Functional Response Research Articles

Microplastic ingestion by an aquatic ciliate: Functional response, modulation, and reduced population growth.

Microplastic particles are ubiquitous in aquatic environments and are considered a major threat to the large range of heterotrophic organisms that involuntarily consume them. However, there is current uncertainty around the mechanisms underpinning microplastic uptake by aquatic consumers and the consequences for both the fate of the microplastics and the growth potential of consumer populations. We performed a feeding experiment, exposing a model freshwater ciliate, Tetrahymena pyriformis, to six different microplastic concentrations and measured microplastic uptake and population growth over the course of several generations. Microplastic uptake increased in a saturating fashion with concentration, consistent with a Type II functional response, with a maximum feeding rate of 22 microplastic particles individual-1h-1. Interestingly, microplastic uptake decreased through time and we observed that, after egestion, microplastic particles aggregated, rendering them too large for re-consumption. We built and tested a simulation model which matched rates of microplastic uptake when incorporating functional response parameters and assuming 50% immobilisation of microplastics after egestion. Nevertheless, ciliate population growth was compromised by the presence of microplastics, decreasing by 43% over the full microplastic concentration range. Taken together, our results demonstrate the potential for aquatic ciliates to play an important role in the uptake, transfer, and modification of microplastics in freshwater environments with associated negative impacts on population fitness.

Huang-Lian-Jie-Du decoction ameliorates sepsis through dynamic regulation of immune response and gut microbiota-metabolite axis.

Sepsis remains a life-threatening condition with high mortality rates despite current therapeutic approaches. While Huang-Lian-Jie-Du Decoction (HLJDD), a traditional Chinese medicine formula, has been historically used to treat inflammatory conditions, its therapeutic potential in sepsis and underlying mechanisms remain unexplored. This study investigated HLJDD's comprehensive effects on sepsis pathophysiology using a rat cecal ligation and puncture (CLP) model. HLJDD significantly improved survival rates and demonstrated sophisticated immunomodulatory effects through temporal regulation of the biphasic immune response characteristic of sepsis. In early sepsis, HLJDD suppressed pro-inflammatory cytokines (IL-1β, IL-6) while maintaining defensive inflammation. During late sepsis, it counteracted immunosuppression by reducing IL-10 levels and CD4+CD25+ T cell populations while protecting CD4+ and CD8+ T cells from apoptosis. Notably, HLJDD demonstrated dynamic regulation of the gut microbiota-metabolite axis. It enhanced beneficial bacterial populations (Firmicutes, Lactobacillus) while suppressing potentially pathogenic species (Bacteroides, Parabacteroides). Metabolomic analysis revealed time-dependent modulation of short-chain fatty acids, with elevated levels at 12h followed by strategic reduction at 18-30h, coordinating with changes in SCFA-producing bacteria. This temporal metabolic regulation corresponded with improved intestinal barrier function and balanced immune responses. The study unveils HLJDD's novel mechanism of action through synchronized modulation of immune responses, gut microbiota, and metabolite profiles, presenting a multi-target therapeutic approach that addresses the complex pathophysiology of sepsis. These findings provide a strong foundation for further clinical investigation of HLJDD as an innovative treatment strategy for sepsis.

Huanglian Ganjiang Decoction alleviates DSS-induced colitis through suppressing inflammation and protecting intestinal barrier: From the perspective of disassembling prescriptions.

