Search Results (1,022)

Seed coat color in peanut (Arachis hypogaea L.) is a critical agronomic trait that affects both nutritional quality and market appeal. In this study, we identified two bHLH transcription factor genes, AhWSC1a and AhWSC1b, homologues of Arabidopsis TRANSPARENT TESTA 8, as indispensable gatekeepers of basal flavonoid pigmentation. QTL-seq analysis of a recombinant inbred line population derived from a black-testa parent (S3) and a white-testa parent (S2) revealed that recessive loss-of-function mutations in both AhWSC1a/1b abolish proanthocyanidin biosynthesis, resulting in a white testa. Integrated metabolomic and transcriptomic profiling confirmed the absence of proanthocyanidins and a strong repression of late anthocyanin-pathway genes (DFR, LDOX) in the mutants. Molecular assays further demonstrated that AhWSC1 physically interacts with the R2R3-MYB regulator AhTc1 to form a functional MBW complex that activates AhDFR and AhLDOX transcription. In this research, we also found that the black testa phenotype may arise from elevated AhTc1 expression associated with a structural variant (SV); however, in the SV background, the introduction of ahwsc1a/1b mutant leads to a significant suppression of AhTc1 expression. Notably, because AhWSC1 is transcriptionally silent in hairy-root systems, overexpression of AhTc1 alone failed to induce these late-stage anthocyanin biosynthesis genes, highlighting AhWSC1 as an indispensable, rate-limiting hub of anthocyanin biosynthesis pathway regulation. Collectively, our findings establish AhWSC1a and AhWSC1b as master regulators of peanut testa pigmentation, elucidate the molecular basis of classical white testa inheritance, and provide genetic targets for precision-breeding of nutritionally enhanced cultivars. Full article

Bacteriophage (phage) therapy, including monophage preparations, phage cocktails, engineered phages, and phage-derived enzymes, has re-emerged as a potential option for difficult-to-treat and biofilm-associated infections in the context of rising antimicrobial resistance. Recent scientific and regulatory developments, such as the 2024 World Health Organization Bacterial Priority Pathogens List and the introduction of the European Pharmacopoeia general chapter 5.31 on phage therapy medicinal products, highlight the growing interest in establishing quality, safety, and governance standards for clinical implementation. This narrative review provides an overview of current clinical applications of phage therapy, drawing on published case reports, case series, early-phase clinical studies, and regulatory experiences across different healthcare settings. Clinical use has been reported in respiratory, urinary tract, musculoskeletal, cardiovascular, and device-associated infections, particularly in cases involving multidrug-resistant pathogens, often in combination with antibiotics. At the same time, the biological characteristics of phages, such as strain specificity, adaptive composition of phage cocktails, and the need for individualized formulations, pose significant regulatory and translational challenges. Access to phage therapy currently relies on heterogeneous regulatory mechanisms, including compassionate use programmes, magistral preparations, named-patient pathways, and other national frameworks. Overall, phage therapy represents a promising strategy for selected infections, but its broader clinical adoption will depend on harmonized regulatory approaches, robust quality standards, and the generation of stronger clinical evidence to support safe and scalable use. Full article

Prostate cancer is one of the most common malignancies in men, and advanced or metastatic disease remains associated with substantial morbidity and mortality. Therapeutic progress in recent years has been driven by the introduction of targeted treatment strategies, notably poly (ADP-ribose) polymerase (PARP) inhibitors, prostate-specific membrane antigen (PSMA)–directed radioligand therapy (RLT), and androgen receptor pathway inhibitors (ARPIs). This review summarizes evidence from phase II and III clinical trials, meta-analyses, and real-world studies evaluating the efficacy, safety, and clinical integration of olaparib, lutetium (¹⁷⁷Lu) vipivotide tetraxetan, and abiraterone in advanced prostate cancer. Emphasis is placed on the practical clinical application of these agents, including patient selection, treatment sequencing, and combination strategies. PARP inhibition with olaparib has demonstrated clear benefits in metastatic castration-resistant prostate cancer (mCRPC) with homologous recombination repair (HRR) mutations, particularly BRCA1/2 alterations. PSMA-directed RLT offers a survival advantage in PSMA-positive mCRPC following AR pathway inhibition, with distinct toxicity considerations that influence patient selection. Abiraterone remains a cornerstone therapy across disease stages and plays an important role both as monotherapy and as a combination partner. Emerging data suggest a potential synergy between PARP inhibitors and AR-targeted agents, while also highlighting the limitations of biomarker-unselected approaches. We conclude that the optimal use of PARP inhibitors, PSMA-targeted RLT, and ARPIs requires a personalized strategy guided by molecular profiling, functional imaging, prior treatment exposure, and safety considerations. This clinically focused overview aims to support evidence-based decision-making in an increasingly complex treatment landscape. Full article

