Effect of impregnation strategy on structural characteristics of Ce-Mn/Al2O3 and its catalytic ozonation of benzoic acid.

Ce-Mn binary oxides supported on Al2O3 (Ce-Mn/Al2O3), with enhanced activity and stability for catalytic ozonation of benzoic acid, were synthesized using a facile impregnation method. The competitive synergetic effects between cerium and manganese significantly influenced the structural characteristics and catalytic performance of the catalysts depending on the impregnation sequence. Catalysts prepared via the one-step impregnation process exhibited a higher concentration of homogeneous Ce3+ species on the catalyst surface. This led to an increase in surface oxygen vacancies, thereby enhancing catalytic activity. In contrast, the two-step impregnation process resulted in fewer oxygen vacancies due to reduced competitive effects between cerium and manganese. Overall, the optimized Ce-Mn/Al2O3 catalysts demonstrated improved catalytic performance in ozonation reactions, highlighting the importance of impregnation method and calcination conditions in tailoring catalyst properties for enhanced activity and stability. Oxygen vacancies play a crucial role as active sites for ozone adsorption and dissociation into *O2 and *O, facilitated by the reduction of Mn4+ to Mn3+ and the oxidation of Ce3+ to Ce4+. This process forms an electron closed loop that maintains electron balance. The synergistic interactions between cerium and manganese enable rapid electron transfer between Ce4+ and Mn3+, facilitating the regeneration of Ce3+ and Mn4+. Due to the increase of the dual redox conjugate pairs and the surface reactive oxygen species, the catalytic ozonation activity and stability of Ce-Mn/Al2O3 was enhanced.

Race and ethnicity and self-reported racial/ethnic discrimination in breast cancer patient interactions with providers in the Pathways Study.

PURPOSE: To examine the association of race and ethnicity groups with self-reported racial/ethnic discrimination in patient-provider interactions during the diagnosis and treatment for breast cancer. METHODS: We analyzed data from the Pathways Study, a prospective cohort of women diagnosed with breast cancer from 2006-2013 in the Kaiser Permanente Northern California Health Care System. Racial/ethnic discrimination in patient-provider interactions was assessed with two questions from the Interpersonal Processes of Care survey at baseline and 6-months and 24-months post-diagnosis. Logistic regression was performed to compare women who self-identified as racial or ethnic minorities with Non-Hispanic White (NHW) women. Covariates included age at diagnosis, country of origin, education level, income, marital status, and medical provider's race/ethnicity. RESULTS: Our sample included 1836 participants: 1350 NHW women and 486 women (87 Black, 208 Asian American, 153 Hispanic, 38 American Indian/Alaskan Native/Pacific Islander [AIANPI]) from racial or ethnic minority groups. In multivariate analysis, minority women were more likely to report racial/ethnic discrimination in patient-provider interactions than NHW women (adjusted odds ratio [aOR]: 4.73; 95% confidence interval [CI] 3.45-6.50). Specifically, Black women were most likely to self-report racial/ethnic discrimination in patient-provider interactions (aOR: 9.65; 95% CI 5.92-15.70), followed by Asian (aOR: 5.39; 95% CI 3.46-8.40), Hispanic (aOR: 2.55; 95% CI 1.54-4.14), and AIANPI (aOR: 1.74; 95% CI 0.58-4.25) women, compared with NHW women. CONCLUSION: Racial/ethnic discrimination was more likely self-reported from minority women diagnosed with breast cancer. Additional studies are needed to understand the mechanisms and impact of racial/ethnic discrimination in patient-provider interactions on disparities.

Quantification of facial symmetry in orthognathic surgery: A novel approach integrating 3D contour maps and hyper-dimensional computing.

