Successive Generations Research Articles

Generation of optical vortex beams with bandwidth exceeding 550 nm using a helical fiber needle exhibiting strong mode coupling.

A strong-coupling helical fiber needle (HFN) is proposed and demonstrated for the realization of bandwidth-enhanced broadband optical vortex beam (OVB) generation. The HFN is based on a single mode fiber and operates at the dispersion-turning-point (DTP) of the lowest radial order of the cladding mode (i.e., LP11) but with a remarkably high mode coupling efficiency. By utilizing this novel, to the best of our knowledge, HFN, successful generation of the first-order OVB with an impressive bandwidth up to 556 nm at -10 dB and a center wavelength of ∼1570 nm has been achieved. This represents the broadest bandwidth demonstrated among all fiber grating-based OVB generators to date. The proposed HFN-based OVB generator exhibits a relatively compact size, ultra-wide bandwidth, and customizable center wavelength, making it highly promising for applications in optical vortex-based endoscopic imaging as well as particle detection and manipulation.

Abstract PO5-14-05: Circulating tumor DNA fraction correlates with residual cancer burden post-neoadjuvant chemotherapy in triple negative breast cancer patients

Abstract Background: Pathologic response after preoperative/neoadjuvant chemotherapy is a continuum that can range from no residual cancer to extensive disease. Viable cancers can shed tumor DNA into the blood and we hypothesized that plasma ctDNA levels can reflect pathologic response as continuum. Patients and methods: Post-neoadjuvant plasma samples were obtained after completion of chemotherapy but before surgery from patients with stage I to III TNBC who received treatment with durvalumab concurrent with weekly nab-paclitaxel followed by dose dense doxorubicin/cyclophosphamide in a single arm neoadjuvant clinical trial (NCT02489448). Up to 3 mL of blood was collected into EDTA- and heparin- containing vacutainer tubes, and plasma cfDNA was extracted and twice purified in the lab at Predicine Inc. Pathologic response was quantified on a continuous scale using the Residual Cancer Burden (RCB) score, and also categorized as RCB-0 (complete pathologic response, n=21), -I (minimal residual cancer, n=7), -II (moderate residual cancer, n=13), and -III (extensive residual cancer, n=3). Median follow-up was 35 months (range 25-70 months). Tumor whole exome sequencing (WES) data was previously generated using HiSeq 4000 at the Yale Center for Genome Analysis (dbGaP: PRJNA558949). A personalized MRD panel of up to 60 personalized variants per patient was designed based on the tumor WES data, and ultra-deep next-generation sequencing (100,000X) of plasma cfDNA was performed using the PredicineBEACON assay for MRD detection by Predicine. CtDNA positivity (MRD) was defined as a weighted score equivalent to 2 or more tumor variants detected in the plasma. cfDNA tumor fraction was measured based on mutant allele fraction of observed variants. Adjusted tumor fraction could be confidently measured for 37 out of 44 patients that had enough confidently called personalized ctDNA variants. We compared tumor fraction versus RCB score as continuous variables, and also compared tumor fraction between RCB categories as ordinal variables. Invasive disease-free survival was examined by Kaplan-Meier analysis. Bioinformatic data analysis was performed using Graphpad Prism and R. Results: 44 of 48 plasma samples yielded successful cfDNA generation and sequencing. Six patients (13.6%) were MRD positive. Among these 6 cases, 3 had RCB-0 response (14.3% of RCB 0 cases), 1 had RCB II response (7.7% of RCB II cases), and 2 had RCB III response (66.7% of RCB III cases). The median cfDNA tumor fraction of patients with pathological complete response to treatment (pCR) was significantly lower than patients with residual disease (RD) (0.06% vs. 0.3%, p=0.02). There was a positive correlation between RCB scores and tumor fraction (r= 0.45, Spearman). Tumor fraction was more strongly correlated with later recurrence than a binary ctDNA positivity call. Tumor fraction was significantly higher in patients that later experienced local or metastatic recurrence (n=8) compared to those with no evidence of disease (n=29) (Wilcoxon test, p=0.02). Both ctDNA positive RCB III cases had metastatic recurrence while the remaining 4 ctDNA positive cases currently remain recurrence-free. Mutational genomic landscape of both tumor WES and plasma ctDNA samples identified hotspot mutations in 19 cancer-associated genes. Novel hot-spot mutations were observed in the plasma of two patients following treatment. TP53 mutations were highly prevalent in tissue and plasma, however no significant association of mutation of any gene with treatment response was detected. Conclusions: PredicineBeacon MRD assay was successfully performed on 3 mL plasma samples collected using from EDTA and heparin-containing tubes. Tumor fraction correlated with residual disease, RCB score and disease recurrence. Citation Format: Naing Lin Shan, Billie Gould, Kim Blenman, Julia Foldi, Pan Du, Frank Zhang, Myles Walsh, Lajos Pusztai. Circulating tumor DNA fraction correlates with residual cancer burden post-neoadjuvant chemotherapy in triple negative breast cancer patients [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-14-05.

