives. Bioassay results showed that compounds 1 and 11 demonstrated cytotoxic effects on human colon cancer SW620 cells with IC50 values of 8.4 and 3.1 µM, respectively. Notably, both compounds exhibited negligible cytotoxicity on the human normal lung epithelial cell BEAS-2B. Compound 11 was selected for preliminary mechanistic study and was found to inhibit cell proliferation and induce apoptosis in human colon cancer SW620 cells. In addition, compound 1 displayed cytotoxic activity against five human leukemia cell lines with IC50 values ranging from 5.7 to 8.9 µM. Our study demonstrated that compound 11 may serve as a potential candidate for the development of anticolorectal cancer agents.

MitoQ Alleviated PM2.5 Induced Pulmonary Epithelial Cells Injury by Inhibiting Mitochondrial-Mediated Apoptosis.

Background: Fine particulate matter (PM2.5), an important component of ambient air pollution, induces significant adverse health effects. MitoQuinone (MitoQ), a mitochondria-targeted antioxidant, has been reported to play a protective role in various diseases. However, the roles of MitoQ in PM2.5 induced pulmonary toxicity remains to be elucidated. Methods: All the experiments were performed at Higher Educational Key Laboratory for Translational Oncology of Fujian Province, Putian City, China in 2023. Pulmonary epithelial cells (A549) were pretreated with 4 µM MitoQ for 2 h and exposed to PM2.5 for 24 h. Cell viability was tested through CCK8 assay. Oxidative stress state and active mitochondria was used to study MitoQ's effect on PM2.5 induced injury, and cell apoptosis was measured using a flow cytometer and analyzed by Bcl-2 family. Results: MitoQ pretreatment significantly relieved a decreased cell viability, subsequently, MitoQ alleviated ROS production and prevented the reduction of T-AOC and GSH and increased the expression of NF-E2-related factor 2 (Nrf2) and p62 in A549 cells exposed to PM2.5. MitoQ restored the decreased mitochondrial dysfunction and dynamics disorder and inhibited activated mitochondrial-mediated apoptosis induced by PM2.5. Furthermore, the decreased ratio of Bcl-2/Bax and expression of Mcl-1 and the enhanced expression of Caspase-3 were reversed by MitoQ pretreatment. Conclusion: MitoQ might be regarded as a potential drug to relieve PM2.5 induced pulmonary epithelial cells damage.

Anatomical Study of the Superior Auricular Artery Using 3-Dimensional Computed Tomography Angiography.

BACKGROUND: The superior auricular artery (SAA)-retroauricular flap is commonly used for the repair of defects of the superior auricle. There are few studies about the anatomy of the SAA. OBJECTIVE: This study mainly analyzed the anatomical pattern of SAA. MATERIALS AND METHODS: Computed tomography (CT) was performed on 26 cadaver heads infused with lead oxide. The anatomical pattern of the SAA was statistically analyzed by 3-dimensional CT images. RESULTS: The SAA was classified into 3 types according to whether it gave off the helix branch or the auricular dorsal branch. The SAA was located mainly in an area 2 cm above and below the horizontal line at the midpoint of the 2 base points (the otobasion superius and the apex of the external auditory canal). The origin of each branch of the SAA was mainly located in Areas 2, 3, and 4 within a circular area that had the otobasion superius as the center of the circle and a radius of 2 cm. CONCLUSION: In this study, the 3 anatomical types and anatomical patterns of the SAA were identified. These findings can provide a reference for the design of SAA-retroauricular flaps and for surgical planning.

Evaluation of the Reproducibility of Auricular Subunit Markers Based on Three-Dimensional Computed Tomography.

