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The cancer paradigm is generally based on the somatic mutation model, asserting that cancer is a disease of genetic origin. The mitochondrial–stem cell connection (MSCC) proposes that tumorigenesis may result from an alteration of the mitochondria, specifically a chronic oxidative phosphorylation (OxPhos) insufficiency in stem cells, which forms cancer stem cells (CSCs) and leads to malignancy. Reviewed evidence suggests that the MSCC could provide a comprehensive understanding of all the different stages of cancer. The metabolism of cancer cells is altered (OxPhos insufficiency) and must be compensated by using the glycolysis and the glutaminolysis pathways, which are essential to their growth. The altered mitochondria regulate the tumor microenvironment, which is also necessary for cancer evolution. Therefore, the MSCC could help improve our understanding of tumorigenesis, metastases, the efficiency of standard treatments, and relapses. [ABSTRACT FROM AUTHOR]

The study of cold-tolerance mechanisms of wheat as a leading cereal crop is very relevant to science. Primary metabolites play an important role in the formation of increased cold tolerance. The aim of this research is to define changes in the content of primary metabolites (soluble proteins and sugars), growth, and photosynthetic apparatus of freezing-tolerant and cold-sustainable wheat (Triticum aestivum L.) genotypes under optimal conditions and after prolonged (7 days) exposure to low temperature (4 °C). In order to gain a deeper comprehension of the mechanisms behind wheat genotypes' adaptation to cold, we determined the expression levels of photosynthetic genes (RbcS, RbcL) and genes encoding cold-regulated proteins (Wcor726, CBF14). The results indicated different cold-adaptation strategies of freezing-tolerant and cold-sustainable wheat genotypes, with soluble proteins and sugars playing a significant role in this process. In plants of freezing-tolerant genotypes, the strategy of adaptation to low temperature was aimed at increasing the content of soluble proteins and modification of carbohydrate metabolism. The accumulation of sugars was not observed in wheat of cold-sustainable genotypes during chilling, but a high content of soluble proteins was maintained both under optimal conditions and after cold exposure. The adaptation strategies of wheat genotypes differing in cold tolerance were related to the expression of photosynthetic genes and genes encoding cold-regulated proteins. The data improve our knowledge of physiological and biochemical mechanisms of wheat cold adaptation. [ABSTRACT FROM AUTHOR]

Simple Summary: We identified the notch gene in the reproductive system of the Basilepta melanopus beetle, a pest affecting oil tea plants. It was discovered that the Notch signaling pathway is crucial for the early development of insect ovaries. Specifically, suppressing the Notch gene expression by RNAi led to impaired ovarian development, decreased mating rates, and reduced egg production. These findings highlight the potential of RNAi-based, Notch-targeted pest control strategies as a practical approach for managing the forest pest B. melanopus populations. Basilepta melanopus is a pest that severely affects oil tea plants, and the Notch signaling pathway plays a significant role in the early development of insect ovaries. In this study, we explored the function of the notch gene within the Notch signaling pathway in the reproductive system of B. melanopus. The functional domains and expression patterns of Bmnotch were analyzed. Bmnotch contains 45 epidermal growth factor-like (EGF-like) domains, one negative regulatory region, one NODP domain and one repeat-containing domain superfamily. The qPCR reveals heightened expression in early developmental stages and specific tissues like the head and ovaries. The RNA interference (RNAi)-based suppression of notch decreased its expression by 52.1%, exhibiting heightened sensitivity to dsNotch at lower concentrations. Phenotypic and mating experiments have demonstrated that dsNotch significantly impairs ovarian development, leading to reduced mating frequencies and egg production. This decline underscores the Notch pathway's crucial role in fecundity. The findings advocate for RNAi-based, Notch-targeted pest control as an effective and sustainable strategy for managing B. melanopus populations, signifying a significant advancement in forest pest control endeavors. [ABSTRACT FROM AUTHOR]

Viruses provide vital insights into gene expression control. Viral transactivators, with other viral and cellular proteins, regulate expression of self, other viruses, and host genes with profound effects on infected cells, underlying inflammation, control of immune responses, and pathogenesis. The multifunctional Tat proteins of lentiviruses (HIV-1, HIV-2, and SIV) transactivate gene expression by recruiting host proteins and binding to transacting responsive regions (TARs) in viral and host RNAs. SARS-CoV-2 nucleocapsid participates in early viral transcription, recruits similar cellular proteins, and shares intracellular, surface, and extracellular distribution with Tat. SARS-CoV-2 nucleocapsid interacting with the replication–transcription complex might, therefore, transactivate viral and cellular RNAs in the transcription and reactivation of self and other viruses, acute and chronic pathogenesis, immune evasion, and viral evolution. Here, we show, by using primary and secondary structural comparisons, that the leaders of SARS-CoV-2 and other coronaviruses contain TAR-like sequences in stem-loops 2 and 3. The coronaviral nucleocapsid C-terminal domains harbor a region of similarity to TAR-binding regions of lentiviral Tat proteins, and coronaviral nonstructural protein 12 has a cysteine-rich metal binding, dimerization domain, as do lentiviral Tat proteins. Although SARS-CoV-1 nucleocapsid transactivated gene expression in a replicon-based study, further experimental evidence for coronaviral transactivation and its possible implications is warranted. [ABSTRACT FROM AUTHOR]

Simple Summary: The premise that certain checkpoint inhibitors are effective anti-cancer treatments beyond their immune modulatory capabilities influences current cancer research and clinical practice as well as future drug versus therapy development. We propose ways and means to enhance immunotherapy in cancer care by combining anti-PD1/L1 with various therapeutic modalities according to an appropriate scientific theory, e.g., stem cell origin of cancer, and based on available clinical evidence, e.g., randomized clinical trials. Although immunotherapy has revolutionized cancer care, there is still an urgent need to enhance its efficacy and ensure its safety. A correct cancer theory and proper scientific method empower pertinent cancer research and enable effective and efficient drug versus therapy development for patient care. In this perspective, we revisit the concept of immune privilege in a cancer cell versus normal cell, as well as in a cancer stem cell versus normal stem cell. We re-examine whether effective immunotherapies are efficacious due to their anti-cancer and/or immune modulatory mechanisms. We reassess why checkpoint inhibitors (CPIs) are not equal. We reconsider whether one can attribute the utility of immunotherapy to specific cancer subtypes and its futility to certain tumor/immune compartments, components, and microenvironments. We propose ways and means to advance immunotherapy beyond CPIs by combining anti-PD1/L1 with various other treatment modalities according to an appropriate scientific theory, e.g., stem cell origin of cancer, and based on available clinical evidence, e.g., randomized clinical trials. We predict that a stem cell theory of cancer will facilitate the design of better and safer immunotherapy with improved selection of its use for the right patient with the right cancer type at the right time to optimize clinical benefits and minimize potential toxic effects and complications. [ABSTRACT FROM AUTHOR]

Impact fracture behavior at low temperatures was investigated in medium manganese steel with bcc-fcc duplex microstructures. The impact energy was above 150 J (−80~20 °C) and the fractography showed dimples for inter-critical annealing at 630 °C (QHA) because of the high retained austenite stability and low martensite dislocation density. The impact energy was from 180 J (20 °C) to 60 J (−80 °C) and the fractography was intergranular for inter-critical annealing at 610 °C (QLA) because of the low stability of RA and carbides precipitated at the prior austenite grain boundaries. The impact energy was below 60 J (−80~20 °C) and the fractography showed cleavage for direct quenching (DQ) because of the high dislocation density of martensite. [ABSTRACT FROM AUTHOR]

Programmed death ligand 1 (PD-L1) plays a pivotal role in cancer immune evasion and is a critical target for cancer immunotherapy. This review focuses on the regulation of PD-L1 through the dynamic processes of ubiquitination and deubiquitination, which are crucial for its stability and function. Here, we explored the intricate mechanisms involving various E3 ubiquitin ligases and deubiquitinating enzymes (DUBs) that modulate PD-L1 expression in cancer cells. Specific ligases are discussed in detail, highlighting their roles in tagging PD-L1 for degradation. Furthermore, we discuss the actions of DUBs that stabilize PD-L1 by removing ubiquitin chains. The interplay of these enzymes not only dictates PD-L1 levels but also influences cancer progression and patient response to immunotherapies. Furthermore, we discuss the therapeutic implications of targeting these regulatory pathways and propose novel strategies to enhance the efficacy of PD-L1/PD-1-based therapies. Our review underscores the complexity of PD-L1 regulation and its significant impact on the tumor microenvironment and immunotherapy outcomes. [ABSTRACT FROM AUTHOR]

