Reduced expression of MYC increases longevity and enhances healthspan.

MYC is a highly pleiotropic transcription factor whose deregulation promotes cancer. In contrast, we find that Myc haploinsufficient (Myc(+/-)) mice exhibit increased lifespan. They show resistance to several age-associated pathologies, including osteoporosis, cardiac fibrosis, and immunosenescence. They also appear to be more active, with a higher metabolic rate and healthier lipid metabolism. Transcriptomic analysis reveals a gene expression signature enriched for metabolic and immune processes. The ancestral role of MYC as a regulator of ribosome biogenesis is reflected in reduced protein translation, which is inversely correlated with longevity. We also observe changes in nutrient and energy sensing pathways, including reduced serum IGF-1, increased AMPK activity, and decreased AKT, TOR, and S6K activities. In contrast to observations in other longevity models, Myc(+/-) mice do not show improvements in stress management pathways. Our findings indicate that MYC activity has a significant impact on longevity and multiple aspects of mammalian healthspan.

Atomic-engineered gradient tunable solid-state metamaterials.

Metamaterial has been captivated a popular notion, offering photonic functionalities beyond the capabilities of natural materials. Its desirable functionality primarily relies on well-controlled conditions such as structural resonance, dispersion, geometry, filling fraction, external actuation, etc. However, its fundamental building blocks-meta-atoms-still rely on naturally occurring substances. Here, we propose and validate the concept of gradient and reversible atomic-engineered metamaterials (GRAM), which represents a platform for continuously tunable solid metaphotonics by atomic manipulation. GRAM consists of an atomic heterogenous interface of amorphous host and noble metals at the bottom, and the top interface was designed to facilitate the reversible movement of foreign atoms. Continuous and reversible changes in GRAM's refractive index and atomic structures are observed in the presence of a thermal field. We achieve multiple optical states of GRAM at varying temperature and time and demonstrate GRAM-based tunable nanophotonic devices in the visible spectrum. Further, high-efficiency and programmable laser raster-scanning patterns can be locally controlled by adjusting power and speed, without any mask-assisted or complex nanofabrication. Our approach casts a distinct, multilevel, and reversible postfabrication recipe to modify a solid material's properties at the atomic scale, opening avenues for optical materials engineering, information storage, display, and encryption, as well as advanced thermal optics and photonics.

Ultrahigh toughness zirconia ceramics.

The attainment of both high strength and toughness is the ultimate goal for most structural materials. Although ceramic material has been considered for use as a structural material due to its high strength and good chemical stability, it suffers from the limitation of low toughness. For instance, although Y2O3-stabilized tetragonal ZrO2 polycrystals (Y-TZPs) exhibit remarkable toughness among ceramics due to their phase transformation toughening mechanism, this toughness is still much weaker than that of metals. Here, we report Y-TZP-based ceramic materials with toughnesses exceeding 20 MPa m1/2, which is comparable to those of metals, while maintaining strengths over 1,200 MPa. The superior mechanical properties are realized by reducing the phase stability of tetragonal zirconia by tailoring the microstructure and chemistry of the Y-TZP. The proposed ceramic materials can further advance the design and application of ceramic-based structural materials.

Atomistic Investigation of Grain Boundary Fracture in Alumina.

Grain boundary (GB) fracture is a major mechanism of material failure in polycrystalline ceramics. However, the intricate atomic arrangements of GBs have impeded our understanding of the atomistic mechanisms of these processes. In this study, we investigated the atomic-scale crack propagation behavior of an α-Al2O3 ∑13 grain boundary, using a combination of in situ transmission electron microscopy (TEM) and scanning TEM. The atomic-scale fracture path along the GB core was directly determined by the observation of the atomic structures of the fractured surfaces, which is consistent with density functional theory calculations. We found that the GB fracture can be attributed to the weaker local bonds and a smaller number of bonds along the fracture path. Our findings provide atomistic insights into the mechanisms of crack propagation along GBs, offering significant implications for GB engineering and the toughening of ceramics.

Nanoscale Localized Phonons at Al2O3 Grain Boundaries.