Rising testicular cancer incidence in Spain despite declining mortality: an age-period-cohort analysis

BackgroundTesticular cancer, primarily affecting young men, has seen an alarming rise globally. This study delves into incidence and mortality trends in Spain from 1990 to 2019 using the Global Burden of Disease (GBD) database and the Age-Period-Cohort (A-P-C) model. MethodsWe analyzed GBD data on testicular cancer cases and deaths in Spain, calculating age-standardized rates (ASIR and ASMR) and employing Joinpoint regression to identify significant shifts. The A-P-C model further dissected the effects of age, period, and birth cohort on these trends. ResultsA striking doubling in testicular cancer incidence was observed, from 3.09 to 5.40 per 100,000 men (1.9% annual increase), while mortality rates remained stable and even decreased in younger age groups (0.34 to 0.26 per 100,000, 0.8% annual decrease). Joinpoint analysis revealed four distinct periods of increasing incidence, with a recent slowdown. The A-P-C model highlighted a consistent rise in incidence risk with each successive generation born after 1935, contrasting with a progressive decline in mortality risk across cohorts, particularly marked for those born since the 1960s. ConclusionWhile mortality rates are encouraging, Spain reflects the global trend of escalating testicular cancer incidence. The A-P-C analysis suggests a generational influence, but the underlying causes remain elusive. Further research is crucial to understand these trends and implement effective prevention strategies to combat this growing health concern.

Tao Hongjing's Medical Health Preservation Philosophy

In the 21st century, the medical paradigm has transitioned from "disease medicine" to "health medicine," with the developmental trend shifting from "treating diseases" to maintaining a "healthy" state. Tao Hongjing, representing the field of health preservation studies during the Southern and Northern Dynasties in ancient China, contributed distinctive principles and methods to traditional Chinese medicine (TCM) health preservation, constituting a crucial aspect of TCM health preservation academic thought. His concise and cost-effective health preservation theories and methods encapsulate profound health preservation insights and philosophical contemplation, earning commendation from successive generations of medical practitioners and holding remarkable research value. Against the backdrop of implementing the "Healthy China" strategy and advocating "universal health," Tao Hongjing's health preservation philosophy holds significant reference value for enhancing human health awareness and promoting harmonious social development, providing strong practical guidance. This paper focuses on Tao Hongjing's medical health preservation philosophy, utilizing works such as Record of Nurturing Life for Longevity, Zhen Gao, Compendium of Materia Medica Annotations, Records of Renowned Physicians, and Collected Works of Tao's Seclusion ( ) as research materials to thoroughly explore Tao Hongjing's medical health preservation methods and academic characteristics.

Reinforcement Learning Algorithm to Optimize Players' Tactical Decisions and Round Planning in Tennis Matches

This paper explores the application of the Ranking Genetic Optimization Reinforcement Learning (RGORL) algorithm to optimize players' tactical decisions and round planning in tennis matches. Leveraging evolutionary principles and reinforcement learning techniques, RGORL offers a data-driven framework for enhancing on-court performance. Extensive simulations demonstrate the algorithm's effectiveness in improving match outcomes, points won percentages, and games won percentages. Results illustrate a steady improvement in fitness scores over successive generations, indicating RGORL's ability to evolve and refine strategies over time. Analysis of tactical decisions reveals the superiority of strategies such as the "Net Approach" in terms of win rates, points won percentages, and games won percentages. Through extensive simulations, RGORL demonstrates a notable improvement in match outcomes, with a maximum increase of 13% in win rates. Analysis of tactical decisions reveals significant enhancements in points won percentages, with improvements of up to 34% observed across various strategies, notably the "Net Approach." Furthermore, the algorithm achieves substantial gains in games won percentages, with increases of up to 25% recorded.