The genes coding for the tumor suppressors p53 and retinoblastoma (Rb) are inactivated in the vast majority of small cell lung cancer (SCLC) tumors. Data support the notion that these two deleterious genetic events represent the initial steps in the development of SCLC, making them essential for a lung epithelial cell to progress toward the acquisition of a malignant phenotype. With the loss of TP53 and RB1, their broad tumor suppressive functions are eliminated and a normal cell is able to proliferate indefinitely, escape entering into cellular senescence, and evade death, no matter the damage it has experienced. Within this setting, lung epithelial cells accumulate further oncogenic mutations and are well on their way to becoming SCLC cells. Understanding the molecular mechanisms of these genetic lesions and their effects within lung epithelial cells is of paramount importance, in order to tackle this aggressive and deadly lung cancer. The present review summarizes the current knowledge on p53 and Rb aberrations, their biological significance, and their prospective therapeutic potential, highlighting completed and ongoing clinical trials with agents that target downstream pathways. [ABSTRACT FROM AUTHOR]

In recent decades, new nonlinear optical materials have been actively developed to create coherent tunable light sources in the mid-infrared (mid-IR) part of the spectrum used in a variety of scientific fields. In the present review, the main attention is focused on barium chalcogenide crystals, including their linear and nonlinear optical properties, laser-induced damage threshold (LIDT), and frequency down-conversion. [ABSTRACT FROM AUTHOR]

Viruses are obligate, intracellular parasites that co-opt host cell machineries for propagation. Critical among these machineries are those that translate RNA into protein and their mechanisms of control. Most regulatory mechanisms effectuate their activity by targeting sequence or structural features at the RNA termini, i.e., at the 5′ or 3′ ends, including the untranslated regions (UTRs). Translation of most eukaryotic mRNAs is initiated by 5′ cap-dependent scanning. In contrast, many viruses initiate translation at internal RNA regions at internal ribosome entry sites (IRESs). Eukaryotic mRNAs often contain upstream open reading frames (uORFs) that permit condition-dependent control of downstream major ORFs. To offset genome compression and increase coding capacity, some viruses take advantage of out-of-frame overlapping uORFs (oORFs). Lacking the essential machinery of protein synthesis, for example, ribosomes and other translation factors, all viruses utilize the host apparatus to generate virus protein. In addition, some viruses exhibit RNA elements that bind host regulatory factors that are not essential components of the translation machinery. SARS-CoV-2 is a paradigm example of a virus taking advantage of multiple features of eukaryotic host translation control: the virus mimics the established human GAIT regulatory element and co-opts four host aminoacyl tRNA synthetases to form a stimulatory binding complex. Utilizing discontinuous transcription, the elements are present and identical in all SARS-CoV-2 subgenomic RNAs (and the genomic RNA). Thus, the virus exhibits a post-transcriptional regulon that improves upon analogous eukaryotic regulons, in which a family of functionally related mRNA targets contain elements that are structurally similar but lacking sequence identity. This "thrifty" virus strategy can be exploited against the virus since targeting the element can suppress the expression of all subgenomic RNAs as well as the genomic RNA. Other 3′ end viral elements include 3′-cap-independent translation elements (3′-CITEs) and 3′-tRNA-like structures. Elucidation of virus translation control elements, their binding proteins, and their mechanisms can lead to novel therapeutic approaches to reduce virus replication and pathogenicity. [ABSTRACT FROM AUTHOR]

Simple Summary: In this study, we have explored the impact of a promising new cancer treatment modality called proton therapy (PT) and compared it to traditional X-ray based photon therapy (XRT) for head and neck cancers. Proton therapy is effective because it can be delivered with precision, thus causing fewer side effects. We demonstrate in this study that, when using proton therapy, there was a significant reduction (75%) in the production of small extracellular vesicles, commonly known as exosomes, from cancer cells, which usually suppress the immune system. XRT did not reduce exosome production. Exosomes from both PT and XRT had similar inhibitory effects on immune cells. Our findings suggest that proton therapy might be better at reducing the immune-suppressing effects of cancer exosomes by producing fewer of them. Proton therapy (PT) is emerging as an effective and less toxic alternative to conventional X-ray-based photon therapy (XRT) for patients with advanced head and neck squamous cell carcinomas (HNSCCs) owing to its clustered dose deposition dosimetric characteristics. For optimal efficacy, cancer therapies, including PT, must elicit a robust anti-tumor response by effector and cytotoxic immune cells in the tumor microenvironment (TME). While tumor-derived exosomes contribute to immune cell suppression in the TME, information on the effects of PT on exosomes and anti-tumor immune responses in HNSCC is not known. In this study, we generated primary HNSCC cells from tumors resected from HNSCC patients, irradiated them with 5 Gy PT or XRT, and isolated exosomes from cell culture supernatants. HNSCC cells exposed to PT produced 75% fewer exosomes than XRT- and non-irradiated HNSCC cells. This effect persisted in proton-irradiated cells for up to five days. Furthermore, we observed that exosomes from proton-irradiated cells were identical in morphology and immunosuppressive effects (suppression of IFN-γ release by peripheral blood mononuclear cells) to those of photon-irradiated cells. Our results suggest that PT limits the suppressive effect of exosomes on cancer immune surveillance by reducing the production of exosomes that can inhibit immune cell function. [ABSTRACT FROM AUTHOR]

Simple Summary: The heterogeneous expression of signaling molecules within the tumor, including kinases, is the major contributor to the acquisition of drug resistance and poor survival observed in small-cell lung cancer (SCLC). The addition of immunotherapy to chemotherapy has only marginally prolonged survival in patients with extensive-stage SCLC (ES-SCLC). Recent clinical trials have combined immunotherapy with the pharmacological inhibitors of kinases often dysregulated in SCLC. However, the regime has not been effective in the long term. Here, we review studies and clinical trials exploring dysregulated kinases in SCLC progression and resistance to chemotherapies and immunotherapies. We also discuss the possibility of repurposing kinase inhibitors against SCLC that have already demonstrated promising results for other types of cancers. SCLC is refractory to conventional therapies; targeted therapies and immunological checkpoint inhibitor (ICI) molecules have prolonged survival only marginally. In addition, ICIs help only a subgroup of SCLC patients. Different types of kinases play pivotal roles in therapeutics-driven cellular functions. Therefore, there is a significant need to understand the roles of kinases in regulating therapeutic responses, acknowledge the existing knowledge gaps, and discuss future directions for improved therapeutics for recalcitrant SCLC. Here, we extensively review the effect of dysregulated kinases in SCLC. We further discuss the pharmacological inhibitors of kinases used in targeted therapies for recalcitrant SCLC. We also describe the role of kinases in the ICI-mediated activation of antitumor immune responses. Finally, we summarize the clinical trials evaluating the potential of kinase inhibitors and ICIs. This review overviews dysregulated kinases in SCLC and summarizes their potential as targeted therapeutic agents. We also discuss their clinical efficacy in enhancing anticancer responses mediated by ICIs. [ABSTRACT FROM AUTHOR]

Simple Summary: Large amounts of conventional insecticides are used to control insect pests in agricultural production worldwide. New sustainable strategies, more specific and environmentally friendly, are urgently needed to combat insect pests. RNA interference (RNAi) is a natural mechanism of gene expression regulation that has been repurposed for biotechnological applications. Double-stranded RNAs homologous to endogenous genes, which could be produced in the crop plant or exogenously synthesized and applied onto crops, efficiently trigger gene silencing in insects, reducing pest damage. Consequently, these molecules are envisioned as the new generation of insecticidal compounds. Insect pests rank among the major limiting factors in agricultural production worldwide. In addition to direct effect on crops, some phytophagous insects are efficient vectors for plant disease transmission. Large amounts of conventional insecticides are required to secure food production worldwide, with a high impact on the economy and environment, particularly when beneficial insects are also affected by chemicals that frequently lack the desired specificity. RNA interference (RNAi) is a natural mechanism gene expression regulation and protection against exogenous and endogenous genetic elements present in most eukaryotes, including insects. Molecules of double-stranded RNA (dsRNA) or highly structured RNA are the substrates of cellular enzymes to produce several types of small RNAs (sRNAs), which play a crucial role in targeting sequences for transcriptional or post-transcriptional gene silencing. The relatively simple rules that underlie RNAi regulation, mainly based in Watson–Crick complementarity, have facilitated biotechnological applications based on these cellular mechanisms. This includes the promise of using engineered dsRNA molecules, either endogenously produced in crop plants or exogenously synthesized and applied onto crops, as a new generation of highly specific, sustainable, and environmentally friendly insecticides. Fueled on this expectation, this article reviews current knowledge about the RNAi pathways in insects, and some other applied questions such as production and delivery of recombinant RNA, which are critical to establish RNAi as a reliable technology for insect control in crop plants. [ABSTRACT FROM AUTHOR]