In struggling against invasive species ravaging riverscape ecosystems, gaps in dispersal pathway knowledge and fragmented approaches across scales have long stalled effective riparian management worldwide. To reduce these limitations and enhance invasion management strategies, selecting appropriate alien species as models for in-depth pathway analysis is essential. Alternanthera philoxeroides (Mart.) Griseb. (alligator weed) emerges as an exemplary model species, boasting an invasion record of around 120 years spanning five continents worldwide, supported by genetic evidence of repeated introductions. In addition, the clonal reproduction of A. philoxeroides supports swift establishment, while its amphibious versatility allows occupation of varied riparian environments, with spread driven by natural water-mediated dispersal (hydrochory) and human-related vectors at multiple scales. Thus, leveraging A. philoxeroides, this review proposes a comprehensive multi-scale framework, which integrates monitoring with remote sensing, environmental DNA, Internet of Things, and crowdsourcing for real-time detection. Also, the framework can further integrate, e.g., MaxEnt (Maximum Entropy Model) for climatic suitability and mechanistic simulations of hydrodynamics and human-mediated dispersal to forecast invasion risks. Furthermore, decision-support systems developed from the framework can optimize controls like herbicides and biocontrol, managing uncertainties adaptively. At the global scale, the dispersal paradigm can employ AI-driven knowledge graphs for genetic attribution, multilayer networks, and causal inference to trace pathways and identify disruptions. Based on the premise that our multi-scale framework can bridge invasion ecology with riverscape management using A. philoxeroides as a model, we contend that the implementation of the proposed framework tackles core challenges, such as sampling biases, shifting environmental dynamics, eco–evolutionary interactions using stratified sampling, and adaptive online algorithms. This methodology is purposed to offer scalable tools for other aquatic invasives, evolving management from reactive measures to proactive, network-based approaches that effectively interrupt dispersal routes. Full article

Gene editing technologies have revolutionized therapeutic development, offering potentially curative and preventative strategies for cardiovascular disease (CVD), which remains a leading global cause of morbidity and mortality. This review provides an introduction to the state-of-the-art gene editing tools—including ZFNs, TALENs, CRISPR/Cas9 systems, base editors, and prime editors—and evaluates their application in lipid metabolic pathways central to CVD pathogenesis. Emphasis is placed on targets such as PCSK9, ANGPTL3, CETP, APOC3, ASGR1, LPA, and IDOL, supported by findings from human genetics, preclinical models, and recent first-in-human trials. Emerging delivery vehicles (AAVs, LNPs, lentivirus, virus-like particles) and their translational implications are discussed. The review highlights ongoing clinical trials employing liver-targeted in vivo editing modalities (LivGETx-CVD) and provides insights into challenges in delivery, off-target effects, genotoxicity, and immunogenicity. Collectively, this review captures the rapid progress of LivGETx-CVD from conceptual innovation to clinical application, and positions gene editing as a transformative, single-dose strategy with the potential to redefine prevention and long-term management of dyslipidemia and atherosclerotic cardiovascular disease. Full article

Introduction: A group of approximately 15 Candida species are frequently found to be responsible for human invasive candidiasis, an infection that appears in patients with prolonged hospitalization, particularly in Intensive Care Units, and in immunosuppressed individuals. Given the considerable burden if not rapidly treated, clinicians face diagnostic challenges in distinguishing infection. The objective of this narrative review is to summarize the clinically applicable biomarkers used for invasive candidiasis and to evaluate their performance and create a diagnostic algorithm for clinical practice. Methods: This narrative review was conducted by searching PubMed and Scopus for studies published between 1990 and 2025, using keywords related to invasive candidiasis and non-culture diagnostic biomarkers. Clinical guidelines and consensus documents from major infectious diseases societies were additionally reviewed to supplement. Results: Blood cultures, which are considered the “gold standard” for diagnosis, face important fallouts caused by the limited sensitivity of 50%. Polymerase Chain Reaction assays can identify Candida species at an early stage when compared to blood cultures, demonstrating high specificity that ranges between 91% and 98, due to their high cost, and the limitations regarding only the identification of certain species, their widespread use remains limited. Non-culture serological tests such as mannan, anti-mannan and 1-3-β-D-glucan can detect fungal cell wall components or antibodies directed towards them. These tests have the advantage of being performed directly from blood samples. Reported sensitivity and specificity are 83% and 86% for mannan/anti-mannan, and 73% and 80% for 1-3-β-D-glucan, respectively. They are used for early detection of candidemia in high-risk patients, including immunocompromised individuals. Conclusions: Our report suggests that the traditional “gold standard” for diagnosing invasive candidiasis can be improved by integrating and combining novel biomarkers in the diagnostic pathways, and, thus, potentially reducing the time spent for diagnosing and facilitating early treatment access. Full article