Telomere-lengthening germline variants predispose to a syndromic papillary thyroid cancer subtype

Papillary thyroid cancer (PTC) is the most common endocrine malignancy. 10% to 15% of individuals show familial clustering with three or more affected members, but the factors underlying this risk are unknown. In a group of recently studied individuals with POT1 pathogenic variants and ultra-long telomere length, PTC was the second most common solid tumor. We tested whether variants in POT1 and four other telomere-maintenance genes associated with familial cancer underlie PTC susceptibility. Among 470 individuals, we identified pathogenic or likely pathogenic variants in three genes encoding telomere-binding proteins: POT1, TINF2, and ACD. They were found in 4.5% and 1.5% of familial and unselected cases, respectively. Individuals harboring these variants had ultra-long telomere length, and 15 of 18 (83%) developed other cancers, of which melanoma, lymphoma, and sarcoma were most common. Among individuals with PTC and melanoma, 22% carried a deleterious germline variant, suggesting that a long telomere syndrome might be clinically recognizable. Successive generations had longer telomere length than their parents and, at times, developed more cancers at younger ages. Tumor sequencing identified a single oncogenic driver, BRAF p.Val600Glu, in 10 of 10 tumors studied, but no telomere-maintenance mechanism, including at the TERT promoter. These data identify a syndromic subset of PTCs with locusheterogeneity and telomere lengthening as a convergent mechanism. They suggest these germline variants lower the threshold to cancer by obviating the need for an acquired telomere-maintenance mechanism in addition to sustaining the longevity of oncogenic mutations.

Design And Realization of A Comprehensive Quality Assessment System for College Students Based on the Bp Neural Network

Educational evaluation plays a crucial role in ensuring the quality and effectiveness of teaching, learning, and institutional performance. Traditional evaluation methods often struggle to capture the complex and multifaceted nature of educational processes, leading to limitations in assessing quality comprehensively. In response, this paper introduces the Fuzzy Interface Memetic Algorithm for Quality Assessment (FIMA-QA), a novel framework that integrates fuzzy logic modeling with memetic algorithm optimization to provide a nuanced and adaptable approach to educational evaluation. FIMA-QA leverages fuzzy logic principles to represent input variables and assessment criteria in linguistic terms, allowing for the expression of qualitative relationships and uncertainties inherent in educational assessment. Through memetic algorithm optimization, FIMA-QA iteratively refines fuzzy rule bases to enhance assessment accuracy and reliability over successive generations. This combination of fuzzy logic modeling and evolutionary optimization enables FIMA-QA to effectively evaluate various dimensions of educational quality, including teaching effectiveness, student engagement, learning outcomes, and institutional performance. Empirical studies demonstrate the efficacy of FIMA-QA in capturing the qualitative nature of assessment criteria and providing accurate and comprehensive evaluations of educational processes. For instance, teaching effectiveness assessments ranged from 7.5 to 9.8, student engagement from 8.2 to 9.5, learning outcomes from 8.0 to 8.9, and institutional performance from 8.7 to 9.4, showcasing the numerical precision of FIMA-QA.

Fate and preservation of the late pleistocene cave bears from Niedźwiedzia Cave in Poland, through taphonomy, pathology, and geochemistry

This comprehensive study examines fossil remains from Niedźwiedzia Cave in the Eastern Sudetes, offering detailed insights into the palaeobiology and adversities encountered by the Pleistocene cave bear Ursus spelaeus ingressus. Emphasising habitual cave use for hibernation and a primarily herbivorous diet, the findings attribute mortality to resource scarcity during hibernation and habitat fragmentation amid climate shifts. Taphonomic analysis indicates that the cave was extensively used by successive generations of bears, virtually unexposed to the impact of predators. The study also reveals that alkaline conditions developed in the cave during the post-depositional taphonomic processes. Mortality patterns, notably among juveniles, imply dwindling resources, indicative of environmental instability. Skeletal examination reveals a high incidence of forelimb fractures, indicating risks during activities like digging or confrontations. Palaeopathological evidence unveils vulnerabilities to tuberculosis, abscesses, rickets, and injuries, elucidating mobility challenges. The cave’s silts exhibit a high zinc concentration, potentially derived from successive bear generations consuming zinc-rich plants. This study illuminates the lives of late cave bears, elucidating unique environmental hurdles faced near their species’ end.

