Population-Based Influenza Vaccine Effectiveness Against Laboratory-Confirmed Influenza Infection in Southern China, 2023-2024 Season.

Background: In China, the 2022-2023 influenza season began earlier and was characterized by higher levels of influenza activity and co-circulation of various respiratory pathogens compared with seasons before the coronavirus disease 2019 (COVID-19) pandemic. Timely and precise estimates of influenza vaccine effectiveness (IVE) against infections can be used to guide public health measures. Methods: A test-negative study was conducted to estimate IVE against laboratory-confirmed influenza using data from the CHinese Electronic health Records Research in Yinzhou (CHERRY) study that prospectively integrated laboratory, vaccination, and health administrative data in Yinzhou, southern China. We included patients who presented influenza-like illness and received nucleic acid tests and/or antigen tests between October 2023 and March 2024. Estimates of IVE were adjusted for age, gender, month of specimen submitted, chronic comorbidities, and hospitalization status. Results: A total of 205 028 participants, including 96 298 influenza cases (7.6% vaccinated) and 108 730 influenza-negative controls (13.4% vaccinated), were eligible for this analysis. The estimates of IVE were 49.4% (95% CI, 47.8%-50.9%), 41.9% (95% CI, 39.8%-44.0%), and 59.9% (95% CI, 57.9%-61.9%) against overall influenza, influenza A, and influenza B, respectively. A lower IVE was observed for individuals aged 7-17 years (38.6%), vs 45.8% for 6 months-6 years, 46.7% for 18-64 years, and 46.1% for ≥65 years. Vaccination reduced the risk of infection by 44.4% among patients with chronic comorbidities. IVEs varied by epidemic weeks with the changes in influenza activity levels and the switch of dominant influenza strains. Conclusions: Influenza vaccination in the 2023-2024 season was protective against infection for the entire population.

FDA Approval Summary: Enfortumab Vedotin Plus Pembrolizumab for Locally Advanced or Metastatic Urothelial Carcinoma.

On December 15, 2023, the FDA granted traditional approval to enfortumab vedotin-ejfv plus pembrolizumab (EV + Pembro) for patients with locally advanced or metastatic urothelial carcinoma (la/mUC). Substantial evidence of effectiveness was obtained from EV-302/KEYNOTE-A39 (NCT04223856), an open-label, randomized, trial evaluating EV + Pembro versus cisplatin or carboplatin plus gemcitabine (Plat + Gem) in patients with previously untreated la/mUC. A total of 886 patients were randomized (1:1) to receive EV 1.25 mg/kg intravenously on days 1 and 8 of each 21-day cycle until disease progression or unacceptable toxicity plus pembrolizumab 200 mg intravenously on day 1 of each 21-day cycle for up to 35 cycles, or Plat + Gem for up to 6 cycles. Dual primary endpoints were progression-free survival (PFS) determined by blinded independent central review and overall survival (OS). Median PFS was 12.5 months (95% CI: 10.4, 16.6) in the EV + Pembro arm and 6.3 months (95% CI: 6.2, 6.5) in the Plat + Gem arm (HR 0.450 [95% CI: 0.377, 0.538]; p-value < 0.0001). Median OS was 31.5 months (95% CI: 25.4, NE) in the EV + Pembro arm and 16.1 months (95% CI: 13.9, 18.3) in the Plat + Gem arm (HR 0.468 [95% CI: 0.376, 0.582]; p-value < 0.0001). The safety profile of EV + pembrolizumab was similar to that observed in EV-103/KEYNOTE-869 in cisplatin-ineligible patients with la/mUC. This article summarizes the data and the FDA thought process supporting traditional approval of EV + pembrolizumab, as well as additional exploratory analyses conducted by FDA.

High temporal resolution prediction of mortality risk for single AML patient via deep learning.