Huanglian Ganjiang decoction (HGD), which is composed of Chinese medicines with cold, warm, and astringent properties, has demonstrated significant therapeutic efficacy in ulcerative colitis (UC). However, the underlying mechanisms remain unclear, highlighting the need for a multi-faceted investigation. Disassembling prescriptions is a crucial approach for investigating compatibility mechanisms. Analyzing the interactions among Chinese herbs through this method can refine treatment focus and provide novel insights into TCM prescription compatibility research. Therefore, HGD was disassembled into three groups: Cold Medicine Removed (C-R), which warm medicine and astringent medicine are combined; Warm Medicine Removed (W-R), which cold medicine and astringent medicine are combined; and Astringent Medicine Removed (A-R), which cold medicine and warm medicine are combined. To elucidate the therapeutic effects of HGD and its three disassembled prescriptions against UC and to uncover their compatibility mechanisms. The chemical composition of HGD and its disassembled prescriptions (HGDADPs) was qualitatively analyzed using UPLC-MS/MS. 3% dextran sulfate sodium (DSS) was used to induce a UC mouse model. The efficacy in treating UC was evaluated by body weight loss, disease activity index (DAI), colon length, spleen index, thymus index, and histopathological score. A compound-UC target network was established utilizing the network pharmacology. The underlying mechanisms were then investigated by assessing intestinal barrier function and inflammatory responses, as well as the APOC1/P38 MAPK and TLR4/NF-κB signaling pathways through qRT-PCR, Western blotting, and immunofluorescence. Subsequently, anisomycin, a P38 MAPK agonist, was used to confirm whether C-R protects the gut barrier via the APOC1/P38 MAPK pathway. Monophosphoryl lipid A (MPLA), a TLR4 agonist, was employed to investigate whether W-R mediates its anti-inflammatory effects via the TLR4/NF-κB signaling pathway. HGDADPs improved colitis symptoms, increasing ZO-1, Occludin, Claudin-1, and E-cadherin levels while reducing blood cell counts and IL-6 and IL-1β levels. HGD was the most effective in reducing inflammation and repairing the intestinal barrier, with A-R showing similar effects. C-R excelled in repairing the barrier, while W-R was better at reducing inflammation. Network pharmacology indicated C-R inhibits the APOC1/P38 MAPK pathway, and W-R suppresses the TLR4/NF-κB pathway, aligning with Western blotting results. ANI and MPLA reversed the effects of C-R and W-R, respectively. The mechanism by which HGDADPs treat colitis is demonstrated for the first time in our study. In HGD, cold medicine serves as the "Jun", primarily exerting anti-inflammatory effects; Warm medicine acts as the "Chen", mainly protecting the intestinal mucosal barrier; And astringent medicine functions as the "Zuo", playing a synergistic role in the treatment of colitis. In addition, the combination of cold and warm medicines (A-R) was the most crucial for HGD' s compatibility. The pairing of warm and astringent medicines (C-R) significantly contributed to the restoration of the gut barrier and the inhibition of the APOC1/P38 MAPK signaling pathway. Meanwhile, the combination of cold and astringent medicines (W-R) primarily contributed to alleviating inflammation and inhibiting the TLR4/NF-κB pathway.

U2AF1 mutation causes an oxidative stress and DNA repair defect in hematopoietic and leukemic cells.

U2AF1 is a core component of spliceosome and controls cell-fate specific alternative splicing. U2AF1 mutations have been frequently identified in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) patients, and mutations in U2AF1 are associated with poor prognosis in hematopoietic malignant diseases. Here, by forced expression of mutant U2AF1 (U2AF1 S34F) in hematopoietic and leukemic cell lines, we find that U2AF1 S34F causes increased reactive oxygen species (ROS) production. In hematopoietic cell line, a defect in mitochondrial function and DNA damage response deficiency are found in U2AF1 S34F expressing 32D cells. In leukemic cell line Molm13 cells, U2AF1 mutation leads to resistance to DNA damaging agents. Accumulation of DNA damage is also found in U2AF1 S34F expressing leukemic cells when treated with DNA damage agent. Finally, in our established hematopoietic-specific U2af1 S34F knock-in mice model, U2AF1 mutation leads to the development of myelodysplastic/myeloproliferative neoplasm (MDS/MPN) and causes DNA damage accumulation in hematopoietic cells. Our study provides evidence that U2AF1 mutation causes DNA damage response deficiency and DNA damage accumulation in hematopoietic cells, and suggests that mutant U2AF1 induced higher ROS production, resistance to DNA damaging agents and increased genomic instability may contribute to poor prognosis of AML patients with U2AF1 mutations.

Chronic stress induces depression-like behavior in rats through affecting brain mitochondrial function and inflammation.