Effects of UV-B Radiation Exposure on Transgenerational Plasticity in Grain Morphology and Proanthocyanidin Content in Yuanyang Red Rice.

The effect of UV-B radiation exposure on transgenerational plasticity, the phenomenon whereby the parental environment influences both the parent's and the offspring's phenotype, is poorly understood. To investigate the impact of exposing successive generations of rice plants to UV-B radiation on seed morphology and proanthocyanidin content, the local traditional rice variety 'Baijiaolaojing' was planted on terraces in Yuanyang county and subjected to enhanced UV-B radiation treatments. The radiation intensity that caused the maximum phenotypic plasticity (7.5 kJ·m-2) was selected for further study, and the rice crops were cultivated for four successive generations. The results show that in the same generation, enhanced UV-B radiation resulted in significant decreases in grain length, grain width, spike weight, and thousand-grain weight, as well as significant increases in empty grain percentage and proanthocyanidin content, compared with crops grown under natural light conditions. Proanthocyanidin content increased as the number of generations of rice exposed to radiation increased, but in generation G3, it decreased, along with the empty grain ratio. At the same time, biomass, tiller number, and thousand-grain weight increased, and rice growth returned to control levels. When the offspring's radiation memory and growth environment did not match, rice growth was negatively affected, and seed proanthocyanidin content was increased to maintain seed activity. The correlation analysis results show that phenylalanine ammonialyase (PAL), cinnamate-4-hydroxylase (C4H), dihydroflavonol 4-reductase (DFR), and 4-coumarate:CoA ligase (4CL) enzyme activity positively influenced proanthocyanidin content. Overall, UV-B radiation affected transgenerational plasticity in seed morphology and proanthocyanidin content, showing that rice was able to adapt to this stressor if previous generations had been continuously exposed to treatment.

Initial experimental testing of a hybrid solar-dish Brayton cycle for combined heat and power (ST-CHP)

The Solar Turbo Combined Heat and Power (ST-CHP) project developed a novel solar-gas hybrid prototype for combined heat and power generation in Pretoria, South Africa. A vacuum-membrane faceted parabolic dish with a large-pipe open-cavity receiver was coupled to a counterflow recuperator, a combustion chamber, a micro gas turbine with air bearings and a phase change thermal energy storage unit containing solar salts. This study aimed to validate the electrical output of the full-scale dish-Brayton prototype, addressing the literature gap on micro-scale dish-Brayton plants' in-field power generation. Solar hybridization of micro gas turbine technology can significantly reduce combustion fuel consumption. A performance analysis under relevant conditions revealed a late afternoon micro gas turbine output intermittently peaking at 0.4kWe and subsequently stabilizing to a steady state of 0.145kWe at 130krpm. A SimuPact numerical model and an analytical model supplemented the telemetry data to reduce interference in the experimental setup and fully characterize the ST-CHP prototype performance, estimating a steady-state turbine isentropic efficiency of 57%, a compressor efficiency of 71% and a collector efficiency of 17% due to the late afternoon steady-state point. Analytical case studies revealed that fuel savings of between 12% and 33% at the combustion chamber were achievable from the solarized preheating. A subsequent test of the micro gas turbine without solar hybridization or a recuperator resulted in 1.05kWe being generated. The study confirms the dish-Brayton prototype's viability for combined heat and power generation, producing an initial full-scale performance characterisation during in-field testing, and highlighting the impact of solar hybridization on turbine electrical output. Optical efficiency, insulation effectiveness, pressure losses, and turbine operating conditions were identified as critical areas requiring optimization to improve electrical output. The lessons learned, and the calibrated numerical model may be used to optimize the performance of the dish-Brayton plant in future work. The successful in-field full-scale power generation of the ST-CHP prototype adds to the available literature on dish-Brayton technology and brings the technology closer to a commercial product.

