Systematic optimization of prime editing for the efficient functional correction of CFTR F508del in human airway epithelial cells.

Prime editing (PE) enables precise and versatile genome editing without requiring double-stranded DNA breaks. Here we describe the systematic optimization of PE systems to efficiently correct human cystic fibrosis (CF) transmembrane conductance regulator (CFTR) F508del, a three-nucleotide deletion that is the predominant cause of CF. By combining six efficiency optimizations for PE-engineered PE guide RNAs, the PEmax architecture, the transient expression of a dominant-negative mismatch repair protein, strategic silent edits, PE6 variants and proximal 'dead' single-guide RNAs-we increased correction efficiencies for CFTR F508del from less than 0.5% in HEK293T cells to 58% in immortalized bronchial epithelial cells (a 140-fold improvement) and to 25% in patient-derived airway epithelial cells. The optimizations also resulted in minimal off-target editing, in edit-to-indel ratios 3.5-fold greater than those achieved by nuclease-mediated homology-directed repair, and in the functional restoration of CFTR ion channels to over 50% of wild-type levels (similar to those achieved via combination treatment with elexacaftor, tezacaftor and ivacaftor) in primary airway cells. Our findings support the feasibility of a durable one-time treatment for CF.

Safety evaluation of outpatient vs inpatient unicompartmental knee arthroplasty: a systematic review and meta-analysis.

PURPOSE: This systematic review and meta-analysis aimed to evaluate the safety of outpatient and inpatient Unicompartmental Knee Arthroplasty (UKA) based on the incidence of adverse events. METHOD: A systematic search of the literature was performed in October 2022 on PubMed, Web of Science, Cochrane library, and Embase. The Meta package for R was used to perform the meta-analysis. RESULT: Five studies with a total of 26,301 patients were included. 5813 patients (22.1%) were treated with outpatient UKA, and 20,488 patients (77.9%) were treated with inpatient UKA. There were no statistically significant differences in the incidence of total complications (RR = 1.36, 95% CI = 0.64-2.89, Z = 0.79, P = 0.43), readmission (RR = 1.02, 95% CI = 0.40-2.60, Z = 0.05, P = 0.96), and venous thrombosis (RR = 1.43, 95% CI = 0.96-2.11, Z = 1.78, P = 0.08). Incidence rates were lower in outpatient UKA regarding urinary tract infection (RR = 1.48, 95% CI = 1.07-2.04, Z = 2.40, P = 0.02), pulmonary embolus (RR = 7.48, 95% CI = 1.80-31.17, Z = 2.76, P < 0.01), and transfusion (RR = 2.77, 95% CI = 1.63-4.71, Z = 3.78, P < 0.01). CONCLUSION: In summary, outpatient UKA shows lower incidences of hospital-acquired complications such urinary tract infection, pulmonary embolus, and transfusion. It's worth noting that the incidences of total complications, readmission, and venous thrombosis in outpatient UKA were not higher than the incidences of inpatient UKA, suggestting that outpatient UKA can be considered a safe alternative to inpatient UKA.

Exploring the potential mechanism of WuFuYin against hypertrophic scar using network pharmacology and molecular docking.

BACKGROUND: Hypertrophic scar (HTS) is dermal fibroproliferative disorder, which may cause physiological and psychological problems. Currently, the potential mechanism of WuFuYin (WFY) in the treatment of HTS remained to be elucidated. AIM: To explore the potential mechanism of WFY in treating HTS. METHODS: Active components and corresponding targets were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. HTS-related genes were obtained from the GeneCards, DisGeNET, and National Center for Biotechnology Information. The function of targets was analyzed by performing Gene Ontology and Kyoto Encyclopaedia of Genes and Genome (KEGG) enrichment analysis. A protein + IBM-protein interaction (PPI) network was developed using STRING database and Cytoscape. To confirm the high affinity between compounds and targets, molecular docking was performed. RESULTS: A total of 65 core genes, which were both related to compounds and HTS, were selected from multiple databases. PPI analysis showed that CKD2, ABCC1, MMP2, MMP9, glycogen synthase kinase 3 beta (GSK3B), PRARG, MMP3, and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma (PIK3CG) were the hub targets and MOL004941, MOL004935, MOL004866, MOL004993, and MOL004989 were the key compounds of WFY against HTS. The results of KEGG enrichment analysis demonstrated that the function of most genes were enriched in the PI3K-Akt pathway. Moreover, by performing molecular docking, we confirmed that GSK3B and 8-prenylated eriodictyol shared the highest affinity. CONCLUSION: The current findings showed that the GSK3B and cyclin dependent kinase 2 were the potential targets and MOL004941, MOL004989, and MOL004993 were the main compounds of WFY in HTS treatment.