BACKGROUND: As a facial feature, the auricle plays an important role in the integrity and aesthetics of the whole face. Auricular subunits are associated with patient satisfaction in auricular reconstruction, but there are few studies on auricular subunits. We want to evaluate the reproducibility of auricular subunits by measuring the coordinates of the marker points of auricular subunits, accordingly provide a reference for the improvement of auricular reconstruction and the aesthetics of auricular injection. METHODS: Mimics 19.0 was used to carry out three-dimensional (3D) reconstruction of the computed tomography (CT) scan data of patients' brains; measure the three-dimensional coordinates of the 13 auricular subunit markers, the morphological auricle length and width, and the physiological auricle length and width; and analyze the reproducibility as well as the differences between group. RESULTS: Reproducibility of auricle subunit markers: There are 1124 (58.82%) high reproducibility, 580 (30.35%) moderate reproducibility, and 207 (10.83%) low reproducibility. The superior tragus notch, tragus, and antitragus had the highest reproducibility. There was no significant difference between the groups in the marking points on the helix, and there were no statistically significant differences in the measurement values of the auricles on the two sides. The physiological ear length and width and the morphological ear length of males were larger than those of females. These showed significant differences between the age groups. CONCLUSION: Most auricular subunit markers have high reproducibility. The subunits with higher reproducibility are the structures that need to be optimized during auricle reconstruction surgery or auricle injection in the future. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. 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 .

Activation of glutamatergic neurons in the somatosensory cortex promotes remyelination in ischemic vascular dementia.

Chronic cerebral hypoperfusion can cause progressive demyelination as well as ischemic vascular dementia, however no effective treatments are available. Here, based on magnetic resonance imaging studies of patients with white matter damage, we found that this damage is associated with disorganized cortical structure. In a mouse model, optogenetic activation of glutamatergic neurons in the somatosensory cortex significantly promoted oligodendrocyte progenitor cell (OPC) proliferation, remyelination in the corpus callosum, and recovery of cognitive ability after cerebral hypoperfusion. The therapeutic effect of such stimulation was restricted to the upper layers of the cortex, but also spanned a wide time window after ischemia. Mechanistically, enhancement of glutamatergic neuron-OPC functional synaptic connections is required to achieve the protection effect of activating cortical glutamatergic neurons. Additionally, skin stroking, an easier method to translate into clinical practice, activated the somatosensory cortex, thereby promoting OPC proliferation, remyelination and cognitive recovery following cerebral hypoperfusion. In summary, we demonstrated that activating glutamatergic neurons in the somatosensory cortex promotes the proliferation of OPCs and remyelination to recover cognitive function after chronic cerebral hypoperfusion. It should be noted that this activation may provide new approaches for treating ischemic vascular dementia via the precise regulation of glutamatergic neuron-OPC circuits.

Fe-doped Cu-based bimetallic metal-organic frameworks as nanoscale microwave sensitizers for enhancing microwave thermal and dynamic therapy for hepatocellular carcinoma.

Microwave ablation (MWA) is recognized as a novel treatment modality that can kill tumor cells by heating the ions and polar molecules in these cells through high-speed rotation and friction. However, the size and location of the tumor affect the effective ablation range of microwave hyperthermia, resulting in residual tumor tissue and a high recurrence rate. Due to their tunable porous structure and high specific surface area, metal-organic frameworks (MOFs) can serve as microwave sensitizers, promoting microwave energy conversion owing to ion collisions in the porous structure of the MOFs. Moreover, iron-based compounds are known to possess peroxidase-like catalytic activity. Therefore, Fe-doped Cu bimetallic MOFs (FCMs) were prepared through a hydrothermal process. These FCM nanoparticles not only increased the efficiency of microwave-thermal energy conversion as microwave sensitizers but also promoted the generation of reactive oxygen species (ROS) by consuming glutathione (GSH) and promoted the Fenton reaction to enhance microwave dynamic therapy (MDT). The in vitro and in vivo results showed that the combination of MWA and MDT treatment effectively destroyed tumor tissues via microwave irradiation without inducing significant side effects on normal tissues. This study provides a new approach for the combined application of MOFs and microwave ablation, demonstrating excellent potential for future applications.

