Multifunctional ytterbium oxide buffer for perovskite solar cells.

Perovskite solar cells (PSCs) comprise a solid perovskite absorber sandwiched between several layers of different charge-selective materials, ensuring unidirectional current flow and high voltage output of the devices1,2. A 'buffer material' between the electron-selective layer and the metal electrode in p-type/intrinsic/n-type (p-i-n) PSCs (also known as inverted PSCs) enables electrons to flow from the electron-selective layer to the electrode3-5. Furthermore, it acts as a barrier inhibiting the inter-diffusion of harmful species into or degradation products out of the perovskite absorber6-8. Thus far, evaporable organic molecules9,10 and atomic-layer-deposited metal oxides11,12 have been successful, but each has specific imperfections. Here we report a chemically stable and multifunctional buffer material, ytterbium oxide (YbOx), for p-i-n PSCs by scalable thermal evaporation deposition. We used this YbOx buffer in the p-i-n PSCs with a narrow-bandgap perovskite absorber, yielding a certified power conversion efficiency of more than 25%. We also demonstrate the broad applicability of YbOx in enabling highly efficient PSCs from various types of perovskite absorber layer, delivering state-of-the-art efficiencies of 20.1% for the wide-bandgap perovskite absorber and 22.1% for the mid-bandgap perovskite absorber, respectively. Moreover, when subjected to ISOS-L-3 accelerated ageing, encapsulated devices with YbOx exhibit markedly enhanced device stability.

Dual-axial engineering on atomically dispersed catalysts for ultrastable oxygen reduction in acidic and alkaline solutions.

Atomically dispersed catalysts are a promising alternative to platinum group metal catalysts for catalyzing the oxygen reduction reaction (ORR), while limited durability during the electrocatalytic process severely restricts their practical application. Here, we report an atomically dispersed Co-doped carbon-nitrogen bilayer catalyst with unique dual-axial Co-C bonds (denoted as Co/DACN) by a smart phenyl-carbon-induced strategy, realizing highly efficient electrocatalytic ORR in both alkaline and acidic media. The corresponding half-wave potential for ORR is up to 0.85 and 0.77 V (vs. reversible hydrogen electrode (RHE)) in 0.5 M H2SO4 and 0.1 M KOH, respectively, representing the best ORR activity among all non-noble metal catalysts reported to date. Impressively, the Zn-air battery (ZAB) equipped with Co/DACN cathode achieves outstanding durability after 1,688 h operation at 10 mA cm-2 with a high current density (154.2 mA cm-2) and a peak power density (210.1 mW cm-2). Density functional theory calculations reveal that the unique dual-axial cross-linking Co-C bonds of Co/DACN significantly enhance the stability during ORR and also facilitate the 4e- ORR pathway by forming a joint electron pool due to the improved interlayer electron mobility. We believe that axial engineering opens a broad avenue to develop high-performance heterogeneous electrocatalysts for advanced energy conversion and storage.

Legionella pneumophila exploits the endo-lysosomal network for phagosome biogenesis by co-opting SUMOylated Rab7.

Legionella pneumophila strains harboring wild-type rpsL such as Lp02rpsLWT cannot replicate in mouse bone marrow-derived macrophages (BMDMs) due to induction of extensive lysosome damage and apoptosis. The bacterial factor directly responsible for inducing such cell death and the host factor involved in initiating the signaling cascade that leads to lysosome damage remain unknown. Similarly, host factors that may alleviate cell death induced by these bacterial strains have not yet been investigated. Using a genome-wide CRISPR/Cas9 screening, we identified Hmg20a and Nol9 as host factors important for restricting strain Lp02rpsLWT in BMDMs. Depletion of Hmg20a protects macrophages from infection-induced lysosomal damage and apoptosis, allowing productive bacterial replication. The restriction imposed by Hmg20a was mediated by repressing the expression of several endo-lysosomal proteins, including the small GTPase Rab7. We found that SUMOylated Rab7 is recruited to the bacterial phagosome via SulF, a Dot/Icm effector that harbors a SUMO-interacting motif (SIM). Moreover, overexpression of Rab7 rescues intracellular growth of strain Lp02rpsLWT in BMDMs. Our results establish that L. pneumophila exploits the lysosomal network for the biogenesis of its phagosome in BMDMs.