Acute myeloid leukemia (AML) is highly heterogeneous, necessitating personalized prognosis prediction and treatment strategies. Many of the current patient classifications are based on molecular features. Here, we classified the primary AML patients by predicted death risk curves and investigated the survival-directly-related molecular features. We developed a deep learning model to predict 5-year continuous-time survival probabilities for each patient and converted them to death risk curves. This method captured disease progression dynamics with high temporal resolution and identified seven patient groups with distinct risk peak timing. Based on clusters of death risk curves, we identified two robust AML prognostic biomarkers and discovered a subgroup within the European LeukemiaNet (ELN) 2017 Favorable category with an extremely poor prognosis. Additionally, we developed a web tool, De novo AML Prognostic Prediction (DAPP), for individualized prognosis prediction and expression perturbation simulation. This study utilized deep learning-based continuous-time risk modeling coupled with clustering-predicted risk distributions, facilitating dissecting time-specific molecular features of disease progression.

Cell factories for biosynthesis of D-glucaric acid: a fusion of static and dynamic strategies.

D-glucaric acid is an important organic acid with numerous applications in therapy, food, and materials, contributing significantly to its substantial market value. The biosynthesis of D-glucaric acid (GA) from renewable sources such as glucose has garnered significant attention due to its potential for sustainable and cost-effective production. This review summarizes the current understanding of the cell factories for GA production in different chassis strains, from static to dynamic control strategies for regulating their metabolic networks. We highlight recent advances in the optimization of D-glucaric acid biosynthesis, including metabolic dynamic control, alternative feedstocks, metabolic compartments, and so on. Additionally, we compare the differences between different chassis strains and discuss the challenges that each chassis strain must overcome to achieve highly efficient GA productions. In this review, the processes of engineering a desirable cell factory for highly efficient GA production are just like an epitome of metabolic engineering of strains for chemical biosynthesis, inferring general trends for industrial chassis strain developments.

Hierarchical core-shelled CoMo layered double hydroxide@CuCo2S4 nanowire arrays/nickel foam for advanced hybrid supercapacitors.

The development of core-shelled heterostructures with the unique morphology can improve the electrochemical properties of hybrid supercapacitors (HSC). Here, CuCo2S4 nanowire arrays (NWAs) are vertically grown on nickel foam (NF) utilizing hydrothermal synthesis. Then, CoMo-LDH nanosheets are uniformly deposited on the CuCo2S4 NWAs by electrodeposition to obtain the CoMo-LDH@CuCo2S4 NWAs/NF electrode. Due to the superior conductivity of CuCo2S4 (core) and good redox activity of CoMo-LDH (shell), the electrode shows excellent electrochemical properties. The electrode's specific capacity is 1271.4 C g-1 at 1 A g-1, and after 10, 000 cycles, its capacity retention ratio is 92.2 % at 10 A g-1. At a power density of 983.9 W kg-1, the CoMo-LDH@CuCo2S4 NWAs/NF//AC/NF device has an energy density of 52.2 Wh kg-1. This indicates that CoMo-LDH@CuCo2S4/NF has a great potential for supercapacitors.

Association of Iron Therapy with Mortality in Patients with Acute Myocardial Infarction and Iron Deficiency.

Iron deficiency (ID) is common in patients with acute myocardial infarction (AMI). It is unknown whether patients with AMI combined with ID will benefit from iron supplementation therapy. This study aimed to assess the relationship between iron therapy and mortality in AMI patients. Retrospective analysis was performed in subjects screened from the Medical Information Mart in Intensive Care-IV database. The data were obtained from ICU patients admitted to Beth Israel Deaconess Medical Center between 2008 and 2019. The patients were divided into two groups according to iron treatment exposure. Propensity score matching (PSM) was performed in the original cohort at a 1:1 ratio. Univariate and multivariate analyses were performed to adjust for confounding factors. The primary outcome was 28-day mortality. A total of 426 patients were included in this study. After 1:1 PSM, 208 patients were analyzed. Iron treatment was associated with a lower risk of 28-day mortality (9 deaths (8.65%) in the iron treatment group vs. 21 deaths (20.19%) in the non-iron treatment group; HR = 0.39; 95% CI = 0.17-0.89; p = 0.025) and in-hospital mortality (4 deaths (3.85%) in the iron treatment group vs. 12 deaths (11.54%) in the non-iron treatment group; OR, 0.15; 95% CI, 0.03-0.74; p = 0.029). Iron treatment was associated with reduced 28-day mortality in patients with AMI combined with ID. Iron treatment had no significant effect on the length of hospitalization or the length of ICU stay. Prospective studies are needed to verify this conclusion.

