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Sisi Mo,1– 3,* Haiming Ru,1– 3,* Maosen Huang,1– 3 Linyao Cheng,1– 3 Xianwei Mo,1– 3 Linhai Yan1– 3 1Department of Gastrointestinal Surgery, Guangxi Medical University Cancer Hospital, Nanning, 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China; 2Guangxi Clinical Research Center for Colorectal Cancer, Nanning, 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China; 3Guangxi Key Laboratory of Colorectal Cancer Prevention and Treatment, Nanning, 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China*These authors contributed equally to this workCorrespondence: Linhai YanDepartment of Gastrointestinal Surgery, Guangxi Medical University Cancer Hospital, Hedi Road No. 71, Nanning, Guangxi Zhuang Autonomous Region, 530021, People’s Republic of China, Tel +86 139 78839969, Email lhyan@gxmu.edu.cnAbstract: It is widely recognized that microbial disorders are involved in the pathogenesis of many malignant tumors. The oral and intestinal tract are two of the overriding microbial habitats in the human body. Although they are anatomically and physiologically continuous, belonging to the openings at both ends of the digestive tract, the oral and intestinal microbiome do not cross talk with each other due to a variety of reasons, including intestinal microbial colonization resistance and chemical barriers in the upper digestive tract. However, this balance can be upset in certain circumstances, such as disruption of colonization resistance of gut microbes, intestinal inflammation, and disruption of the digestive tract chemical barrier. Evidence is now accruing to suggest that the oral microbiome can colonize the gut, leading to dysregulation of the gut microbes. Furthermore, the oral-gut microbes create an intestinal inflammatory and immunosuppressive microenvironment conducive to tumorigenesis and progression of colorectal cancer (CRC). Here, we review the oral to intestinal microbial transmission and the inflammatory and immunosuppressive microenvironment, induced by oral-gut axis microbes in the gut. A superior comprehension of the contribution of the oral-intestinal microbes to CRC provides new insights into the prevention and treatment of CRC in the future.Keywords: oral-intestinal microbiota, colorectal cancer, inflammatory microenvironment, immunosuppressive microenvironment

Abstract Reconfigurable phototransistors featuring bipolar photoresponses are favorable for manipulating high-performance neuromorphic vision sensory. Here, we present a momentum-conserved reconfigurable phototransistor based on the van der Waals heterojunction between methylammonium lead iodide perovskite and two-dimensional Bi2O2Se semiconductor, which exhibits a synergistic interplay of interband hot-carrier transitions and reconfigurable heterointerface band alignments, eventually achieving the ultrahigh bipolar optoelectronic performances with the photoresponsivity of 6×107 AW−1, accompanied by the specific detectivity of 5.2×1011 Jones, and the dynamic range of 110 dB. Moreover, A 3×3 heterotransistor array is fabricated to perform in-sensor analog multiply-accumulate operations even under the challenging dim illumination of 0.1 μWcm−2 that comparable to natural moonlight. The reconfigurable heterotransistor array can be further adopted to enhance the traffic-light detection under dim-light conditions. Our advancement in momentum-conserved reconfigurable heterotransistor signifies a leap forward in real-time, energy-efficient, and low-light image processing for neuromorphic vision sensors.