Chronic stress is involved in pathophysiology of depression, and causes some neurochemical alterations in brain. Both mitochondrial dysfunction and neuroinflammation are implicated in mediating the depression-like behavior. The objectives of present study were, at first, to confirm that chronic unpredictable mild stress (CUMS) induces depression-like behavior and alters mitochondrial function and inflammatory responses within the brain, and then to explore the role of mitochondria in the development of this depression-like behavior. It has been found that CUMS exposure induced depression-like behavior, mitochondrial dysfunction, increased IL-1, IL-6, IFN-γ and TNF-α levels in hippocampus and PFC. Moreover, the level of ATP, the key index of mitochondrial function, was inversely correlated with the levels of proinflammatory cytokine. Intracerebroventricular (ICV) injection of the mitochondrial targeted antioxidant MnTBAP significantly alleviated depression-like behavior in CUMS group. These findings suggested that CUMS results in depression-like behavior, mitochondrial dysfunction as well as neuroinflammation, and mitochondria dysfunction contributes to depression-like behavior caused by CUMS.

Structural and functional responses of soil fungal and bacterial communities to a lithium contamination gradient.

The use of lithium (Li) in decarbonization strategies has positioned it as a central component of modern technological advances, particularly in battery applications. However, the increasing demand for Li has raised concerns about its environmental consequences, which are poorly documented. This study aimed to fill this knowledge gap by examining the impact of Li on soil bacterial/fungal communities. Using a microcosm approach, we explored the impacts of increasing Li concentrations on both microbial community structure and activities. Our results revealed significant changes in bacterial/fungal communities, particularly in the bacterial communities. Most of the indicator species were negatively correlated with the Li gradient, reinforcing the harmful effect of Li. Proteobacteria dominated at low concentrations, whereas Firmicutes were the most abundant at high concentrations. OTUs affiliated with the genus Alicyclobacillus represented >29% of the total affiliated OTUs at the highest Li concentrations. Moreover, Alicyclobacillus fastidiosus showed resilience and specific adaptation to Li. Fungal communities showed less pronounced changes, with Mucoromycota remaining the dominant phylum at all concentrations. Nevertheless, some genera presented correlations with Li concentration, particularly the plant mutualists Leptodontidium, Oidiodendron, and Solicoccozyma. In addition, rapid decreases in several enzymatic activities crucial for the functioning of the carbon, nitrogen and phosphorus cycles were noted. Accordingly, microbial respiration was also impacted by high Li concentrations. Finally, a correlative analysis linked the decreases in enzyme activity to decreases in the abundances of both Proteobacteria and Ascomycota. These results underline the multiple impacts of Li on bacterial/fungal communities, highlighting both structural alterations and changes in microbial activities.

Epoxyeicosatrienoic acids (EETs): A novel class of second messengers of hormonal functional responses.

Epoxyeicosatrienoic acids (EETs) are a class of cytochrome P450 (P450) arachidonic acid (AA) metabolites with diverse biological activities including anti-hypertensive, vasodilatory, angiogenic, and anti-inflammatory properties. While their functions as autocrine and paracrine mediators in cardiovascular and renal systems are well established, their mechanism of action and roles in hormonal functional responses are yet to be fully defined. In this review, we highlight extant evidence of their participation in hormonal transmembrane signal transduction leading to the activation of the ERK1/2 or Akt serine/threonine kinases. Based on studies with EGF (Epidermal Growth Factor), VEGF (Vascular Endothelial Growth Factor) and insulin binding to their membrane bound receptors, we propose to include EETs to the inventory of intracellular mediators associated with the functional responses elicited upon selected hormone/receptor interactions.

Assessing the phytosanitary threats of two non-native crickets under temperature change

Abstract Numerous phytosanitary threats challenge global agriculture, ecosystems, and food security. These threats are exacerbated by non-native species and diseases that are projected to intensify in the future due to global warming and anthropogenic habitat alterations. Assessments of the ecological impacts of overlooked phytosanitary threats are urgently needed under shifting environments. In this study, the potential effects of two non-native Orthoptera species (the house cricket Acheta domesticus and the two-spotted cricket Gryllus bimaculatus) were assessed using functional response analyses. We quantified their potential impacts on agriculturally relevant crops (millet) under increasing temperatures (20 °C, 25 °C, and 30 °C) as individuals and between interspecific pairs. The experiments revealed similar impacts on seeds between both species and across temperatures. Temperature tended to amplify consumption rates and functional responses. The combined interspecific cricket presence generally yielded an additive effect on seeds, with a few instances of synergistic interactions, whereby non-trophic interaction strengths significantly interacted with resource density and temperature. Both species demonstrated remarkable adaptability to varying temperatures, with low mortality accentuating their capacity for impacts under current and future temperatures. This emphasizes the imperative of including both species in phytosanitary assessments. Moreover, population monitoring and the implementation of effective management strategies emerge as pivotal measures for safeguarding agricultural productivity and conserving local ecosystems in the future. The study’s findings thus underscore the potential impact of A. domesticus and G. bimaculatus, particularly in the context of steadily ascending temperatures, to pose a risk to agricultural productivity and food security.