Tandem mass tag (TMT) quantitative proteomic and flavonoid-targeted metabolomic analyses were applied to evaluate the unintended effects of five herbicide-resistant soybean varieties, in addition to three natural genotypic soybean varieties. A total of 65, 29, 56, 38, and 26 differentially expressed proteins (DEPs) were identified in ZLD6010, FD3003, JY2812, ZLD8001, and ZLD2426, respectively, compared with ZH13. Twenty-four and 16 DEPs were identified in ZLD2426 compared with JD12 and KS1, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that most of the DEPs were involved in ribosome, protein processing in the endoplasmic reticulum, and tropane, piperidine, and pyridine alkaloid biosynthesis. Proteomic analysis of the studied soybean seeds revealed no significant changes in herbicide-resistant soybean varieties compared with natural genotypic soybean varieties. Flavonoid-targeted metabolomics analysis detected and quantified 12 flavonoids. Daidzein, genistein/apigenin, taxifolin, and luteolin contents in the herbicide-resistant soybean variety seeds were significantly greater than those in the natural genotypic soybean variety seeds. Their contents in the seeds of three natural genotypic soybean varieties also significantly differed according to pairwise reciprocal comparisons. The introduction of 3-phosphoshikimate 1-carboxyvinyltransferase (EPSPS) might affect flavonoid accumulation of herbicide-resistant soybean varieties. The genetic background of soybean also influences its flavonoid metabolomic profile. Full article

Introduction: Chagas disease, caused by the protozoan Trypanosoma cruzi, remains a major public health concern due to the limited effectiveness of current treatments, especially in the chronic stage. Objective: Here, we wanted to advance a library of 30 N,N′-disubstituted diamines as promising antichagasic agents and gain insight into the mechanism of action. Methods: The library was evaluated for activity against the T. cruzi amastigote stage and trypanocidal efficacy. In addition, selected compounds were tested as potential polyamine transport inhibitors, and a fluorescent analog was employed to investigate compound internalization. Results: Five compounds exhibited potent activity (pIC₅₀ > 6.0), particularly those with short aliphatic linkers (3–6 carbon atoms), suggesting a structure–activity relationship favouring shorter chains. Mechanistic studies showed that compound 3c strongly inhibited polyamine transport, a vital pathway in T. cruzi, though this was not a universal mechanism among active hits, indicating the potential for multiple targets. A fluorescent analog confirmed intracellular uptake in amastigotes but lacked antiparasitic activity, likely due to disrupted pharmacophoric features. Importantly, none of the compounds demonstrated trypanocidal activity in long-term assays, and some showed cytotoxicity, particularly in the benzyloxy-substituted series. Conclusions: These findings position N,N′-disubstituted diamines as a viable scaffold for Chagas disease drug discovery. However, further optimization is required to enhance selectivity, achieve trypanocidal effects, and better understand the underlying mechanisms of action. Full article