Establishment of Human Pituitary Neuroendocrine Tumor Derived Organoid and Its Pilot Application for Drug Screening.

Precision medicine for pituitary neuroendocrine tumors (PitNETs) is limited by the lack of reliable research models. To generate patient-derived organoids (PDOs), which could serve as a platform for personalized drug screening for PitNET patients. From July 2019 to May 2022, a total of 32 human PitNET specimens were collected for the establishment of organoids with an optimized culture protocol. This study was conducted at Sun Yat-Sen University Cancer Center. PitNET patients who were pathologically confirmed were enrolled in this study. Histological staining and whole-exome sequencing were utilized to confirm the pathologic and genomic features of PDOs. A drug response assay on PDOs was also performed. PDOs retained key genetic and morphological features of their parental tumors. PDOs were successfully established from various types of PitNET samples with an overall success rate of 87.5%. Clinical nonfunctioning PitNETs-derived organoids (22/23, 95.7%) showed a higher likelihood of successful generation compared to those from functioning PitNETs (6/9, 66.7%). Preservation of cellular structure, subtype-specific neuroendocrine profiles, mutational features, and tumor microenvironment heterogeneity from parental tumors was observed. A distinctive response profile in drug tests was observed among the organoids from patients with different subtypes of PitNETs. With the validation of key characteristics from parental tumors in histological, genomic, and microenvironment heterogeneity consistency assays, we demonstrated the predictive value of the PDOs in testing individual drugs. The established PDOs, retaining typical features of parental tumors, indicate a translational significance in innovating personalized treatment for refractory PitNETs.

Neutrino model with broken [formula omitted] -[formula omitted] symmetry and unflavored leptogenesis with dihedral flavor symmetry

We propose a new neutrino flavor model based on a D4×U(1) flavor symmetry providing predictions for neutrino masses and mixing along with a successful generation of the observed Baryon Asymmetry of the Universe (BAU). After the spontaneous breaking of the flavor symmetry, the type I seesaw mechanism leads to a light neutrino mass matrix with broken μ−τ symmetry. By performing a numerical analysis, we find that the model favors a normal mass hierarchy with the lightest neutrino mass lies in the range m1∈[2.516,21.351] meV. The phenomenological implications of the neutrino sector are explored in detail and the results are discussed. Moreover, the generation of BAU is addressed via the leptogenesis mechanism from the decay of three right-handed neutrinos Ni. Through analytical and numerical analysis of the baryon asymmetry parameter YB, a successful unflavored leptogenesis takes place within the allowed parameter space obtained from neutrino phenomenology. We also examine interesting correlations between YB and low energy observables and provide a comprehensive discussion of the results.

Upcycling Waste Biomass–Production of Porous Carbonaceous Supports from Paper Mill Sludge and Application to CO2 Conversion

AbstractThe urgent need for sustainable waste management strategies has led to the exploration of innovative approaches for the valorization of waste. In this study, a method is proposed for carbonizing waste biomass materials, particularly paper mill waste sludges (primary and biological) and knots, to produce porous carbonaceous supports. Through an initial hydrothermal carbonization followed by carbonization with nitrogen flow, porous carbon materials are successfully generated. The findings of this investigation validate the successful generation of effective carbonaceous supports utilizing waste biomass materials. These materials are then evaluated for their effectiveness as porous supports in the ionic liquid‐catalyzed cycloaddition reaction of CO2 to styrene oxide, achieving a remarkable conversion rate of up to 98% and an impressive selectivity exceeding 99%. Additionally, the results underscore the significant impact of the selected IL on the overall conversion process. Overall, this study presents a promising pathway for the valorization of paper mill waste sludge through the production of porous carbon materials with potential applications in catalysis and beyond.

Life cycle exposure to titanium dioxide nanoparticles (TiO2-NPs) induces filial toxicity and population decline in the nematode Caenorhabditis elegans.