220. A Phase 2 Double-Blind, Placebo-Controlled Study Showing Oral Tableted Norovirus Vaccine VXA-G1.1-NN is Immunogenic, Efficacious, and Reduces Viral Shedding Following Norovirus Challenge

Abstract Background Norovirus (NV) is a leading cause of acute gastroenteritis worldwide. Currently no specific therapy exists for norovirus gastroenteritis (NVG). VXA-G1.1-NN is a nonreplicating adenovirus-vectored thermostable oral NV vaccine shown in clinical trials to be safe, well-tolerated and generates robust serum and mucosal immune responses. This study investigated safety, immunogenicity, and protective efficacy of VXA-G1.1-NN following NV GI.1 challenge.Figure 1.Clinical outcomes (norovirus infection and norovirus gastroenteritis) after norovirus challenge 28 days post vaccination with VXA-G1.1-NN or placebo Methods 165 healthy adults ages 18-49 were randomized 1:1 to a single oral vaccination of VXA-GI.1-NN or placebo. At 28 days post-vaccination, 141 eligible subjects were challenged with 1x106 genomic copies NV GI.1 inoculum. Solicited symptoms of reactogenicity were recorded for 1 week after vaccination and unsolicited adverse events (AEs) through 28 days post challenge. NVG was assessed by incidence of acute gastroenteritis (AGE) with evidence of NV+ infection. NV shedding was evaluated by qPCR in stool and emesis. VP1-specific GI.1 IgA antibody secreting cells (ASC), serum IgA and IgG, and Norovirus Blocking Antibody Assay (NBAA) were assessed. Totality of evidence analysis was used to assess overall vaccine protective effect.Figure 2.Viral shedding in stool by qPCR through 7 days post challenge with GI.1 NN virus inoculum following vaccination with VXA-G1.1-NN or placebo Results VXA-G1.1-NN was safe and well tolerated.VXA-G1.1-NN induced strong serum and cellular immunogenicity with substantial increases in VP1 GI.1- specific ASC and serum antibodies. Serum functional antibody responses, determined by NBAA, were significantly higher in subjects in the vaccine group compared to placebo. VP1 specific IgA was significantly increased in nasal secretions and saliva in the vaccine group. Protective efficacy for prevention of NVG was 21% (p= 0.149) and for NV infection was 29% (p= 0.003). An 85% decrease in geometric mean viral shedding in stool in the VXA-G1.1-NN group was also observed. Totality of evidence analysis for all 6 outcomes simultaneously provided a z-score of 5.56 (p< 0.001), indicating protective benefit of VXA-G1.1-NN.Figure 3.Cellular and serum immune responses following vaccination with VXA-G1.1-NN or placebo Conclusion VXA-G1.1-NN was safe, immunogenic, and reduced both viral shedding and NV infection following NV challenge. VXA-G1.1-NN tableted vaccine may help limit outbreaks by reducing viral shedding. Totality of evidence analysis for treatment effect provided a strong statistical signal supporting a protective effect of VXA-G1.1-NN. Disclosures Susan Greco, MD, MPH, Vaxart, Inc: Stocks/Bonds (Public Company) Becca A. Flitter, PhD, MPH, Vaxart Inc: Stocks/Bonds (Public Company) Lam Nguyen, MD, CVS Health: Stocks/Bonds (Public Company)|Vaxart: Author is either employed and/or has received stock options from Vaxart as part of this work.|Vaxart: Stocks/Bonds (Public Company) Darreann Carmela Hailey, MS, Bionano Genomics: Stocks/Bonds (Public Company)|Vaxart, Inc.: Stocks/Bonds (Public Company) Sean N. Tucker, PhD, Vaxart, Inc.: Grant/Research Support|Vaxart, Inc.: patent|Vaxart, Inc.: Ownership Interest|Vaxart, Inc.: Stocks/Bonds (Public Company) James F. Cummings, MD, VAXART: Stocks/Bonds (Public Company)

Dynamical behavior of stochastic fractional-order predator–prey system with nonlinear functional response and Allee effect

Dynamical behavior of stochastic fractional-order predator–prey system with nonlinear functional response and Allee effect

Trigeminal nerve microstructure is linked with neuroinflammation and brainstem activity in migraine.