Crohn's patients and healthy infants share immunodominant B cell response to commensal flagellin peptide epitopes.

BACKGROUND AND AIMS: Inflammatory bowel disease is a chronic manifestation of dysregulated immune response to the gut microbiota in genetically pre-disposed hosts. Nearly half of patients with Crohn's disease (CD) develop selective serum IgG response to flagellin proteins expressed by bacteria in the Lachnospiraceae family. This study aimed to identify the binding epitopes of these IgG antibodies and assess their relevance in CD and in homeostasis. METHODS: Sera from an adult CD cohort, a treatment-naïve pediatric CD cohort, and three independent non-IBD infant cohorts were analyzed using novel techniques including a flagellin peptide microarray and a flagellin peptide cytometric bead array. RESULTS: A dominant B cell peptide epitope in CD patients was identified, locating in the highly conserved "hinge region" between the D0 and D1 domains at the amino-terminus of Lachnospiraceae flagellins. Elevated serum IgG reactivity to the hinge peptide was strongly associated with incidence of CD and the development of disease complications in children with CD up to five years in advance. Notably, high levels of serum IgG to the hinge epitope were also found in most infants from 3 different geographic regions (Uganda, Sweden, and the USA) at one year of age, which decrements rapidly afterwards. CONCLUSIONS: These findings identified a distinct subset of CD patients, united by a shared reactivity to a dominant commensal bacterial flagellin epitope that may represent failure of a homeostatic response to the gut microbiota beginning in infancy.

TRANSPARENT TESTA GLABRA1 Regulates High-Intensity Blue Light-Induced Phototropism by Reducing CRYPTOCHROME1 Levels.

The asymmetrical distribution of auxin supports high intensity blue light (HBL)-mediated phototropism. Flavonoids, secondary metabolites induced by blue light and TRANSPARENT TESTA GLABRA1 (TTG1), alter auxin transport. However, the role of TTG1 in HBL-induced phototropism in Arabidopsis (Arabidopsis thaliana) remains unclear. We found that TTG1 regulates HBL-mediated phototropism. HBL-induced degradation of CRYPTOCHROME 1 (CRY1) was repressed in ttg1-1, and depletion of CRY1 rescued the phototropic defects of the ttg1-1 mutant. Moreover, overexpression of CRY1 in a cry1 mutant background led to phototropic defects in response to HBL. These results indicated that CRY1 is involved in the regulation of TTG1-mediated phototropism in response to HBL. Further investigation showed that TTG1 physically interacts with CRY1 via its N-terminus and that the added TTG1 promotes the dimerization of CRY1. The interaction between TTG1 and CRY1 may promote HBL-mediated degradation of CRY1. TTG1 also physically interacted with blue light inhibitor of cryptochrome 1 (BIC1) and Light-Response Bric-a-Brack/Tramtrack/Broad 2 (LRB2), and these interactions either inhibited or promoted their interaction with CRY1. Exogenous gibberellins (GA) and auxins, two key plant hormones that crosstalk with CRY1, may confer the recovery of phototropic defects in the ttg1-1 mutant and CRY1-overexpressing plants. Our results revealed that TTG1 participates in the regulation of HBL-induced phototropism by modulating CRY1 levels, which are coordinated with GA or IAA signaling.

Revealing the Effect of the [CoO]6 Microstructure in Pseudocapacitance by Controlled Delithium of LiCoO2.

Revealing the in-depth structure-property relationship and designing specific capacity electrodes are particularly important for supercapacitors. Despite many efforts made to tune the composition and electronic structure of cobalt oxide for pseudocapacitance, insight into the [CoO]6 octahedron from the microstructure is still insufficient. Herein, we present a tunable [CoO]6 octahedron microstructure in LiCoO2 by a chemical delithiation process. The c-strained strain of the [CoO]6 octahedron is induced to form higher valence Co ions, and the (003) crystalline layer spacing increases to allow more rapid participation of OH- in the redox reaction. Interestingly, the specific capacity of L0.75CO2 is nearly four times higher than that of LiCoO2 at 10 mA g-1. The enhanced activity originated from the asymmetric strain [CoO]6 octahedra, resulting in enhanced electronic conductivity and Co-O hybridization for accelerated redox kinetics. This finding provides new insights into the modification strategy for pseudocapacitive transition metal oxides.