Abstract Anaplastic thyroid cancer (ATC) is among the most aggressive and metastatic malignancies, often resulting in fatal outcomes due to the lack of effective treatments. Prosapogenin A (PA), a bioactive compound prevalent in traditional Chinese herbs, has shown potential as an antineoplastic agent against various human tumors. However, its effects on ATC and the underlying mechanism remain unclear. Here, we demonstrate that PA exhibits significant anti-ATC activity both in vitro and in vivo by inducing GSDME-dependent pyroptosis in ATC cells. Mechanistically, PA promotes lysosomal membrane permeabilization (LMP), leading to the release of cathepsins that activate caspase 8/3 to cleave GSDME. Remarkably, PA significantly upregulates three key functional subunits of V-ATPase—ATP6V1A, ATP6V1B2, and ATP6V0C—resulting in lysosomal over-acidification. This over-acidification exacerbates LMP and subsequent lysosomal damage. Neutralization of lysosomal lumen acidification or inhibition/knockdown of these V-ATPase subunits attenuates PA-induced lysosomal damage, pyroptosis and growth inhibition of ATC cells, highlighting the critical role for lysosomal acidification and LMP in PA’s anticancer effects. In summary, our findings uncover a novel link between PA and lysosomal damage-dependent pyroptosis in cancer cells. PA may act as a V-ATPase agonist targeting lysosomal acidification, presenting a new potential therapeutic option for ATC treatment.

Introdução/objetivos: Dados brasileiros sobre a carga do vírus sincicial respiratório (VSR) em adultos são limitados. As vacinas contra o VSR recentemente aprovadas visam reduzir a carga do VSR em adultos mais velhos. Este estudo tem como objetivo usar uma abordagem de modelagem para estimar a carga do VSR e projetar o potencial impacto na saúde pública da introdução da Vacina VSR Adjuvantada (RSVPreF3) para imunização de adultos com 60 anos ou mais no Brasil. Materiais e métodos: Um modelo de Markov estático de ciclo mensal foi desenvolvido para avaliar o número de casos sintomáticos de VSR com e sem vacinação. O modelo captura casos de VSR em pacientes com doença respiratória aguda (DRA-VSR), doença do trato respiratório inferior (DTRI-VSR), doença do trato respiratório superior (DTRS-VSR), complicações de pneumonia devido à DTRI-VSR, hospitalizações (assumidas conservadoramente apenas às DTRI-VSR) e mortes em um período de três anos. A cobertura vacinal para uma dose única considerada no modelo foi de 30% a 70%. Os dados demográficos são valores específicos do Brasil (2024) provenientes das Nações Unidas. Os dados epidemiológicos foram recuperados de banco de dados público (FluNet) e complementados por revisão sistemática da literatura. A eficácia da vacina foi obtida do estudo clínico de fase 3 AReSVi-006 (NCT04886596). Resultados: No Brasil, a coorte incluiu 33.859.754 adultos ≥ 60 anos. Na ausência de vacinação, o modelo projetou 6.641.784 casos de DRA-VSR (3.480.113 de DTRS-VSR e 3.161.671 de DTRI- VSR), 243.205 casos de pneumonia, 264.214 hospitalizações e 25.083 mortes por VSR em três anos. Com a cobertura aumentando de 30% para 70%, o modelo projetou que a vacinação pode prevenir de 780.189 a 1.820.442 casos de DRA-VSR (264.146 a 616.341 de DTRS-VSR e 516.043 a 1.204.101 de DTRI-VSR), 39.696 a 92.623 casos de pneumonia, 43.125 a 100.624 hospitalizações e 4.094 a 9.553 mortes por VSR. O número necessário para vacinar para prevenir um caso de DRA-VSR e um caso de DTRI-VSR foi estimado em 13 e 20, respectivamente. Conclusões: Os resultados revelam que aproximadamente 20% da população brasileira com idade ≥ 60 anos está em risco de infecção por VSR nos próximos três anos, e a carga ao sistema de saúde é substancial. A prevenção por meio da vacinação com RSVPreF3 tem o potencial de produzir consideráveis benefícios, reduzindo a morbidade, a utilização de serviços de saúde e a mortalidade associadas às infecções por VSR. Palavras-chave: Vírus Sincicial Respiratório, Vacina VSR Adjuvantada, ≥ 60 anos. Conflitos de interesse: RH, AG, BdV, LM, OC, DVO and JG are GSK employees. AG and JG hold shares in GSK. These authors declare no other financial and non-financial relationships and activities. Ética e financiamentos: Estudo financiado por: GlaxoSmithKline Biologicals SA (GSK study identifier: VEO-000975).