Strength assessment for thermal barrier coatings (TBCs) is vital in the safety design of hot-section components in engines. However, several crucial factors, including thermally grown oxide (TGO) growth and creep–plasticity interaction, have been less considered in thermo-mechanical analyses for TBCs near air holes. In this study, a unified viscoplastic constitutive model incorporating TGO growth is developed and integrated into a finite element framework. The model considers multiple factors, including TGO growth, creep–plasticity interaction, interface undulation, and temperature gradient. Additionally, an analytical solution for the non-uniform temperature field of a TBC is derived. The model is then applied to calculate interfacial stresses and accumulated strain energies in the TBC near an air hole, which promote interface debonding. The obtained results can be utilized to investigate the mechanisms of hole edge delamination in TBCs, considering the combined effects of multiple complex factors. A competition for the potential failure initiation location is revealed between the first oxide layer and the evolving TGO/bond coat interface. The developed viscoplasticity model demonstrates effective capability in modelling a range of dynamic behaviors that collectively contribute to hole edge delamination failure. [ABSTRACT FROM AUTHOR]

Because large oil-immersed transformers are enclosed by a metal shell, the on-site localization means it is difficult to achieve the accurate location of the patrol micro-robot inside a given transformer. To address this issue, a spatial ultrasonic localization method based on wavelet decomposition and PHAT-β-γ generalized cross correlation is proposed in this paper. The method is carried out with a five-element stereo ultrasonic array for the location of a transformer patrol robot. Firstly, the localization signal is decomposed into wavelet coefficients of different scales, which would realize the adaptive decomposition of the frequency of the localization signal from low frequencies to high frequencies. Then, the wavelet coefficients are denoised and reconstructed by using the semi-soft threshold function. Second, a modified phase transform-beta-gamma (PHAT-β-γ) method is used to calculate the exact time delay between different sensors by increasing the weights of the PHAT weighting function and introducing a correlation function. Finally, by using the proposed method, the accurate localization of the transformer patrol micro-robot is achieved with a five-element stereo ultrasonic array. The simulation and test results show that inside a transformer experimental oil tank (120 cm × 100 cm × 100 cm, L × W × H), the relative error of transformer patrol micro-robot spatial localization is within 4.1%, and the maximum localization error is less than 3 cm, which meets the requirement of engineering localization. [ABSTRACT FROM AUTHOR]

Cu-Be alloys exhibit excellent comprehensive performance in electrics, thermotics, and mechanics, and hence, they attract much attention. Among them, low-Be copper alloys are more environmentally friendly and promising. This study explores the effects of different Ni contents and heat treatment parameters on the properties, microstructures, and precipitates of Cu-0.2 wt% Be-x wt% Ni (0 < x < 2.0) alloys. The experimental results demonstrate that the fast cooling rate of cast alloys during solidification contributes to retention of the solute atoms in the copper matrix, which is beneficial for subsequent solid solution treatment. Furthermore, solid solution treatment slightly reduces the electrical conductivities, microhardness values, and compressive yield strengths of Cu-0.2 wt% Be-1.0/1.6 wt% Ni alloys. The optimal solution temperature and time are about 925 ℃ and 60 min, respectively. Aging treatment significantly increases the electrical conductivities, microhardness values, and compressive yield strengths of Cu-0.2 wt% Be-1.0/1.6 wt% Ni alloys. The best aging temperature is around 450 ℃. However, the properties of Cu-0.2 wt%Be-0.4 wt%Ni alloys remain unaffected by solution and aging treatments. Around x = 1.0, Cu-0.2 wt% Be-x wt% Ni alloys possess the best comprehensive properties, which are about 72%IACS of electrical conductivity, 241 HV of microhardness, and 281MPa of compressive yield strength, respectively. TEM and EDS analyses reveal that the precipitate evolution of Cu-0.2 wt% Be-1.0 wt% Ni alloys with aging time is GP zones → γ″ → γ′. Notably, a distinct double-peak age strengthening phenomenon emerges with Cu-0.2 wt% Be-1.0/1.6 wt% Ni alloys. The precipitation of plenty of GP zones at the early stage of aging should account for the first strengthening peak, and the strengthening mechanism transformation of the γ″ or γ′ phase from shear to Orowan should induce the second strengthening peak. This work may help to design new low-Be copper alloys and their preparation processes. [ABSTRACT FROM AUTHOR]

Electric buses have been vigorously promoted and implemented in major countries worldwide and have generated a huge demand for charging stations. Optimizing the daily charging experience of electric buses, adapting the daily operation scheduling, improving the utilization rate of charging stations, reducing the load on the power grid, and improving the operation efficiency of electric bus line networks require the reasonable layout of the charging stations. In this study, public transportation charging station layout and siting is the research object. We summarize the progress of analysis methods from the charging station and vehicle sides; introduce related research on the planning and layout of charging stations based on optimization models, including cost analysis and siting and layout for electric bus systems; summarize the data-driven station planning and siting research; and provide an overview of the current charging demand estimation, accuracy, and charging efficiency. Finally, we address the problems of the charging demand estimation accuracy, the mismatch between the charging station layouts for electric buses, and the charging demand on a long time scale. We suggest that research be conducted on data fusion for the temporal and spatial refinement of charging demand prediction in the context of the electrification of public transportation systems and the big data of telematics. [ABSTRACT FROM AUTHOR]

Replication Factor C Subunit 4 (RFC4), an oncogene implicated in many human cancers, has yet to be extensively studied in many cancer types to determine its expression patterns and tumor tissue function. Various bioinformatics tools were used to analyze RFC4 as a potential oncogene and therapeutic target across many cancers. We first examined RFC4 expression levels in several human tumor types to determine relationships with tumor grade, stage, metastasis, and patient survival. We also examined RFC4's genetic changes, epigenetic methylation, and effect on tumor microenvironment (TME) immune cell infiltration. We also analyzed RFC4's connections with immunological checkpoints to identify potential molecular pathways involved in carcinogenesis. Our findings show that RFC4 is upregulated in several tumor types and associated with poor prognoses in many human cancers. This study shows that RFC4 significantly affects the tumor immunological microenvironment, specifically immune cell populations. Finally, we screened for RFC4-inhibiting pharmacological compounds with anti-cancer potential. This study fully elucidates RFC4's carcinogenic activities, emphasizing its potential as a prognostic biomarker and a target for anti-cancer therapy. [ABSTRACT FROM AUTHOR]

At the turn of the 21st century, the importance of maintaining a balanced microbiome was brought to the forefront of the microbiology, immunology, and physiology research fields. Exploring the complex interactions between vaccine administration, mucosal microbiome, oral tolerance, and enteric inflammation in health and disease is challenging since environmental factors (such as diet and sanitation) have major influences on gut microbiota composition. High enteric pathogen load has been shown to contribute to dampened cell-mediated and humoral immune responses to vaccines in human case studies, either through elevated enteric inflammation or increased tolerance to environmental microbes. Although antibiotic and probiotic interventions have been evaluated in human health as well as research animal models, effective measures to mediate vaccine hyporesponsiveness are still ill-defined. Research in this field is becoming increasingly important for managing flock health in commercial poultry production, especially as antibiotic-free production is more prevalent and vaccination programs remain extensive during the first weeks of a bird's life. By understanding the cellular interactions between commensal microbiota, vaccine antigens, and the host immune system (particularly in avian models), advancements in bacterial and viral vaccine immunogenicity could lead to improved flock health in meat-type and egg-type chickens in the future. [ABSTRACT FROM AUTHOR]

Various privacy-preserving frameworks that respect the individual’s privacy in the analysis of data have been developed in recent years. However, available model classes such as simple statistics or generalized linear models lack the flexibility required for a good approximation of the underlying data-generating process in practice. In this paper, we propose an algorithm for a distributed, privacy-preserving, and lossless estimation of generalized additive mixed models (GAMM) using component-wise gradient boosting (CWB). Making use of CWB allows us to reframe the GAMM estimation as a distributed fitting of base learners using the L 2 -loss. In order to account for the heterogeneity of different data location sites, we propose a distributed version of a row-wise tensor product that allows the computation of site-specific (smooth) effects. Our adaption of CWB preserves all the important properties of the original algorithm, such as an unbiased feature selection and the feasibility to fit models in high-dimensional feature spaces, and yields equivalent model estimates as CWB on pooled data. Next to a derivation of the equivalence of both algorithms, we also showcase the efficacy of our algorithm on a distributed heart disease data set and compare it with state-of-the-art methods. [ABSTRACT FROM AUTHOR]