Nanoscale defects like grain boundaries (GBs) would introduce local phonon modes and affect the bulk materials' thermal, electrical, optical, and mechanical properties. It is highly desirable to correlate the phonon modes and atomic arrangements for individual defects to precisely understand the structure-property relation. Here we investigated the localized phonon modes of Al2O3 GBs by combination of the vibrational electron energy loss spectroscopy (EELS) in scanning transmission electron microscope and density functional perturbation theory (DFPT). The differences between GB and bulk obtained from the vibrational EELS show that the GB exhibited more active vibration at the energy range of <50 meV and >80 meV, and further DFPT results proved the wide distribution of bond lengths at GB are the main factor for the emergence of local phonon modes. This research provides insights into the phonon-defect relation and would be of importance in the design and application of polycrystalline materials.

Prediction of CAF-related genes in immunotherapy and drug sensitivity in hepatocellular carcinoma: a multi-database analysis.

This study aims to identify the cancer-associated fibroblasts (CAF)-related genes that can affect immunotherapy and drug sensitivity in hepatocellular carcinoma (HCC). Expression data and survival data associated with HCC were obtained in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Weighted correlation network analysis (WGCNA) analysis was performed to obtain CAF-related genes. Least Absolute Shrinkage and Selection Operator (LASSO) regression was used for regression analysis and risk models. Subsequently, Gene Set Enrichment Analysis (GSEA) analysis, Gene Set Enrichment Analysis (ssGSEA) analysis, Tumor Immune Dysfunction and Exclusion (TIDE) analysis and drug sensitivity analysis were performed on the risk models. Survival analysis of CAF scores showed that the survival rate was lower in samples with high CAF scores than those with low scores. However, this difference was not significant, suggesting CAF may not directly influence the prognosis of HCC patients. Further screening of CAF-related genes yielded 33 CAF-related genes. Seven risk models constructed based on CDR2L, SPRED1, PFKP, ENG, KLF2, FSCN1 and VCAN, showed significant differences in immunotherapy and partial drug sensitivity in HCC. Seven CAF-related genes may have important roles in immunotherapy, drug sensitivity and prognostic survival in HCC patients.

Sex differences in zymosan-induced behavioral visceral hypersensitivity and colorectal afferent sensitization.

Sex differences in visceral nociception have been reported in clinical and preclinical studies, but the potential differences in sensory neural encoding of the colorectum between males and females are not well understood. In this study, we systematically assessed sex differences in colorectal neural encoding by conducting high-throughput optical recordings in intact dorsal root ganglia (DRGs) from control and visceral hypersensitive mice. We found an apparent sex difference in zymosan-induced behavioral visceral hypersensitivity: enhanced visceromotor responses to colorectal distension were observed only in male mice, not in female mice. In addition, a higher number of mechanosensitive colorectal afferents were identified per mouse in the zymosan-treated male group than in the saline-treated male group, whereas the mechanosensitive afferents identified per mouse were comparable between the zymosan- and saline-treated female groups. The increased number of identified afferents in zymosan-treated male mice was predominantly from thoracolumbar (TL) innervation, which agrees with the significant increase in the TL afferent proportion in the zymosan group as compared with the control group in male mice. In contrast, female mice showed no difference in the proportion of colorectal neurons between saline- and zymosan-treated groups. Our results revealed a significant sex difference in colorectal afferent innervation and sensitization in the context of behavioral visceral hypersensitivity, which could drive differential clinical symptoms in male and female patients.NEW & NOTEWORTHY We used high-throughput GCaMP6f recordings to study 2,275 mechanosensitive colorectal afferents in mice. Our results revealed significant sex differences in the zymosan-induced behavioral visceral hypersensitivity, which were present in male but not female mice. Male mice also showed sensitization of colorectal afferents in the thoracolumbar pathway, whereas female mice did not. These findings highlight sex differences in sensory neural anatomy and function of the colorectum, with implications for sex-specific therapies for treating visceral pain.

Morphological, molecular, and functional characterization of mouse glutamatergic myenteric neurons.

