Replacement Strategies Research Articles

Natural occurrence of Wolbachia in Anopheles sp. and Aedes aegypti populations could compromise the success of vector control strategies

Wolbachia is a maternally inherited bacterium commonly detected in approximately 50% of arthropod species, including mosquito vector species. Wolbachia species have been detected in different mosquito vectors, but in most malaria vectors, their occurrence in natural populations were reported 10 years ago. Aedes aegypti, the main vector of dengue virus, is generally uninfected by Wolbachia, and records of infection are rare and only include a few populations. This bacterium impacts the biology, ecology, and evolution of vector populations. Wolbachia has attracted considerable interest because of its role in reducing disease transmission. Moreover, this bacterium is known to manipulate insect reproduction by inducing cytoplasmic incompatibility (CI), thus providing new avenues for vector control strategies. Interestingly, wMel or wAlbB Wolbachia infections in Aedes populations exhibit a stable high frequency in most areas and contribute to the reduction of local dengue transmission. In natural populations of Anopheles, although Wolbachia was found, little is known about its role and effect on Plasmodium. If the incompatible insect technique (IIT) and population replacement strategy resulted in significant decreases in the dengue transmission in endemic countries such as the USA, Taiwan, Australia, and Brazil, natural Wolbachia detection in mosquitoes may pose a threat to these vector control strategies, raising the following question: “Does the natural occurrence of Wolbachia in Anopheles sp. and Ae. aegypti populations compromise the success of vector control strategies? This review presents recent achievements of Wolbachia in natural Anopheles and Ae. aegypti populations in terms of prevalence and provides guidelines for the development of Wolbachia-based vector control.

Minimalist strategy: Conflict delegation and proxy use on transparent battlefields

This article examines contemporary proxy war literature, highlighting a distinguishable pattern in the post-9/11 era. The Deniability Strategy, characterized by indirect intervention and plausible deniability, is juxtaposed with the emerging Minimalist Strategy, which emphasizes transparent state involvement using in-lieu-of actors (ILOA) as proxies. The Minimalist Strategy accounts for modern military and information technology, which reduces the effectiveness of non-attributional tactics. The article identifies three infra-strategies within the Minimalist Strategy: Auxiliary, Replacement, and Front Strategies, each serving different state needs in conflict. Through analysis of the Russo-Ukrainian War, the article demonstrates the viability of the Minimalist Strategy and its implications for future proxy wars, offering a complementary framework to enhance existing scholarship.

Investigation Lubricity Performance of Lubricating Oil Used in Marine Diesel Engine—Fuel Injection Pump

Diesel engines commonly suffer from oil contamination by fuel and other chemicals during operation and maintenance. This contamination alters the oil’s lubricating properties, leading to increased wear, corrosion, and other potential problems. Therefore, it is crucial to understand how oil degrades and becomes contaminated due to different replacement strategies is crucial for both engine operators and manufacturers. This study focuses on the impact of fuel dilution on specific properties of engine oil under real-world operating conditions in a marine diesel engine. Oil samples were collected regularly from the crankcase of the engine fuel injection pump and tribological tests were performed. These tests aimed to assess how marine gas oil affects the oil lubricity performance and how it maintains its useful life. The results confirm that diesel dilution primarily affects the oil lubricating abilities as well as overall performance.

PaIRS-UniNa: A Robust And Accurate Free Tool For Digital Particle Image Velocimetry And Optical Camera Calibration