The role of Pleckstrin homology-like domain family B member 2 (PHLDB2) in the regulation of cell migration has been extensively studied. However, the exploration of PHLDB2 in head and neck squamous cell carcinoma (HNSCC) is still limited in terms of expression, function, and therapeutic potential. In this study, we discovered an upregulation of PHLDB2 expression in HNSCC tissues which was correlated with a negative prognosis in patients with HNSCC. Additionally, we determined that a high level of expression of PHLDB2 is crucial for maintaining cell migration through the regulation of the epithelial–mesenchymal transition (EMT). Furthermore, we demonstrated that the ablation of PHLDB2 in tumor cells inhibited tumorigenicity in a C3H syngeneic tumor-bearing mouse model. Mechanistically, PHLDB2 was found to be involved in the regulation of T cell anti-tumor immunity, primarily by enhancing the activation and infiltration of CD8+ T cells. In light of these findings, PHLDB2 emerges as a promising biomarker and therapeutic target for interventions in HNSCC. [ABSTRACT FROM AUTHOR]

In order to improve the accuracy and convergence speed of the steering law under the conditions of high dynamics, high bandwidth, and a small deflection angle, and in an effort to improve attitude measurement and control accuracy of the spacecraft, a spacecraft attitude measurement and control method based on variable speed magnetically suspended control sensitive gyroscopes (VSMSCSGs) and the fractional-order zeroing neural network (FO-ZNN) steering law is proposed. First, a VSMSCSG configuration is designed to realize attitude measurement and control integration in which the VSMSCSGs are employed as both actuators and attitude-rate sensors. Second, a novel adaptive steering law using FO-ZNN is designed. The matrix pseudoinverses are replaced by FO-ZNN outputs, which solves the problem of accuracy degradation in the traditional pseudoinverse steering laws due to the complexity of matrix pseudoinverse operations under high dynamics conditions. In addition, the convergence and robustness of the FO-ZNN are proven. The results show that the proposed FO-ZNN converges faster than the traditional zeroing neural network under external disturbances. Finally, a new weighting function containing rotor deflection angles is added to the steering law to ensure that the saturation of the rotor deflection angles can be avoided. Semi-physical simulation results demonstrate the correctness and superiority of the proposed method. [ABSTRACT FROM AUTHOR]

The present review draws attention to the specific role of angiotensin peptides [angiotensin II (Ang II), angiotensin-(1-7) (Ang-(1-7)], vasopressin (AVP), and insulin in the regulation of the coronary blood flow and cardiac contractions. The interactions of angiotensin peptides, AVP, and insulin in the heart and in the brain are also discussed. The intracardiac production and the supply of angiotensin peptides and AVP from the systemic circulation enable their easy access to the coronary vessels and the cardiomyocytes. Coronary vessels and cardiomyocytes are furnished with AT1 receptors, AT2 receptors, Ang (1-7) receptors, vasopressin V1 receptors, and insulin receptor substrates. The presence of some of these molecules in the same cells creates good conditions for their interaction at the signaling level. The broad spectrum of actions allows for the engagement of angiotensin peptides, AVP, and insulin in the regulation of the most vital cardiac processes, including (1) cardiac tissue oxygenation, energy production, and metabolism; (2) the generation of the other cardiovascular compounds, such as nitric oxide, bradykinin (Bk), and endothelin; and (3) the regulation of cardiac work by the autonomic nervous system and the cardiovascular neurons of the brain. Multiple experimental studies and clinical observations show that the interactions of Ang II, Ang(1-7), AVP, and insulin in the heart and in the brain are markedly altered during heart failure, hypertension, obesity, and diabetes mellitus, especially when these diseases coexist. A survey of the literature presented in the review provides evidence for the belief that very individualized treatment, including interactions of angiotensins and vasopressin with insulin, should be applied in patients suffering from both the cardiovascular and metabolic diseases. [ABSTRACT FROM AUTHOR]

Calabrian Glycyrrhiza glabra is one of the most appreciated licorice varieties worldwide, and its leaves are emerging as a valuable source of bioactive compounds. Nevertheless, this biomass is usually discarded, and its valorization could contribute to boost the economic value of the licorice production chain. In this study, the effects of production area and harvest time on the specialized metabolite content of G. glabra leaves (GGL) and also the antioxidant and anti-aging properties are evaluated to explore the potential of this untapped resource and to select the most optimal harvesting practices. GGL exhibited high levels of specialized metabolites (4–30 g/100 g of dry leaf) and the most abundant ones are pinocembrin, prenylated flavanones (licoflavanone and glabranin), and prenylated dihydrostilbenes. Their levels and antioxidant capacity in extracts are influenced by both production area and harvest time, showing a decisive role on specialized metabolites accumulation. Interestingly, GGL extracts strongly attenuate the toxicity of α-synuclein, the intracellular reactive oxygen species (ROS) content, and cellular senescence on Saccharomyces cerevisiae expressing human α-synuclein model, showing great potential to prevent aging and age-related disorders. These results provide insights into the phytochemical dynamics of GGL, identifying the best harvesting site and period to obtain bioactive-rich sources with potential uses in the food, nutraceutical, and pharmaceutical sectors. [ABSTRACT FROM AUTHOR]

The target can deceive the flight vehicle by releasing an infrared decoy to make the line-of-sight (LOS) angle rate deflect greatly, thus causing the flight vehicle to miss the target. Therefore, in order to accurately strike the target in complex adversarial scenarios, this paper proposes a finite-time convergence guidance law (FTCG) combined with a finite-time disturbance observer (FTDO). The complex adversarial scenario is established by combining the relative motion model between the flight vehicle and the target and the motion model of the infrared decoy. Based on this, considering the dynamic characteristic of the flight vehicle's autopilot, a guidance model is obtained. Utilizing sliding mode control theory and finite-time control theory, an FTCG of the LOS angle rate is designed. Then, the finite-time convergence of the guidance law is proved and the total convergence time is derived. Finally, for the target maneuvering that is difficult to measure in the guidance law, an FTDO is used to estimate and compensate for the target maneuvering in the guidance law. Simulation results show that the FTCG can make the LOS angle rate quickly converge and accurately strike the target in different scenarios, with a good guidance accuracy and robustness. Compared with the sliding mode guidance law (SMGL) and the adaptive sliding mode guidance law (ASMGL) based on an extended state observer (ESO), the advantages of the designed guidance law are illustrated. Finally, FTCG is extended to be three dimensional and compared with the proportional navigation guidance law (PNG) to further illustrate its effectiveness in a three-dimensional coordinate system. [ABSTRACT FROM AUTHOR]

Small cell lung cancer (SCLC) stands out as the most aggressive form of lung cancer, characterized by an extremely high proliferation rate and a very poor prognosis, with a 5-year survival rate that falls below 7%. Approximately two-thirds of patients receive their diagnosis when the disease has already reached a metastatic or extensive stage, leaving chemotherapy as the remaining first-line treatment option. Other than the recent advances in immunotherapy, which have shown moderate results, SCLC patients cannot yet benefit from any approved targeted therapy, meaning that this cancer remains treated as a uniform entity, disregarding intra- or inter-tumoral heterogeneity. Continuous efforts and technological improvements have enabled the identification of new potential targets that could be used to implement novel therapeutic strategies. In this review, we provide an overview of the most recent approaches for SCLC treatment, providing an extensive compilation of the targeted therapies that are currently under clinical evaluation and inhibitor molecules with promising results in vitro and in vivo. [ABSTRACT FROM AUTHOR]

One of the main concerns related to SARS-CoV-2 infection is the symptoms that could be developed by survivors, known as long COVID, a syndrome characterized by persistent symptoms beyond the acute phase of the infection. This syndrome has emerged as a complex and debilitating condition with a diverse range of manifestations affecting multiple organ systems. It is increasingly recognized for affecting the Central Nervous System, in which one of the most prevalent manifestations is cognitive impairment. The search for effective therapeutic interventions has led to growing interest in Mesenchymal Stem Cell (MSC)-based therapies due to their immunomodulatory, anti-inflammatory, and tissue regenerative properties. This review provides a comprehensive analysis of the current understanding and potential applications of MSC-based interventions in the context of post-acute neurological COVID-19 syndrome, exploring the underlying mechanisms by which MSCs exert their effects on neuroinflammation, neuroprotection, and neural tissue repair. Moreover, we discuss the challenges and considerations specific to employing MSC-based therapies, including optimal delivery methods, and functional treatment enhancements. [ABSTRACT FROM AUTHOR]