Although the pathophysiology of migraine involves a complex ensemble of peripheral and central nervous system changes that remain incompletely understood, the activation and sensitization of the trigeminovascular system is believed to play a major role. However, non-invasive, in vivo neuroimaging studies investigating the underlying neural mechanisms of trigeminal system abnormalities in human migraine patients are limited. Here, we studied 60 patients with migraine (55 females, mean age ± SD: 36.28 ± 11.95 years) and 20 age-/sex-matched healthy controls (19 females, mean age ± SD: 35.45 ± 13.30 years) using ultra-high field 7 Tesla diffusion tensor imaging and functional MRI, as well as PET with the translocator protein ligand [11C]-PBR28. We evaluated MRI diffusivity measures and PET signal at the trigeminal nerve root, as well as brainstem functional MRI response to innocuous, ophthalmic trigeminal nerve territory stimulation. Patients with migraine demonstrated altered white matter microstructure at the trigeminal nerve root (n=53), including reduced fractional anisotropy, compared to healthy controls (n=18). Furthermore, in patients, lower fractional anisotropy was accompanied by 1) higher neuroinflammation (i.e. elevated [11C]-PBR28 PET signal) at the nerve root (n=36) and 2) lower functional MRI activation in an ipsilateral pontine cluster consistent with spinal trigeminal nucleus (n=51). These findings were more robust on the right side, which was consistent with the observation that right headache dominant patients demonstrated higher migraine severity compared to left headache dominant patients in our cohort. Multimodal imaging of the integrated neural mechanisms that characterize migraine underscores the importance of trigeminal system remodeling as both a key aspect of the dynamics underlying migraine pathophysiology and a target for therapeutic interventions.

ИСПОЛЬЗОВАНИЕ БИОКАТАЛИЗА ДЛЯ ПОЛУЧЕНИЯ ПИЩЕВЫХ ИНГРЕДИЕНТОВ НА ОСНОВЕ РАЗЛИЧНЫХ ВИДОВ ЗЕРНОВОГО СЫРЬЯ

The purpose of the work is to develop methods for the effective biotechnological transformation of grain types of raw materials to obtain new food ingredients. The chemical composition of various types of grain raw materials for the main polymers, as well as the quantitative content of phytic acid, was studied. Studies have been carried out on the selection of various enzyme systems for the hydrolysis of grain raw materials, taking into account the use of the enzyme lysate as a functional response in food products. In the course of the work, five different variants of enzymatic treatment were investigated, containing enzymes: proteases, alpha- and glucoamylases, lipases and phytases for the bioconversion of various types of grain. It has been established that the maximum degree of hydrolysis is ensured by the use of a complex that exhibits proteolytic, cellulolytic, phytolytic and lipase hydrolytic abilities. In the process of enzymatic treatment, a maximum increase in low-molecular products of hydrolysis of raw materials was revealed: amino acids – by 20–40 %, reducing substances – by 40–60 % and a decrease in phytic substances – by 20–45 % when exposed to the enzyme system (option 5). The use of this enzyme complex will increase the nutritional and biological value of ingredients, reduce anti-nutritional properties by reducing phytic acid and increasing the availability of trace elements for absorption by the body. Based on the experimental data, a block diagram for obtaining ingredients with improved properties has been developed. The ingredients obtained on the basis of the presented technology can be used in the preparation of food products for functional and preventive purposes.