Effects of nasal allergens and environmental particulate matter on brainstem metabolites and the consequence of brain-spleen axis in allergic rhinitis.

BACKGROUND: The growing consensus links exposure to fine particulate matter (PM2.5) with an increased risk of respiratory diseases. However, little is known about the additional effects of particulate matter on brainstem function in allergic rhinitis (AR). Furthermore, it is unknown to what extent the PM2.5-induced effects in the brainstem affect the inflammatory response in AR. This study aimed to determine the effects, mechanisms and consequences of brainstem neural activity altered by allergenic stimulation and PM2.5 exposure. METHODS: Using an AR model of ovalbumin (OVA) elicitation and whole-body PM2.5 exposure, the metabolic profile of the brainstem post-allergen stimulation was characterized through in vivo proton magnetic resonance imaging (1H-MRS). Then, the transient receptor potential vanilloid-1 (TRPV1) neuronal expression and sensitivity in the trigeminal nerve in AR were investigated. The link between TRPV1 expression and brainstem differential metabolites was also determined. Finally, we evaluated the mediating effects of brainstem metabolites and the consequences in the brain-spleen axis in the inflammatory response of AR. RESULTS: Exposure to allergens and PM2.5 led to changes in the metabolic profiles of the brainstem, particularly affecting levels of glutamine (Gln) and glutamate (Glu). This exposure also increased the expression and sensitivity of TRPV1+ neurons in the trigeminal nerve, with the levels of TRPV1 expression closely linked to the brainstem metabolism of Glu and Gln. Moreover, allergens increased the activity of p38, while PM2.5 led to the phosphorylation of p38 and ERK, resulting in the upregulation of TRPV1 expression. The brainstem metabolites Glu and Gln were found to partially mediate the impact of TRPV1 on AR inflammation, which was supported by the presence of pro-inflammatory changes in the brain-spleen axis. CONCLUSION: Brainstem metabolites are altered under allergen stimulation and additional PM2.5 exposure in AR via sensitization of the trigeminal nerve, which exacerbates the inflammatory response via the brain-splenic axis.

Persistent enrichment of multidrug-resistant Klebsiella in oral and nasal communities during long-term starvation.

BACKGROUND: The human oral and nasal cavities can act as reservoirs for opportunistic pathogens capable of causing acute infection. These microbes asymptomatically colonize the human oral and nasal cavities which facilitates transmission within human populations via the environment, and they routinely possess clinically significant antibiotic resistance genes. Among these opportunistic pathogens, the Klebsiella genus stands out as a notable example, with its members frequently linked to nosocomial infections and multidrug resistance. As with many colonizing opportunistic pathogens, the essential transmission factors influencing the spread of Klebsiella species among both healthy and diseased individuals remain unclear. RESULTS: Here, we explored a possible explanation by investigating the ability of oral and nasal Klebsiella species to outcompete their native microbial community members under in vitro starvation conditions, which could be analogous to external hospital environments or the microenvironment of mechanical ventilators. When K. pneumoniae and K. aerogenes were present within a healthy human oral or nasal sample, the bacterial community composition shifted dramatically under starvation conditions and typically became enriched in Klebsiella species. Furthermore, introducing K. pneumoniae exogenously into a native microbial community lacking K. pneumoniae, even at low inoculum, led to repeated enrichment under starvation. Precise monitoring of K. pneumoniae within these communities undergoing starvation indicated rapid initial growth and prolonged viability compared to other members of the microbiome. K. pneumoniae strains isolated from healthy individuals' oral and nasal cavities also exhibited resistance to multiple classes of antibiotics and were genetically similar to clinical and gut isolates. In addition, we found that in the absence of Klebsiella species, other understudied opportunistic pathogens, such as Peptostreptococcus, increased in relative abundance under starvation conditions. CONCLUSIONS: Our findings establish an environmental and microbiome community circumstance that allows for the enrichment of Klebsiella species and other opportunistic pathogens. Klebsiella's enrichment may hinge on its ability to quickly outgrow other members of the microbiome. The ability to outcompete other commensal bacteria and to persist under harsh environmental conditions could be an important factor that contributes to enhanced transmission in both commensal and pathogenic contexts. Video Abstract.