Tartary buckwheat is a cereal crop that has both medicinal and food origins. However, the underlying factors that contribute to Tartary buckwheat's flowering and seed-setting characteristics, effective grain formation, and physiological changes are still not well understood. This study aimed to investigate the flowering and seed-setting characteristics of different parts of Tartary buckwheat, as well as the grain-filling characteristics after flowering. To achieve this, Tartary buckwheat cultivars with high (QK3) and low (XQ2) seed-setting rates were selected for pot and field experiments. The study found that Tartary buckwheat undergoes flowering and seed setting simultaneously. Many wilted flowers and grains were observed 45 and 51 d after flowering. Compared to XQ2, QK3 exhibited a higher grain formation rate and seed-setting rate by 7.42% and 26.16%, respectively. Additionally, QK3 had a significantly lower grain abortion rate by 12.03%. The 1000-grain weight and average grain-filling rate of QK3 were 11.10% and 14.81% higher than those of XQ2, respectively. QK3 exhibited a faster maximum grain-filling rate (Rmax), reaching 18.38% faster than XQ2. Additionally, the dry matter average distribution rate in the main stem and branched grains of QK3 was 13.26% and 23.07% higher than that of XQ2, respectively. The sucrose concentration, SS, and SSS enzyme activities of QK3 were all higher than those of XQ2, by 0.29–25.99%, 5.22–11.62%, and 6.64–12.47%, respectively. Correlation analysis revealed a significant positive correlation between sucrose, soluble sugar, and starch concentration during the grain formation process and SS and SSS activities. This suggests that the levels of SS, SSS, soluble sugar, and sucrose in the grain play a crucial role in grain filling. [ABSTRACT FROM AUTHOR]

Lung cancer stands as the first cause of death by cancer in the world. Despite the improvement in patients' outcomes in the past decades through the development of personalized medicine approaches, a substantial portion of patients remains ineligible for targeted therapies due to the lack of a "druggable" molecular target. HER2, a receptor tyrosine kinase member of the EGFR/ErbB family, is known to show oncogenic properties. In this review, we focus on the different HER2 dysregulation mechanisms that have been observed in non-small cell lung cancer (NSCLC): gene mutation, gene amplification, protein overexpression and protein hyper-phosphorylation, the latter suggesting that HER2 dysregulation can occur independently of any molecular aberration. These HER2 alterations inevitably have consequences on tumor biology. Here, we discuss how they are not only involved in abnormal proliferation and survival of cancer cells but also potentially in increased angiogenic properties, mesenchymal features and tumor immune escape. Finally, we review the impact of these HER2 alterations in various therapeutic approaches. While standard chemotherapy and groundbreaking immunotherapy seem rather ineffective for HER2-altered NSCLCs, the development of HER2-targeted therapies such as tyrosine kinase inhibitors, anti-HER2 antibodies and especially antibody–drug conjugates could provide new hopes for patients. [ABSTRACT FROM AUTHOR]

Simple Summary: The phylogenetic status of the family Nitidulidae and its sister group relationship remain controversial. Also, the phylogenetic status of the subfamily Meligethinae and its phylogenetic relationships with other subfamilies of Nitidulidae are not fully understood. Mitochondrial genome sequences can be used to study species identification, phylogeny, and population genetic structure, and to provide valuable molecular markers for further genetic studies. In this paper, two complete mitochondrial genomes of Meligethinae were provided for the first time, and the phylogenetic status of the family Nitidulidae and subfamily Meligethinae were explored based on the complete mitochondrial genomes. A comparative analysis of the general characteristics and non-coding region patterns of the complete mitochondrial genomes of Meligethinus tschungseni and Brassicogethes affinis revealed that the base composition and mitochondrial genome structure of these two species are markedly different. Given the results of the phylogenetic analysis based on 20 mitochondrial genomes, the status of Nitidulidae and its sister group relationship is discussed. We also attempted to analyze the taxonomic status of Meligethinae and its sister group relationship. This study will provide a basis for further studies on the higher phylogeny of Nitidulidae. The phylogenetic status of the family Nitidulidae and its sister group relationship remain controversial. Also, the status of the subfamily Meligethinae is not fully understood, and previous studies have been mainly based on morphology, molecular fragments, and biological habits, rather than the analysis of the complete mitochondrial genome. Up to now, there has been no complete mitochondrial genome report of Meligethinae. In this study, the complete mitochondrial genomes of Meligethinus tschungseni and Brassicogethes affinis (both from China) were provided, and they were compared with the existing complete mitochondrial genomes of Nitidulidae. The phylogenetic analysis among 20 species of Coleoptera was reconstructed via PhyloBayes analysis and Maximum likelihood (ML) analysis, respectively. The results showed that the full lengths of Meligethinus tschungseni and Brassicogethes affinis were 15,783 bp and 16,622 bp, and the AT contents were 77% and 76.7%, respectively. Each complete mitochondrial genome contains 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs), 2 ribosomal RNA genes (rRNAs), and a control region (A + T-rich region). All the PCGs begin with the standard start codon ATN (ATA, ATT, ATG, ATC). All the PCGs terminate with a complete terminal codon, TAA or TAG, except cox1, cox2, nad4, and nad5, which terminate with a single T. Furthermore, all the tRNAs have a typical clover-leaf secondary structure except trnS1, whose DHU arm is missing in both species. The two newly sequenced species have different numbers and lengths of tandem repeat regions in their control regions. Based on the genetic distance and Ka/Ks analysis, nad6 showed a higher variability and faster evolutionary rate. Based on the available complete mitochondrial genomes, the results showed that the four subfamilies (Nitidulinae, Meligethinae, Carpophilinae, Epuraeinae) of Nitidulidae formed a monophyletic group and further supported the sister group relationship of Nitidulidae + Kateretidae. In addition, the taxonomic status of Meligethinae and the sister group relationship between Meligethinae and Nitidulinae (the latter as currently circumscribed) were also preliminarily explored. [ABSTRACT FROM AUTHOR]

Slow transit constipation (STC) has an estimated prevalence of 2–4% of the general population, and although it is the least prevalent of the chronic constipation phenotypes, it more commonly causes refractory symptoms and is associated with significant psychosocial stress, poor quality of life, and high healthcare costs. This review provides an overview of the pathophysiology, diagnosis, and management options in STC. STC occurs due to colonic dysmotility and is thought to be a neuromuscular disorder of the colon. Several pathophysiologic features have been observed in STC, including reduced contractions on manometry, delayed emptying on transit studies, reduced numbers of interstitial cells of Cajal on histology, and reduced amounts of excitatory neurotransmitters within myenteric plexuses. The underlying aetiology is uncertain, but autoimmune and hormonal mechanisms have been hypothesised. Diagnosing STC may be challenging, and there is substantial overlap with the other clinical constipation phenotypes. Prior to making a diagnosis of STC, other primary constipation phenotypes and secondary causes of constipation need to be ruled out. An assessment of colonic transit time is required for the diagnosis and can be performed by a number of different methods. There are several different management options for constipation, including lifestyle, dietary, pharmacologic, interventional, and surgical. The effectiveness of the available therapies in STC differs from that of the other constipation phenotypes, and prokinetics often make up the mainstay for those who fail standard laxatives. There are few available management options for patients with medically refractory STC, but patients may respond well to surgical intervention. STC is a common condition associated with a significant burden of disease. It can present a clinical challenge, but a structured approach to the diagnosis and management can be of great value to the clinician. There are many therapeutic options available, with some having more benefits than others. [ABSTRACT FROM AUTHOR]

The low heritability of reproduction traits such as total number born (TNB), number born alive (NBA) and adjusted litter weight until 21 days at weaning (ALW) poses a challenge for genetic improvement. In this study, we aimed to identify genetic variants that influence these traits and evaluate the accuracy of genomic selection (GS) using these variants as genomic features. We performed single-step genome-wide association studies (ssGWAS) on 17 823 Large White (LW) pigs, of which 2770 were genotyped by 50K single nucleotide polymorphism (SNP) chips. Additionally, we analyzed runs of homozygosity (ROH) in the population and tested their effects on the traits. The genomic feature best linear unbiased prediction (GFBLUP) was then carried out in an independent population of 350 LW pigs using identified trait-related SNP subsets as genomic features. As a result, our findings identified five, one and four SNP windows that explaining more than 1% of genetic variance for ALW, TNB, and NBA, respectively and discovered 358 hotspots and nine ROH islands. The ROH SSC1:21814570-27186456 and SSC11:7220366-14276394 were found to be significantly associated with ALW and NBA, respectively. We assessed the genomic estimated breeding value accuracy through 20 replicates of five-fold cross-validation. Our findings demonstrate that GFBLUP, incorporating SNPs located in effective ROH (p-value < 0.05) as genomic features, might enhance GS accuracy for ALW compared with GBLUP. Additionally, using SNPs explaining more than 0.1% of the genetic variance in ssGWAS for NBA as genomic features might improve the GS accuracy, too. However, it is important to note that the incorporation of inappropriate genomic features can significantly reduce GS accuracy. In conclusion, our findings provide valuable insights into the genetic mechanisms of reproductive traits in pigs and suggest that the ssGWAS and ROH have the potential to enhance the accuracy of GS for reproductive traits in LW pigs., (© 2024 Stichting International Foundation for Animal Genetics.)