Objective: This study compares endoscopic thyroidectomy by gasless unilateral axillary approach (ETGUA) and sternocleidomastoid leading-edge approach (SLEA) with conventional open thyroidectomy (COT) in hemithyroidectomy. The main focus is on the protection of neck muscles (sternocleidomastoid, omohyoid, sternothyroid) and the postoperative function of voice and swallowing yielded through these common approaches. Methods: A total of 302 patients who underwent hemithyroidectomy were enrolled and divided into three groups: ETGUA (n = 101), SLEA (n = 100), and COT (n = 101). Ultrasound was used to measure the thickness of bilateral neck muscles, including the sternocleidomastoid, omohyoid, and sternothyroid. The changes in thickness on the surgical side compared to the non-surgical side. Analyzed factors included muscle thickness changes, Swallowing Impairment Score (SIS), Voice Handicap Index (VHI), Scar Cosmesis Assessment and Rating (SCAR), Neck Injury Index (NII), surgery duration, drainage volume, hospitalization, and number of lymph nodes. Results: The clinical characteristics among the three groups were consistent except for differences in sex, age, and BMI. Metrics such as sternocleidomastoid muscle, NII, hypocalcemia, postoperative PTH, transient hoarseness, and number of lymph nodes showed no significant differences among the three groups. However, significant differences were found in the duration of surgery, drainage volume, hospitalization period omohyoid muscle, Sternohyoid muscle, VHI, SIS, and SCAR (all p

Melanoma, a malignant skin cancer arising from melanocytes, exhibits rapid metastasis and a high mortality rate, especially in advanced stages. Current treatment modalities, including surgery, radiation, and immunotherapy, offer limited success, with immunotherapy using immune checkpoint inhibitors (ICIs) being the most promising. However, the high mortality rate underscores the urgent need for robust, non-invasive biomarkers to predict patient response to adjuvant therapies. The immune microenvironment of melanoma comprises various immune cells, which influence tumor growth and immune response. Melanoma cells employ multiple mechanisms for immune escape, including defects in immune recognition and epithelial-mesenchymal transition (EMT), which collectively impact treatment efficacy. Single-cell analysis technologies, such as single-cell RNA sequencing (scRNA-seq), have revolutionized the understanding of tumor heterogeneity and immune microenvironment dynamics. These technologies facilitate the identification of rare cell populations, co-expression patterns, and regulatory networks, offering deep insights into tumor progression, immune response, and therapy resistance. In the realm of biomarker discovery for melanoma, single-cell analysis has demonstrated significant potential. It aids in uncovering cellular composition, gene profiles, and novel markers, thus advancing diagnosis, treatment, and prognosis. Additionally, tumor-associated antibodies and specific genetic and cellular markers identified through single-cell analysis hold promise as predictive biomarkers. Despite these advancements, challenges such as RNA-protein expression discrepancies and tumor heterogeneity persist, necessitating further research. Nonetheless, single-cell analysis remains a powerful tool in elucidating the mechanisms underlying therapy response and resistance, ultimately contributing to the development of personalized melanoma therapies and improved patient outcomes.