This contribution presents PaIRS-UniNa (PArticle Image Reconstruction Software – University of Naples “Federico II”), a free software application designed to perform digital particle image velocimetry (PIV). PaIRS-UniNa relies on a powerful C library designed for speed, robustness and accuracy, and a user-friendly graphical interface (Figure 1) running in Python environment on all operating systems, including Windows, Linux and MacOS. At the current stage, it features modules to perform two-component (2C) PIV, stereoscopic PIV and optical camera calibration for multi-camera systems. The processing of PIV and stereoscopic PIV data is based on an iterative image deformation method, which can be customized by the user varying different parameters in such a way to find the best compromise between accuracy and computational speed. These parameters include the size, shape and number of interrogation windows, the number of process iterations and the type of interpolating functions for both image deformation and displacement interpolation (such as bilinear, bicubic, methods based on simplexes or the FFT shift theorem and B-splines of varying orders). Additionally, it is possible to select a range of weighting windows for cross-correlation estimation and velocity field filtering, including rectangular, Blackman, Gaussian, Harris, Hann windows, among others, and several vector validation strategies for outlier detection and replacement. Such a level of customization enables to effectively adjust the modulation transfer function of the PIV process to meet specific application requirements. For the stereoscopic PIV process two different approaches are possible: mapping, which involves applying PIV to de-warped images for 2D-2C displacement fields, and warping, which applies PIV to raw images and combine 3C reconstruction and image dewarping in a single subsequent step. In order to accurately estimate the laser sheet plane location and correct errors due to misalignment and inaccurate displacement vector positions, a disparity correction procedure is also available. The calibration module (CalVi) supports accurate calibration with the camera models mostly used in the PIV community: polynomials, rational functions and the pinhole camera model. Moreover, it supports the integration of the pinhole camera model with a refractive correction model for cylindrical geometries and camera calibration procedures working with unknown positions and orientations of the calibration target. In such a way, the target may be moved by hand without losing accuracy in comparison with a conventional calibration, in which the target is displaced with the aid of translational and rotational stages and knowledge of the target positions is strictly required. Already used in numerous experimental studies by the Experimental Thermo-Fluid Dynamics group of University of Naples “Federico II” and international collaborating groups, PaIRS-UniNa offers a rapid and effective free alternative to commercial PIV software for research and industrial use.

Overview of infectious complications among CAR T- cell therapy recipients.

Chimeric antigen receptor-modified T cell (CAR T-cell) therapy has revolutionized the management of hematological malignancies. In addition to impressive malignancy-related outcomes, CAR T-cell therapy has significant toxicity-related adverse events, including cytokine release syndrome (CRS), immune effector cell associated neurotoxicity syndrome (ICANS), immune effector cell-associated hematotoxicity (ICAHT), and opportunistic infections. Different CAR T-cell targets have different epidemiology and risk factors for infection, and these targets result in different long-term immunodeficiency states due to their distinct on-target and off- tumor effects. These effects are exacerbated by the use of multimodal immunosuppression in the management of CRS and ICANS. The most effective course of action for managing infectious complications involves determining screening, prophylactic, and monitoring strategies and understanding the role of immunoglobulin replacement and re-vaccination strategies. This involves considering the nature of prior immunomodulating therapies, underlying malignancy, the CAR T-cell target, and the development and management of related adverse events. In conclusion, we now have an increasing understanding of infection management for CAR T-cell recipients. As additional effector cells and CAR T-cell targets become available, infection management strategies will continue to evolve.

Examining how media age affects organic matter removal in activated carbon filtration

AbstractWater samples from Waiora Drinking Water Treatment Plant in New Zealand were analyzed using excitation‐emission matrix fluorescence spectroscopy (EEMS) and parallel factor (PARAFAC) analysis to evaluate organic matter removal across the plant. The assessment also included the individual granular activated carbon (GAC) filters since the filters had varying media ages due to partial media replacement over a 10‐month period, presenting a unique assessment opportunity. PARAFAC analysis identified humic‐like, tyrosine‐protein‐like, and tryptophan‐protein‐like components representing fluorescent dissolved organic matter groups. The humic‐like component strongly correlated with total organic carbon (TOC) concentration and removal was significantly influenced by filter media age. However, protein‐like components had minimal TOC correlation and were not effectively removed by the overall plant treatment irrespective of filter media age. These findings have implications for disinfection, taste and odor, and bacterial regrowth and require an improved media replacement strategy. Further study of the protein‐like components is required.

Kanıta Dayalı Bireysel Psikoloji Uygulaması: Örüntü Odaklı Adleryan Terapi

Adlerian Pattern-Focused Therapy is an evidence-based practice based on Individual Psychology. This paper explores the therapy's definition, historical development, the specific processes involved in the therapeutic sessions, and how case conceptualization is approached. Central to this therapy is its goal to transform maladaptive behavioral and cognitive patterns into healthier, adaptive ones. The structured approach encompasses a series of 10 sessions, focusing primarily on the strategy of pattern replacement. Tools like the Patient Health Questionnaire–9, Outcome Rating Scale, and Session Rating Scale play a pivotal role in these counseling sessions, providing measurable outcomes and feedback. While Adlerian Pattern-Focused Therapy has gained notable traction in contemporary mental health discourse, its widespread adoption remains limited within Türkiye. Nevertheless, its evidence-based foundation and pragmatic application render it a promising avenue for enhancing mental health services, not only in Türkiye but also across global contexts. By providing information about this therapy, this study may contribute to its implementation and execution within the scope of mental health services.