Jasmonic acid (JA) and salicylic acid (SA) phytohormone pathways are important regulators of stress tolerance. Knowledge regarding the diversity, phylogeny and functionality of wheat genes involved in JA and SA response is limited. Using Arabidopsis, rice and wheat genomic and wheat disease transcriptomic data, we deduced the size, phylogenetic diversity and pathogen-responsiveness of seven hormone-responsive gene families, and thus selected 14 candidates as potential hormone responsive gene markers. Gene-specific expression studies assessed the impact of exogenous JA and SA on their transcriptional activation in leaves of two distinct wheat cultivars. RNAseq data were interrogated to assess their disease responsiveness and tissue-specific expression. This study elucidated the number, phylogeny and pathogen-responsiveness of wheat genes from seven families, including 12 TaAOS, 6 TaJAMyb, 256 TaWRKY group III, 85 TaPR1, 205 TaPR2, 76 TaPR3 and 124 TaPR5. This included the first description of the wheat AOS, JAMyb, PR2, PR3 and PR5 gene families. Gene expression studies delineated TaAOS1-5B and TaJAMyb-4A as JA-responsive in leaves, but not significantly responsive to SA treatment, while TaWRKY45-B was a SA- but not a JA-responsive marker. Other candidate genes were either unresponsive or non-specific to SA or JA. Our findings highlight that all seven gene families are greatly expanded in wheat as compared to other plants (up to 7.6-fold expansion), and demonstrate disparity in the response to biotic stress between some homoeologous and paralogous sequences within these families. The SA- and JA-responsive marker genes identified herein will prove useful tools to monitor these signalling pathways in wheat., (© 2024 The Authors. Plant Biology published by John Wiley & Sons Ltd on behalf of German Society for Plant Sciences, Royal Botanical Society of the Netherlands.)

We highlight the recent 5 years of research that contributed to our understanding of the mechanisms of RNA interference (RNAi) in insects. Since its first discovery, RNAi has contributed enormously as a reverse genetic tool for functional genomic studies. RNAi is also being used in therapeutics, as well as agricultural crop and livestock production and protection. Yet, for the wider application of RNAi, improvement of its potency and delivery technologies is needed. A mechanistic understanding of every step of RNAi, from cellular uptake of RNAi trigger molecules to targeted mRNA degradation, is key for developing an efficient strategy to improve RNAi technology. Insects provide an excellent model for studying the mechanism of RNAi due to species-specific variations in RNAi efficiency. This allows us to perform comparative studies in insect species with different RNAi sensitivity. Understanding the mechanisms of RNAi in different insects can lead to the development of better strategies to improve RNAi and its application to manage agriculturally and medically important insects., (© 2024 Royal Entomological Society.)

Freezing stress in spring often causes the death and abnormal development of young ears of wheat, leading to a significant reduction in grain production. However, the mechanisms of young wheat ears responding to freezing are largely unclear. In this study, the role of the ascorbic acid–glutathione cycle (AsA–GSH cycle) in alleviating freezing-caused oxidative damage in young wheat ears at the anther connective tissue formation phase (ACFP) was investigated. The results showed that the release rate of reactive oxygen species (ROS) and the relative electrolyte conductivity in young ears of Jimai22 (JM22, freezing-tolerant) were significantly lower than those in young ears of Xumai33 (XM33, freezing-sensitive) under freezing. The level of the GSH pool (231.8~392.3 μg/g FW) was strikingly higher than that of the AsA pool (98.86~123.4 μg/g FW) in young wheat ears at the ACFP. Freezing significantly increased the level of the AsA pool and the activities of ascorbate peroxidase (APX) and monodehydroascorbate reductase (MDHAR) in the young ears of both varieties. The level of the GSH pool increased in the young ears of XM33 under freezing but decreased in the young ears of JM22. The young ears of JM22 showed higher activities of glutathione reductase (GR), glutathione-S-transferase (GST) and glutathione peroxidase (GPX) than the young ears of XM33 under freezing. Collectively, these results suggest that the AsA–GSH cycle plays a positive role in alleviating freezing-induced oxidative damage in young wheat ears. Furthermore, the ability of utilizing GSH as a substrate to scavenge ROS is an important factor affecting the freezing tolerance of young wheat ears. In addition, abscisic acid (ABA), salicylic acid (SA), 3-indolebutyric acid (IBA) and cis-zeatin (cZ) may be involved in regulating the AsA–GSH cycle metabolism in young wheat ears under freezing. [ABSTRACT FROM AUTHOR]

Adolescent idiopathic scoliosis (AIS) is the predominant orthopedic disorder in children, affecting 1–3% of the global population. Research in this field has tried to delineate the genetic factors behind scoliosis and its association with heredity since AIS is considered a polygenic disease and has different genetic and epigenetic factors. The current study conducted a narrative review of the literature, focusing on biomarkers in the pathophysiology of muscle in AIS patients. Articles were collected from Scopus, Pubmed, and Web of Science. The key screening parameters were scoliosis classification, sampling, and the biomarkers evaluated. This review emphasizes potential key mechanisms and molecular regulators in muscle tissue. While there has been limited focus on the proteins contributing to muscle changes in AIS, significant attention has been given to genomic studies of single-nucleotide polymorphisms, particularly in LBX1. Despite these efforts, the exact causes of AIS remain elusive, with several theories suggesting genetic and hormonal factors. This review identified critical protein biomarkers such as Gi-protein alpha subunits, fibrillin-1 and -2, and various differentially expressed proteins, which may be linked to muscle alterations in AIS. This field of research is still limited due to a lack of homogeneity in the distinction of patients by groups and curve severity. Although the pathophysiology of AIS is still unclear, molecular research is important to guide the treatment of AIS before achieving skeletal maturity, thus avoiding serious problems associated with posture changes and low quality of life. In the future, a more comprehensive synergy between orthopedic and molecular research might ameliorate the diagnosis and treatment of AIS patients. [ABSTRACT FROM AUTHOR]

We aimed to determine the risk factors for postoperative overactive bladder (OAB) in patients treated with an adjustable trans-obturator male system (ATOMS) for stress incontinence after radical treatment of prostate cancer. A prospective study was performed on 56 patients implanted with an ATOMS for PPI. Clinical and urodynamic information was recorded before and after ATOMS implantation. We built a multivariate model to find out the clinical and urodynamic factors that independently influenced postoperative OAB and the prognostic factors that influenced the efficacy of medical treatment of OAB. We found that the clinical risk factors were the preoperative intensity of urinary incontinence (number of daily pads used and amount of urinary leakage), International Consultation on Incontinence Questionnaire (ICIQ) score, postoperative number of ATOMS adjustments, final cushion volume, and incontinence cure. The urodynamic data associated with OAB were cystometric bladder capacity, voided volume, volume at initial involuntary contraction (IC), maximum flow rate, bladder contractility index (BCI), and urethral resistance (URA). The prognostic factors for the efficacy of oral treatment of OAB were the volume at the first IC (direct relationship) and the maximum abdominal voiding pressure (inverse relationship). The multivariate model showed that the independent clinical risk factors were the daily pad count before the implantation and the ICIQ score at baseline and after treatment. The independent urodynamic data were the volume at the first IC (inverse relationship) and the URA value (direct relationship). Both predictive factors of treatment efficacy were found to be independent. Detrusor overactivity plays an important role in postoperative OAB, although other urodynamic and clinical factors such as the degree of urethral resistance and abdominal strength may influence this condition. [ABSTRACT FROM AUTHOR]

The current review work studies the adiabatic shear banding (ASB) mechanism in metals and alloys, focusing on its microstructural characteristics, dominant evolution mechanisms and final fracture. An ASB reflects a thermomechanical deformation instability developed under high strain and strain rates, finally leading to dynamic fracture. An ASB initially occurs under severe shear localization, followed by a significant rise in temperature due to high strain rate adiabatic conditions. That temperature increase activates thermal softening and mechanical degradation mechanisms, reacting to strain instability and facilitating micro-voiding, which, through its coalescence, results in cracking failure. This work aims to summarize and review the critical characteristics of an ASB's microstructure and morphology, evolution mechanisms, the propensity of materials against an ASB and fracture mechanisms in order to highlight their stage-by-stage evolution and attribute them a more consecutive behavior rather than an uncontrollable one. In that way, this study focuses on underlining some ASB aspects that remain fuzzy, allowing for further research, such as research on the interaction between thermal and damage softening regarding their contribution to ASB evolution, the conversion of strain energy to internal heat, which proved to be material-dependent instead of constant, and the strain rate sensitivity effect, which also concerns whether the temperature rise reflects a precursor or a result of ASB. Except for conventional metals and alloys like steels (low carbon, stainless, maraging, armox, ultra-high-strength steels, etc.), titanium alloys, aluminum alloys, magnesium alloys, nickel superalloys, uranium alloys, zirconium alloys and pure copper, the ASB propensity of nanocrystalline and ultrafine-grained materials, metallic-laminated composites, bulk metallic glasses and high-entropy alloys is also evaluated. Finally, the need to develop a micro-/macroscopic coupling during the thermomechanical approach to the ASB phenomenon is pointed out, highlighting the interaction between microstructural softening mechanisms and macroscopic mechanical behavior during ASB evolution and fracture. [ABSTRACT FROM AUTHOR]