Impact of Direct Contact and Ingestion of Selected Insecticides on the Predator Harmonia axyridis of Citrus Psyllids

The Asian citrus psyllid, Diaphorina citri, serves as the primary vector for Huanglongbing (HLB) by transmitting Candidatus Liberibacter asiaticus. Lambda-cyhalothrin and thiamethoxam are commonly employed for the control of D. citri. The multicolored Asian lady beetle, or harlequin ladybird, Harmonia axyridis, is an important predator of D. citri in both greenhouse and field settings. The effectiveness of integrated pest management (IPM) relies on the judicious use of selective insecticides that minimize harm to natural enemies. However, the effects of these insecticides on H. axyridis’ predation of D. citri remain thoroughly unexplored. In this study, we assessed the toxicity of lambda-cyhalothrin and thiamethoxam to H. axyridis and examined their impact on the functional response of this predator to D. citri using direct contact exposure methods. We also evaluated the indirect effects on predator voracity through ingestion exposure. Our results demonstrated that exposure to both insecticides at LC50 concentrations significantly prolonged the developmental durations of H. axyridis larval stages. The type-II functional response model effectively described the prey consumption patterns of H. axyridis, revealing a significant reduction in predation capacity across all life stages, particularly among second instar larvae, which experienced reductions of 85.30% and 88.58% following lambda-cyhalothrin and thiamethoxam treatments, respectively. Furthermore, H. axyridis’ predation significantly declined when feeding on D. citri contaminated at LC50 concentrations. These findings indicate that lambda-cyhalothrin and thiamethoxam adversely affect the predation of H. axyridis, both via direct contact and ingestion. Evaluating the potential impacts of these insecticides on H. axyridis is critical for the development of effective IPM strategies targeting D. citri.

Liposomes-Loaded miR-9-5p Alleviated Hypoxia-Ischemia-Induced Mitochondrial Oxidative Stress by Targeting ZBTB20 to Inhibiting Nrf2/Keap1 Interaction in Neonatal Mice.

Aims: Hypoxia ischemia (HI) is a leading cause of cerebral palsy and long-term neurological sequelae in infants. Given that mitochondrial dysfunction in neurons contributes to HI brain damage, this study aimed to investigate the regulatory role of miR-9-5p in mitochondrial function following HI injury. Results: Overexpression of miR-9-5p in HI mice or H2O2-exposed PC12 cells suppressed neuronal injury, associated with increased mitochondrial copy number, normalizing mitochondrial membrane potential, improved nuclear factor-erythroid factor 2-related factor 2 (Nrf2) activation, and downregulation of Keap1. This was mediated, in part, through the ability of this miR-9-5p to bind and regulate the transcriptional activity of zinc finger and BTB domain-containing protein 20 (ZBTB20). Further study suggested that the knockdown of ZBTB20 exerts neuroprotection by inhibiting Nrf2/Keap1 interaction to promote the translocation of Nrf2 from the cytoplasm to the nucleus and the consequent expression of antioxidant proteins. Notably, the protective effects of miR-9-5p overexpression against HI-induced mitochondrial damage were reversed by the Nrf2 inhibitor ML385. Finally, the utilization of liposomes for the delivery of miR-9-5p (miR-9-5p@Lip) presents a promising therapeutic strategy for the treatment of HI injury. Innovation: miR-9-5p is a potential therapeutic agent for ischemic stroke through its modulation of the ZBTB20/Nrf2/Keap1 signaling pathway, influencing mitochondrial function and antioxidant response. Furthermore, the use of liposomal delivery for miR-9-5p offers a promising therapeutic strategy for HI injury. Conclusion: Overexpression of miR-9-5p protects against cerebral HI injury by modulating mitochondrial function through the ZBTB20/Nrf2/Keap1 signaling pathway. Antioxid. Redox Signal. 00, 000-000.

The Diagnostic Assessment of Platelet Function Defects.