Introduction: The appropriate use of antibiotic prophylaxis (AP) in surgical procedures is an ongoing debate. There is a lack of evidence, and urological guidelines provide limited, procedure-specific recommendations. Our aim was to develop a generic model of an audit to define the need for AP in urological procedures, as well as in other surgical specialties. Material and Methods: Based on our experience with the Global Prevalence of Infections in Urology (GPIU) study and a literature review, we defined benchmark standards for 30-day infection rates, including sepsis, and estimated the number of patients needed to be included in a comparative study of AP versus no AP for a surgical procedure within one year. The generic study model was developed during a modified consensus process within the UTISOLVE research group. Urology departments giving and not giving AP were invited to join our development project as an extension of GPIU. Results: Radical prostatectomy was used as a model procedure. Ca. 60 urology centers performing more than 50 radical prostatectomies per year signed up. There was variation in AP practice among sites. Our own review showed that infection rates were ca. 5%, with severe infections, including sepsis, occurring in <0.5% of cases. A sample of 1825 patients would be required to achieve a 95% confidence interval half-width of ±1.0% for general infections. For sepsis, assuming an incidence of 0.5%, a sample of 2124 patients would be needed to reach a 95% confidence interval precision of ±0.30%. Enrollment of 2070 consecutive procedures would be needed to yield precisions of ±0.94% for infection and ±0.30% for sepsis. Based on the number of procedures performed and the number of interested study sites, we agreed on a prospective, multi-center, non-interventional service evaluation, expected to collect standardized data over a 3-month period. The primary outcome was defined as the 30-day incidence of infectious complications. All patients will undergo 30-day post-procedure follow-up through routine clinical care pathways. Conclusions: Our audit model is based on benchmarking of relevant outcomes. It defines how to assess AP in surgical procedures and clarifies a series of issues necessary to defend the status of a generic study model. We regard DEEP-URO to be a comprehensive, multi-center-based initiative that will help balance infection prevention with antimicrobial stewardship and improve the quality of clinical practice and personalized medicine. Full article

Introduction: Overweight and obesity are becoming increasingly prevalent. Incretin-based obesity treatments—glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual glucagon-like peptide-1 receptor/glucose-dependent insulinotropic polypeptide receptor agonists (GIP/GLP-1 RAs or dual agonists)—are a major stride in the evolution of obesity management. However, like weight loss with other means, they are associated with an inadvertent significant loss of lean body mass, including muscle. This has led to a resurgence in research for the preservation of lean body mass, the loss of which occurs with weight loss. The purpose of this narrative review is to discuss the mechanisms involved with lean body loss and capture the research landscape of the different classes of pharmacological agents being developed to address this problem. Methodology: We queried PubMed, Medline, and Scopus for randomized controlled trials and phase II or phase III trials using key words to capture the breath of this topic—obesity, weight loss, muscle loss, lean mass, and muscle preservation. Animal studies were excluded. We analyzed the studies conducted to date. Results: Weight loss, regardless of the method used to achieve it, is inadvertently accompanied by lean body mass loss, to varying degrees. There are several mechanisms that govern the loss of lean body mass and, more specifically, the loss of muscle mass; as such, several classes of medications have been explored, targeting different pathways and receptors—including bimagrumab (activin receptor agonist), tesamorelin (growth hormone releasing hormone agonists), and enobosarm (selective androgen receptor modulator). Most of these drugs are in the early phases of research development, but some show great promise. Conclusion: This narrative review attempts to detail the physiology of muscle mass loss when accompanied by weight loss and identify pharmacological targets that can be utilized to minimize it with mechanisms, effects, side effects, and research developmental progress. Full article

Cross-ecosystem transmission of plant pathogens from crops to natural forests is increasingly recognized as a key factor in disease emergence and biodiversity loss. Agricultural systems serve as major sources of inoculum, with landscape interfaces—such as crop–forest edges, riparian zones, abandoned orchards, and nursery–wildland transitions—acting as active epidemiological gateways. Biological vectors, abiotic dispersal, and human activities collectively enable pathogen movement across these boundaries. Host-range expansion, recombination, and hybridization allow pathogens to infect both cultivated and wild hosts, leading to generalist and recombinant lineages that survive across diverse habitats. In natural ecosystems, such introductions can alter community composition, decrease resilience, and intensify the impacts of climate-driven stress. Advances in molecular diagnostics, genomic surveillance, environmental DNA, and remote sensing–GIS (Geographic Information System) approaches now enable high-resolution detection of pathogen flow across landscapes. Incorporating these tools into interface-focused monitoring frameworks offers a pathway to earlier detection, better risk assessment, and more effective mitigation. A One Health, landscape-based approach that treats agro–wild interfaces as key control points is essential for reducing spillover risk and safeguarding both agricultural productivity and the health of natural forest ecosystems. Full article