Microsatellite markers were used for the assessment of genetic diversity and genetic structure in a germplasm collection of yellow mustard, Sinapis alba L. The comprehensive collection of genetic resources represented 187 registered varieties, landraces, and breeding materials. Microsatellites generated 44 polymorphic alleles in 15 loci. Eleven of them were medium to highly polymorphic, and the high levels of observed heterozygosity (0.12–0.83) and Nei's gene diversity index (0.11–0.68) indicated a high level of polymorphism. Based on PCoA and neighbor joining analyses, the genetic resources were divided into two groups. The range of genetic dissimilarity in the analysed collection was in the range of 0.00–1.00. The high level of dissimilarity between the accessions was documented by the high WAM value (33.82%). Bayesian clustering algorithms were performed in the STRUCTURE 2.3.4 software. The number of clusters was estimated at K = 2. The accessions were classified according to Q1/Q2 values. The low average values of the parameters Fst_1 (0.3482), Fst_2 (0.1916), and parameter alpha (0.0602) indicated substantial mating barriers between varieties and reproductive isolation due to the limited exchange of genetic resources between breeders. These results demonstrated the importance of extensive collections of genetic resources for the maintenance of genetic diversity and indicated considerable genetic differentiation among accessions. [ABSTRACT FROM AUTHOR]

Flax is an important cash crop globally with a variety of commercial uses. It has been widely used for fiber, oil, nutrition, feed and in composite materials. Growth regulatory factor (GRF) is a transcription factor family unique to plants, and is involved in regulating many processes of growth and development. Bioinformatics analysis of the GRF family in flax predicted 17 LuGRF genes, which all contained the characteristic QLQ and WRC domains. Equally, 15 of 17 LuGRFs (88%) are predicted to be regulated by lus-miR396 miRNA. Phylogenetic analysis of GRFs from flax and several other well-characterized species defined five clades; LuGRF genes were found in four clades. Most LuGRF gene promoters contained cis-regulatory elements known to be responsive to hormones and stress. The chromosomal locations and collinearity of LuGRF genes were also analyzed. The three-dimensional structure of LuGRF proteins was predicted using homology modeling. The transcript expression data indicated that most LuGRF family members were highly expressed in flax fruit and embryos, whereas LuGRF3, LuGRF12 and LuGRF16 were enriched in response to salt stress. Real-time quantitative fluorescent PCR (qRT-PCR) showed that both LuGRF1 and LuGRF11 were up-regulated under ABA and MeJA stimuli, indicating that these genes were involved in defense. LuGRF1 was demonstrated to be localized to the nucleus as expected for a transcription factor. These results provide a basis for further exploration of the molecular mechanism of LuGRF gene function and obtaining improved flax breeding lines. [ABSTRACT FROM AUTHOR]

Acute lung injury (ALI) is characterized by endothelial barrier disruption and associated inflammatory responses, and transient receptor potential cation channel 6 (TRPC6)—mediated Ca2+ influx is critical for endothelial hyperpermeability. In this study, we investigated the role of TRPC6 in LPS—induced ALI, analyzed gene expression in WT and TRPC6-/- lungs using RNA sequencing, and explored the effects of TRPC6 in the LPS—induced hyperpermeability in human umbilical vein endothelial cells (HUVECs) to elucidate the underlying mechanisms. Intratracheal instillation of LPS caused edema in the mouse lungs. Deletion of TRPC6 reduced LPS—induced lung edema and decreased cell infiltration. RNA sequencing analysis suggested that downregulated cell adhesion molecules in TRPC6-/- lungs may be responsible for their resistance to LPS—induced injury. In addition, downregulation of TRPC6 significantly alleviated the LPS—induced decrease in eNOS expression in lung tissue as well as in HUVECs. Moreover, inhibition of TRPC6 with the channel antagonist larixyl led to a decrease in LPS—induced hyperpermeability and ROS production in HUVECs, which could be reversed by blocking eNOS. Our findings suggest that inhibition of TRPC6 ameliorates LPS—induced ALI, which may be achieved by acting on the cell adhesion molecule signaling pathway and participating in the regulation of eNOS levels in endothelial cells. [ABSTRACT FROM AUTHOR]

Simple Summary: This comprehensive review focuses on the role of epigenetics in oral squamous cell carcinoma (OSCC), a prevalent type of oral cancer. The review highlights the importance of epigenetic changes, including DNA methylation, histone modifications, and miRNAs, in OSCC development and progression. Aberrant DNA methylation of tumor suppressor genes (TSGs) promotes tumor growth, making gene methylation patterns potential biomarkers for OSCC detection. Histone modifications, such as acetylation, methylation, phosphorylation, and ubiquitination, impact gene expression by modifying chromatin structure. Dysregulated miRNAs also contribute to OSCC progression. Epigenetic-targeted therapies, such as DNMT and HDAC inhibitors, show promise in modifying abnormal gene expression patterns, potentially leading to improved treatment outcomes for OSCC. However, challenges remain in biomarker identification and developing effective combination treatments. Understanding and targeting these epigenetic processes offer potential strategies to overcome drug resistance and improve OSCC treatment efficacy. Overall, the review highlights the potential of understanding and targeting epigenetic processes to overcome challenges and improve the efficacy of OSCC treatment, offering valuable insights for society in the diagnosis and treatment of oral cancer. Oral squamous cell carcinoma (OSCC) is a prevalent and significant type of oral cancer that has far-reaching health implications worldwide. Epigenetics, a field focused on studying heritable changes in gene expression without modifying DNA sequence, plays a pivotal role in OSCC. Epigenetic changes, encompassing DNA methylation, histone modifications, and miRNAs, exert control over gene activity and cellular characteristics. In OSCC, aberrant DNA methylation of tumor suppressor genes (TSG) leads to their inactivation, subsequently facilitating tumor growth. As a result, distinct patterns of gene methylation hold promise as valuable biomarkers for the detection of OSCC. Oral cancer treatment typically involves surgery, radiation therapy, and chemotherapy, but even with these treatments, cancer cells cannot be effectively targeted and destroyed. Researchers are therefore exploring new methods to target and eliminate cancer cells. One promising approach is the use of epigenetic modifiers, such as DNA methyltransferase (DNMT) inhibitors and histone deacetylase (HDAC) inhibitors, which have been shown to modify abnormal epigenetic patterns in OSCC cells, leading to the reactivation of TSGs and the suppression of oncogenes. As a result, epigenetic-targeted therapies have the potential to directly alter gene expression and minimize side effects. Several studies have explored the efficacy of such therapies in the treatment of OSCC. Although studies have investigated the efficacy of epigenetic therapies, challenges in identifying reliable biomarkers and developing effective combination treatments are acknowledged. Of note, epigenetic mechanisms play a significant role in drug resistance in OSCC and other cancers. Aberrant DNA methylation can silence tumor suppressor genes, while alterations in histone modifications and chromatin remodeling affect gene expression related to drug metabolism and cell survival. Thus, understanding and targeting these epigenetic processes offer potential strategies to overcome drug resistance and improve the efficacy of cancer treatments in OSCC. This comprehensive review focuses on the complex interplay between epigenetic alterations and OSCC cells. This will involve a deep dive into the mechanisms underlying epigenetic modifications and their impact on OSCC, including its initiation, progression, and metastasis. Furthermore, this review will present the role of epigenetics in the treatment and diagnosis of OSCC. [ABSTRACT FROM AUTHOR]

Broccoli (Brassica oleracea L. var. italica) has a large, edible green flower head, which is one of its critical economic traits. A prerequisite of broccoli flower head formation is flower bud differentiation (FBD). Low-temperature treatment is an effective way to induce FBD in broccoli. However, the molecular mechanism underlying low-temperature-induced broccoli FBD remains largely unclear. In this study, using broccoli cultivar Zhongqing 10 as the experimental material, we investigated the effects of low-temperature treatment on FBD by comparing the plants grown at low temperatures (17 °C/9 °C, 16 h/8 h) with the control plants grown under normal temperature conditions (25 °C/17 °C, 16 h/8 h). After 15 days of different temperature treatments, the flower buds of the plants growing under the low-temperature condition started to differentiate. However, the control plants remained in the vegetative growth stage, indicating that low temperature successfully induced flower bud formation. Subsequently, a global transcriptomic analysis was conducted to detect the differentially expressed genes (DEGs) during low-temperature-induced FBD in broccoli. A total of 14 DEGs in five phytohormone signaling pathways, 42 DEGs in nine transcription factor families, and 16 DEGs associated with the floral development pathways were identified. More DEGs were present in the auxin signaling pathway than in other phytohormone signaling pathways, which indicated that the auxin signaling pathway played a critical role in modulating low-temperature-induced FBD in broccoli. Furthermore, four TF classes, including bZIP, GCM domain factors, MADS-box factors, and C2H2 zinc finger factors, possessed enriched motifs, indicating that their closely related DETFs ABI5, HY5L, WRKY11, WRKY15, WRKY22, SOC1, AGL8, FLC, SPL8, and SPL15 may be directly involved in the transcription regulation of broccoli FBD. This study provides an important basis for further investigation of the molecular regulatory mechanism of broccoli flower development under low temperatures. [ABSTRACT FROM AUTHOR]