Anomalous pulmonary venous drainage due to malposition of septum primum: two case reports and literature review.

Background: Anomalous pulmonary venous connection with malposition of septum primum (MSP) is a rare pediatric cardiovascular malformation. Although reports in the literature are scarce, accurate pre-operative imaging diagnosis is crucial for selecting the appropriate clinical intervention and determining the prognosis for affected children. Case description: In both case reports, the cardiovascular malformations were incidental findings. In the second case, an enlarged cardiac silhouette was observed on chest x-ray due to pneumonia, which was subsequently confirmed by ultrasound. Combined with computed tomography angiography examination, the diagnosis of MSP-type anomalous pulmonary venous connection was established. Conclusions: Comprehensive imaging examinations are essential in reducing misdiagnosis and achieving an accurate diagnosis of MSP-type anomalous pulmonary venous connection. The typical imaging findings for MSP-type anomalous pulmonary venous connection include absence or hypoplasia of the superior limbic band of the septum secundum, leftward displacement of the septum primum, and partial or total pulmonary vein drainage into the anatomical right atrium.

An N-terminal heptad repeat trimer-based peptide fusion inhibitor exhibits potent anti-H1N1 activity.

Influenza viruses are susceptible to seasonal influenza, which has repeatedly caused global pandemics and jeopardized human health. Vaccines are only used as preventive medicine due to the extreme mutability of influenza viruses, and antiviral medication is the most significant clinical treatment to reduce influenza morbidity and mortality. Nevertheless, the clinical application of anti-influenza virus agents is characterized by the narrow therapeutic time window, the susceptibility to drug resistance, and relatively limited effect on severe influenza. Therefore, it is of great significance to develop novel anti-influenza virus drugs to fulfill the urgent clinical needs. Influenza viruses enter host cells through the hemagglutinin (HA) mediated membrane fusion process, and fusion inhibitors function antivirally by blocking hemagglutinin deformation, promising better therapeutic efficacy and resolving drug resistance, with targets different from marketed medicines. Previous studies have shown that unnatural peptides derived from Human Immunodeficiency Virus Type 1 (HIV-1) membrane fusion proteins exhibit anti-HIV-1 activity. Based on the similarity of the membrane fusion protein deformation process between HIV-1 and H1N1, we selected sequences derived from the gp41 subunit in the HIV-1 fusion protein, and then constructed N-trimer spatial structure through inter-helical isopeptide bond modification, to design the novel anti-H1N1 fusion inhibitors. The results showed that the novel peptides could block 6-HB formation during H1N1 membrane fusion procedure, and thus possessed significant anti-H1N1 activity, comparable to the positive control oseltamivir. Our study demonstrates the design viability of peptide fusion inhibitors based on similar membrane fusion processes among viruses, and furthermore provides an important idea for the novel anti-H1N1 inhibitors development.

Chromosome-scale pearl millet genomes reveal CLAMT1b as key determinant of strigolactone pattern and Striga susceptibility.