Inflammatory bowel disease (IBD) is a chronic inflammatory disease characterized by intestinal barrier dysfunction, inflammatory synergistic effects and excessive tissue injury. Gallic acid (GA) is renowned for its remarkable biological activity, encompassing anti-inflammatory and antioxidant properties. However, the underlying mechanisms by which GA protects against intestinal inflammation have not been fully elucidated. The aim of this study is to investigate the effect of GA on the inflammation of a lipopolysaccharide (LPS)-stimulated human colon carcinoma cell line (Caco-2) and on the intestinal barrier dysfunction, and explore the underlying molecular mechanism involved. Our findings demonstrate that 5 μg/mL GA restores the downregulation of the mRNA and protein levels of Claudin-1, Occludin, and ZO-1 and decreases the expressions of inflammatory factors such as IL-6, IL-1β and TNF-α induced by LPS. In addition, GA exhibits a protective effect by reducing the LPS-enhanced early and late apoptotic ratios, downregulating the mRNA levels of pro-apoptotic factors (Bax, Bad, Caspase-3, Caspase-8, and Caspase-9), and upregulating the mRNA levels of anti-apoptotic factor Bcl-2 in Caco-2 cells. GA also reduces the levels of reactive oxygen species increased by LPS and restores the activity of antioxidant enzymes, namely, superoxide dismutase and catalase, as well as the level of glutathione. More importantly, GA exerts its anti-inflammatory effects by inhibiting the LPS-induced phosphorylation of key signaling molecules in the NF-κB/MAPK pathway, including p65, IκB-α, p38, JNK, and ERK, in Caco-2 cells. Overall, our findings show that GA increases the expressions of tight junction proteins, reduces cell apoptosis, relieves oxidative stress and suppresses the activation of the NF-κB/MAPK pathway to reduce LPS-induced intestinal inflammation in Caco-2 cells, indicating that GA has potential as a therapeutic agent for intestinal inflammation.

Abstract Introduction Herpes zoster (HZ) can cause substantial patient morbidity and lead to large healthcare costs. However, the disease burden of HZ in Southeast Asia may be underestimated. This study aimed to estimate the public health burden of HZ and the impact of vaccinating adults aged ≥ 50 years old in five Southeast Asian countries (Indonesia, Malaysia, Philippines, Thailand, and Vietnam), with adjuvanted recombinant zoster vaccine (RZV) compared with no vaccination. Methods For each country, we adapted a static multicohort Markov model developed with a 1-year cycle length and lifetime horizon. Demographics were obtained from the World Health Organization, HZ incidence from a worldwide meta-regression reporting Asian-specific values, proportions of postherpetic neuralgia (PHN) and non-PHN complications from local/regional studies, and vaccine efficacy from a long-term follow-up trial. First-dose coverage and second-dose compliance were assumed to be 30% and 70%, respectively. A one-way deterministic sensitivity analysis (OWSA) and probabilistic sensitivity analysis (PSA) were performed to assess the robustness and uncertainty of inputs for each country. Results Without RZV, it was estimated that there would be a total of approximately 10 million HZ cases, 2.1 million PHN cases, and 1.4 million non-PHN complications in individuals aged ≥ 50 years included in the model. Introducing RZV under 30% coverage could avoid approximately 2.2 million (22%) HZ cases, almost 500,000 (21%) PHN cases, and around 300,000 (22%) non-PHN complications. OWSA showed that first-dose coverage and initial HZ incidence had the largest impact on the estimated number of HZ cases avoided. The number needed to vaccinate ranged from 15 to 21 to prevent one case of HZ and from 68 to 104 to prevent one case of PHN across each country. Conclusions This study demonstrated that there is substantial HZ disease burden in older adults for the five selected countries in Southeast Asia, negatively impacting national healthcare systems. Introducing RZV could potentially reduce this burden. A graphical abstract is available with this article. Graphical Abstract

Abstract Conventional circuit elements are constrained by limitations in area and power efficiency at processing physical signals. Recently, researchers have delved into high-order dynamics and coupled oscillation dynamics utilizing Mott devices, revealing potent nonlinear computing capabilities. However, the intricate yet manageable population dynamics of multiple artificial sensory neurons with spatiotemporal coupling remain unexplored. Here, we present an experimental hardware demonstration featuring a capacitance-coupled VO2 phase-change oscillatory network. This network serves as a continuous-time dynamic system for sensory pre-processing and encodes information in phase differences. Besides, a decision-making module for special post-processing through software simulation is designed to complete a bio-inspired dynamic sensory system. Our experiments provide compelling evidence that this transistor-free coupling network excels in sensory processing tasks such as touch recognition and gesture recognition, achieving significant advantages of fewer devices and lower energy-delay-product compared to conventional methods. This work paves the way towards an efficient and compact neuromorphic sensory system based on nano-scale nonlinear dynamics.