The enteric nervous system (ENS) functions largely independently of the central nervous system (CNS). Glutamate, the dominant neurotransmitter in the CNS and sensory afferents, is not a primary neurotransmitter in the ENS. Only a fraction (∼2%) of myenteric neurons in the mouse distal colon and rectum (colorectum) are positive for vesicular glutamate transporter type 2 (VGLUT2), the structure and function of which remain undetermined. Here, we systematically characterized VGLUT2-positive enteric neurons (VGLUT2-ENs) through sparse labeling with adeno-associated virus, single-cell mRNA sequencing (scRNA-seq), and GCaMP6f calcium imaging. Our results reveal that the majority of VGLUT2-ENs (29 of 31, 93.5%) exhibited Dogiel type I morphology with a single aborally projecting axon; most axons (26 of 29, 89.7%) are between 4 and 10 mm long, each traversing 19 to 34 myenteric ganglia. These anatomical features exclude the VGLUT2-ENs from being intrinsic primary afferent or motor neurons. The scRNA-seq conducted on 52 VGLUT2-ENs suggests different expression profiles from conventional descending interneurons. Ex vivo GCaMP6f recordings from flattened colorectum indicate that almost all VGLUT2-EN (181 of 215, 84.2%) are indirectly activated by colorectal stretch via nicotinic cholinergic neural transmission. In conclusion, VGLUT2-ENs are a functionally unique group of enteric neurons with single aborally projecting long axons that traverse multiple myenteric ganglia and are activated indirectly by colorectal mechanical stretch. This knowledge will provide a solid foundation for subsequent studies on the potential interactions of VGLUT2-EN with extrinsic colorectal afferents via glutamatergic neurotransmission.NEW & NOTEWORTHY We reveal that VGLUT2-positive enteric neurons (EN), although constituting a small fraction of total EN, are homogeneously expressed in the myenteric ganglia, with a slight concentration at the intermediate region between the colon and rectum. Through anatomic, molecular, and functional analyses, we demonstrated that VGLUT2-ENs are activated indirectly by noxious circumferential colorectal stretch via nicotinic cholinergic transmission, suggesting their participation in mechanical visceral nociception.

Multi-Enzyme Activity of MIL-101 (Fe)-Derived Cascade Nano-Enzymes for Antitumor and Antimicrobial Therapy.

The clinical application of oncology therapy is hampered by high glutathione concentrations, hypoxia, and inefficient activation of cell death mechanisms in cancer cells. In this study, Fe and Mo bimetallic sulfide nanomaterial (FeS2@MoS2) based on metal-organic framework structure is rationally prepared with peroxidase (POD)-, catalase (CAT)-, superoxide dismutase (SOD)-like activities and glutathione depletion ability, which can confer versatility for treating tumors and mending wounds. In the lesion area, FeS2@MoS2 with SOD-like activity can facilitate the transformation of superoxide anions (O2 -) to hydrogen peroxide (H2O2), and then the resulting H2O2 serves as a substrate for the Fenton reaction with FMS to produce highly toxic hydroxyl radicals (∙OH). Simultaneously, FeS2@MoS2 has an ability to deplete glutathione (GSH) and catalyze the decomposition of nicotinamide adenine dinucleotide phosphate (NADPH) to curb the regeneration of GSH from the source. Thus it can realize effective tumor elimination through synergistic apoptosis-ferroptosis strategy. Based on the alteration of the H2O2 system, free radical production, glutathione depletion and the alleviation of hypoxia in the tumor microenvironment, FeS2@MoS2 NPS can not only significantly inhibit tumors in vivo and in vitro, but also inhibit multidrug-resistant bacteria and hasten wound healing. It may open the door to the development of cascade nanoplatforms for effective tumor treatment and overcoming wound infection.

Metabolic and Molecular Insights Into Nicotiana benthamiana Trichome Exudates: An Ammunition Depot for Plant Resistance Against Insect Pests.