Serum GSDMD for Early Diagnosis of Bloodstream Infection and Differentiating Bacterial from Fungal Infections.

BACKGROUND: The role of Gasdermin D (GSDMD) in bloodstream infection (BSI) diagnosis is unknown. METHODS: Serum GSDMD levels were measured in BSI patients. Endothelial cells and PBMCs were isolated, infected with bacteria/fungi, and intracellular/extracellular GSDMD concentrations were measured. An animal model was established to investigate the association between serum GSDMD levels and BSI incidence/progression. RESULTS: ROC curve analysis indicated that GSDMD could be a potential early diagnostic biomarker for BSI (AUC = 0.9885). Combining GSDMD with procalcitonin (PCT) improved the differential diagnosis of Gram-positive and Gram-negative bacteria (AUC = 0.6699, 66.15% specificity), and early diagnosis of Gram-positive bacteria (98.46% sensitivity), while PCT was not significantly elevated. The combined GSDMD and G-test had higher sensitivity (AUC = 0.7174) for differential diagnosis of bacterial and fungal infections, and early detection of fungal infections (98.44% sensitivity). In vitro and in vivo experiments confirmed that GSDMD levels increased significantly within 2 hours, peaked at 16 hours, and exhibited a time-dependent upward trend. CONCLUSIONS: Serum GSDMD, alone or combined with other biomarkers, has potential for early diagnosis and differential diagnosis of BSI caused by various pathogens. This finding offers a new strategy for early detection and treatment of BSI.

NPS-2143 inhibit glioma progression by suppressing autophagy through mediating AKT-mTOR pathway.

Gliomas are the most common tumours in the central nervous system. In the present study, we aimed to find a promising anti-glioma compound and investigate the underlying molecular mechanism. Glioma cells were subjected to the 50 candidate compounds at a final concentration of 10 µM for 72 h, and CCK-8 was used to evaluate their cytotoxicity. NPS-2143, an antagonist of calcium-sensing receptor (CASR), was selected for further study due to its potent cytotoxicity to glioma cells. Our results showed that NPS-2143 could inhibit the proliferation of glioma cells and induce G1 phase cell cycle arrest. Meanwhile, NPS-2143 could induce glioma cell apoptosis by increasing the caspase-3/6/9 activity. NPS-2143 impaired the immigration and invasion ability of glioma cells by regulating the epithelial-mesenchymal transition process. Mechanically, NPS-2143 could inhibit autophagy by mediating the AKT-mTOR pathway. Bioinformatic analysis showed that the prognosis of glioma patients with low expression of CASR mRNA was better than those with high expression of CASR mRNA. Gene set enrichment analysis showed that CASR was associated with cell adhesion molecules and lysosomes in glioma. The nude mice xenograft model showed NPS-2143 could suppress glioma growth in vivo. In conclusion, NPS-2143 can suppress the glioma progression by inhibiting autophagy.

Unveiling the Role of Fluorination in Hexacyclic Coordinated Ether Electrolytes for High-Voltage Lithium Metal Batteries.