Titanium dioxide nanoparticle (TiO2-NP) exposure has raised significant concern due to their potential toxicity and adverse ecological impacts. Despite their ubiquitous presence in various environmental compartments, the long-term consequences of TiO2-NPs remain poorly understood. In this study, we combined data of in vivo toxicity and modeling to investigate the potential negative impacts of TiO2-NP exposure. We employed the nematode Caenorhabditis elegans, an environmental organism, to conduct a full life cycle TiO2-NP toxicity assays. Moreover, to assess the potential impact of TiO2-NP toxicity on population dynamics, we applied a stage-constructed matrix population model (MPM). Results showed that TiO2-NPs caused significant reductions in reproduction, survival, and growth of parental C. elegans (P0) at the examined concentrations. Moreover, these toxic effects were even more pronounced in the subsequent generation (F1) when exposed to TiO2-NPs. Furthermore, parental TiO2-NP exposure resulted in significant toxicity in non-exposed C. elegans progeny (TiO2-NPs free), adversely affecting their reproduction, survival, and growth. MPM analysis revealed decreased transition probabilities of surviving (Pi), growth (Gi), and fertility (Fi) in scenarios with TiO2-NP exposure. Additionally, the population growth rate (λmax) was found to be less than 1 in both P0 and F1, indicating a declining population trend after successive generations. Sensitivity analysis pinpointed L1 larvae as the most vulnerable stage, significantly contributing to the observed population decline in both P0 and F1 generations under TiO2-NP exposure. Our findings provide insight into the potential risk of an environmental organism like nematode by life cycle exposure to TiO2-NPs.

Long-term suitability of an alternative host for rearing the sugarcane stalk borer parasitoid Tetrastichus howardi.

The continuous utilisation of an alternative host may influence parasitoid performance across successive generations due to conditioning in natal hosts. Tetrastichus howardi (Olliff) has successfully been reared using Tenebrio molitor L. pupae as a feasible alternative host. However, the extended rearing of T. howardi on this alternative host may impact the biological features of the parasitoids. Parasitoids were reared using T. molitor pupae for 30 consecutive generations. Quality criteria were assessed during the generations F5, F15, and F30, offering pupae of the target pest, Diatraea saccharalis (Fabr.), and compared with the F0 generation (parasitoids reared in D. saccharalis pupae). Criteria included assessments of parasitism performance, host selection, and wing form variation in the parasitoid wasps. Additionally, we examined the fecundity of T. howardi females that emerged from both hosts, considering their age, egg loading before and after one oviposition, as well as parasitism of sugarcane stalk borer pupae. Rearing T. howardi using pupae of T. molitor did not affect its biological traits or preference for the target pest for 30 generations. After parasitism, the parasitoid left the host pupa inside the stalk, and one oviposition was enough to kill D. saccharalis pupae and obtain viable parasitoid progeny. Female sexual maturation and egg loading occurred 72 and 96 h after parasitoid emergence. Egg-loading recovery after parasitism did not happen within 24 h. T. howardi can be reared for up to 30 generations using alternative hosts without compromising its parasitism performance or egg loading.

Colour change in potato (Solanum tuberosum L.) tubers by disruption of the anthocyanin pathway via ribonucleoprotein complex delivery of the CRISPR/Cas9 system

Potato is an important part of the traditional Norwegian diet, and the crop faces several challenges with respect to pests and diseases, as well as the increasingly challenging changes in climate. Genome editing may provide tools to improve the resilience of Norwegian potato cultivars to new climate challenges. We have altered the skin colour of two potato cultivars, ‘Desirée’ and ‘Nansen’ from red to yellow, as a proof-of-concept for the use of CRISPR/Cas9 in a Norwegian cultivar. Our method has involved the use of protoplasts and we have grown the regenerants for three successive clonal tuber generations to evaluate the stability of the edited plants over time and under varying temperature conditions in contained rooms in a greenhouse. We found that the protoplast method is well suited to achieving CRISPR/Cas9 applications. The results show that the yellow skin is consistent over the three generations of tuber propagation. We found some suspected somaclonal variation in the protoplast regenerants. Some of the variation which we observed under high temperatures (up to nearly 40ºC) during the second growth cycle, disappeared when cultivated under lower temperatures in the third cultivation cycle.