Nicotiana benthamiana, a widely acknowledged laboratory model plant for molecular studies, exhibits lethality to certain insect pests and can serve as a dead-end trap plant for pest control in the field. However, the underlying mechanism of N. benthamiana's resistance against insects remains unknown. Here, we elucidate that the lethal effect of N. benthamiana on the whitefly Bemisia tabaci arises from the toxic glandular trichome exudates. By comparing the metabolite profiles of trichome exudates, we found that 51 metabolites, including five O-acyl sugars (O-AS) with medium-chain acyl moieties, were highly accumulated in N. benthamiana. Silencing of two O-AS biosynthesis genes, branched-chain keto acid dehydrogenase (BCKD) and Isopropyl malate synthase-C (IPMS-C), significantly reduced the O-AS levels in N. benthamiana and its resistance against whiteflies. Additionally, we demonstrated that the higher expression levels of BCKD and IPMS-C in the trichomes of N. benthamiana contribute to O-AS synthesis and consequently enhance whitefly resistance. Furthermore, overexpression of NbBCKD and NbIPMS-C genes in the cultivated tobacco Nicotiana tabacum enhanced its resistance to whiteflies. Our study revealed the metabolic and molecular mechanisms underlying the lethal effect of N. benthamiana on whiteflies and presents a promising avenue for improving whitefly resistance.

Rare-Earth Metal Phosphinidene Complexes: A Trip from Bridging One to Terminal One.

ConspectusAs phosphorus analogues of alkylidene (or carbene) and imido (or nitrene) complexes, phosphinidene complexes have received great attention not only for their fundamental scientific merits but also for their ability to build new phosphorus-containing molecules. A large number of phosphinidene complexes in bridging, mononuclear, or terminal coordination modes have been synthesized, and their reactivity has been extensively explored. However, the synthesis of rare-earth metal (scandium, yttrium, and lanthanide metal) phosphinidene complexes lagged behind the transition metal and actinide congeners for decades. Rare-earth metal ions are among the hardest Lewis acids, whereas phosphinidene ligands are soft Lewis bases; rare-earth metal-phosphinidene coordination is thus mismatched based on the Pearson's HSAB principle. The bridging rare-earth metal phosphinidene complexes were not reported until 2008, and the synthesis of the mononuclear and terminal species is even more challenging, which has only recently been achieved.Our group reported a bis(µ2-phosphinidene)dineodymium complex in 2008. In the following >10 years, we have been pursuing the terminal rare-earth metal phosphinidene complexes. Due to the high instability of rare-earth metal-phosphorus multiple bonds, the synthesis and stabilization of these complexes are extremely difficult. Finally, by using suitable phosphinidene ligands and supporting ligands, we obtained the first mononuclear rare-earth metal phosphinidene complex in 2018 and the first terminal rare-earth metal phosphinidene complex in 2020. In these more than ten years of research, we have also found some interesting reactivity of the rare-earth metal phosphinidene complexes. The rare-earth metal bridging phosphinidene complexes can act as two-electron reductants based on the oxidative coupling of two phosphinidene ligands into a diphosphene ligand. The mononuclear rare-earth metal phosphinidene complexes catalyze the hydrogenation of terminal alkenes under mild conditions, and the joint experimental/DFT studies indicate that the hydrogenation reaction proceeds in a 1,2-addition/elimination mechanism rather than the common σ-bond metathesis mechanism. These reactivities are new and important for the rare-earth metal complexes. In addition, the ligand design in our study may contribute to the synthesis of rare-earth metal-arsenic multiple bonding complexes and alkaline-earth metal-phosphorus multiple bonding complexes, which have not yet been realized. Herein, we present an account of our investigations into rare-earth metal phosphinidene complexes, a trip from bridging one to terminal one. To give the readers an overall image of the development of the rare-earth metal phosphinidene complexes, some findings from other researchers are also included.

CNN-based multi-modal radiomics analysis of pseudo-CT utilization in MRI-only brain stereotactic radiotherapy: a feasibility study.