Congenital platelet disorders are rare and targeted treatment is usually not possible. Inherited platelet function disorders (iPFDs) can affect surface receptors and multiple platelet responses such as defects of platelet granules, signal transduction, and procoagulant activity. If iPFDs are also associated with a reduced platelet count (thrombocytopenia), it is not uncommon to be misdiagnosed as immune thrombocytopenia. Because the bleeding tendency of the different platelet disorders is variable, a correct diagnosis of the platelet defect based on phenotyping, function analysis, and genotyping is essential, especially in the perioperative setting. In the case of a platelet receptor deficiency, such as Bernard-Soulier syndrome or Glanzmann thrombasthenia, not only the bleeding tendency but also the risk of isoimmunization after platelet transfusions or pregnancy has to be considered. Platelet granule disorders are commonly associated with either intrinsically quantitative or qualitative granule defects due to impaired granulopoiesis, or granule release defects, which can also affect additional signaling pathways. Functional platelet defects require expertise in the clinical bleeding tendency in terms of the disorder when using antiplatelet agents or other medications that affect platelet function. Platelet defects associated with hematological-oncological diseases require comprehensive information about the patient including the clinical implication of the genetic testing. This review focuses on genetics, clinical presentation, and laboratory platelet function analysis of iPFDs with or without reduced platelet number. As platelet defects affecting the cytoskeleton usually show thrombocytopenia, but less impaired or normal platelet functional responses, they are not specifically addressed.

Investigating the impact of synonymous gene recoding on a recombinantly expressed monoclonal antibody under different process parameters

AbstractMonoclonal antibodies (mAbs) are commonly used biologic therapeutics with a wide variety of clinical applications. During the development process, manufacturers consider different production parameters to improve protein yield and achieve appropriate quality of the product. Synonymous gene recoding is one of such attributes that is often considered and implemented to enhance protein expression. However, it has to be used with caution, as it may lead to protein misfolding and ER stress, which complicates efforts to manufacture the desired mAb. To investigate how changing mRNA sequence composition under different protein production parameters might affect the quality of recombinantly produced mAbs, we performed a comprehensive and systematic study assessing impact of synonymous gene recoding (commonly referred to as codon optimization) strategies in the context of varied cell culture parameters on product quality, biochemical and functional characteristics. We report the impact of these parameters on mAb glycosylation profiles, charge variant profile, aggregation, fragmentation, and mAb functional response from combinations of different production parameters. These results uncovered a complex interplay of sequence composition and manufacturing parameters and emphasize the importance of assessing changes to key quality attributes when optimizing mAb manufacturing, including the use of synonymous gene recoding.

MDRM model and its application in hybrid reliability analysis

The high-dimensional model decomposition method is an effective approach for solving the reliability of engineering structures or composite materials with a large number of uncertain parameters. The multiplicative dimensionality reduction method is a high-dimensional model decomposition technique that decomposes a high-dimensional function into a combination of low-dimensional functions and approximates the overall response of the high-dimensional function by solving the responses of these low-dimensional functions. This paper begins by discussing the extrema of functions based on the multiplicative dimensionality reduction method. Then, by combining it with Taylor series expansion, a method for approximating the extremum of a high-dimensional function was proposed. Furthermore, based on the multiplicative dimensionality reduction method, first-order reliability method, and Taylor series expansion, the functional relationship between upper and lower bounds of failure probability and interval variables was derived. Finally, using the algorithm proposed in this paper, the extrema of high-dimensional functions can be calculated to solve the upper and lower bounds of failure probability under random-interval hybrid uncertainty. This paper presents two engineering structures and a numerical example to demonstrate the efficiency and accuracy of the proposed method.

Acupuncture for ankylosing spondylitis: An updated systematic review and meta-analysis

Background: Existing evidence is insufficient to support that acupuncture is effective in treating ankylosing spondylitis (AS) due to the constraints of acupuncture site and manipulation, and relatively straightforward study treatments and indicators. Objective: By incorporating high-quality original literature, this study aims to evaluate the effectiveness of acupuncture for AS and to demonstrate acupuncture as a non-drug supplementary and alternative means for treating AS. Methods: We searched seven databases from their inception to March 31, 2023. Only randomized controlled trials (RCTs) with PEDro score ≥ 6 that compared traditional acupuncture alone or in combination with non-acupuncture therapy on diagnostic AS were considered. The PEDro, ROB2, and STATA tools were used for quality evaluation and statistical analysis. Results: A total of 21 RCTs covering 1884 patients were included. Meta-analysis showed that acupuncture had positive effects on Western medicine effective rate (RR = 1.223, 95%CI: 1.150, 1.301, P < 0.001), traditional Chinese medicine effective rate (RR = 1.175, 95%CI: 1.111, 1.243, P < 0.001), pain score (visual analogue scale, SMD = −0.666, 95%CI: −0.801, −0.531, P < 0.001), spinal function including bath ankylosing spondylitis function index score (SMD = −0.827, 95%CI: −0.945, −0.708, P < 0.001), bath ankylosing spondylitis disease activity index score (SMD = −1.069, 95%CI: −1.190, −0.949, P < 0.001), and bath ankylosing spondylitis metrology index score (SMD = −0.699, 95%CI: −0.887, −0.511, P < 0.001), ankylosing spondylitis quality of life score(SMD = −0.619, 95%CI: −0.917, −0.322, P < 0.001), C-reactive protein levels (SMD = −0.980, 95%CI: −1.092, −0.868, P < 0.001) and erythrocyte sedimentation rate value (SMD = −0.701, 95%CI: −0.810, −0.591, P < 0.001). Conclusion: Though with a high risk of bias, the high-quality studies indicate that acupuncture is a beneficial complementary and alternative therapy for AS patients, as it can reduce pain intensity and improve effective rate, spinal function, and anti-inflammatory response.