Lactate modulates zygotic genome activation through H3K18 lactylation rather than H3K27 acetylation.

In spite of its essential role in culture media, the precise influence of lactate on early mouse embryonic development remains elusive. Previous studies have implicated lactate accumulation in medium affecting histone acetylation. Recent research has underscored lactate-derived histone lactylation as a novel epigenetic modification in diverse cellular processes and diseases. Our investigation demonstrated that the absence of sodium lactate in the medium resulted in a pronounced 2-cell arrest at the late G2 phase in embryos. RNA-seq analysis revealed that the absence of sodium lactate significantly impaired the maternal-to-zygotic transition (MZT), particularly in zygotic gene activation (ZGA). Investigations were conducted employing Cut&Tag assays targeting the well-studied histone acetylation and lactylation sites, H3K18la and H3K27ac, respectively. The findings revealed a noticeable reduction in H3K18la modification under lactate deficiency, and this alteration showed a significant correlation with changes in gene expression. In contrast, H3K27ac exhibited minimal correlation. These results suggest that lactate may preferentially influence early embryonic development through H3K18la rather than H3K27ac modifications.

The emerging role of Piezo1 in the musculoskeletal system and disease.

Piezo1, a mechanosensitive ion channel, has emerged as a key player in translating mechanical stimuli into biological signaling. Its involvement extends beyond physiological and pathological processes such as lymphatic vessel development, axon growth, vascular development, immunoregulation, and blood pressure regulation. The musculoskeletal system, responsible for structural support, movement, and homeostasis, has recently attracted attention regarding the significance of Piezo1. This review aims to provide a comprehensive summary of the current research on Piezo1 in the musculoskeletal system, highlighting its impact on bone formation, myogenesis, chondrogenesis, intervertebral disc homeostasis, tendon matrix cross-linking, and physical activity. Additionally, we explore the potential of targeting Piezo1 as a therapeutic approach for musculoskeletal disorders, including osteoporosis, muscle atrophy, intervertebral disc degeneration, and osteoarthritis.

Identification and functional analysis of a deduced geraniol synthase from Camphora officinarum.

The market demand for essential oil containing citral is increasing. Our research group identified a rare chemotype of Camphora officinarum whose leaves are high in citral content by examining over 1000 wild trees across the entire native distribution area of C. officinarum in China. Because C. officinarum is suitable for large-scale cultivation, it is therefore seen as a promising source of natural citral. However, the molecular mechanism of citral biosynthesis in C. officinarum is poorly understood. In this study, transcriptomic analyses of C. officinarum with different citral contents revealed a strong positive correlation between the expression of a putative geraniol synthase gene (CoGES) and citral content. The CoGES cDNA was cloned, and the CoGES protein shared high similarity with other monoterpene synthases. Enzymatic assays of CoGES with geranyl diphosphate (GPP) as substrate yielded geraniol as the single product, which is the precursor of citral. Further transient expression of CoGES in Nicotiana benthamiana resulted in a higher relative content of geranial and the appearance of a new substance, neral. These findings indicate that CoGES is a geraniol synthase-encoding gene, and the encoded protein can catalyze the transformation of GPP into geraniol, which is further converted into geranial and neral through an unknown mechanism in vivo. These findings expand our understanding of citral biosynthesis in Lauraceae plants. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01463-4.

Modified five times simulated body fluid for efficient biomimetic mineralization.