This study aimed to enhance the evaluation of facial symmetry crucial for planning and assessing outcomes of orthognathic surgery (OGS). An innovative approach combining three-dimensional (3D) facial contour lines with hyperdimensional (HD) computing was developed for this purpose. Data were collected using 3D cone beam computed tomography (CBCT) at Chang Gung Memorial Hospital from 2016 to 2021. A comprehensive dataset was compiled, including images from 150 normal individuals and 2500 patients, totaling 5150 preoperative and postoperative facial images. A machine learning model was trained to analyze these images, and 3D contour data were used to create a facial symmetry quantification system with HD computing. Additionally, 3D CBCT data from 200 patients before and after OGS were retrospectively reviewed for clinical application. The developed facial symmetry algorithm demonstrated an overall accuracy of 84.1 %. Postoperative facial symmetry scores improved significantly, with a mean score increase of 53 %, from 2.40 to 3.63. The study culminated in the creation of a web-based system that leverages HD computing and 3D contour mapping to automate facial symmetry assessment. This system offers a user-friendly interface for rapid and accurate evaluations, facilitating better communication between clinicians and patients.

Design and biological evaluation of candidate drugs against zoonotic porcine deltacoronavirus (PDCoV).

Porcine deltacoronavirus (PDCoV) is an emerging swine enteric coronavirus with zoonotic potential. PDCoV spillovers were recently detected in Haitian children with acute undifferentiated febrile illness, underscoring the urgent need to develop anti-PDCoV therapeutics. Coronavirus 3C-like protease (CoV 3CLpro) is essential for viral replication, and therefore provides an attractive target for drugs directed against CoV. Here, we initially evaluated the anti-PDCoV effect of Nirmatrelvir (PF-07321332), an FDA-approved anti-SARS-CoV-2 drug targeting viral 3CLpro. Regrettably, a very limited anti-PDCoV effect was achieved. By analyzing the binding modes of Nirmatrelvir with PDCoV 3CLpro and SARS-CoV-2 3CLpro, we demonstrated that the S2 pocket of 3CLpro is the primary factor underlying the differential inhibitory potency of Nirmatrelvir against different CoV 3CLpros. Based on the specific characteristics of the S2 pocket of PDCoV 3CLpro, four derivatives of Nirmatrelvir (compounds T1-T4) with substituted P2 moieties were synthesized. Compound T1, with an isobutyl at the P2 site, displayed improved anti-PDCoV activity invitro (cell infection model) and invivo (embryonated chicken egg infection model), and therefore is a potential candidate drug to combat PDCoV. Together, our results identify the substrate-binding mode and substrate specificity of PDCoV 3CLpro, providing insight into the optimization of Nirmatrelvir as an antiviral therapeutic agent against PDCoV.

Characterisation of Antimicrobial Resistance in Special-Fed Veal Production Environments.

INTRODUCTION: Antimicrobial resistance (AMR) is one of the leading public health threats globally. AMR genes can be transferred between bacteria through lateral gene transfer, and AMR organisms can spread through environments by contaminated water, agriculture and animals. Thus, widespread environmental dissemination of bacteria and lateral gene transfer facilitate AMR transmission pathways. Farm environments in dairy and calf production are known to harbour AMR bacteria that pose a risk for food contamination and to workers in direct or indirect contact with animals. Escherichia coli is present in farm environments and is known to participate in lateral gene transfer, providing a good marker of resistance genes in each environment. METHODS: In this study, E. coli from nine cohorts of calves was isolated at different time points from nine barns, nine trailers and one slaughterhouse environment in a single special-fed veal calf production facility. The antimicrobial susceptibility to 15 antimicrobials, classified as highly or critically important by the World Health Organization, was characterised for E. coli isolates using Kirby-Bauer disk diffusion. RESULTS: The highest proportion of isolates showing multidrug resistance was present in barn environments (51.7%), where calves were housed from their arrival at < 2 weeks of age until they were transported to slaughter. Additionally, 15 E. coli isolates were resistant to 11 of the 15 antimicrobials tested. Trailer and slaughterhouse environments had greater prevalence of resistance after accommodating calves, including resistance to third-generation cephalosporins. CONCLUSION: These data highlight the importance of calf environments in the dissemination of resistant bacteria and gives insight into where interventions could be most effective in combatting antimicrobial-resistant bacteria that could infect humans and livestock.