Abstract Objective Metabolic risks play a key role in the progression of pancreatic cancer. This study aimed to present global, regional and national data on mortality and disability-adjusted life-year (DALY) for pancreatic cancer attributable to metabolic risk and to forecast mortality to 2030 using data from the Global Burden of Disease (GBD). Methods Data on mortality and DALYs due to pancreatic cancer attributable to metabolic risks were obtained from GBD 2019. Metabolic risks include high fasting plasma glucose (FPG) and high body mass index (BMI). Total numbers and age-standardized rates per 100,000 people for mortality and DALYs were reported by age, sex, region and country/territory from 1990 to 2019. The “Bayes age-period-cohort” method was used for projections of mortality to 2030. Results Globally, there was a 3.5-fold increase in the number of pancreatic cancer deaths attributable to metabolic risk, from 22,091 in 1990 to 77,215 in 2019. High-income North America and Central Europe had the highest age-standardized mortality rates (ASMRs) of pancreatic cancer attributable to high FPG and high BMI in 2019, respectively. From 1990 to 2019, the global ASMR of pancreatic cancer attributable to high FPG and high BMI increased. Countries with high healthcare access quality had much higher age-standardized DALY rates. In the next 10 years, the ASMR of pancreatic cancer attributable to high FPG and high BMI will continue to increase. Conclusion Pancreatic cancer mortality and DALYs attributable to metabolic factors remain high, particularly in high-income regions or countries. Studies on the metabolic mechanism of pancreatic cancer and effective treatment strategies are needed.

Field-effect transistors (FETs) switched by quantum band-to-band tunneling (BTBT) mechanism, rather than conventional thermionic emission mechanism, are emerging as an exciting device candidate for future ultralow-power electronics due to their exceptional electronic properties of subthermionic subthreshold swing. However, fundamental limitations in drive current have hindered such technology encountering for high-performance and high-speed operations, especially for silicon-based device. Here, we demonstrate a novel pathway of integrating tunneling and thermionic emission mechanisms together, to circumvent their respective limitation and design a hybrid adaptively modulated FET (HamFET) that orients power saving and performance enhancement simultaneously. This transistor architecture, utilizing a nested source configuration without cost or area penalties, exhibits both ultrasteep (subthermionic) subthreshold swing and the largest “on” and “off” current ratio over the state-of-the-art tunneling transistors. Our design methodology of hybrid switching mechanism is also applicable to other mechanism, material, and architecture systems, opening the doors to a range of high-speed application opportunities for ultralow-power but performance-insufficient electronics.

Cancer remains a significant global challenge, with escalating incidence rates and a substantial burden on healthcare systems worldwide. Herein, we present an in-depth exploration of the intricate interplay between cancer cell death pathways and tumor immunity within the tumor microenvironment (TME). We begin by elucidating the epidemiological landscape of cancer, highlighting its pervasive impact on premature mortality and the pronounced burden in regions such as Asia and Africa. Our analysis centers on the pivotal concept of immunogenic cell death (ICD), whereby cancer cells succumbing to specific stimuli undergo a transformation that elicits robust anti-tumor immune responses. We scrutinize the mechanisms underpinning ICD induction, emphasizing the release of damage-associated molecular patterns (DAMPs) and tumor-associated antigens (TAAs) as key triggers for dendritic cell (DC) activation and subsequent T cell priming. Moreover, we explore the contributions of non-apoptotic RCD pathways, including necroptosis, ferroptosis, and pyroptosis, to tumor immunity within the TME. Emerging evidence suggests that these alternative cell death modalities possess immunogenic properties and can synergize with conventional treatments to bolster anti-tumor immune responses. Furthermore, we discuss the therapeutic implications of targeting the TME for cancer treatment, highlighting strategies to harness immunogenic cell death and manipulate non-apoptotic cell death pathways for therapeutic benefit. By elucidating the intricate crosstalk between cancer cell death and immune modulation within the TME, this review aims to pave the way for the development of novel cancer therapies that exploit the interplay between cell death mechanisms and tumor immunity and overcome Challenges in the Development and implementation of Novel Therapies.