SIRT5 exacerbates eosinophilic chronic rhinosinusitis by promoting polarization of M2 macrophage.

BACKGROUND: Previous studies implied that local M2 polarization of macrophage promoted mucosal edema and exacerbated TH2 type inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP). However, the specific pathogenic role of M2 macrophages and the intrinsic regulators in the development of CRS remains elusive. OBJECTIVE: We sought to investigate the regulatory role of SIRT5 in the polarization of M2 macrophages and its potential contribution to the development of CRSwNP. METHODS: Real-time reverse transcription-quantitative PCR and Western blot analyses were performed to examine the expression levels of SIRT5 and markers of M2 macrophages in sinonasal mucosa samples obtained from both CRS and control groups. Wild-type and Sirt5-knockout mice were used to establish a nasal polyp model with TH2 inflammation and to investigate the effects of SIRT5 in macrophage on disease development. Furthermore, in vitro experiments were conducted to elucidate the regulatory role of SIRT5 in polarization of M2 macrophages. RESULTS: Clinical investigations showed that SIRT5 was highly expressed and positively correlated with M2 macrophage markers in eosinophilic polyps. The expression of SIRT5 in M2 macrophages was found to contribute to the development of the disease, which was impaired in Sirt5-deficient mice. Mechanistically, SIRT5 was shown to enhance the alternative polarization of macrophages by promoting glutaminolysis. CONCLUSIONS: SIRT5 plays a crucial role in promoting the development of CRSwNP by supporting alternative polarization of macrophages, thus providing a potential target for CRSwNP interventions.

Structural optimization of Moracin M as novel selective phosphodiesterase 4 inhibitors for the treatment of idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and high mortality lung disease. Although the antifibrotic drugs pirfenidone and nintedanib could slow the rate of lung function decline, the usual course of the condition is inexorably to respiratory failure and death. Therefore, new approaches and novel therapeutic drugs for the treatment of IPF are urgently needed. And the selective PDE4 inhibitor has in vivo and in vitro anti-fibrotic effects in IPF models. But the clinical application of most PDE4 inhibitors are limited by their unexpected and severe side effects such as nausea, vomiting, and diarrhea. Herein, structure-based optimizations of the natural product Moracin M resulted in a novel a novel series of 2-arylbenzofurans as potent PDE4 inhibitors. The most potent inhibitor L13 has an IC50 of 36 ± 7 nM with remarkable selectivity across the PDE families and administration of L13·citrate (10.0 mg/kg) exhibited comparable anti-pulmonary fibrosis effects to pirfenidone (300 mg/kg) in a bleomycin-induced IPF mice model, indicate that L13 is a potential lead for the treatment of IPF.

Efficient Fabrication of Quartz Glass Using Laser Coaxial Powder-Fed Additive Manufacturing Approach.

This article investigates a laser-directed energy deposition additive manufacturing (AM) method, based on coaxial powder feeding, for preparing quartz glass. Through synergistic optimization of line deposition and plane deposition experiments, key parameters of laser coaxial powder feeding AM were identified. The corresponding mechanical properties, thermal properties, and microstructure of the bulk parts were analyzed. The maximum mechanical strength of the obtained quartz glass element reached 72.36 ± 5.98 MPa, which is ca. 95% that of quartz glass prepared by traditional methods. The thermal properties of the obtained quartz glass element were also close to those prepared by traditional methods. The present research indicates that one can use laser AM technology that is based on coaxial powder feeding to form quartz glass with high density and good thermodynamic properties. Such quartz glass has substantial potential in, for example, optics and biomedicine.

Predicting the pathways of string-like motions in metallic glasses via path-featurizing graph neural networks.