Low temperature Cu-Cu direct bonding in air ambient by ultrafast surface grain growth.

Fine-grain copper (Cu) films (grain size: 100.36 nm) with a near-atomic-scale surface (0.39 nm) were electroplated. Without advanced post-surface treatment, Cu-Cu direct bonding can be achieved with present-day fine-grain Cu films at 130℃ in air ambient with a minimum pressure of 1 MPa. The instantaneous growth rate on the first day is 164.29 nm d-1. Also, the average growth rate (∆R/∆t) is evaluated by the present experimental results: (i) 218.185 nm d-1 for the first-day period and (ii) 105.58 nm d-1 during the first 14-day period. Ultrafast grain growth and near-atomic-scale surface facilitate grain boundary motion across the bonding interface, which is the key to achieve Cu-Cu direct bonding at 130℃ in air ambient.

Type 1 diabetes, celiac disease, and autoimmune thyroiditis autoantibodies in population-based type 2 diabetes patients.

Aims: The study aims were to determine autoantibodies associated with type 1 diabetes (T1D), celiac disease (CD) and autoimmune thyroid disease (AITD) in individuals living with type 2 diabetes (T2D) compared to T1D and matched controls. Methods: Individuals with T1D and T2D were randomly identified in health-care registers. Blood was collected through home-capillary sampling and autoantibodies associated with either T1D against glutamic acid decarboxylase (GADA), insulin (IAA), insulinoma antigen-2 (IA-2A), and zinc transporter 8 (ZnT8A), CD against tissue transglutaminase (tTGA) or AITD against thyroid peroxidase (TPOA) were determined in an automated, multiplex Antibody Detection by Agglutination-PCR (ADAP) assay. Results: GADA were detected in 46 % (88/191) of T1D and increased to 6.2 % (23/372) in T2D compared to 2.6 % (7/259) of controls (p = 0.0367). tTGA was low (1.1-2.6 %) and not different in between the study cohorts, nonetheless, in T1D tTGA was associated to islet autoantibodies. TPOA was more frequent in T1D, 27.1 % (53/191), compared to either T2D, 14.8 % (55/372; p = 0.0002) or controls, 14.3 % (37/259) (p = 0.0004). Overall, TPOA was more frequent in GADA positive (34.8 %; 8/23) than negative (13.5 %; 47/349; p = 0.0053) T2D individuals. Conclusion: It's suggested that analyzing GADA and TPOA may refine the autoimmune landscape in individuals clinically classified as T2D.

Diagnosing Maxillary Occlusal Cant with average 3D Skeletofacial Model Template.

BACKGROUND: Diagnosing maxillary occlusal cant involves varied methods, yet classification remains incomplete. This includes determining if the cant results from equal faults on both sides or if one side exhibits overdevelopment while the other underdevelops. This study introduces an innovative average 3D skull template for classifying maxillary occlusal cant instances. METHODS: Sixty adult patients were divided into two groups: 30 with a mesoprosopic facial type and 30 with a leptoprosopic facial type. Using seven pairs of anatomical landmarks (N, Or (L, R), Lo (L, R), Zy (L, R)), the average skull models were aligned and superimposed onto the patients' skull models. Image resizing facilitated optimal registration area fitting. Vertical distances from the U6 mesial buccal cusp tip to the FH plane were measured to analyze occlusal cant, classified into three classes: overdevelopment (Class A), underdevelopment (Class B) and equal fault on both sides (Class C). RESULTS: In the mesoprosopic group, Class B t was most common (40%), followed by Class A (27%) and Class C (33%). In the leptoprosopic facial type group, Class B remained prevalent (50%), followed by Class A (43%) and Class C (7%). Statistical analysis revealed a significant association between facial types and the three classes. CONCLUSIONS: Contrary to expectations, equal fault patterns were not predominant; instead, underdevelopment of the maxilla constituted the majority of occlusal cant cases. Utilizing average 3D skeletofacial models as templates emerges as an effective tool and alternative for diagnosing the instance of maxillary occlusal cant. RISK STUDIES/LEVEL OF EVIDENCE: Therapeutic, II.