The yield of pearl millet, a resilient cereal crop crucial for African food security, is severely impacted by the root parasitic weed Striga hermonthica, which requires host-released hormones, called strigolactones (SLs), for seed germination. Herein, we identify four SLs present in the Striga-susceptible line SOSAT-C88-P10 (P10) but absent in the resistant 29Aw (Aw). We generate chromosome-scale genome assemblies, including four gapless chromosomes for each line. The Striga-resistant Aw lacks a 0.7 Mb genome segment containing two putative CARLACTONOIC ACID METHYLTRANSFERASE1 (CLAMT1) genes, which may contribute to SL biosynthesis. Functional assays show that P10CLAMT1b produces the SL-biosynthesis intermediate methyl carlactonoate (MeCLA) and that MeCLA is the precursor of P10-specific SLs. Screening a diverse pearl millet panel confirms the pivotal role of the CLAMT1 section for SL diversity and Striga susceptibility. Our results reveal a reason for Striga susceptibility in pearl millet and pave the way for generating resistant lines through marker-assisted breeding or direct genetic modification.

An acidic polysaccharide promoting GLP-1 secretion from Dendrobium huoshanense protocorm-like bodies: Structure validation and activity exploration.

Glucagon-like peptide-1 (GLP-1) as a multifunctional hormone is secreted mainly from enteroendocrine L-cells, and enhancing its endogenous secretion has potential benefits of regulating glucose homeostasis and controlling body weight gain. In the present study, a novel polysaccharide (h-DHP) with high ability to enhance plasma GLP-1 level in mice was isolated from Dendrobium huoshanense protocorm-like bodies under the guidance of activity evaluation. Structural identification showed that h-DHP was an acidic polysaccharide with the molecular weight of 1.38 × 105 Da, and was composed of galactose, glucose, arabinose and glucuronic acid at a molar ratio of 15.7: 11.2: 4.5: 1.0 with a backbone consisting of →5)-α-L-Araf-(1→, →3)-α-D-Galp-(1→, →6)-α-D-Galp-(1→, →3,6)-α-D-Galp-(1→, →6)-ß-D-Glcp-(1→ and →4,6)-ß-D-Glcp-(1→ along with branches consisting of α-L-Araf-(1→, α-D-Galp-(1→, α-D-GlcAp-(1→, ß-D-Glcp-(1→ and →4)-ß-D-Glcp-(1→. Animal experiments with different administration routes demonstrated that h-DHP-enhanced plasma GLP-1 level was attributed to h-DHP-promoted GLP-1 secretion in the enteroendocrine L-cells, which was supported by h-DHP-enhanced extracellular GLP-1 level in STC-1 cells. Inhibition of adenylate cyclase and phospholipase C indicated that cAMP and cAMP-triggered intracellular Ca2+ increase participated in h-DHP-promoted GLP-1 secretion. These results suggested that h-DHP has the potential of enhancing endogenous GLP-1 level through h-DHP-promoted and cAMP-mediated GLP-1 secretion from enteroendocrine cells.

Multiomics and machine learning-based analysis of pancancer pseudouridine modifications.

Pseudouridine widely affects the stability and function of RNA. However, our knowledge of pseudouridine properties in tumors is incomplete. We systematically analyzed pseudouridine synthases (PUSs) expression, genomic aberrations, and prognostic features in 10907 samples from 33 tumors. We found that the pseudouridine-associated pathway was abnormal in tumors and affected patient prognosis. Dysregulation of the PUSs expression pattern may arise from copy number variation (CNV) mutations and aberrant DNA methylation. Functional enrichment analyses determined that the PUSs expression was closely associated with the MYC, E2F, and MTORC1 signaling pathways. In addition, PUSs are involved in the remodeling of the tumor microenvironment (TME) in solid tumors, such as kidney and lung cancers. Particularly in lung cancer, increased expression of PUSs is accompanied by increased immune checkpoint expression and Treg infiltration. The best signature model based on more than 112 machine learning combinations had good prognostic ability in ACC, DLBC, GBM, KICH, MESO, THYM, TGCT, and PRAD tumors, and is expected to guide immunotherapy for 19 tumor types. The model was also effective in identifying patients with tumors amenable to etoposide, camptothecin, cisplatin, or bexarotene treatment. In conclusion, our work highlights the dysregulated features of PUSs and their role in the TME and patient prognosis, providing an initial molecular basis for future exploration of pseudouridine. Studies targeting pseudouridine are expected to lead to the development of potential diagnostic strategies and the evaluation and improvement of antitumor therapies.