Distance-based dynamic caching and replacement strategy in NDN-IoT networks

The amount of data on the Internet has risen noticeably due to the exponential increase in the number of Internet of Things (IoT) devices. Recently, Information-Centric Networking (ICN) is acknowledged as a suitable framework for creating IoT network protocols. One notable feature of ICN is in-network caching, which stores the data packets on intermediate routers/nodes that can be accessed by the subscribers when required. This work proposes a novel Distance-based dynamic caching and replacement strategy (DBDCRS) which involves a light weight calculation that utilizes the request aggregation to find the request weight of the requests stored in Pending interest table (PIT) and node weight of a node based on the distance from the subscriber and IoT publisher to accomplish the caching decision. To eliminate the data redundancy, the scheme caches a particular content on a single node along the specific interest-data path. Additionally, a custom cache replacement policy is introduced which retains the essential contents in cache. Simulation results show that our proposed DBDCRS scheme outperform other in-network cache placement schemes in terms of cache hit ratio, server hit reduction ratio, average response latency, and energy consumption.

Varieties of future‐contingency

AbstractI here examine some of the main contentions of Todd's “The Open Future”. I argue first that a future contingent need not contain locutions such as “will” or cognates and that once this is recognized a trilemma emerges for Todd, putting pressure on him to relinquish one of the book's main aims. Then after noting (Section II) Todd's response to a puzzle A.N. prior had raised for betting on an open‐future style view, I turn (Sections IIIa and IIIb) to his discussion of whether his approach is committed to demanding that ordinary speakers reform their talk about the future. I conclude (Section IV) that the objective of the replacement strategy that Todd recommends could be achieved with less violence to ordinary linguistic practices with the help of a view on which “will” and cognates are polysemous.

Replacement Strategies for Tunneled Hemodialysis Catheters with Complications: A Nationwide Cohort Study.

Tunneled hemodialysis catheters often have infectious or mechanical complications that require unplanned removal and replacement, but the optimal replacement strategy is unknown. This study described the real-world use of two strategies in Australia and compared the survival of replacement catheters inserted by either strategy. Observational data from the REDUCCTION trial, which enrolled a nationwide cohort of 6400 adults who received an incident hemodialysis catheter (2016-2020) was used for this secondary analysis. Tunneled catheters were replaced by either catheter exchange through the existing tunnel tract or removal and replacement through a new tract. The effect of the replacement strategy on the time to catheter removal due to infection or dysfunction was estimated by emulating a hypothetical pragmatic randomized trial among a subset of 434 patients with mechanical tunneled catheter failure. Out of 9974 tunneled hemodialysis catheters inserted during the trial, 380 had infectious and 945 had mechanical complications that required replacement. Almost all infected hemodialysis catheters (97%) were removed and separately replaced through a new tunnel tract, whereas nephrology services differed widely in their replacement practices for catheters with mechanical failure (median = 50% guidewire exchanged, interquartile range= 30%-67%). Service-level differences accounted for 29% of the residual variation after adjusting for patient factors. In the target trial emulation cohort of mechanical failure (N=434 patients), catheter exchange was not associated with lower complication-free survival at one, six, or 12 months (counterfactual survival difference at one month = 5.9%, 95% CI = -2%, 14%). Guidewire exchange for mechanical failure of catheter was not associated with lower catheter survival and may be preferable for patients.

Therapeutic potential of human microglia transplantation in a chimeric model of CSF1R-related leukoencephalopathy

Microglia replacement strategies are increasingly being considered for the treatment of primary microgliopathies like adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP). However, available mouse models fail to recapitulate the diverse neuropathologies and reduced microglia numbers observed in patients. In this study, we generated a xenotolerant mouse model lacking the fms-intronic regulatory element (FIRE) enhancer within Csf1r, which develops nearly all the hallmark pathologies associated with ALSP. Remarkably, transplantation of human induced pluripotent stem cell (iPSC)-derived microglial (iMG) progenitors restores a homeostatic microglial signature and prevents the development of axonal spheroids, white matter abnormalities, reactive astrocytosis, and brain calcifications. Furthermore, transplantation of CRISPR-corrected ALSP-patient-derived iMG reverses pre-existing spheroids, astrogliosis, and calcification pathologies. Together with the accompanying study by Munro and colleagues, our results demonstrate the utility of FIRE mice to model ALSP and provide compelling evidence that iMG transplantation could offer a promising new therapeutic strategy for ALSP and perhaps other microglia-associated neurological disorders.