Impact of aging on long-term cardiac outcomes of true-lumen recanalized chronic total occlusions in patients with overweight/obesity.

BACKGROUND: Obesity paradox addressing all-cause mortality has been described in several chronic total occlusion (CTO) studies. However, the impact of aging on long-term cardiac events in patients with overweight and obesity with CTO recanalization were less studied. METHODS: A total of 458 patients (64.4 ± 11.3 years, 403 male) with CTO interventions were enrolled. The overweight/obesity group included 311 patients with body mass index (BMI) ≧24 kg/m2 and the non-obesity group included 147. With a median follow-up of 40.0 (17.9-61.4) months, 422 patients with successful true-lumen recanalization were further assessed for target lesion failure [TLF: cardiac death, target vessel myocardial infarction (TVMI), target lesion revascularization (TLR)]. RESULTS: At follow-up, the rates of cardiac death, TVMI, TLR, TLF, and stent thrombosis were 1.9%, 1.9%, 9.2%, 10.7%, and 0.5%, respectively. The TVMI-free survival was borderline better (p = 0.067 by log-rank test) in overweight/obesity than non-obesity group. Among patients <65 years of age, the TVMI-free survival was significantly better in the overweight/obesity group (p = 0.013 compared to non-obesity group by log-rank test). In multivariate Cox regression model, the non-obesity patients younger than 65 years were at a higher risk of TVMI, not only among those <65 years of age (hazard ratio = 11.0, 95% CI = 1.1-106.0) but also among the whole patients (hazard ratio=6.9, 95% CI = 1.4-35.1) with successful CTO recanalization. CONCLUSIONS: For those with true-lumen recanalized CTO, the higher risk of TVMI after successful recanalization was rather evident in patients <65 years of age and without overweight/obesity, suggesting that aging might attenuate prognostic significance of "obesity paradox" for CTO interventions.

Socioeconomic inequalities in uptake of outreach mammography before and after accessibility improvement of Taiwan's national universal breast cancer screening policy.

BACKGROUND: Taiwan implemented the Cancer Screening Quality Improvement Program (CAQIP) in 2010. The program sought to enhance mass breast cancer screening accessibility. This study aimed to examine socioeconomic disparities in outreach screening utilization pre-CAQIP (2005-2009) and post-CAQIP (2010-2014). METHOD: We conducted a nationwide population-based observational study in Taiwan, analyzing four population databases to evaluate socioeconomic disparities among women aged 50 to 69 years undergoing their first mammography screening pre-CAQIP. Multivariate logistic regression was used to examine changes in utilization of outreach screening pre- and post-CAQIP implementation, and to estimate the Slope Index of Inequity (SII) and Relative Index of Inequity (RII) values. RESULTS: Utilization of outreach screening through mobile mammography units (MMUs) increased from 6.12 to 32.87% between the two periods. Following CAQIP, a higher proportion of screened women were older, less educated, and from suburban or rural areas. The SII and RII for age, income, and urbanization levels decreased post-CAQIP. However, regarding education level, SII was - 0.592 and RII was 0.392 in the pre-CAQIP period, increasing to -0.173 and 0.804 post-CAQIP, respectively. CONCLUSIONS: Our study observed that utilization of outreach screening through MMUs increased after CAQIP. The MMUs made outreach screening services more accessible in Taiwan. Expanding outreach screening services and educational programs to promote mammography uptake in local communities could help reduce the potential effect of socioeconomic disparities, and thus may enhance early detection of breast cancer. Further study could focus on the accessibility of outreach screening and breast cancer outcomes.