This study explored the effects of the sowing stage and nitrogen application rate on the grain yield and its allocation of light-temperature resources over a 9-year experiment from 2011 to 2019. Measurement indicators include the effective accumulative temperature on different growth durations, leaf area index (LAI), above-ground biomass production, and harvest index (HI). Methods: A split-plot design was arranged in the treatment, with N supply as the main plot and the sowing stage as the subplot. The main plots consisted of two nitrogen treatments: low nitrogen (LN: 120 kg ha−1) and high nitrogen (HN: 180 kg ha−1). The subplots contained two sowing stages: the early sowing stage (ES) and the late sowing stage (LS). Results: Compared with LNLS, LNES, and HNLS from 2011 to 2019, HNES of HHZ increased the grain yield by 9.5%, 2.5%, and 5.3%, while the difference in grain yield in YY8 was higher than HHZ, especially under HNES. Compared with LNLS, LNES, and HNLS from 2011 to 2019, HNES of HHZ increased the panicle number by 6.0%, 5.9%, and 1.0%, and HNES of YY8 increased by 12.7%, 11.4%, and 3.8%. Compared with HNLS of HHZ, LNES, LNLS, and HNES decreased the spikelets per panicle by 2.3%, 2.9%, and 1.1%, and decreased by 3.5%, 1.9%, and 2.2% in YY8. The early sowing or increasing N supply significantly increased the dry matter accumulated, grain weight, LAI, and HI. The higher grain yield in LNES was more closely related to the average temperature and the number of spikelets per panicle. The grain yield in HNES was more dependent on the effective accumulative temperature. Conclusions: Sowing in mid-May and increasing the N application (180 kg ha−1) are beneficial to the allocation of light temperature and the increase in yield. Therefore, this research provides a theoretical basis for improving rice yield and optimizing the utilization of light-temperature resources in the future. [ABSTRACT FROM AUTHOR]

Oogenesis in insects is a carefully orchestrated process, facilitating the formation of female gametes, which is regulated by multiple extrinsic and intrinsic factors, including ovary serine protease (Osp). As a member of the serine protease family, Osp is a homolog of Nudel, a maternally required protease defining embryonic dorsoventral polarity in Drosophila. In this study, we used CRISPR/Cas9-mediated mutagenesis to functionally characterize Osp in the Asian corn borer, Ostrinia furnacalis, a devastating maize pest throughout Asia and Australia. Building on previous knowledge, we hypothesized that knockout of Osp would disrupt embryonic development in O. furnacalis females. To examine this overarching hypothesis, we (1) cloned and characterized Osp from O. furnacalis, (2) designed target sites on exons 1 and 4 to construct a CRISPR/Cas9 mutagenesis system, and (3) documented phenotypic impacts among O. furnacalis Osp mutants. As a result, we (1) examined the temporal-spatial expression profiles of OfOsp, which has an open reading frame of 5648 bp in length and encodes a protein of 1873 amino acids; (2) established O. furnacalis Osp mutants; and (3) documented recessive, female-specific sterility among OfOspF mutants, including absent or deformed oviducts and reduced fertility in female but not male mutants. Overall, the combined results support our initial hypothesis that Osp is required for embryonic development, specifically ovarian maturation, in O. furnacalis females. Given its substantial impacts on female sterility, Osp provides a potential target for the Sterile Insect Technique (SIT) to manage Lepidoptera pests in general and the species complex Ostrinia in particular. [ABSTRACT FROM AUTHOR]

Simple Summary: According to the stem cell theory of cancer, we should be judicious with immunotherapy in cancer care. When we do not realize that cancer originates from a stem cell and has stem-ness capabilities, immunotherapy could be gratifying for the wrong reasons and challenging with a cautionary tale. A simple way to understand the immune system is to separate the self from non-self. If it is self, the immune system tolerates and spares. If it is non-self, the immune system attacks and destroys. Consequently, if cancer has a stem cell origin and is a stem cell disease, we have a serious problem and a major dilemma with immunotherapy. Because many refractory cancers are more self than non-self, immunotherapy may become an uphill battle and pyrrhic victory in cancer care. In this article, we elucidate cancer immunity. We demonstrate for whom, with what, as well as when and how to apply immunotherapy in cancer care. We illustrate that a stem cell theory of cancer affects our perspectives and narratives of cancer. Without a pertinent theory about cancer's origin and nature, we may unwittingly perform misdirected cancer research and prescribe misguided cancer treatments. In the ongoing saga of immunotherapy, we are at a critical juncture. Because of the allure and promises of immunotherapy, we will be treating more patients not immediately threatened by their cancer. They may have more to lose than to gain, if we have a misconception and if we are on a wrong mission with immunotherapy. According to the stem cell theory of cancer, we should be careful with immunotherapy. When we do not know or realize that cancer originates from a stem cell and has stem-ness capabilities, we may cause more harm than good in some patients and fail to separate the truth from the myth about immunotherapy in cancer care. [ABSTRACT FROM AUTHOR]

Creating new insecticide lead compounds based on the design and modification of natural products is a novel process, of which chlorfenapyr is a typical successful example. Chlorfenapyr is an arylpyrrole derivative that has high biological activity, a wide insecticidal spectrum, and a unique mode of action. For decades, a series of chlorfenapyr derivatives were designed and synthesized continuously, of which many highly active insecticidal compounds were discovered sequentially. However, due to the widespread application of chlorfenapyr and its degradation properties, some adverse effects, including pest resistance and environmental toxicity, occurred. In this review, a brief history of the discovery and development of chlorfenapyr is first introduced. Then, the synthesis, structural modification, structure activity relationship, and action mechanism of arylpyrroles are summarized. However, challenges and limitations still exist, especially in regard to the connection with pest resistance and environmental toxicology, which is discussed at the end of this review. This comprehensive summary of chlorfenapyr further promotes its progress and sensible application for pest management. [ABSTRACT FROM AUTHOR]

The primary innovation of this study lies in the development of an integrated modeling framework that combines downscaled climate projections, land-use-change simulations, and copula-based risk analysis. This framework allows for the assessment of localized sub-seasonal and seasonal drought hazards under future scenarios. The BCC-CSM1-1 climate model projections from the NASA Earth Exchange Global Daily Downscaled Projections (NEX-GDDP) dataset are utilized to represent the future climate for 2025–2060 under RCP 4.5 and 8.5 scenarios. The CA-Markov model is employed to predict future land-use-change distributions. The climate–land use–drought modeling nexus enables the generation of refined spatio-temporal projections of meteorological and hydrological drought risks in the Yellow River Basin (YRB) in the future period of 2025–2060. The results highlight the increased vulnerability of the upper YRB to sub-seasonal meteorological droughts, as well as the heightened sub-seasonal hydrological drought risks in the Loess Plateau. Furthermore, downstream areas experience escalated seasonal hydrological drought exposure due to urbanization. By providing actionable insights into localized future drought patterns, this integrated assessment approach advances preparedness and climate adaptation strategies. The findings of the study enhance our understanding of potential changes in this integral system under the combined pressures of global climate change and land use shifts. [ABSTRACT FROM AUTHOR]

Power transformers are essential for the distribution and transmission of electricity, but they are prone to degradation due to faults early on. Partial Discharge (PD) is the most significant pointer of insulation breakdown in high-voltage apparatus. Dissolved Gas Analysis (DGA) is a commonly used technique for detecting and diagnosing PD. However, DGA data often contain missing values, which can significantly affect the accuracy of PD diagnosis. To mitigate the issues of missing values, this paper proposes using the k-Nearest Neighbors (kNN) technique to impute the missing values in the dataset. Further, it combines kNN with a Support Vector Machine (SVM) to detect the possibility of a PD source in the high-voltage apparatus. The approach was evaluated on a real-world DGA dataset and achieved high classification performance and discriminatory power for distinguishing between PD and non-PD instances. The effectiveness of the missing value imputation technique was evaluated, and the proposed approach demonstrated improved accuracy and precision compared to methods without imputation. The proposed approach offers a current solution for PD analysis in power transformers using DGA data with missing values. [ABSTRACT FROM AUTHOR]