Intraocular mRNA delivery with endogenous MmPEG10-based virus-like particles

Virus-like particles (VLP) are a promising tool for intracellular gene delivery, yet their potential in ocular gene therapy remains underexplored. In this study, we bridged this knowledge gap by demonstrating the successful generation and application of vesicular stomatitis virus glycoprotein (VSVG)-pseudotyped mouse PEG10 (MmPEG10)-VLP for intraocular mRNA delivery. Our findings revealed that PEG10-VLP can efficiently deliver GFP mRNA to adult retinal pigment epithelial cell line-19 (ARPE-19) cells, leading to transient expression. Moreover, we showed that MmPEG10-VLP can transfer SMAD7 to inhibit epithelial-mesenchymal transition (EMT) in RPE cells effectively. In vivo experiments further substantiated the potential of these vectors, as subretinal delivery into adult mice resulted in efficient transduction of retinal pigment epithelial (RPE) cells and GFP reporter gene expression without significant immune response. However, intravitreal injection did not yield efficient ocular expression. We also evaluated the transduction characteristics of MmPEG10-VLP following intracameral delivery, revealing transient GFP protein expression in corneal endothelial cells without significant immunotoxicities. In summary, our study established that VSVG pseudotyped MmPEG10-based VLP can transduce mitotically inactive RPE cells and corneal endothelial cells in vivo without triggering an inflammatory response, underscoring their potential utility in ocular gene therapy.

IVF exposure induced intergenerational effects on metabolic phenotype in mice

Research questionWhat is the potential transmission of metabolic phenotype from IVF offspring to the subsequent generation? DesignAn IVF mouse model was established. The F1 generation mice were produced though IVF or natural mating and the F2 generation was obtained through the mating of F1 generation males with normal females. Their metabolic phenotype, including systemic and hepatic glucolipid metabolism, was examined. ResultsIt was found that IVF F1 males exhibited metabolic changes. Compared with the control group, the IVF F1 generation showed increased body weight, elevated fasting glucose and insulin, and increased serum triglyceride concentrations. IVF F1 mice also showed an increased expression of hepatic lipogenesis and autophagy genes. Moreover, IVF F1 males transmitted some metabolic changes to their own male progeny (IVF F2) in the absence of a dietary challenge. IVF F2 mice had increased peri-epididymal and subcutaneous fat and decreased insulin sensitivity. Under the ‘second hit’ of a high-fat diet, IVF F2 mice further showed increased hepatic lipid deposition with unaltered autophagy levels. ConclusionThis research demonstrates the impact of IVF on hepatic glucose–lipid metabolism in two successive generations of offspring, highlighting the need for additional investigation. Enhanced understanding of the mechanisms underlying the transmission of multigenerational effects induced by IVF could potentially lead to the advancement of therapeutic interventions for individuals experiencing infertility.

Spectral analysis for weighted extended Vicsek polygons

Because of the application of fractal networks and their spectral properties in various fields of science and engineering, they have become a hot topic in network science. Moreover, deterministic weighted graphs are widely used to model complex real-world systems. This paper studys weighted extended Vicsek polygons W(G m,t ), which are based on the Vicsek fractal model and the extended fractal cactus model. The structure of these polygons is controlled by the positive integer coefficient m and the number of iterations t. From the construction of the graph, we derive recursive relations of all eigenvalues and their multiplicities of normalized Laplacian matrices from the two successive generations of the weighted extended Vicsek polygons. Then, we use the spectra of the normalized Laplacian matrices to study Kemeny’s constant, the multiplicative Kirchhoff index, and the number of weighted spanning trees and derive their exact closed-form expressions for the weighted extended Vicsek polygons. The above results help to analyze the topology and dynamic properties of the network model, so it has potential application prospects.

In memory of Dr. Valene L. Smith

Valene L. Smith is best known as the editor of the successful book Hosts and Guests: The Anthropology of Tourism. Her life was dedicated to the anthropological study of tourism. In this article commemorating her life, I look at her work, particularly from the Japanese context in which I developed my anthropological study of tourism. This year, 2024, marks the 50th anniversary of the publication of Hosts and Guests. A classic book like this will be read and updated by successive generations around the world.