The deepening of the “Belt and Road” Initiative urgently requires breaking through the dilemmas of symbolization, unidirectionality, and contextual de-embedding in the export of traditional cultural heritage. This paper takes the 2023 China-Germany “Tracing the Belt and Road” cultural heritage exchange project as the research object, employing a single-case exploratory research method to construct a theoretical model of “narrative carrier innovation—cultural heritage dimension adaptation” aimed at enhancing the effectiveness of cultural heritage dissemination. The study finds that international communication projects for cultural heritage can systematically deconstruct the cultural core (“Dao”) and innovatively adapt modernized, localized dissemination forms familiar to the audiences in the host regions (“Qi”), thereby achieving a paradigm shift from passive introduction to active resonance. The paper specifically elucidates how four types of innovative carriers-digital narrative, public participatory, competitive co-creative, and academic artistic-adapt to the dimensions of historical cognition, aesthetic experience, creative interaction, and value identification in Han Dynasty cultural heritage. This adaptation ultimately forms effective cross-cultural dissemination pathways. This research provides an operable theoretical framework and practical paradigm for “Belt and Road” humanistic exchanges, offering insights for the international dissemination of cultural heritage. Full article

Microplastics (MPs) and nanoplastics (NPs) are widespread environmental contaminants with documented impacts on human health, particularly on the female reproductive system. Defined as polymeric fragments smaller than 5 mm, MPs (typically ranging from 1 µm to 5 mm) and NPs (smaller than 1 µm, often <100 nm) originate either from primary sources—intentionally manufactured for specific industrial applications—or from secondary sources through physical, chemical, or biological degradation of macroplastics. Human exposure occurs via multiple routes, including ingestion, inhalation, dermal absorption, and iatrogenic introduction, with growing evidence that these particles can accumulate in the ovaries, oocytes, and placental tissue. Experimental studies in rodents demonstrate that MPs and NPs induce oxidative stress, trigger inflammatory responses, and promote granulosa cell apoptosis, ultimately diminishing ovarian reserve and impairing folliculogenesis. Clinical and pilot human studies have confirmed the presence of MPs in placentas, umbilical cord blood, and meconium, indicating exposure from the earliest stages of development. Moreover, MPs and NPs may disrupt the hypothalamic–pituitary–ovarian axis, contributing to endocrine dysregulation and hormonal imbalance. Analytical methods such as Fourier-transform infrared spectroscopy, Raman spectroscopy, and scanning electron microscopy enable detection of these particles in biological samples, although methodological standardization remains insufficient. This paper summarizes current evidence on the exposure pathways, toxicological effects, and reproductive consequences of MPs and NPs in women. It further highlights existing research gaps and evaluates available analytical approaches to support future studies and develop strategies aimed at mitigating their detrimental impact on women’s reproductive health and fertility. Full article

Over the past decade, significant progress has been made in the treatment of chronic hepatitis C virus (HCV) infection. The introduction of direct-acting antivirals (DAAs) has revolutionized the treatment of HCV infection, offering nearly 100% efficacy. Furthermore, additional therapeutic regimens with pangenotypic efficacy have been registered. These drugs are also characterized by a few adverse events and good treatment tolerance. As DAA therapy is now accessible to virtually all patients, including those with multimorbidity who often take multiple medications, drug interactions (DDIs) have become a significant clinical challenge. One of the groups of patients who are frequently infected with HCV is those with mental disorders. Due to frequently overlapping metabolic pathways, DDIs can occur, affecting the effectiveness of both psychiatric and antiviral therapy. Knowledge of these interactions is crucial in these cases and influences patient management. This paper discusses the most significant interactions between pangenotypic DAA regimens and psychotropic medications. Full article

Rapid and effective clearance of apoptotic cells, known as efferocytosis, is essential for maintaining tissue homeostasis. Efferocytosis removes apoptotic cells before the occurrence of membrane rupture from which the cell contents, often inflammatory and toxic, are released into surrounding tissues. Through this way, efferocytosis protects the surrounding tissues from toxic enzymes and oxides inside the apoptotic cells as well as from cellular contents such as anti-proteinase and cystatins. Driven by the ongoing advancements in bioinformatics and molecular biology, many researchers have explored the mechanism of efferocytosis and its association with systemic diseases. Multiple studies have demonstrated that impaired efferocytosis mechanisms significantly contribute to the onset and progression of chronic inflammation. The presence of chronic inflammation significantly exacerbates the advancement of cardiovascular diseases, including atherosclerosis, myocardial infarction, heart failure subsequent to myocardial infarction, and even myocarditis. This review aims to provide a brief introduction to the mechanisms involved in cellular efferocytosis, followed by an examination of the molecular and pathway aspects of efferocytosis with the risk of cardiovascular diseases, contributing to the identification of potential therapeutic targets for related diseases. Full article