Simulated body fluid (SBF) is widely utilized in preclinical research for estimating the mineralization efficacy of biomaterials. Therefore, it is of great significance to construct an efficient and stable SBF mineralization system. The conventional SBF solutions cannot maintain a stable pH value and are prone to precipitate homogeneous calcium salts at the early stages of the biomimetic process because of the release of gaseous CO2. In this study, a simple but efficient five times SBF buffered by 5 % CO2 was developed and demonstrated to achieve excellent mineralized microstructure on a type of polymer-aligned nanofibrous scaffolds, which is strikingly similar to the natural human bone tissue. Scanning electron microscopy and energy-dispersive X-ray examinations indicated the growth of heterogeneous apatite with a high-calcium-to-phosphate ratio on the aligned nanofibers under 5 times SBF buffered by 5 % CO2. Moreover, X-ray diffraction spectroscopy and Fourier transform infrared analyses yielded peaks associated with carbonated hydroxyapatite with less prominent crystallization. In addition, the biomineralized aligned polycaprolactone nanofibers demonstrated excellent cell attachment, alignment, and proliferation characteristics in vitro. Overall, the results of this study showed that 5 × SBFs buffered by 5 % CO2 partial pressure are attractive alternatives for the efficient biomineralization of scaffolds in bone tissue engineering, and could be used as a model for the prediction of the bone-bonding bioactivity of biomaterials.

VlMYB4 and VlCDF3 co-targeted the VlLOG11 promoter to regulate fruit setting in grape (Vitis vinifera L).

KEY MESSAGE: The VlLOG11 mediates the cytokinin signaling pathway to regulate grape fruit setting. Fruit set, as an accepted agronomic trait, is inextricably linked with fruit quality and yield. Previous studies have demonstrated that exogenous treatment with the synthetic cytokinin analog, forchlorfenuron (CPPU), significantly enhances fruit set. In this study, a significant reduction in endogenous cytokinins was found by measuring the content of cytokinins in young grape berries after CPPU treatment. LONELY GUYs (VlLOGs), a key cytokinin-activating enzyme working in the biosynthesis pathway of cytokinins, exhibited differential expression. Some differentially expressed VlLOGs genes were presented by RNA seq data and their functions and regulation patterns were further investigated. The results showed that VlLOG11 was differentially expressed in young grape berries after CPPU treatment. Overexpression of VlLOG11 in tomato increases the amount of fruit set, and upregulated the expression of genes associated with cytokinin signaling including SlHK4, SlHK5, SlHP3, SlHP4, SlPHP1, SlPHP2. VlMYB4 and VlCDF3 could regulate the expression of VlLOG11 by directly binding to its promoter in young grape berries during fruit set. These results strongly demonstrated that VlMYB4/VlCDF3-VlLOG11 regulatory module plays a key role in the process of fruit setting in grape. This provided a basis for the molecular mechanism of VlLOG11-mediated cytokinin biosynthesis in young grape fruit set.

[Retracted] Association between vascular endothelial growth factor gene polymorphisms and the risk of osteonecrosis of the femoral head: Systematic review.

[This retracts the article DOI: 10.3892/br.2015.527.].

Effects of thinning and understory removal on soil phosphorus fractions in subtropical pine plantations.

Forest management changes the physical environments and nutrient dynamics and then regulates the forest productivity. Soil phosphorus (P) availability is critical for productivity in tropical and subtropical forests. However, it was still poorly understood how soil P content and fraction respond to various forest management practices in these regions. Here, we measured the soil total P, available P, and Hedley's P fractions, including inorganic and organic P (Pi and Po), in subtropical pine plantations treated with understory removal (UR), non-dominant species thinning (NDST) and dominant species thinning (DST) after nine years. Compared to plantations without management (CK), treatments such as UR, NDST, and DST decreased soil total P at 0-10 cm and soil available P at 0-10 cm and 10-20 cm. Increases in resin-Pi, NaOH-Pi, and C.HCl-Pi resulted in a higher total Pi in 0-10 cm (p < 0.05) in treated plots (UR, NDST, and DST) than in CK plots. UR, NDST, and DST treatments increased NaHCO3-Po and NaOH-Po (p < 0.05) but decreased C.HCl-Po at a depth of 0-10 cm. Regardless of management treatments, soil total P, available P, and P fractions in 0-10 cm showed higher contents than those in 10-20 cm. There were positive relationships between total P and total Po (p < 0.01) and between available P and total Pi. There were also positive relationships between total P, available P, NaHCO3-Pi, and NaOH-Pi (p < 0.05). In conclusion, forest management such as UR, NDST, and DST decreased soil total P and available P, and transforming soil P fractions to available P will meet the P demand following management in the pine plantations of subtropical China.