Design and optimization of a new NiTi-based shape memory alloy structures for damping applications via additive manufacturing

Abstract Shape Memory Alloys (SMA), such as NiTi-based systems, are functional materials suitable for damping applications due to their pseudoelastic effect. This property allows to obtain simple, lightweight structures capable of absorbing energy through a mechanical hysteresis and able to recover significant deformations. For this reason, SMA are attractive candidates for the development of novel devices in many fields, such as the biomedical one or in aerospace and in automotive. Recently, the development of Additive Manufacturing (AM) of metals has considerably expanded the design and production possibilities of SMA-based devices, potentially overcoming the limited workability of these materials through conventional manufacturing techniques, which is one of the main limitations to their wider adoption. This study presents a preliminary investigation of a NiTi octahedral cell structure fabricated via Laser Powder Bed Fusion (L-PBF) starting from a NiTi powder with Ni content of 50.8 at. %. Cells of different sizes were manufactured and subjected to compression tests up to 0.8 mm displacement in order to evaluate their mechanical and functional performances. Furthermore, a numeric model was used to redesign the geometry in order to optimize the structure's damping capacity. The material input data of the numerical model were obtained from mechanical and thermal analyses on square prisms, which were printed with the primary axis oriented perpendicular and at an inclination of 60° to the building platform. Finally, the optimized cell was manufactured and mechanically tested at different temperatures. The obtained results prove the high efficiency of the structure when used for damping applications and highlight the potential of AM to produce NiTi structures that combine load-bearing capabilities and functional responses.

Unveiling the feeding response of Spodoptera litura to natural host and artificial diet

AbstractBehavioral studies play a crucial role in assessing food utilization in insects. However, there exists a gap in our understanding of the phenotypic plasticity in Spodoptera litura (Fabricius) (Lepidoptera: Noctuidae) and how it impacts their growth, development, and potential for plant damage. This study aimed to investigate the phenotypic plasticity of S. litura, with a focus on its immature stages, and evaluate the consequences of plant damage and pest management. We conducted in vitro experiments using both a standard artificial diet and tobacco (Nicotiana tabacum L., Solanaceae) plants to assess the growth, development, survival, longevity, reproductive capacity, and egg‐laying capability of S. litura larvae and adults. A type II functional response was estimated for all larval instars, utilizing the Likelihood Holling's Disk model, which provided two key coefficients: the search rate (a) and handling time (Th). Our findings revealed that sixth instars exhibited exceptional agility and efficiency, requiring the shortest time to process each milligram of diet compared with other larval stages. Moreover, when larvae were fed on tobacco, they displayed the shortest developmental time and the highest fecundity. This trend extended to pupal weight, pupal duration, pupal emergence, fecundity, and longevity, which were all significantly higher in individuals fed on tobacco. Additionally, S. litura larvae that fed on tobacco exhibited greater efficiency in converting digested food and lower approximate digestibility compared to larvae fed the artificial diet. These results underscore the importance of focusing on the management of fourth, fifth, and sixth instars, which have the potential to cause severe plant damage. Understanding the functional and nutritional response of S. litura larvae enhances the efficiency of integrated pest management strategies (IPM) at early stages while minimizing ecological impact.