BACKGROUND: Pseudo-computed tomography (pCT) quality is a crucial issue in magnetic resonance image (MRI)-only brain stereotactic radiotherapy (SRT), so this study systematically evaluated it from the multi-modal radiomics perspective. METHODS: 34 cases (< 30 cm³) were retrospectively included (2021.9-2022.10). For each case, both CT and MRI scans were performed at simulation, and pCT was generated by a convolutional neural network (CNN) from planning MRI. Conformal arc or volumetric modulated arc technique was used to optimize the dose distribution. The SRT dose was compared between pCT and planning CT with dose volume histogram (DVH) metrics and gamma index. Wilcoxon test and Spearman analysis were used to identify key factors associated with dose deviations. Additionally, original image features were extracted for radiomic analysis. Tumor control probability (TCP) and normal tissue complication probability (NTCP) were employed for efficacy evaluation. RESULTS: There was no significant difference between pCT and planning CT except for radiomics. The mean value of Hounsfield unit of the planning CT was slightly higher than that of pCT. The Gadolinium-based agents in planning MRI could increase DVH metrics deviation slightly. The median local gamma passing rates (1%/1 mm) between planning CTs and pCTs (non-contrast) was 92.6% (range 63.5-99.6%). Also, differences were observed in more than 85% of original radiomic features. The mean absolute deviation in TCP was 0.03%, and the NTCP difference was below 0.02%, except for the normal brain, which had a 0.16% difference. In addition, the number of SRT fractions and lesions, and lesion morphology could influence dose deviation. CONCLUSIONS: This is the first multi-modal radiomics analysis of CNN-based pCT from planning MRI for SRT of small brain lesions, covering dosiomics and radiomics. The findings suggest the potential of pCT in SRT plan design and efficacy prediction, but caution needs to be taken for radiomic analysis.

Maternal Vitamin D3 Supplementation in an Oxidized-Oil Diet Protects Fetus from Developmental Impairment and Ameliorates Oxidative Stress in Mouse Placenta and Fetus.

BACKGROUND: Fried food has increased in popularity worldwide. However, deep frying can increase the production of peroxidative toxins in food, which might be harmful to fetal development. The antioxidative effect of vitamin D3 (VD3) has been reported previously. OBJECTIVES: This study aimed to explore how maternal VD3 supplementation in an oxidized-oil diet during gestation affects fetal antioxidative ability and development. METHODS: Pregnant mice were randomly assigned into 3 groups: Control group (diet with fresh soybean oil), OSO group [diet with oxidized soybean oil (OSO)], and OSOV group (diet with OSO and 10,000 IU/Kg VD3). Mice were fed with the corresponding diet during gestation. On day 16.5 of gestation, the placenta and fetus were harvested to analyze antioxidative status. RESULTS: Maternal oxidized-oil diet during gestation significantly reduced placental vessel abundance, labyrinth zone area, and fetal body weight. However, dietary VD3 supplementation prevented these negative effects of oxidized-oil diet. Maternal intake of oxidized-oil diet increased serum concentrations of malondialdehyde, total-nitric oxide synthase, and inducible nitric oxide synthase, whereas VD3 supplementation showed a protection effect on it. Additionally, maternal VD3 supplementation increased the levels of antioxidative enzymes and the nuclear translocation of nuclear factor erythroid 2-related factor 2 (NRF2), thereby protecting placenta and fetus from apoptosis and oxidative stress caused by an oxidized-oil diet. The gene expression and protein levels of a fatty acid transporter solute carrier family 27 member 1 in the fetal liver were increased by maternal VD3 supplementation under oxidized-oil diet. Notably, NRF2 could be co-immunoprecipitated with the VD receptor in the placenta. CONCLUSIONS: Maternal VD3 supplementation could protect fetus from oxidized-oil diet induced developmental impairment by alleviating oxidative stress in the placenta and fetus through the VD receptor/NRF2 pathway, at least partially. Thus, ensuring adequate levels of VD3 through supplementation is often critical during pregnancy.

Liver-derived FGF21 is required for the effect of time-restricted feeding on high-fat diet-induced fatty liver in mice.

Nonalcoholic fatty liver disease (NAFLD), which leads to insulin resistance, steatosis, and even hepatocellular carcinoma, is the most common chronic liver disease worldwide, however, effective treatment is still lacking. This study determined the role of liver FGF21 and the mechanisms underlying the protective effects of time-restricted feeding (TRF) in NAFLD. FGF21 liver knockout (FGF21 LKO) mice and C57BL/6 wild-type (WT) mice were fed either a normal or a high-fat diet (HFD) for 16 weeks. Mice with diet-induced obesity (DIO) were also used. The mice were fed either ad libitum or in a time-restricted manner. Serum FGF21 levels were significantly increased after 16 weeks of TRF. TRF prevented body weight gain, improved glucose homeostasis, and protected against high-fat diet-induced hepatosteatosis and liver damage. The expression of genes related to liver lipogenesis and inflammation was reduced in TRF mice, but the expression of genes involved in fatty acid ß-oxidation was increased. However, those beneficial effects of TRF were blunted in the FGF21 LKO mice. Moreover, TRF promoted improvements in insulin sensitivity and liver damage in DIO mice. Our data show that liver FGF21 signaling was involved in the effect of TRF on high-fat diet-induced fatty liver.