Evaluation of pilocarpine iontophoresis vs. exercise-induced sweat sodium concentrations at different exercise intensities

Differences between passive versus active sweat sodium concentration ([Na+]) may alter sodium replacement strategies. The primary purpose of this pilot trial was to compare pharmacologically induced sweat [Na+] (passive) with exercise-induced sweat [Na+] (active) at three different exercise intensities. Methods: This was an internal validation trial, reviewed by Wayne State University’s IRB (IRB 23-02-5555). WSU’s IRB determined that this retrospective, observational, data collection did not fall within the scope of human research regulations. As such, fifteen endurance cyclists participated in four cycling trials (different days, separated by a week) at three exercise intensities (50, 75, and 100% of functional threshold power/FTP) for 20 minutes. Sweat was collected prior to each trial via pilocarpine iontophoresis (passively induced sweat). Then, a macroduct™ (Wescor Inc, Logan, UT) sweat collector was affixed to the same forearm (at a different location than the passively induced sweat collection) and the athlete cycled at the given intensity to collect exercise-induced sweat. Sweat samples were analysed for sweat [Na+] immediately (Sweat Chek Conductivity Analyzer, Wescor Inc, Logan UT), which was the main outcome variable. One-way ANOVA was utilised to detect differences in passive and active sweat [Na+] levels across different exercise intensities. Statistical significance was set a priori at P < 0.05. Results: Fifteen highly trained cyclists between 19-45 years (10 male, 5 female, weight 69 ± 9 kg, FTP 4.16 ± 0.56 W/kg, passive sweat [Na+] 55.6 ± 18.5 mmol/L [range 30-89 mmol/L]) completed this trial. No statistically significant differences were noted between pre (passive) to post (active) sweat [Na+] levels during the 50% FTP, 75% FTP, or 100% FTP conditions. However, when assessing exercise-induced sweat [Na+] minus passive-induced sweat [Na+], significant differences were noted between the 50% (−12.4 ± 7.6mmol/L), 75% (1.3 ± 6.2mmol/L) and 100% FTP (7.5 ± 6.8 mmol/L) exercise intensity conditions (P < 0.001; R2 = 0.61). Although sweat rate was different between the 50% (0.62 ± 0.21 L/h), 75% (1.26 ± 0.34 L/h), and 100% FTP (1.89 ± 0.50 L/h) conditions; P < 0.001; R2 = 0.68, there were no significant associations between sweat rate versus sweat [Na+] change except for the 100% FTP condition (R2 = 0.29; P = 0.04). Conclusions: Exercise-induced sweat approximates pharmacologically induced sweat at cycling intensities around 75% FTP, with lower sweat [Na+] readings at lower (50% FTP) intensities and higher sweat [Na+] readings at higher (100% FTP) cycling intensities.

Peripheral expression of brain-penetrant progranulin rescues pathologies in mouse models of frontotemporal lobar degeneration.

Progranulin (PGRN) haploinsufficiency is a major risk factor for frontotemporal lobar degeneration with TAR DNA-binding protein 43 (TDP-43) pathology (FTLD-GRN). Multiple therapeutic strategies are in clinical development to restore PGRN in the CNS, including gene therapy. However, a limitation of current gene therapy approaches aimed to alleviate FTLD-associated pathologies may be their inefficient brain exposure and biodistribution. We therefore developed an adeno-associated virus (AAV) targeting the liver (L) to achieve sustained peripheral expression of a transferrin receptor (TfR) binding, brain-penetrant (b) PGRN variant [AAV(L):bPGRN] in two mouse models of FTLD-GRN, namely, Grn knockout and GrnxTmem106b double knockout mice. This therapeutic strategy avoids potential safety and biodistribution issues of CNS-administered AAVs and maintains sustained concentrations of PGRN in the brain after a single dose. AAV(L):bPGRN treatment reduced several FTLD-GRN-associated pathologies including severe motor function deficits, aberrant TDP-43 phosphorylation, dysfunctional protein degradation, lipid metabolism, gliosis, and neurodegeneration in the brain. The potential translatability of our findings was tested in an in vitro model using cocultured human induced pluripotent stem cell (hiPSC)-derived microglia lacking PGRN and TMEM106B and wild-type hiPSC-derived neurons. As in mice, aberrant TDP-43, lysosomal dysfunction, and neuronal loss were ameliorated after treatment with exogenous TfR-binding protein transport vehicle fused to PGRN (PTV:PGRN). Together, our studies suggest that peripherally administered brain-penetrant PGRN replacement strategies ameliorate FTLD-GRN relevant phenotypes including TDP-43 pathology, neurodegeneration, and behavioral deficits. Our data provide preclinical proof of concept for the use of this AAV platform for treatment of FTLD-GRN and potentially other CNS disorders.