Association between fast eating speed and metabolic dysfunction-associated steatotic liver disease: a multicenter cross-sectional study and meta-analysis.

BACKGROUND: With the fast pace of modern life, people have less time for meals, but few studies have examined the association between the habit of fast eating and metabolic diseases. OBJECTIVE: Combining the results of the current study and the prior ones, we aimed to investigate the possible relationship between fast eating and the risk of metabolic dysfunction-associated steatotic liver disease (MASLD). METHODS: This is a sub-analysis of a multicenter cross-sectional study of 1965 participants investigated the association between fast eating and MASLD in Chinese. Fast eating was defined as meal time less than five minutes and participants were divided into three categories based on their self-reported frequency of fast eating: ≤1 time/month, ≤1 time/week and ≥2 times/week. We further conducted a literature search for available studies published before November, 2023 as well as a meta-analysis to investigate the association between fast eating and MASLD. RESULTS: The proportion of MASLD was 59.3%, 50.5%, and 46.2% in participants with fast eating ≥2 times/week, ≤1 time/week and ≤1 time/month, respectively (P for trend <0.001). The frequency of fast eating was independently associated with risk of MASLD after multiple adjustment for sex, age, demographics, smoking and drinking status, BMI and clinical metabolic parameters (OR, 1.29; 95%CI, 1.09-1.53). Participants who ate fast frequently (≥2 times/week) had 81% higher risk of MASLD (P = 0.011). A meta-analysis of five eligible studies confirmed that frequent fast eating was associated with increased risk of MASLD (pooled OR, 1.22; 95%CI, 1.07-1.39). CONCLUSIONS: Frequent fast eating was associated with an increased risk of MASLD.

Regulation of the hematopoietic stem cell pool by C-Kit-associated trogocytosis.

Hematopoietic stem cells (HSCs) are routinely mobilized from the bone marrow (BM) to the blood circulation for clinical transplantation. However, the precise mechanisms by which individual stem cells exit the marrow are not understood. This study identified cell-extrinsic and molecular determinants of a mobilizable pool of blood-forming stem cells. We found that a subset of HSCs displays macrophage-associated markers on their cell surface. Although fully functional, these HSCs are selectively niche-retained as opposed to stem cells lacking macrophage markers, which exit the BM upon forced mobilization. Macrophage markers on HSCs could be acquired through direct transfer by trogocytosis, regulated by receptor tyrosine-protein kinase C-Kit (CD117), from BM-resident macrophages in mouse and human settings. Our study provides proof of concept that adult stem cells utilize trogocytosis to rapidly establish and activate function-modulating molecular mechanisms.

Prognostic factors in Chinese patients with immunoglobulin light chain amyloidosis: a scoping review and meta-analysis.

OBJECTIVE: This scoping review and meta-analysis aimed to map the evidence regarding prognostic factors in Chinese patients with immunoglobulin light chain (AL) amyloidosis and to identify current research gaps. METHODS: We searched EMBASE, PubMed, and CNKI databases from their inception to 15 September 2021. All studies investigated the association between any prognostic factor and target outcomes, including overall survival (OS), progression-free survival (PFS), and end-stage renal disease (ESRD) in Chinese patients with AL amyloidosis. RESULTS: This scoping review included 52 studies, of which 44 with 6,432 patients contributed to the multivariate prognostic analysis. Multivariate analysis identified a total of 106 factors that correlated with OS, 16 factors with PFS, and 18 factors with ESRD. Five prognostic factors were significantly associated with PFS, and 11 prognostic factors were significantly associated with ESRD. Meta-analysis was only available for prognostic factors without heterogeneous cutoff values, for which hazard ratios (HRs) and their 95% confidence intervals (CIs) were reported. Meta-analysis showed that bone marrow plasma cells (BMCs) (HR: 1.96, 95% CI: 1.21-3.19, p < 0.05) and interventricular septal thickness (IVST) (HR: 1.23, 95% CI: 1.10-1.38, p < 0.05) were independently associated with OS. CONCLUSION: The significant prognostic factors associated with OS, PFS, and ESRD in Chinese patients with AL amyloidosis were related to plasma cell tumor load, biological characteristics, cardiac involvement, renal involvement, population characteristics, and treatment. Further studies should explore additional prognostic factors in patients with AL amyloidosis to develop prognostic models.