String-like motions (SLMs)-cooperative, "snake"-like movements of particles-are crucial for dynamics in diverse glass formers. Despite their ubiquity, questions persist: Do SLMs prefer specific paths? If so, can we predict these paths? Here, in Al-Sm glasses, our isoconfigurational ensemble simulations reveal that SLMs do follow certain paths. By designing a graph neural network (GNN) to featurize the environment around directional paths, we achieve a high-fidelity prediction of likely SLM pathways, solely based on the static structure. GNN gauges a structural measure to assess each path's propensity to engage in SLMs, akin to a "softness" metric, but for paths rather than for atoms. Our GNN interpretation reveals the critical role of the bottleneck zone along a path in steering SLMs. By monitoring "path softness," we elucidate that SLM-favored paths transit from fragmented to interconnected upon glass transition. Our findings reveal that, beyond atoms or clusters, glasses have another dimension of structural heterogeneity: "paths."

Amorphous conversion in pyrolytic symmetric trinuclear nickel clusters trigger trifunctional electrocatalysts.

The pursuit of multifunctional electrocatalysts holds significant importance due to their comprehension of material chemistry. Amorphous materials are particularly appealing, yet they pose challenges in terms of rational design due to their structural disorder and thermal instability. Herein, we propose a strategy that entails the tandem (low-temperature/250-350 °C) pyrolysis of molecular clusters, enabling preservation of the local short-range structures of the precursor Schiff base nickel (Ni3[2(C21H24N3Ni1.5O6)]). The temperature-dependent residuals demonstrate exceptional activity and stability for at least three distinct electrocatalytic processes, including the oxygen evolution reaction (η10 = 197 mV), urea oxidation reaction (η10 = 1.339 V), and methanol oxidation reaction (1358 mA cm-2 at 0.56 V). Three distinct nickel atom motifs are discovered for three efficient electrocatalytic reactions (Ni1 and Ni1' are preferred for UOR/MOR, while Ni2 is preferred for OER). Our discoveries pave the way for the potential development of multifunctional electrocatalysts through disordered engineering in molecular clusters under tandem pyrolysis.

Immune checkpoint inhibitors and anti-vascular endothelial growth factor antibody/tyrosine kinase inhibitors with or without transarterial chemoembolization as first-line treatment for advanced hepatocellular carcinoma (CHANCE2201): a target trial emulation study.

Background: The role of transarterial chemoembolization (TACE) in the treatment of advanced hepatocellular carcinoma (HCC) is unconfirmed. This study aimed to assess the efficacy and safety of immune checkpoint inhibitors (ICIs) plus anti-vascular endothelial growth factor (anti-VEGF) antibody/tyrosine kinase inhibitors (TKIs) with or without TACE as first-line treatment for advanced HCC. Methods: This nationwide, multicenter, retrospective cohort study included advanced HCC patients receiving either TACE with ICIs plus anti-VEGF antibody/TKIs (TACE-ICI-VEGF) or only ICIs plus anti-VEGF antibody/TKIs (ICI-VEGF) from January 2018 to December 2022. The study design followed the target trial emulation framework with stabilized inverse probability of treatment weighting (sIPTW) to minimize biases. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), and safety. The study is registered with ClinicalTrials.gov, NCT05332821. Findings: Among 1244 patients included in the analysis, 802 (64.5%) patients received TACE-ICI-VEGF treatment, and 442 (35.5%) patients received ICI-VEGF treatment. The median follow-up time was 21.1 months and 20.6 months, respectively. Post-application of sIPTW, baseline characteristics were well-balanced between the two groups. TACE-ICI-VEGF group exhibited a significantly improved median OS (22.6 months [95% CI: 21.2-23.9] vs 15.9 months [14.9-17.8]; P < 0.0001; adjusted hazard ratio [aHR] 0.63 [95% CI: 0.53-0.75]). Median PFS was also longer in TACE-ICI-VEGF group (9.9 months [9.1-10.6] vs 7.4 months [6.7-8.5]; P < 0.0001; aHR 0.74 [0.65-0.85]) per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. A higher ORR was observed in TACE-ICI-VEGF group, by either RECIST v1.1 or modified RECIST (41.2% vs 22.9%, P < 0.0001; 47.3% vs 29.7%, P < 0.0001). Grade ≥3 adverse events occurred in 178 patients (22.2%) in TACE-ICI-VEGF group and 80 patients (18.1%) in ICI-VEGF group. Interpretation: This multicenter study supports the use of TACE combined with ICIs and anti-VEGF antibody/TKIs as first-line treatment for advanced HCC, demonstrating an acceptable safety profile. Funding: National Natural Science Foundation of China, National Key Research and Development Program of China, Jiangsu Provincial Medical Innovation Center, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, and Nanjing Life Health Science and Technology Project.