Tailoring Drug Release Kinetics by the Design and Optimization of Substituents in Azobenzene Molecules in the Photosensitive Liposomal System.

A light-sensitive moiety, e.g., azobenzene, for the light-sensitive liposomal drug carrier has shown advantages as an advanced drug delivery system in site-specific smart therapy due to its reversible photoisomerization characteristics. In this work, a series of 4-position-cholesterol-functionalized azobenzene derivatives with 4'-position substituted pyridine, quinoline, isoquinoline, triethylamine, or ethylenediamine were synthesized, and the relationship between the molecular structure and drug release behaviors was clarified. We found that the charge and electrophilicity of substituents were two important factors (expressed as the characteristic time) that can precisely regulate the isomerization ratio in the liposomal system. There was an approximately linear correlation between the characteristic time of photoisomerization and the fitted first-order constant of photoinduced drug release rate. The photoinduced drug release could be achieved at the desired time and in an appropriate amount by tailoring the substituents at the 4'-position of azobenzene-cholesterol derivatives.

Gender differences in the relationship between the triglyceride-glucose index and serum Klotho concentrations among the middle-aged and elderly: a cross-sectional analysis.

BACKGROUND: The triglyceride-glucose (TyG) index is recognized as a robust indicator for evaluating insulin resistance (IR). Despite the well-documented anti-aging biological functions of Klotho protein, its correlation with the TyG index remains unexplored. METHODS: A cross-sectional analysis was conducted involving participants from the National Health and Nutrition Examination Surveys (NHANES) 2007-2016. The TyG index was computed using laboratory data, while serum Klotho concentrations was determined using ELISA kit. After adjusting potential confounding variables, multivariate regression models were employed to evaluate the association between the TyG index and Klotho protein levels among middle-aged and elderly females and males separately. Additionally, smooth curve fitting and segmented regression model were applied to investigate potential threshold effects and identify the inflection point. RESULTS: A total of 6,573 adults qualified for inclusion, comprising 3,147 (47.88%) males and 3,426 (52.12%) females. Multivariate regression analysis revealed that females with a higher TyG index exhibited significantly lower serum Klotho concentrations (ß=-83.41, 95% CI: -124.23 to -42.60, P < 0.0001). This association was not statistically significant in males (ß = 15.40, 95% CI: -19.16 to 49.95, P = 0.3827). Subgroup analyses revealed a significant interaction effect by diabetes status in females (P-interaction = 0.0121), where non-diabetic females showed a stronger negative association between TyG index and serum Klotho levels compared to diabetic females. In the female group, when TyG index was divided into quartiles, individuals in the highest quartile of TyG index exhibited reduced levels of Klotho protein (Q4: -88.77 pg/ml) compared to those in the lowest quartile (Q1) after full adjustment (P = 0.0041). Segmented regression analysis indicated a turning point value of 9.4 in females. Notably, a 1-unit increase in TyG index was significantly associated with a decrease in Klotho levels by -111.43 pg/ml (95% CI: -157.34 to -65.52, P < 0.0001) when TyG index was below 9.4, while above this threshold, the association was not significant (Log likelihood ratio test: 0.009). CONCLUSIONS: The findings highlight a non-linear correlation between the TyG index and serum Klotho concentrations among females, indicative of a saturation effect. This relationship was particularly pronounced in non-diabetic women. In contrast, no statistically significant association was observed in male participants.

Integrated transcriptome and metabolome analysis revealed that HaMYB1 modulates anthocyanin accumulation to deepen sunflower flower color.