The significant prognostic factors associated with OS, PFS, and ESRD in Chinese patients with AL amyloidosis were related to plasma cell tumor load, biological characteristics, cardiac involvement, renal involvement, population characteristics, and treatment.Meta-analysis showed there was a significant association between BMCs or interventricular septal thickness and OS.

Palladium-catalyzed decarboxylative (4 + 3) cycloadditions of bicyclobutanes with 2-alkylidenetrimethylene carbonates for the synthesis of 2-oxabicyclo[4.1.1]octanes.

While cycloaddition reactions of bicyclobutanes (BCBs) have emerged as a potent method for synthesizing (hetero-)bicyclo[n.1.1]alkanes (usually n ≤ 3), their utilization in the synthesis of bicyclo[4.1.1]octane derivatives (BCOs) is still underdeveloped. Here, a palladium-catalyzed formal (4 + 3) reaction of BCBs with 1,4-O/C dipole precursors for the synthesis of oxa-BCOs is described. Unlike previous catalytic polar (3 + X) cycloadditions of BCBs, which are typically achieved through the activation of BCB substrates, the current reaction represents a novel strategy for realizing the cycloaddition of BCBs through the activation of the "X" cycloaddition partner. Moreover, the obtained functionalized oxa-BCOs products can be readily modified through various synthetic transformations.

The SCR-17 and SCR-18 glycans in human complement Factor H enhance its regulatory function.

Human complement factor H (CFH) plays a central role in regulating activated C3b to protect host cells. CFH contain 20 short complement regulator (SCR) domains and eight N-glycosylation sites. The N-terminal SCR domains mediate C3b degradation while the C-terminal CFH domains bind to host cell surfaces to protect these. Our earlier study of Pichia-generated CFH fragments indicated a self-association site at SCR-17/18 that comprises a dimerization site for human factor H. Two N-linked glycans are located on SCR-17 and SCR-18. Here, when we expressed SCR-17/18 without glycans in an E. coli system, analytical ultracentrifugation showed that no dimers were now formed. To investigate this novel finding, full-length CFH and its C-terminal fragments were purified from human plasma and Pichia pastoris respectively, and their glycans were enzymatically removed using PNGase F. Using size-exclusion chromatography, mass spectrometry, and analytical ultracentrifugation, SCR-17/18 from Pichia showed notably less dimer formation without its glycans, confirming that the glycans are necessary for the formation of SCR-17/18 dimers. By surface plasmon resonance, affinity analyses interaction showed decreased binding of deglycosylated full-length CFH to immobilised C3b, showing that CFH glycosylation enhances the key CFH regulation of C3b. We conclude that our study revealed a significant new aspect of CFH regulation based on its glycosylation and its resulting dimerisation.

Enhancing methane production from corn straw via illumination-assisted Fe3O4/g-C3N4 nanocomposite in anaerobic digestion.