Combination of static and dynamic neural imaging features to distinguish sensorineural hearing loss: a machine learning study.

Purpose: Sensorineural hearing loss (SNHL) is the most common form of sensory deprivation and is often unrecognized by patients, inducing not only auditory but also nonauditory symptoms. Data-driven classifier modeling with the combination of neural static and dynamic imaging features could be effectively used to classify SNHL individuals and healthy controls (HCs). Methods: We conducted hearing evaluation, neurological scale tests and resting-state MRI on 110 SNHL patients and 106 HCs. A total of 1,267 static and dynamic imaging characteristics were extracted from MRI data, and three methods of feature selection were computed, including the Spearman rank correlation test, least absolute shrinkage and selection operator (LASSO) and t test as well as LASSO. Linear, polynomial, radial basis functional kernel (RBF) and sigmoid support vector machine (SVM) models were chosen as the classifiers with fivefold cross-validation. The receiver operating characteristic curve, area under the curve (AUC), sensitivity, specificity and accuracy were calculated for each model. Results: SNHL subjects had higher hearing thresholds in each frequency, as well as worse performance in cognitive and emotional evaluations, than HCs. After comparison, the selected brain regions using LASSO based on static and dynamic features were consistent with the between-group analysis, including auditory and nonauditory areas. The subsequent AUCs of the four SVM models (linear, polynomial, RBF and sigmoid) were as follows: 0.8075, 0.7340, 0.8462 and 0.8562. The RBF and sigmoid SVM had relatively higher accuracy, sensitivity and specificity. Conclusion: Our research raised attention to static and dynamic alterations underlying hearing deprivation. Machine learning-based models may provide several useful biomarkers for the classification and diagnosis of SNHL.

Distinct oral-associated gastric microbiota and Helicobacter pylori communities for spatial microbial heterogeneity in gastric cancer.

The gastric microbial community plays a fundamental role in gastric cancer (GC), and the two main anatomical subtypes of GC, non-cardia and cardia GC, are associated with different risk factors (Helicobacter pylori for non-cardia GC). To decipher the different microbial spatial communities of GC, we performed a multicenter retrospective analysis to characterize the gastric microbiota in 223 GC patients, including H. pylori-positive or -negative patients, with tumors and paired adjacent normal tissues, using third-generation sequencing. In the independent validation cohort, both dental plaque and GC tumoral tissue samples were collected and sequenced. The prevalence of H. pylori and oral-associated bacteria was verified using fluorescence in situ hybridization (FISH) assays in GC tumoral tissues and matched nontumoral tissues. We found that the vertical distribution of the gastric microbiota, at the upper, middle, and lower third sites of GC, was likely an important factor causing microbial diversity in GC tumor tissues. The oral-associated microbiota cluster, which included Veillonella parvula, Streptococcus oralis, and Prevotella intermedia, was more abundant in the upper third of the GC. However, H. pylori was more abundant in the lower third of the GC and exhibited a significantly high degree of microbial correlation. The oral-associated microbiota module was co-exclusive with H. pylori in the lower third site of the GC tumoral tissue. Importantly, H. pylori-negative GC patients with oral-associated gastric microbiota showed worse overall survival, while the increase in microbial abundance in H. pylori-positive GC patients showed no difference in overall survival. The prevalence of V. parvula in both the dental plaque and GC tissue samples was concordant in the independent validation phase. We showed that the oral-associated species V. parvula and S. oralis were correlated with overall survival. Our study highlights the roles of the oral-associated microbiota in the upper third of the GC. In addition, oral-associated species may serve as noninvasive screening tools for the management of GC and an independent prognostic factor for H. pylori-negative GCs. IMPORTANCE: Our study highlights the roles of the oral-associated microbiota in the upper third of gastric cancer (GC).We showed that the oral-associated species Veillonella parvula and Streptococcus oralis were correlated with overall survival. In addition, oral-associated species may serve as noninvasive screening tools for the management of GC and an independent prognostic factor for Helicobacter pylori-negative GCs.