Fluorinated ethers have become promising electrolyte solvent candidates for lithium metal batteries (LMBs) because they are endowed with high oxidative stability and high Coulombic efficiencies of lithium metal stripping/plating. Up to now, most reported fluorinated ether electrolytes are -CF3-based, and the influence of ion solvation in modifying degree of fluorination has not been well-elucidated. In this work, we synthesize a hexacyclic coordinated ether (1-methoxy-3-ethoxypropane, EMP) and its fluorinated ether counterparts with -CH2F (F1EMP), -CHF2 (F2EMP), or -CF3 (F3EMP) as terminal group. With lithium bis(fluorosulfonyl)imide as single salt, the solvation structure, Li-ion transport behavior, lithium deposition kinetics, and high-voltage stability of the electrolytes were systematically studied. Theoretical calculations and spectra reveal the gradually reduced solvating power from nonfluorinated EMP to fully fluorinated F3EMP, which leads to decreased ionic conductivity. In contrast, the weakly solvating fluorinated ethers possess higher Li+ transference number and exchange current density. Overall, partially fluorinated -CHF2 is demonstrated as the desired group. Further full cell testing using high-voltage (4.4 V) and high-loading (3.885 mAh cm-2) LiNi0.8Co0.1Mn0.1O2 cathode demonstrates that F2EMP electrolyte enables 80% capacity retention after 168 cycles under limited Li (50 µm) and lean electrolyte (5 mL Ah-1) conditions and 129 cycles under extremely lean electrolyte (1.8 mL Ah-1) and the anode-free conditions. This work deepens the fundamental understanding on the ion transport and interphase dynamics under various degrees of fluorination and provides a feasible approach toward the design of fluorinated ether electrolytes for practical high-voltage LMBs.

Targeted serum proteome profiling reveals nicotinamide adenine dinucleotide phosphate (NADPH)-related biomarkers to discriminate linear IgA bullous disorder from dermatitis herpetiformis.

Linear IgA bullous dermatosis (LABD) and dermatitis herpetiformis (DH) represent the major subtypes of IgA mediated autoimmune bullous disorders. We sought to understand the disease etiology by using serum proteomics. We assessed 92 organ damage biomarkers in LABD, DH, and healthy controls using the Olink high-throughput proteomics. The positive proteomic serum biomarkers were used to correlate with clinical features and HLA type. Targeted proteomic analysis of IgA deposition bullous disorders vs. controls showed elevated biomarkers. Further clustering and enrichment analyses identified distinct clusters between LABD and DH, highlighting the involvement of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Comparative analysis revealed biomarkers with distinction between LABD and DH and validated in the skin lesion. Finally, qualitative correlation analysis with DEPs suggested six biomarkers (NBN, NCF2, CAPG, FES, BID, and PXN) have better prognosis in DH patients. These findings provide potential biomarkers to differentiate the disease subtype of IgA deposition bullous disease.

A Clinicopathological Appraisal of Duodenal Neuroendocrine Tumors at a Racially Diverse Safety Net Hospital.

INTRODUCTION: Significant knowledge gaps exist regarding clinicopathological profiling as well as treatment, surveillance, and survival of duodenal neuroendocrine tumors (dNETs). METHODS: We clinicopathologically characterized and identified racial differences among patients with dNETs at a large safety net hospital. Tumor grades were updated based on the World Health Organization 2019 NET classification, and overall survival was determined. RESULTS: We identified 17 dNETs and found no differences in clinicopathologic characteristics across racial groups. Pathological diagnosis was upgraded in 35% of dNETs, and age >65 years significantly shortened overall survival. DISCUSSION: Larger-scale studies are needed to determine the significance of these findings.

Effects of non-pharmacological interventions for adults with subjective cognitive decline: a network meta-analysis and component network meta-analysis.