Resonant exchange of chiral Majorana Fermions modulated by two parallel quantum dots.

Resonant exchange of the chiral Majorana fermions (MFs) that is coupled to two parallel Majorana zero modes (MZMs) or two parallel quantum dots (QDs) is investigated. We find that, in the two QDs coupling case, the resonant exchange for the chiral MFs is analogous to that in the MZM coupling case. We further propose a circuit based on topological superconductor, which is formed by the proximity coupling of a quantum anomalous Hall insulator and a s-wave superconductor, to observe the resonant exchange of chiral MFs pairs. The numerical calculations show that the resonant transmission of the chiral MFs can be adjusted by varying the coupling parameters at superconductor phase differenceΔφ=π. It is particularly noteworthy that, by only modulating the coupling strength between the two QDs, the resonant exchange may be switched on or off. By adding another MZM, the non-Abelian braiding like operation can be realized. Therefore, our design scheme may provide another way for non-Abelian braiding operation of MFs and the findings may have potential application value in the realization of topological quantum computers.

Regulation of Burkholderia cenocepacia virulence by the fatty acyl-CoA ligase DsfR as a response regulator of quorum sensing signal.

Quorum sensing (QS) is a cell-to-cell communication mechanism mediated by small diffusible signaling molecules. Previous studies showed that RpfR controls Burkholderia cenocepacia virulence as a cis-2-dodecenoic acid (BDSF) QS signal receptor. Here, we report that the fatty acyl-CoA ligase DsfR (BCAM2136), which efficiently catalyzes in vitro synthesis of lauryl-CoA and oleoyl-CoA from lauric acid and oleic acid, respectively, acts as a global transcriptional regulator to control B. cenocepacia virulence by sensing BDSF. We show that BDSF binds to DsfR with high affinity and enhances the binding of DsfR to the promoter DNA regions of target genes. Furthermore, we demonstrate that the homolog of DsfR in B. lata, RS02960, binds to the target gene promoter, and perception of BDSF enhances the binding activity of RS02960. Together, these results provide insights into the evolved unusual functions of DsfR that control bacterial virulence as a response regulator of QS signal.

Transarterial Chemoembolization Combined with Tyrosine Kinase Inhibitors Plus Immune Checkpoint Inhibitors Versus Tyrosine Kinase Inhibitors Plus Immune Checkpoint Inhibitors in Unresectable Hepatocellular Carcinoma with First- or Lower-Order Portal Vein Tumor Thrombosis.