KEY MESSAGE: HanMYB1 was found to play positive roles in the modulation of anthocyanins metabolism based on the integrative analysis of different color cultivars and the related molecular genetic analyses. As a high value ornamental and edible crop with various colors, sunflowers (Helianthus annuus L.) provide an ideal system to understand the formation of flower color. Anthocyanins are major pigments in higher plants, which is associated with development of flower colors and ability of oxidation resistance. Here, we performed an integrative analysis of the transcriptome and flavonoid metabolome in five sunflower cultivars with different flower colors. According to differentially expressed genes and differentially accumulated flavonoids, these cultivars could be grouped into yellow and red. The results showed that more anthocyanins were accumulated in the red group flowers, especially the chrysanthemin. Some anthocyanins biosynthesis-related genes like UFGT (UDP-glycose flavonoid glycosyltransferase) also expressed more in the red group flowers. A MYB transcriptional factor, HanMYB1, was found to play vital positive roles in the modulation of anthocyanins metabolism by the integrative analysis. Overexpressed HanMYB1 in tobacco could deepen the flower color, increase the accumulation of anthocyanins and directly active the express of UFGT genes. Our findings indicated that the MYB transcriptional factors provide new insight into the dynamic regulation of the anthocyanin biosynthesis in facilitating sunflower color formation and anthocyanin accumulation.

High-efficiency fourth harmonic generation and polarization smoothing based on an orthogonal cascade of DKDP crystals: publisher's note.

This publisher's note corrects an error in Appl. Opt.63, 1411 (2024)APOPAI0003-693510.1364/AO.512229.

High-efficiency fourth harmonic generation and polarization smoothing based on an orthogonal cascade of DKDP crystals.

Because of the high efficiency of frequency conversion and beam-target coupling, a fourth harmonic (4ω) laser has a splendid application prospect in a high-power laser facility. The polarization smoothing (PS) crystal is preferably after the frequency conversion crystal to flexibly obtain the best uniformity illumination of the target. However, as a high irradiance 4ω laser beam propagates through the PS crystal, the transverse stimulated Raman scattering (TSRS) effect of the PS crystal will be stronger, resulting in significant energy dissipation and crystal damage. This paper proposes a novel, to the best of our knowledge, fourth harmonic generation (FHG) scheme based on an orthogonal cascade of the DKDP crystals. This orthogonal cascaded FHG (OC-FHG) scheme employs two cascaded FHG crystals with orthogonal optical axes, and the PS crystal is in the middle. The PS crystal can rotate the polarization direction of the 2ω laser by 90°, while the polarization direction of the 4ω laser is maintained to a great extent. This OC-FHG scheme realizes the FHG by two steps, and the laser intensity at the PS crystal cuts down nearly 50%. The output intensity of the 4ω laser can be increased from 1.8G W/c m 2 to about 3.6G W/c m 2 under the condition of effectively inhibiting the TSRS effect. Meanwhile, the output 4ω laser contains two orthogonal polarized beams realizing in-beam polarization smoothing instantaneously. In addition, the novel FHG scheme can also have a high conversion efficiency and bandwidth tolerance.

Short-Term but Not Long-Term Knee Symptoms and Functional Improvements of Tissue Engineering Strategy for Meniscus Defects: A Systematic Review of Clinical Studies.

PURPOSE: To investigate the up-to-date clinical outcomes of tissue-engineered meniscus implants for meniscus defects. METHODS: A search was performed by 3 independent reviewers on PubMed, MEDLINE, EMBASE, and Cochrane from 2016 to June 18, 2023, with the term "meniscus" with all the following terms: "scaffolds," "constructs," "implant," and "tissue engineering." Inclusion criteria included "Clinical trials" and "English language articles" that involved isolated meniscus tissue engineering strategies for meniscus injuries. Only Level I to IV clinical studies were considered. The modified Coleman Methodology score was used for quality analysis of included clinical trials. The Methodological Index for Non-Randomized Studies was employed for analysis of the risk of study bias and methodological quality. RESULTS: The search identified 2,280 articles, and finally 19 original clinical trials meeting the inclusion criteria were included. Three types of tissue-engineered meniscus implants (CMI-Menaflex, Actifit, and NUsurface) have been clinically evaluated for meniscus reconstruction. Lack of standardized outcome measures and imaging protocols limits comparison between studies. CONCLUSIONS: Tissue-engineered meniscus implants can provide short-term knee symptom and function improvements, but no implants have been shown to propose significant long-term benefits for meniscus defects. LEVEL OF EVIDENCE: Level IV, systematic review of Level I to IV studies.