BACKGROUND: Non-pharmacological interventions have a myriad of available intervention options and contain multiple components. Whether specific components of non-pharmacological interventions or combinations are superior to others remains unclear. The main aim of this study is to compare the effects of different combinations of non-pharmacological interventions and their specific components on health-related outcomes in adults with subjective cognitive decline. METHODS: PubMed, Embase, Cochrane, CINAHL, PsycINFO, CENTRAL, Web of Science, and China's two largest databases, CNKI and Wanfang, were searched from inception to 22nd, January 2023. Randomized controlled trials using non-pharmacological interventions and reporting health outcomes in adults with subjective cognitive decline were included. Two independent reviewers screened studies, extracted data, and assessed risk of bias. Component network meta-analysis was conducted employing an additive component model for network meta-analysis. This study followed the PRISMA reporting guideline and the PRISMA checklist is presented in Additional file 2. RESULTS: A total of 39 trials with 2959 patients were included (range of mean ages, 58.79-77.41 years). Resistance exercise might be the optimal intervention for reducing memory complaints in adults with subjective cognitive decline; the surface under the cumulative ranking p score was 0.888, followed by balance exercise (p = 0.859), aerobic exercise (p = 0.832), and cognitive interventions (p = 0.618). Music therapy, cognitive training, transcranial direct current stimulation, mindfulness therapy, and balance exercises might be the most effective intervention components for improving global cognitive function (iSMD, 0.83; 95% CI, 0.36 to 1.29), language (iSMD, 0.31; 95% CI, 0.24 to 0.38), ability to perform activities of daily living (iSMD, 0.55; 95% CI, 0.21 to 0.89), physical health (iSMD, 3.29; 95% CI, 2.57 to 4.00), and anxiety relief (iSMD, 0.71; 95% CI, 0.26 to 1.16), respectively. CONCLUSIONS: The form of physical activity performed appears to be more beneficial than cognitive interventions in reducing subjective memory complaints for adults with subjective cognitive decline, and this difference was reflected in resistance, aerobic, and balance exercises. Randomized clinical trials with high-quality and large-scale are warranted to validate the findings. TRIAL REGISTRATION: PROSPERO registry number. CRD42022355363.

Production of species-specific anthocyanins through an inducible system in plant hairy roots.

Anthocyanins are widely distributed pigments in flowering plants with red, purple or blue colours. Their properties in promoting heath make anthocyanins perfect natural colourants for food additives. However, anthocyanins with strong colour and stability at neutral pH, suitable as food colourants are relatively rare in nature. Acylation increases anthocyanin stability and confers bluer colour. In this study, we isolated two anthocyanin regulators SbMyb75 and SbDel from S. baicalensis, and showed that constitutive expression of the two TFs led to accumulation of anthocyanins at high levels in black carrot hairy roots. However, these hairy roots had severe growth problems. We then developed a ß-estradiol inducible system using XVE and a Lex-35S promoter, to initiate expression of the anthocyanin regulators and induced this system in hairy roots of black carrot, tobacco and morning glory. Anthocyanins with various decorations were produced in these hairy roots without any accompanying side-effects on growth. We further produced highly acylated anthocyanins with blue colour in a 5 L liquid culture in a bioreactor of hairy roots from morning glory. We provide here a strategy to produce highly decorated anthocyanins without the need for additional engineering of any of the genes encoding decorating enzymes. This strategy could be transferred to other species, with considerable potential for natural colourant production for the food industries.

Association of non-insulin-based insulin resistance indices with disease severity and adverse outcome in idiopathic pulmonary arterial hypertension: a multi-center cohort study.

BACKGROUND: Insulin resistance (IR) plays an important role in the pathophysiology of cardiovascular disease. Recent studies have shown that diabetes mellitus and impaired lipid metabolism are associated with the severity and prognosis of idiopathic pulmonary arterial hypertension (IPAH). However, the relationship between IR and pulmonary hypertension is poorly understood. This study explored the association between four IR indices and IPAH using data from a multicenter cohort. METHODS: A total of 602 consecutive participants with IPAH were included in this study between January 2015 and December 2022. The metabolic score for IR (METS-IR), triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, triglyceride and glucose (TyG) index, and triglyceride-glucose-body mass index (TyG-BMI) were used to quantify IR levels in patients with IPAH. The correlation between non-insulin-based IR indices and long-term adverse outcomes was determined using multivariate Cox regression models and restricted cubic splines. RESULTS: During a mean of 3.6 years' follow-up, 214 participants experienced all-cause death or worsening condition. Compared with in low to intermediate-low risk patients, the TG/HDL-C ratio (2.9 ± 1.7 vs. 3.3 ± 2.1, P = 0.003) and METS-IR (34.5 ± 6.7 vs. 36.4 ± 7.5, P < 0.001) were significantly increased in high to intermediate-high risk patients. IR indices correlated with well-validated variables that reflected the severity of IPAH, such as the cardiac index and stroke volume index. Multivariate Cox regression analyses indicated that the TyG-BMI index (hazard ratio [HR] 1.179, 95% confidence interval [CI] 1.020, 1.363 per 1.0-standard deviation [SD] increment, P = 0.026) and METS-IR (HR 1.169, 95% CI 1.016, 1.345 per 1.0-SD increment, P = 0.030) independently predicted adverse outcomes. Addition of the TG/HDL-C ratio and METS-IR significantly improved the reclassification and discrimination ability beyond the European Society of Cardiology (ESC) risk score. CONCLUSIONS: IR is associated with the severity and long-term prognosis of IPAH. TyG-BMI and METS-IR can independently predict clinical worsening events, while METS-IR also provide incremental predictive performance beyond the ESC risk stratification.