A label-free fluorescence aptamer sensor for point-of-care serotonin detection

Serotonin, a pivotal neurotransmitter regulating various physiological functions, plays a crucial role in disease diagnosis, necessitating precise monitoring of its levels in biological fluids for accurate assessment. Aptamers, known for their high specificity and affinity, have emerged as innovative molecular probes for serotonin analysis. However, existing serotonin aptamer sensing platforms exhibit limitations in terms of portability and rapid detection capabilities. In this study, we introduce a novel, portable, label-free serotonin aptamer sensor utilizing a dye replacement strategy, achieving a short sample-to-result turnaround time and convenient signal readout through a smartphone. The performance of this aptamer sensor was thoroughly assessed across diverse physiological media, demonstrating robust stability in buffer, urine, and serum. Importantly, the detection limit was in the nanomolar range, emphasizing its suitability for the rapid, sensitive, and user-friendly detection of serotonin. This research pioneers an approach for the development of a point-of-care testing (POCT) system for serotonin with practical implications, particularly in resource-limited settings.

A universal solvent-replacement strategy to convert alginate hydrogels into mechanically strong and transparent alginate eutectogels for sensitive strain sensors

Eutectogels based on natural polymers have attracted significant attention as an alternative to easily dehydrated hydrogels and expensive ionogels in the development of flexible strain sensors. The feasibility of employing eutectogels derived from pure natural polymers could be greatly enhanced if their mechanical properties satisfy the requirements of applications. Herein, alginate eutectogels (AEs) with high mechanical properties (tensile strain 217 % and strength 2.26 MPa at fracture), and excellent transparency (over 90 %) are acquired via CaCl2 inducing ionic crosslinking and subsequent deep eutectic solvents (DESs, composed of glycerol and choline chloride) initiating physical crosslinking with a universal solvent- replacement strategy. Among them, sodium alginate, a natural polysaccharide polymer, is selected as representative supporting scaffolds and forms water-insoluble alginate hydrogels (AHs) in CaCl2 coagulation bath. The exchange of DESs with water of AHs not only restrengthens the polymer network by physical crosslinking, but also endows the obtained AEs with long-term solvent retention and high temperature resistance. In addition, the AEs not only have high reliability but also exhibit better linear sensitivity in a wide strain range (0–200 %). In particular, the AEs display multiple sensitivity to stretching, bending, and human motions, demonstrating feasibility as sensitive strain sensors.

Advancing primatology through ethical and scientific perspectives on rhesus monkey (Macaca mulatta) cloning.

A critical turning point was reached in research with the recent success in cloning rhesus monkeys (Macaca mulatta), a major advancement in primatology. This breakthrough marks the beginning of a new age in biomedical research, ushered by improved somatic cell nuclear transfer techniques and creative trophoblast replacement strategies. The successful cloning of rhesus monkeys presents the possibility of producing genetically homogeneous models that are highly advantageous for studying complex biological processes, testing drugs, and researching diseases. However, this achievement raises important ethical questions, particularly regarding animal welfare and the broader ramifications of primate cloning. Approaching the future of primate research with balance is critical, as the scientific world stands on the brink of these revolutionary breakthroughs. This paper aims to summarise the consequences, ethical challenges and possible paths forward in primatology arising from rhesus monkey cloning.

Discovery of oral chemotherapeutic reversal agents for treating multidrug resistance cancer

The major limitation of cancer treatment is multidrug resistance (MDR), which leads to the inactivation of chemotherapeutic drugs and greater than 90% mortality. To solve this ordeal, we applied ligand-based drug design and bioiosteric replacement strategy from an indazole to a pyrazole ring to discover compounds 27 and 43 with good potential for reversing drug resistance in combination with paclitaxel, and their reversal fold values were 53.2 and 51.0 at 5 μM, respectively, against an MDR cancer cell line (KBvin). Based on the PK profile results, we selected compound 43 with a longer half-life for mechanistic and animal experiments. Combination treatment with compound 43 and paclitaxel-induced apoptosis and enhanced subG1 by decreasing mitochondrial membrane potential in KBvin cells. In addition, 43 also inhibited P-gp function by interfering with ATPase activity. Meanwhile, cotreatment with compound 43 and paclitaxel significantly suppressed tumor growth (TGI = 55.5%) at a dose of 200 mg/kg (PO) in a xenograft model and showed no obvious liver or kidney toxicity by H&E staining. Overall, compound 43 may serve as a safe and effective oral resistance reversal chemotherapeutic agent.