Supramolecular artificial Nano-AUTACs enable tumor-specific metabolism protein degradation for synergistic immunotherapy.

Autophagy-targeting chimera (AUTAC) has emerged as a powerful modality that can selectively degrade tumor-related pathogenic proteins, but its low bioavailability and nonspecific distribution significantly restrict their therapeutic efficacy. Inspired by the guanine structure of AUTAC molecules, we here report supramolecular artificial Nano-AUTACs (GM NPs) engineered by AUTAC molecule GN [an indoleamine 2,3-dioxygenase (IDO) degrader] and nucleoside analog methotrexate (MTX) through supramolecular interactions for tumor-specific protein degradation. Their nanostructures allow for precise localization and delivery into cancer cells, where the intracellular acidic environment can disrupt the supramolecular interactions to release MTX for eradicating tumor cells, modulating tumor-associated macrophages, activating dendritic cells, and inducing autophagy. Specifically, the induced autophagy facilitates the released GN for degrading immunosuppressive IDO to further enhance effector T cell activity and inhibit tumor growth and metastasis. This study offers a unique strategy for building a nanoplatform to advance the field of AUTAC in tumor immunotherapy.

Pengzhenrongella frigida sp. nov., isolated from a glacier.

A Gram-stain-positive, rod-shaped bacterium, designated as HLT2-17T, was isolated from soil sample taken from the Hailuogou glacier in Sichuan province, PR China. Strain HLT2-17T was capable of growing at 4-25°C and in NaCl concentrations ranging from 0 to 2% (w/v). The highest level of 16S rRNA gene sequence similarity was observed with Pengzhenrongella phosphoraccumulans M0-14T (98.3 %) and Pengzhenrongella sicca LRZ-2T (98.2 %). The average nucleotide identity and digital DNA-DNA hybridization values between strain HLT2-17T and its closest relatives, P. phosphoraccumulans M0-14T and P. sicca LRZ-2T, were 80.0-84.0 % and 23.3-27.7 %, respectively. Phylogenomic analysis indicated that strain HLT2-17T clustered together with strains P. phosphoraccumulans M0-14T and P. sicca LRZ-2T. Strain HLT2-17T contained C16 : 0 and anteiso-C15 : 0 as the major fatty acids, and MK-9(H4) as the menaquinone. Therefore, based on a polyphasic approach, we propose that strain HLT2-17T (=CGMCC 1.11116T= NBRC 110443T) represents a novel species of the genus Pengzhenrongella and suggest the name Pengzhenrongella frigida sp. nov.

The TF/Nrf2/GSTP1 pathway is involved in stress-induced hepatocellular injury through ferroptosis.

Stress triggers a comprehensive pathophysiological cascade in organisms. However, there is a substantial gap in the research regarding the effects of stress on liver function. This study aimed to investigate the impact of restraint stress on hepatocellular damage and elucidate the underlying molecular mechanisms. An effective mouse restraint stress model was successfully developed, and liver function analysis was performed using laser speckle imaging, metabolomics and serum testing. Alterations in hepatocyte morphology were assessed using haematoxylin and eosin staining and transmission electron microscopy. Oxidative stress in hepatocytes was assessed using lipid reactive oxygen species and malondialdehyde. The methylation status and expression of GSTP1 were analysed using DNA sequencing and, real-time PCR, and the expression levels of GPX4, TF and Nrf2 were evaluated using real-time quantitative PCR, western blotting, and immunohistochemical staining. A stress-induced model was established in vitro by using dexamethasone-treated AML-12 cells. To investigate the underlying mechanisms, GSTP1 overexpression, small interfering RNA, ferroptosis and Nrf2 inhibitors were used. GSTP1 methylation contributes to stress-induced hepatocellular damage and dysfunction. GSTP1 is involved in ferroptosis-mediated hepatocellular injury induced by restraint stress via the TF/Nrf2 pathway. These findings suggest that stress-induced hepatocellular injury is associated with ferroptosis, which is regulated by TF/Nrf2/GSTP1.