Generative Adversarial Networks with Radiomics Supervision for Lung Lesion Generation.

Data-driven methods for lesion generation are quickly emerging due to the need for realistic imaging targets for image quality assessment and virtual clinical trials. We proposed a generative adversarial network (GAN) architecture for conditional generation of lung lesions based on user-specified classes of lesion size and solidity. The network consists of two discriminators, one for volumetric lesion data, and one for radiomics features derived from the lesion volume. A Wasserstein loss with gradient penalty was adopted for each discriminator. Training data were drawn from contoured and annotated lesions from a public lung CT database. Four quantitative evaluation methods were devised to assess the network performance: 1) overfitting (similarity between generated and real lesions), 2) diversity (similarity among generated lesions), 3) conditional consistency (capability of generating lesions according to user-specified classes), and 4) similarity in distributions of various lesion properties between the generated and real lesions. Ablation studies were also performed to investigate the importance of individual network component. The proposed network was found to generate lesions that resemble real lesions by visual inspection. Solid lesions are distinct from non-solid ones, and lesion sizes largely correspond to their specified classes. With a classifier trained on real lesions, the classification accuracies of generated and real lesions in both solid and non-solid classes are similar. Radiomics features of generated and real lesions were found to have similar distributions, indicated by the relatively low Kullback-Leibler (KL) divergence values. Furthermore, the correlations between pairwise radiomics features in generated lesions were comparable to those of real lesions. The proposed network presents a promising approach for generating realistic lesions with clinically relevant features crucial for the comprehensive assessment of medical imaging systems.

Role of calcification in J-CTO score: a viewpoint of intraplaque guidewire tracking techniques.

BACKGROUND: As the burden and distribution of calcification within chronic total occlusion (CTO) lesions can be diverse, its effect on CTO recanalization using multiple devices and techniques is debatable. This study investigated the role of calcification in wiring-based intraplaque tracking techniques for CTO recanalization. METHODS: A modified J-CTO score without counting calcification was used to analyze the procedures of 458 consecutive patients who underwent CTO interventions. Failed guidewire crossing and intraplaque tracking were considered procedural failures. Recanalization time details were analyzed for successful procedures. RESULTS: In patients with calcified CTO, the rate of procedural success only significantly declined to be lower than that of noncalcified CTO when the modified J-CTO score was ≥3 (77% vs. 94%, p = 0.008). In 422 patients with successful procedures, the presence of calcification was irrelevant to guidewire crossing time, but was accompanied with longer time from guidewire cross to final angiogram when the modified J-CTO score was 1-2 (53 ± 35 vs. 35 ± 17 [noncalcified] min, p < 0.001). Multivariate analyses showed that calcification was independently associated with procedural failure (odds ratio [OR] = 5.1, 95% confidence interval [CI] = 1.4-18.3) in lesions with modified J-CTO ≥3, and prolonged angioplasty/stenting procedures >60 min (OR = 4.8, 95% CI = 2.2-10.2) in successfully recanalized lesions with modified J-CTO score 1-2. CONCLUSIONS: Using intraplaque guidewire tracking, calcification was unfavorable for very difficult CTO lesions, and caused prolongation of angioplasty time for lesions with moderate complexity. This suggested that the role of calcification in the J-CTO score could be altered when different recanalization techniques were applied for CTO interventions.

Since several commonly used scoring systems for grading the difficulty of CTO-PCI are derived from multiple recanalization techniques and devices, their application should be fundamental. However, most CTO interventionists usually have their own favored recanalization techniques in the real-world. As one of the parameters of J-CTO score, the findings of the study suggest that the interpretation of calcification during CTO-PCI could be altered and should be cautious if different recanalization technique was used.