IntroductionFreshwater ecosystems are susceptible to invasion by alien macrophytes due to their connectivity and various plant dispersal vectors. These ecosystems often experience anthropogenic nutrient enrichment, favouring invasive species that efficiently exploit these resources. Propagule pressure (reflecting the quantity of introduced individuals) and habitat invasibility are key determinants of invasion success. Moreover, the enemy release hypothesis predicts that escape from natural enemies, such as herbivores, allows alien species to invest more resources to growth and reproduction rather than defense, enhancing their invasive potential. Yet, the combined impact of propagule pressure, herbivory, and nutrient enrichment on the competitive dynamics between invasive alien macrophytes and native macrophyte communities is not well understood due to a paucity of studies.MethodsWe conducted a full factorial mesocosm experiment to explore the individual and combined effects of herbivory, nutrient levels, propagule pressure, and competition on the invasion success of the alien macrophyte Myriophyllum aquaticum into a native macrophyte community comprising Vallisneria natans, Hydrilla verticillata, and Myriophyllum spicatum. This setup included varying M. aquaticum densities (low vs. high, simulating low and high propagule pressures), two levels of herbivory by the native snail Lymnaea stagnalis (herbivory vs no-herbivory), and two nutrient conditions (low vs. high). Myriophyllum aquaticum was also grown separately at both densities without competition from native macrophytes. ResultsThe invasive alien macrophyte M. aquaticum produced the highest shoot and total biomass when simultaneously subjected to conditions of high-density intraspecific competition, no herbivory, and low-nutrient availability treatments. Moreover, a high propagule pressure of M. aquaticum significantly reduced the growth of the native macrophyte community in nutrient-rich conditions, but this effect was not observed in nutrient-poor conditions. DiscussionThese findings indicate that M. aquaticum has adaptive traits enabling it to flourish in the absence of herbivory (supporting the enemy release hypothesis) and in challenging environments such as intense intraspecific competition and low nutrient availability. Additionally, the findings demonstrate that when present in large numbers, M. aquaticum can significantly inhibit the growth of native macrophyte communities, particularly in nutrient-rich environments. Consequently, reducing the propagule pressure of M. aquaticum could help control its spread and mitigate its ecological impact. Overall, these findings emphasize that the growth and impacts of invasive alien plants can vary across different habitat conditions and is shaped by the interplay of biotic and abiotic factors.

The burgeoning development of next-generation technologies, especially the Industrial Internet of Things (IIoT), has heightened interest in predictive maintenance (PdM). Accurate failure forecasting and prompt responses to downtime are essential for improving the industrial efficiency. Traditional PdM methods often suffer from high false alarm rates and inefficiencies in complex environments. This paper introduces a predictive maintenance framework using identity resolution and a transformer model. Devices receive unique IDs via distributed identifiers (DIDs), followed by a state awareness model to assess device health from sensor signals. A sequence prediction model forecasts future signal sequences, which are then used with the state awareness model to determine future health statuses. Combining these predictions with unique IDs allows for the rapid identification of facilities needing maintenance. Experimental results show superior performance, with 99% accuracy for the state awareness model and a mean absolute error (MAE) of 0.062 for the sequence prediction model, underscoring the effectiveness of the framework.