A Novel PiGF@Diamond Color Converter with a Record Thermal Conductivity for Laser-Driven Projection Display.

High-brightness laser lighting is confronted with crucial challenges in developing laser-excitable color converting materials with effective heat dissipation and super optical performance. Herein, a novel composite of phosphor-in-glass film on transparent diamond (PiGF@diamond) is designed and fabricated via a facile low-temperature co-sintering strategy. The as-prepared La3Si6N11:Ce3+ (LSN:Ce) PiGF@diamond with well-retained optical properties of raw phosphor shows a record thermal conductivity of ≈599 W m-1 K-1, which is about 60 times higher than that of currently well-used PiGF@sapphire (≈10 W m-1 K-1). As a consequence, this color converter can bear laser power density up to 40.24 W mm-2 and a maximum luminance flux of 5602 lm without luminescence saturation due to efficient inhibition of laser-induced heat accumulation. By further supplementing red spectral component of CaAlSiN3:Eu2+ (CASN:Eu), the PiGF@diamond based white laser diode is successfully constructed, which can yield warm white light with a high color rendering index of 89.3 and find practical LD-driven applications. The findings will pave the way for realizing the commercial application of PiGF composite in laser lighting and display.

Primary oocytes with cellular senescence features are involved in ovarian aging in mice.

In mammalian females, quiescent primordial follicles serve as the ovarian reserve and sustain normal ovarian function and egg production via folliculogenesis. The loss of primordial follicles causes ovarian aging. Cellular senescence, characterized by cell cycle arrest and production of the senescence-associated secretory phenotype (SASP), is associated with tissue aging. In the present study, we report that some quiescent primary oocytes in primordial follicles become senescent in adult mouse ovaries. The senescent primary oocytes share senescence markers characterized in senescent somatic cells. The senescent primary oocytes were observed in young adult mouse ovaries, remained at approximately 15% of the total primary oocytes during ovarian aging from 6 to 12 months, and accumulated in aged ovaries. Administration of a senolytic drug ABT263 to 3-month-old mice reduced the percentage of senescent primary oocytes and the transcription of the SASP factors in the ovary, in addition, led to increased numbers of primordial and total follicles and a higher rate of oocyte maturation. Our study provides experimental evidence that primary oocytes, a germline cell type that is arrested in meiosis, become senescent in adult mouse ovaries and that senescent cell clearance reduced primordial follicle loss and mitigated ovarian aging phenotypes.

Highly Selective CO2 Electroreduction to C2H4 Using a Dual-Sites Cu(II) Porphyrin Framework Coupled with Cu2O Nanoparticles via a Synergetic-Tandem Strategy.

Low *CO coverage on the active sites is a major hurdle in the tandem electrocatalysis, resulting in unsatisfied C2H4 production efficiencies. In this work, we developed a synergetic-tandem strategy to construct a copper-based composite catalyst for the electroreduction of CO2 to C2H4, which was constructed via the template-directed polymerization of ultrathin Cu(II) porphyrin organic framework incorporating atomically isolated Cu(II) porphyrin and Cu(II) bipyridine sites on a carbon nanotube (CNT) scaffold, and then Cu2O nanoparticles were uniformly dispersed on the CNT scaffold. The presence of dual active sites within the Cu(II) porphyrin organic framework create a synergetic effect, leading to an increase in local *CO availability to enhance the C-C coupling step implemented on the adjacent Cu2O nanoparticles for further C2H4 production. Accordingly, the resultant catalyst affords an exceptional CO2-to-C2H4 Faradaic efficiency (FEC2H4) of 71.0 % at -1.1 V vs reversible hydrogen electrode (RHE), making it one of the most effective copper-based tandem catalysts reported to date. The superior performance of the catalyst is further confirmed through operando infrared spectroscopy and theoretic calculations.