Self-assembled Fe3O4-COOH @ hydrogen-bonded organic framework composites for magnetic solid-phase extraction of tetracycline in food samples coupled with HPLC determination.

Magnetic solid-phase extraction (MSPE) technology for tetracycline (TCC) was developed by employing the novel and pre-designed Fe3O4-COOH@hydrogen-bonded organic frameworks (HOFs) adsorbents in complex food samples. The HOF shell was grown onto the Fe3O4-COOH core by in-situ self-assembled method. The excellent MSPE performances with less solvent, less adsorbent and time consumption were derived from the hydrogen bonding, π-π and hydrophobic interactions between HOF shell and TCC. Combined with HPLC analysis, Fe3O4@ HOFs adsorbent reduced matrix effects and the established MSPE-HPLC method for TCC gave the linearity of 0.001-6 µg mL-1 with the limit of detection 0.0003 µg mL-1. The recoveries in pure milk, canned yellow peach and carrot were 82.4-103.7 %. The method provided a simple, efficient and dependable alternative to monitor trace TCC antibiotics in food or environmental samples.

Serum ceruloplasmin oxidase activity: A neglected diagnostic biomarker for Wilson disease.

BACKGROUND: Low serum ceruloplasmin concentration is considered robust marker for Wilson disease (WD) screening, measuring serum ceruloplasmin oxidase activity might be an even more valuable diagnostic tool, but it has not been sufficiently studied. METHODS: All patients who were assessed for serum ceruloplasmin oxidase activity between January 1, 2016, and September 2, 2019, were enrolled in this study. The diagnostic performance of serum ceruloplasmin oxidase activity was analyzed using receiver operating characteristic curve analysis (ROC), Spearman's rank correlation, and Mann-Whitney U test. RESULTS: Serum ceruloplasmin oxidase activity was significantly decreased in WD patients (0.87 U/L, IQR 0.61-1.54). The optimal cut-off of serum ceruloplasmin oxidase activity to identified WD is 7 U/L, with sensitivity and specificity of 97.03 % and 98.19 %, respectively. Furthermore, this study revealed a positive correlation between enzymatic and immunoreactive serum ceruloplasmin tests. As primary diagnostic methods, serum ceruloplasmin levels below the diagnostic cut-offs for either the enzymatic or immunoreactive tests were observed in 818 out of 842 WD patients (97.15 %). Compared with the presence of K-F rings in asymptomatic patients, the accuracy of serum ceruloplasmin tests was significantly higher (56.12 % VS 95.08 %). Moreover, the positive rate of cranial MRI in neurological patients was similar to the tests of serum ceruloplasmin (92.91 % VS 97.40 %). Moreover, 71 patients had ambiguous genetic results, complicating the diagnosis. However, serum ceruloplasmin tests successfully identified 65 out of these 71 patients (91.55 %). CONCLUSION: Serum ceruloplasmin oxidase activity has excellent performance in diagnosing WD, which should be widely used as preferred test in WD patients.

Data-driven identification of environmental variables influencing phenotypic plasticity to facilitate breeding for future climates.

Phenotypic plasticity describes a genotype's ability to produce different phenotypes in response to different environments. Breeding crops that exhibit appropriate levels of plasticity for future climates will be crucial to meeting global demand, but knowledge of the critical environmental factors is limited to a handful of well-studied major crops. Using 727 maize (Zea mays L.) hybrids phenotyped for grain yield in 45 environments, we investigated the ability of a genetic algorithm and two other methods to identify environmental determinants of grain yield from a large set of candidate environmental variables constructed using minimal assumptions. The genetic algorithm identified pre- and postanthesis maximum temperature, mid-season solar radiation, and whole season net evapotranspiration as the four most important variables from a candidate set of 9150. Importantly, these four variables are supported by previous literature. After calculating reaction norms for each environmental variable, candidate genes were identified and gene annotations investigated to demonstrate how this method can generate insights into phenotypic plasticity. The genetic algorithm successfully identified known environmental determinants of hybrid maize grain yield. This demonstrates that the methodology could be applied to other less well-studied phenotypes and crops to improve understanding of phenotypic plasticity and facilitate breeding crops for future climates.