Effects of malnutrition on disease severity and adverse outcomes in idiopathic pulmonary arterial hypertension: a retrospective cohort study.

BACKGROUND: Malnutrition is common in patients with chronic cardiovascular disease and is associated with significantly higher all-cause mortality. Approximately one-third of patients with heart failure are malnourished. However, the relationship between malnutrition and idiopathic pulmonary arterial hypertension (IPAH) remains unclear. This study aimed to clarify the prognostic value of malnutrition in patients with IPAH. METHODS: A total of 432 consecutive participants with IPAH were included in this study between March 2013 and August 2021. Three common malnutrition assessment tools, including the geriatric nutritional risk index (GNRI), prognostic nutritional index (PNI), and controlling nutritional status (CONUT) score, were used to evaluate the nutritional status of patients with IPAH. The relationships between the malnutrition tools and long-term adverse outcomes were determined using restricted cubic splines and multivariate Cox regression models. RESULTS: During a mean follow-up of 3.1 years, 158 participants experienced clinical worsening or all-cause death. Patients were stratified into the low-, intermediate- and high-risk groups based on the European Society of Cardiology (ESC) risk stratification, and the PNI (55.9 ± 5.7 vs. 54.4 ± 7.2 vs. 51.1 ± 7.1, P = 0.005) and CONUT score (2.1 ± 0.9 vs. 2.5 ± 1.2 vs. 3.3 ± 1.1, P < 0.001) identified these patient groups better than the GNRI. All three malnutrition tools were associated with well-validated variables that reflected IPAH severity, such as the World Health Organization functional class, 6-min walk distance, and N-terminal pro-brain natriuretic peptide level. The CONUT score exhibited better predictive ability than both the GNRI (ΔAUC = 0.059, P < 0.001) and PNI (ΔAUC = 0.095, P < 0.001) for adverse outcomes and significantly improved reclassification and discrimination beyond the ESC risk score. Multivariable Cox regression analysis indicated that only the CONUT score (hazard ratio = 1.363, 95% confidence interval 1.147, 1.619 per 1.0-standard deviation increment, P < 0.001) independently predicted adverse outcomes. CONCLUSIONS: The malnutrition status was associated with disease severity in patients with IPAH. The CONUT score provided additional information regarding the risk of clinically worsening events, making it a meaningful risk stratification tool for these patients.

Topological Photonic Alloy.

We present the new concept of photonic alloy as a nonperiodic topological material. By mixing nonmagnetized and magnetized rods in a nonperiodic 2D photonic crystal configuration, we realized photonic alloys in the microwave regime. Our experimental findings reveal that the photonic alloy sustains nonreciprocal chiral edge states even at very low concentration of magnetized rods. The nontrivial topology and the associated edge states of these nonperiodic systems can be characterized by the winding of the reflection phase. Our results indicate that the threshold concentrations for the investigated system within the first nontrivial band gap to exhibit topological behavior approach zero in the thermodynamic limit for substitutional alloys, while the threshold remains nonzero for interstitial alloys. At low concentration, the system exhibits an inhomogeneous structure characterized by isolated patches of nonpercolating magnetic domains that are spaced far apart within a topologically trivial photonic crystal. Surprisingly, the system manifests chiral edge states despite a local breakdown of time-reversal symmetry rather than a global one. Photonic alloys represent a new category of disordered topological materials, offering exciting opportunities for exploring topological materials with adjustable gaps.