To address the issues of recast layer and heat affected zone (HAZ) in laser processing in the air, a new waterjet-assisted laser scanning machining (WALSM) was adopted. Laser processing experiments were conducted on DD6 single crystal (SC) superalloy plate to study the effects of various parameters on the microgroove and microhole machining quality, efficiency and taper angle. Results show that WALSM process can eliminate the recast layer, decrease the taper angle, and reduce the HAZ thickness with no microcracks. Orthogonal analysis shows that the waterjet velocity and pulse frequency are the most significant factors affecting the efficiency of WALSM. To further improve the machining efficiency of WALSM in a larger depth, a hybrid laser processing and WALSM process were proposed for drilling large depth holes with high machining efficiency, high accuracy and good surface quality. The hybrid machining process holds great potential in drilling shaped cooling holes on the turbine blades in the aviation industry. [ABSTRACT FROM AUTHOR]

In order to reduce the processing volume of multi-camera real-time video data in smart city scenarios, a video collaborative analysis method based on machine learning algorithms at the edge was proposed.Firstly, for the important objects detected by each camera, different key windows were designed to filter the region of interest (RoI) in the video, reduce the video data volume and extract its features.Then, based on the extracted data features, the same objects in the videos from different cameras were annotated, and a strategy for calculating the association degree value between cameras was designed for further reducing the video data volume.Finally, the GC-ReID algorithm based on graph convolutional network (GCN) and re-identification (ReID) was proposed, aiming at achieving the collaborative analysis of multi-camera videos.The experimental results show that proposed method can effectively reduce the system latency and improve the video compression rate while ensuring the high accuracy, compared with the existing video analysis methods.

Abstract Radiation tolerance is determined as the ability of crystalline materials to withstand the accumulation of the radiation induced disorder. Nevertheless, for sufficiently high fluences, in all by far known semiconductors it ends up with either very high disorder levels or amorphization. Here we show that gamma/beta (γ/β) double polymorph Ga2O3 structures exhibit remarkably high radiation tolerance. Specifically, for room temperature experiments, they tolerate a disorder equivalent to hundreds of displacements per atom, without severe degradations of crystallinity; in comparison with, e.g., Si amorphizable already with the lattice atoms displaced just once. We explain this behavior by an interesting combination of the Ga- and O- sublattice properties in γ-Ga2O3. In particular, O-sublattice exhibits a strong recrystallization trend to recover the face-centered-cubic stacking despite the stronger displacement of O atoms compared to Ga during the active periods of cascades. Notably, we also explained the origin of the β-to-γ Ga2O3 transformation, as a function of the increased disorder in β-Ga2O3 and studied the phenomena as a function of the chemical nature of the implanted atoms. As a result, we conclude that γ/β double polymorph Ga2O3 structures, in terms of their radiation tolerance properties, benchmark a class of universal radiation tolerant semiconductors.

Abstract Background Mouse embryonic stem cells (mESCs) not only retain the property of self-renewal but also have the ability to develop into primordial germ cell-like cells (PGCLCs). However, knowledge about the mechanisms of transcriptional regulation is still limited. Rhox6, a member of the homeobox family that is located on the X chromosome, is highly expressed within PGCLCs in vivo and in vitro. However, the detailed effects of Rhox6 on PGCLC specification and mESC maintenance remain unclear. Results In this study, we found that overexpression of Rhox6 favors the formation of PGCLCs, while depletion of Rhox6 inhibits the generation of PGCLCs. Mechanistically, Rhox6 directly induces the expression of Nanos3 during the specification of PGCLCs. Subsequently, downregulation of Nanos3 expression is sufficient to decrease the ability of Rhox6 to induce PGCLC formation. Moreover, we found that depletion of Rhox6 expression facilitates the self-renewal of mESCs. High-throughput sequencing revealed that suppression of Rhox6 transcription significantly increases the expression of pluripotency genes. Functional studies further demonstrated that Rhox6 directly represses the transcription of Tbx3. Therefore, knockdown of the expression of the latter impairs the self-renewal of mESCs promoted by Rhox6 downregulation. Conclusions Our study reveals that overexpression of Rhox6 is beneficial for PGCLC generation through induction of Nanos3, while downregulation of Rhox6 contributes to mESC self-renewal by increasing Tbx3. These findings help elucidate the early development of mouse embryos.