Safety of proteasome inhibitor drugs for the treatment of multiple myeloma post-marketing: a pharmacovigilance investigation based on the FDA adverse event reporting system.

BACKGROUND: The use of proteasome inhibitors (PIs), namely Bortezomib and Carfilzomib, revolutionized multiple myeloma (MM) treatment. Understanding their distinct adverse event (AE) profiles aids in tailored treatment plans. RESEARCH DESIGN AND METHODS: We analyzed FDA Adverse Event Reporting System (FAERS) data (Q1 2012-Q4 2023) for Bortezomib and Carfilzomib, utilizing reporting odds ratio (ROR), proportional reporting ratio (PRR), and Bayesian confidence propagation neural network (BCPNN). RESULTS: FAERS yielded 19,720 Bortezomib and 12,252 Carfilzomib AE reports. Males aged 45-65 exhibited higher AE susceptibility. Common AE systems included Infections, Nervous System Disorders, Blood Disorders, General Disorders, Cardiac Disorders, and Renal Disorders. New Bortezomib signals were sepsis and colitis. Carfilzomib exhibited elevated cardiac and renal toxicity but reduced peripheral neuropathy and thrombocytopenia. CONCLUSIONS: FAERS analysis revealed new AE signals (sepsis, colitis) for Bortezomib and highlighted Carfilzomib's heightened cardiac and renal risks compared to Bortezomib. Balancing PIs' benefits and risks is crucial for clinical decision-making.

Galectins induced from hemocytes bridge phosphatidylserine and N-glycosylated Drpr/CED-1 receptor during dendrite pruning.

During neuronal pruning, phagocytes engulf shed cellular debris to avoid inflammation and maintain tissue homeostasis. How phagocytic receptors recognize degenerating neurites had been unclear. Here, we identify two glucosyltransferases Alg8 and Alg10 of the N-glycosylation pathway required for dendrite fragmentation and clearance through genetic screen. The scavenger receptor Draper (Drpr) is N-glycosylated with complex- or hybrid-type N-glycans that interact specifically with galectins. We also identify the galectins Crouching tiger (Ctg) and Hidden dragon (Hdg) that interact with N-glycosylated Drpr and function in dendrite pruning via the Drpr pathway. Ctg and Hdg are required in hemocytes for expression and function, and are induced during dendrite injury to localize to injured dendrites through specific interaction with exposed phosphatidylserine (PS) on the surface membrane of injured dendrites. Thus, the galectins Ctg and Hdg bridge the interaction between PS and N-glycosylated Drpr, leading to the activation of phagocytosis.

Efficacy of a Haemonchus contortus vaccine under field conditions in young alpacas.