PURPOSE: To compare the efficacy of transarterial chemoembolization (TACE) combined with tyrosine kinase inhibitors (TKIs) plus immune checkpoint inhibitors (ICIs) (TACE-TKI-ICI) versus TKIs plus ICIs (TKI-ICI) for unresectable hepatocellular carcinoma (HCC) with first- or lower-order portal vein tumor thrombosis (PVTT). MATERIALS AND METHODS: A retrospective study was performed in HCC patients with first- or lower-order PVTT receiving TKIs (Lenvatinib or sorafenib) plus ICIs (camrelizumab, sintilimab, or atezolizumab) with or without TACE from four institutions between January 2019 and January 2022. Propensity score-based method was performed to minimize bias by confounding factors. Tumor response, progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were evaluated and compared between the two groups. RESULTS: After inverse probability of treatment weighting, two balanced pseudopopulations were created: 106 patients in the TACE-TKI-ICI group and 109 patients in the TKI-ICI group. The objective response rate was higher in the TACE-TKI-ICI group (50.9% vs. 28.4%, P < 0.001). The median PFS and OS were significantly longer in the TACE-TKI-ICI group than in the TKI-ICI group (PFS: 9.1 vs. 5.0 months, P = 0.005; OS: 19.1 vs. 12.7 months, P = 0.002). In Cox regression, TACE-TKI-ICI treatment was an independent predictor of favorable OS. Treatment-related grade 3/4 AEs were comparable between the two groups (22.6% vs. 17.9%, P = 0.437). CONCLUSION: TACE-TKI-ICI therapy contributed to better tumor control, PFS and OS than TKI-ICI therapy in unresectable HCC patients with first- or lower-order PVTT.

The Ideal Proportion of the Auricle Exposure via a Morphometric Analysis in Asian Women.

BACKGROUND: Ears are an important aesthetic feature that is vital to the overall attractiveness of the face. Although there have been many studies on the aesthetics of the auricle, there is currently a lack of consensus on the ideal proportion of auricle exposure for Asian women in frontal view. OBJECTIVES: This study aimed to investigate ideal proportion of auricle exposure in Asian women. METHODS: An observational study was carried out on the photographs of 84 women on the list of the 100 most beautiful faces in Asia (published by TCC Asia in 2020). The proportion of the distance between the outer canthus and the outermost point of auricle to the distance between the inner canthus and the outermost point of auricle was calculated as the auricle exposure proportion. Evaluators were asked to rank a set of photographs of the volunteer with varying auricle exposure proportions from most attractive to least attractive. RESULTS: Measurements of the photographs of the 84 women showed a mean ear exposure proportion of 0.600. With 487 questionnaire responses received, the proportion of auricle exposure that the evaluators considered most attractive was 0.600. People with aesthetic experience considered 0.625 the most attractive proportion, while the general group considered 0.600 the most attractive. CONCLUSIONS: The ideal proportion of the auricle exposure for Asian women is in the range of 0.60-0.625, which may help surgeons reconstruct aesthetically pleasing ears. LEVEL OF EVIDENCE V: 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 .

Cross-kingdom RNA interference mediated by insect salivary microRNAs may suppress plant immunity.

Communication between insects and plants relies on the exchange of bioactive molecules that traverse the species interface. Although proteinic effectors have been extensively studied, our knowledge of other molecules involved in this process remains limited. In this study, we investigate the role of salivary microRNAs (miRNAs) from the rice planthopper Nilaparvata lugens in suppressing plant immunity. A total of three miRNAs were confirmed to be secreted into host plants during insect feeding. Notably, the sequence-conserved miR-7-5P is specifically expressed in the salivary glands of N. lugens and is secreted into saliva, distinguishing it significantly from homologues found in other insects. Silencing miR-7-5P negatively affects N. lugens feeding on rice plants, but not on artificial diets. The impaired feeding performance of miR-7-5P-silenced insects can be rescued by transgenic plants overexpressing miR-7-5P. Through target prediction and experimental testing, we demonstrate that miR-7-5P targets multiple plant genes, including the immune-associated bZIP transcription factor 43 (OsbZIP43). Infestation of rice plants by miR-7-5P-silenced insects leads to the increased expression of OsbZIP43, while the presence of miR-7-5P counteracts this upregulation effect. Furthermore, overexpressing OsbZIP43 confers plant resistance against insects which can be subverted by miR-7-5P. Our findings suggest a mechanism by which herbivorous insects have evolved salivary miRNAs to suppress plant immunity, expanding our understanding of cross-kingdom RNA interference between interacting organisms.