Hesperetin activates CISD2 to attenuate senescence in human keratinocytes from an older person and rejuvenates naturally aged skin in mice.

BACKGROUND: CDGSH iron-sulfur domain-containing protein 2 (CISD2), a pro-longevity gene, mediates healthspan in mammals. CISD2 is down-regulated during aging. Furthermore, a persistently high level of CISD2 promotes longevity and ameliorates an age-related skin phenotype in transgenic mice. Here we translate the genetic evidence into a pharmaceutical application using a potent CISD2 activator, hesperetin, which enhances CISD2 expression in HEK001 human keratinocytes from an older person. We also treated naturally aged mice in order to study the activator's anti-aging efficacy. METHODS: We studied the biological effects of hesperetin on aging skin using, firstly, a cell-based platform, namely a HEK001 human keratinocyte cell line established from an older person. Secondly, we used a mouse model, namely old mice at 21-month old. In the latter case, we investigate the anti-aging efficacy of hesperetin on ultraviolet B (UVB)-induced photoaging and naturally aged skin. Furthermore, to identify the underlying mechanisms and potential biological pathways involved in this process we carried out transcriptomic analysis. Finally, CISD2 knockdown HEK001 keratinocytes and Cisd2 knockout mice were used to study the Cisd2-dependent effects of hesperetin on skin aging. RESULTS: Four findings are pinpointed. Firstly, in human skin, CISD2 is mainly expressed in proliferating keratinocytes from the epidermal basal layer and, furthermore, CISD2 is down-regulated in the sun-exposed epidermis. Secondly, in HEK001 human keratinocytes from an older person, hesperetin enhances mitochondrial function and protects against reactive oxygen species-induced oxidative stress via increased CISD2 expression; this enhancement is CISD2-dependent. Additionally, hesperetin alleviates UVB-induced damage and suppresses matrix metalloproteinase-1 expression, the latter being a major indicator of UVB-induced damage in keratinocytes. Thirdly, transcriptomic analysis revealed that hesperetin modulates a panel of differentially expressed genes that are associated with mitochondrial function, redox homeostasis, keratinocyte function, and inflammation in order to attenuate senescence. Intriguingly, hesperetin activates two known longevity-associated regulators, namely FOXO3a and FOXM1, in order to suppress the senescence-associated secretory phenotype. Finally, in mouse skin, hesperetin enhances CISD2 expression to ameliorate UVB-induced photoaging and this occurs via a mechanism involving CISD2. Most strikingly, late-life treatment with hesperetin started at 21-month old and lasting for 5 months, is able to retard skin aging and rejuvenate naturally aged skin in mice. CONCLUSIONS: Our results reveal that a pharmacological elevation of CISD2 expression at a late-life stage using hesperetin treatment is a feasible approach to effectively mitigating both intrinsic and extrinsic skin aging and that hesperetin could act as a functional food or as a skincare product for fighting skin aging.

Development and validation of a clinical and ultrasound features-based nomogram for preoperative differentiation of renal urothelial carcinoma and central renal cell carcinoma.

PURPOSE: This study aimed to develop and validate an ultrasound (US)-based nomogram for the preoperative differentiation of renal urothelial carcinoma (rUC) from central renal cell carcinoma (c-RCC). METHODS: Clinical data and US images of 655 patients with 655 histologically confirmed malignant renal tumors (521 c-RCCs and 134 rUCs) were collected and divided into training (n = 455) and validation (n = 200) cohorts according to examination dates. Conventional US and contrast-enhanced US (CEUS) tumor features were analyzed to determine those that could discriminate rUC from c-RCC. Least absolute shrinkage and selection operator regression was applied to screen clinical and US features for the differentiation of rUC from c-RCC. Using multivariate logistic regression analysis, a diagnostic model of rUC was constructed and visualized as a nomogram. The diagnostic model's performance was assessed in the training and validation cohorts by calculating the area under the receiver operating characteristic curve (AUC) and calibration plot. Decision curve analysis (DCA) was used to assess the clinical usefulness of the US-based nomogram. RESULTS: Seven features of both clinical features and ultrasound imaging were selected to build the diagnostic model. The nomogram achieved favorable discrimination in the training (AUC = 0.996, 95% CI: 0.993-0.999) and validation (AUC = 0.995, 95% CI: 0.974, 1.000) cohorts, and good calibration (Brier scores: 0.019 and 0.016, respectively). DCA demonstrated the clinical usefulness of the US-based nomogram. CONCLUSION: A noninvasive clinical and US-based nomogram combining conventional US and CEUS features possesses good predictive value for differentiating rUC from c-RCC.