A biologically inspired fluorescent probe with enhanced sensing performance for detection of Al3+ based on metal replacement strategy

Salicylaldehyde acyl-hydrazone derivatives have been widely applied to design fluorescent probe for Al3+ detection, but they are always restricted to detect Al3+ in water and actual samples by their poor solubility, low sensitivity, and long response time. Biologically inspired, four salicylaldehyde acyl-hydrazone compounds were designed and synthesized and H4L1 as one of them was selected for in-situ assembly of the ytterbium complex (FP-Al), which has been developed to be a new fluorescent probe for Al3+ detection by the central mental displacement process. The in-situ structure transformation from FP-Al to Al-L was fully characterized by X-ray crystal structure analysis, 1H NMR, FT-IR, and spectral analysis. The intrinsic driving force was explained and elaborated by theoretical calculation. FP-Al showed a significant visible fluorescence enhancement and near-infrared luminescence decreased upon the addition of Al3+. Compared with the ligand H4L1, FP-Al showed enhanced sensing performance during Al3+ detection, especially in improving water solubility and selectivity to Al3+, promoting response speed, reducing background fluorescence and increase cell-membrane permeability. The application of spontaneous metal replacement reaction might be able to provide a new strategy to develop high-performance optical chemo-sensors.

Rationale and design of the early valve replacement in severe asymptomatic aortic stenosis trial

Aortic valve replacement in asymptomatic severe aortic stenosis is controversial. The Early valve replacement in severe ASYmptomatic Aortic Stenosis (EASY-AS) trial aims to determine whether early aortic valve replacement improves clinical outcomes, quality of life and cost-effectiveness compared to a guideline recommended strategy of 'watchful waiting'. In a pragmatic international, open parallel group randomized controlled trial (NCT04204915), 2844 patients with severe aortic stenosis will be randomized 1:1 to either a strategy of early (surgical or transcatheter) aortic valve replacement or aortic valve replacement only if symptoms or impaired left ventricular function develop, or other cardiac surgery becomes nessessary. Exclusion criteria include other severe valvular disease, planned cardiac surgery, ejection fraction <50%, previous aortic valve replacement or life expectancy <2 years. The primary outcome is a composite of cardiovascular mortality or heart failure hospitalization. The primary analysis will be undertaken when 663 primary events have accrued, providing 90% power to detect a reduction in the primary endpoint from 27.7% to 21.6% (hazard ratio 0.75). Secondary endpoints include disability-free survival, days alive and out of hospital, major adverse cardiovascular events and quality of life. Recruitment commenced in March 2020 and is open in the UK, Australia, New Zealand, and Serbia. Feasibility requirements were met in July 2022, and the main phase opened in October 2022, with additional international centers in set-up. The EASY-AS trial will establish whether a strategy of early aortic valve replacement in asymptomatic patients with severe aortic stenosis reduces cardiovascular mortality or heart failure hospitalization and improves other important outcomes.

Velvet Family Protein FpVelB Affects Virulence in Association with Secondary Metabolism in Fusarium pseudograminearum.

Fusarium pseudograminearum causes destructive crown disease in wheat. The velvet protein family is a crucial regulator in development, virulence, and secondary metabolism of fungi. We conducted a functional analysis of FpVelB using a gene replacement strategy. The deletion of FpVelB decreased radial growth and enhanced conidial production compared to that of wild type. Furthermore, FpVelB modulates the fungal responses to abiotic stress through diverse mechanisms. Significantly, virulence decreased after the deletion of FpVelB in both the stem base and head of wheat. Genome-wide gene expression profiling revealed that the regulation of genes by FpVelB is associated with several processes related to the aforementioned phenotype, including "immune", "membrane", and "antioxidant activity", particularly with regard to secondary metabolites. Most importantly, we demonstrated that FpVelB regulates pathogen virulence by influencing deoxynivalenol production and modulating the expression of the PKS11 gene. In conclusion, FpVelB is crucial for plant growth, asexual development, and abiotic stress response and is essential for full virulence via secondary metabolism in F. pseudograminearum.