This study proposes a novel anaerobic digestion (AD) strategy combining recyclable photoactivated nanomaterials with illumination to enhance electronic transfer for anaerobic microorganisms. Results showed that 7000 Lux illumination increased methane production yield and rate. Incorporating Fe3O4 into graphite carbon nitride (g-C3N4) created a recyclable Fe3O4/g-C3N4 (FG) nanocomposite with improved light absorption, conductivity, redox properties, and methane promotion. The highest methane yield from corn straw was achieved with 7000 Lux and 1.5 g/L FG nanocomposite, 22.6% higher than the dark control. The AD system exhibited increased adenosine triphosphate content, improved redox performance, reduced electron transfer resistance, and higher photocurrent intensity. These improvements bolstered the microorganisms and key genes involved in hydrolysis and acidification, which in turn optimized the acetoclastic pathway. Furthermore, this strategy promoted microorganisms associated with direct interspecies electron transfer, fostering a favorable environment for methanogenic activities, paving the way for future anaerobic reactor developments.

Remediation of AMD based on hydrogeochemical zonation: A typical metal mine in China.

Mining activities disrupt the natural oxidative balance underground, increasing the oxidation of metal sulfides like pyrite. This process leads to the formation of highly acidic mine drainage (AMD) with elevated concentrations of iron (Fe) and sulfate (SO42-). However, generic plugging and backfilling methods, when applied without considering the specific post-mining oxidative environments of different metal mines, often yields minimal results. To clarify the distribution of the underground redox environment after mining of a metal mine in Dexing, China, fifteen water samples from flood and dry periods, as well as fifteen borehole samples, were collected for hydrogeological and chemical analysis. For the first time, the study proposed that the redox zone could be identified and delineated through vertical analysis of water storage media, mineral composition, and hydrochemical characteristics. A hydrogeochemical cause model was constructed, revealing that AMD formation primarily occurs in oxidative and transition zones. Based on the redox zone characteristics of the study area, actual engineering sealing was performed on the oxidation and transition zones of cavity No. 23. As a result, the pH increased from 2.5 before remediation to 4.5, indicating a reduction in acidity. The concentrations of SO42- and Fe significantly decreased, reducing from 1360.0 mg/L and 147.0 mg/L before treatment to 726.0 mg/L and 23.6 mg/L after treatment; the total decrease amounting to 46.6 % and 84.0 %, respectively. The concentrations of Mn and Cu similarly, decreased by 10.7 % and 15.6 %, respectively. This study provides a novel approach and valuable reference for the refined identification and classification of redox zones after metal mine exploitation, as well as for the targeted plugging and treatment of cavities that produce AMD.

What are the main proteins in the hemolymph of Haemaphysalis flava ticks?

Background: Haemaphysalis flava is a notorious parasite for humans and animals worldwide. The organs of H. flava are bathed in hemolymph, which is a freely circulating fluid. Nutrients, immune factors, and waste can be transported to any part of the body via hemolymph. The main soluble components in hemolymph are proteins. However, knowledge of the H. flava proteome is limited. Methods: The hemolymph was collected from fully engorged H. flava ticks by leg amputation. Hemolymph proteins were examined by both blue native polyacrylamide gel electrophoresis (BN-PAGE) and sodium dodecyl sulfate PAGE (SDS-PAGE). Proteins extracted from the gels were further identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results: Two bands (380 and 520 kDa) were separated from tick hemolymph by BN-PAGE and were further separated into four bands (105, 120, 130, and 360 kDa) by SDS-PAGE. LC-MS/MS revealed that seven tick proteins and 13 host proteins were present in the four bands. These tick proteins mainly belonged to the vitellogenin (Vg) family and the α-macroglobulin family members. In silico structural analysis showed that these Vg family members all had common conserved domains, including the N-terminus lipid binding domain (LPD-N), the C-terminus von Willebrand type D domain (vWD), and the domain of unknown function (DUF). Additionally, two of the Vg family proteins were determined to belong to the carrier protein (CP) by analyzing the unique N-terminal amino acid sequences and the cleaving sites. Conclusion: These findings suggest that the Vg family proteins and α-macroglobulin are the primary constituents of the hemolymph in the form of protein complexes. Our results provide a valuable resource for further functional investigations of H. flava hemolymph effectors and may be useful in tick management.