Anaerolentibacter hominis gen. nov. sp. nov., Diplocloster hominis sp. nov. and Pilosibacter fragilis gen. nov. sp. nov., isolated from human faeces.

Three Gram-positive, obligately anaerobic bacterial strains, namely CSJ-1T, CSJ-3T, and CSJ-4T, were isolated from faeces of healthy persons. They were characterized through a combination of whole-genome sequencing, phenotypic traits, and metabolomic analysis. The genome sizes of CSJ-1T, CSJ-4T, and CSJ-3T were 3.3, 3.8, and 6.1 Mbp, with DNA G+C contents of 47.2, 48.3, and 48.8 mol%, respectively. Strain CSJ-3T was identified as representing a novel species, Diplocloster hominis (type strain CSJ-3T=CGMCC 1.18033T=JCM 36512T) of the genus Diplocloster. The 16S rRNA gene sequence similarity and whole genome average nucleotide identity (gANI) of CSJ-4T to its closest related species, Diplocloster modestus ASD 4241T, were 98.3 and 91.4 %, respectively. Comparative analysis of 16S rRNA gene sequences showed 91.6 % similarity between CSJ-1T and its closest phylogenetic neighbour, Catenibacillus scindens DSM 106146T, and 93.3 % similarity between CSJ-4T and its closest relative strain, Clostridium fessum SNUG30386T. Based on the polyphasic taxonomic results, we proposed two novel genera and three novel species. Strain CSJ-1T was identified as representing a novel species of novel genus, Anaerolentibacter hominis gen. nov. sp. nov. (type strain CSJ-1T=CGMCC 1.18046T=JCM 36511T) of the family Lachnospiraceae, and strain CSJ-4T was identified as representing a novel species of novel genus Pilosibacter fragilis gen. nov. sp. nov. (type strain CSJ-4T=CGMCC 1.18026T= JCM 36513T) of the family Clostridiaceae.

Ultraconserved elements from transcriptome and genome data provide insight into the phylogenomics of Sternorrhyncha (Insecta: Hemiptera).

Sternorrhyncha, one of the four major suborders of Hemiptera, is a phytophagous taxon inclusive of nearly 18 000 described species. The phylogenetic relationships within the taxon and the earliest-branching lineage of its infraorders remain incompletely understood. This study attempted to illuminate the phylogenetic relationships within Sternorrhyncha through the use of maximum likelihood, Bayesian inference and maximum parsimony analyses, employing ultraconserved element (UCE) data from 39 genomic and 62 transcriptomic datasets and thereby representing most families within the taxon. The probe set Hemiptera 2.7Kv1 was used to recover a total of 2731 UCE loci: from 547 to 1699 (with an average of 1084) across all genomic datasets and from 108 to 849 (with an average of 329) across all transcriptomic datasets. All three types of phylogenetic analyses employed in this study produced robust statistical support for Sternorrhyncha being a monophyletic group. The different methods of phylogenetic analysis produced inconsistent descriptions of topological structure at the infraorder level: while maximum likelihood and Bayesian inference analyses produced strong statistical evidence (100%) indicating the clade Psylloidea + Aleyrodoidea to be a sister of the clade Aphidoidea (Aphidomorpha) + Coccoidea (Coccomorpha), the maximum parsimony analysis failed to recover a similar result. Our results also provide detail on the phylogenetic relationships within each infraorder. This study presents the first use of UCE data to investigate the phylogeny of Sternorrhyncha. It also shows the viability of amalgamating genomic and transcriptomic data in studies of phylogenetic relationships, potentially highlighting a resource-efficient approach for future inquiries into diverse taxa through the integration of varied data sources.