Anthelmintic resistance to Haemonchus contortus creates increasing management challenges with small ruminants and camelids. The commercial vaccine, Barbervax®, contains H11 and H-gal-GP antigens, derived from gut mucosal membrane enzymes of H. contortus involved in digesting blood. Antibody neutralization of these antigens causes failure of H. contortus to digest blood, resulting in parasite death. H11 and H-gal-GP are considered "hidden" antigens, meaning the host immune system does not encounter these proteins under natural infection. Therefore, repeat immunization is required to maintain protective humoral responses. One previous study evaluated the safety of Barbervax® in camelids but the efficacy could not be assessed due to lack of successful infection in the controls. The objective of the current study was to evaluate clinical parameters of anemia, fecal egg counts (FECs), and humoral immune responses of healthy alpacas after immunizing with Barbervax® compared to non-vaccinated controls, all under natural environmental exposure on parasite-laden pastures. A crossover-like study was performed where twenty alpacas (298 ± 66 days of age) were assigned to be initially vaccinated with Barbervax® (n=10) or receive no treatment (n=10). Three doses of Barbervax® were administered at three-week intervals. Feces and blood were collected on Day -10, 0, 21, 43, 64, 85, 106, and 135 to evaluate FECs, packed cell volume (PCV), and antibody titers. Each group was kept on separate adjacent pastures. Tracer sheep (n=2 per study group) were introduced on Day 43 for a three-week period to ensure parasite acquisition. For the crossover-like component on Day 85, the initial non-vaccinated group was administered Barbervax® with dosing repeated on Day 106 and 135. Results indicated all initially vaccinated alpacas produced antibody titers to vaccine antigen that corresponded to lower mean FECs compared to the initially non-vaccinated group. A reduced mean FEC in the vaccinate group was observed 21 days after peak antibody titers. Similarly, when pooled vaccinate antibody titers were noted to wane on Day 106, an increase in FEC was observed at the following time point (Day 135). Conclusions from our study support the use of Barbervax® to reduce H. contortus burdens in alpacas. Furthermore, a less than 30-day lag time between antibody titer and resultant effect in FECs was observed. Additional studies assessing the ability of Barbervax® to reduce H. contortus burdens during subsequent grazing seasons would provide even greater information regarding the use of Barbervax® within alpaca herds to modulate H. contortus infections, refugia, and anthelmintic use.

Actin-bundling protein fimbrin serves as a new auxin biosynthesis orchestrator in Arabidopsis root tips.

Plants delicately regulate endogenous auxin levels through the coordination of transport, biosynthesis, and inactivation, which is crucial for growth and development. While it is well-established that the actin cytoskeleton can regulate auxin levels by affecting polar transport, its potential role in auxin biosynthesis has remained largely unexplored. Using LC-MS/MS-based methods combined with fluorescent auxin marker detection, we observed a significant increase in root auxin levels upon deletion of the actin bundling proteins AtFIM4 and AtFIM5. Fluorescent observation, immunoblotting analysis, and biochemical approaches revealed that AtFIM4 and AtFIM5 affect the protein abundance of the key auxin synthesis enzyme YUC8 in roots. AtFIM4 and AtFIM5 regulate the auxin synthesis enzyme YUC8 at the protein level, with its degradation mediated by the 26S proteasome. This regulation modulates auxin synthesis and endogenous auxin levels in roots, consequently impacting root development. Based on these findings, we propose a molecular pathway centered on the 'actin cytoskeleton-26S proteasome-YUC8-auxin' axis that controls auxin levels. Our findings shed light on a new pathway through which plants regulate auxin synthesis. Moreover, this study illuminates a newfound role of the actin cytoskeleton in regulating plant growth and development, particularly through its involvement in maintaining protein homeostasis via the 26S proteasome.

Synthesis of a dendritic cell-targeted self-assembled polymeric nanoparticle for selective delivery of mRNA vaccines to elicit enhanced immune responses.

Recent development of SARS-CoV-2 spike mRNA vaccines to control the pandemic is a breakthrough in the field of vaccine development. mRNA vaccines are generally formulated with lipid nanoparticles (LNPs) which are composed of several lipids with specific ratios; however, they generally lack selective delivery. To develop a selective delivery method for mRNA vaccine formulation, we reported here the synthesis of polymeric nanoparticles (PNPs) composed of a guanidine copolymer containing zwitterionic groups and a dendritic cell (DC)-targeted aryl-trimannoside ligand for encapsulation and selective delivery of an mRNA to dendritic cells. A DC-targeted SARS-CoV-2 spike mRNA-PNP vaccine was shown to elicit a stronger protective immune response in mice compared to the traditional mRNA-LNP vaccine and those without the selective delivery design. It is anticipated that this technology is generally applicable to other mRNA vaccines for DC-targeted delivery with enhanced immune response.