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Embolization microspheres can be used for the embolization of hypervascular malignant tumors of parenchymal organs. They can also be used as an adjuvant therapy for surgery to reduce perioperative bleeding through preoperative intravascular embolization of tumors. This study summarizes the clinical guidelines and consensus on embolization microspheres and introduces the guidance document for embolization microspheres issued by the Food and Drug Administration (FDA). Additionally, this study presents the authors' thoughts on clinical review of embolization microspheres, aiming to provide insights for the clinical evaluation and technical review of such products.

Systemic sclerosis (SSc) is a complex autoimmune disease with clinical symptoms of vascular damage, immune disorders, and fibrosis, presenting significant treatment challenges and limited therapeutic options. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have been demonstrated in numerous studies as more effective than MSCs in treating autoimmune diseases. Recent studies demonstrate that MSC-EVs can significantly ameliorate the symptoms of SSc and mitigate pathological changes such as vascular injury, immune dysregulation, and fibrosis. These findings underscore the promising therapeutic potential of MSC-EVs in the treatment of SSc. MSC-EVs promote angiogenesis, modulate immune dysfunction, and combat fibrosis. This article summarizes the therapeutic applications and possible mechanisms of MSC-EVs for SSc, thereby offering a novel therapeutic direction for the treatment of SSc.

BackgroundIron deficiency and iron deficiency anemia cause a huge disease burden worldwide. Diet is an important factor affecting the iron levels. This study aims to explore the dietary patterns of school-aged children in rural areas of Guangzhou and their association with iron deficiency.MethodsData on dietary surveys, lifestyle, demographic and laboratory tests were gathered from rural school-age children in Guangzhou. Factor analysis was applied to derive dietary patterns. Robust Poisson regression and subgroup analysis were used to analyze the association between dietary patterns and iron deficiency.ResultsA total of 2,530 children and adolescents aged 9–17 years were enrolled. The prevalence of iron deficiency was 13.36%. Four dietary patterns were identified including snack and fast-food pattern, fruit and vegetable pattern, cereal and tuber pattern and meat and offal pattern. Both children and adolescents in the Q4 group (the highest propensity) of snack and fast-food pattern and cereal and tuber pattern had a higher risk of iron deficiency than the Q1 group (the lowest propensity). Both children and adolescents in the Q4 group of meat and offal pattern and fruit and vegetable pattern had a lower risk of iron deficiency than the Q1 group. The results of stratified analysis showed the negative effect of snack and fast-food pattern and the protective benefits of meat and offal pattern are more obvious for boys, and the negative effect of cereal and tuber pattern were obvious for girls. The negative effect or protective benefits of the four dietary patterns were obvious for children aged 9–13.ConclusionFemales, older children, and those with shorter sleep duration are at higher risk of iron deficiency. Snack and fast-food pattern and cereal and tuber pattern are risk factors for iron deficiency, and fruit and vegetable pattern and meat and offal pattern are protective factors for iron deficiency. The impact of diet on body iron levels is more obvious in boys and younger children. The findings of this study can provide evidence for formulating prevention and control measures on children and adolescents iron deficiency and iron deficiency anemia.

ObjectiveThe applications of personalized abutments and abutment crown bridge products have increased year by year, but there is no clear requirement for clinical evaluation of the same variety of such products. This study mainly introduces the clinical evaluation concerns of personalized abutments and abutment crown bridge products, in order to provide reference for the declaration and registration of such products. MethodsThe clinical evaluation of personalized abutments and crown bridge products are summarized, and the research content of clinical evaluation is clarified. ResultsThe clinical evaluation requirements that need to be considered by enterprises are introduced. ConclusionPersonalized abutment and abutment crown bridge products can refer to this study when they are launched in China, mainly using in vitro performance comparison tests for equivalence verification.

Abstract Background Ventricular remodeling is the adaptive process in which the heart undergoes changes due to stress, leading to heart failure (HF). The progressive decline in cardiac function is considered to contribute to intestinal barrier impairment. LuQi Formula (LQF) is a traditional Chinese medicine preparation widely used in the treatment of ventricular remodeling and HF. However, the role of LQF in the impairment of intestinal barrier function induced by ventricular remodeling remains unclear. Materials and methods Ventricular remodeling was induced in rats by permanently ligating the left anterior descending branch coronary artery, and cardiac function indexes were assessed using echocardiography. Heart and colon tissue morphology were observed by hematoxylin–eosin, Masson’s trichrome and Alcian Blue Periodic acid Schiff staining. Myocardial cell apoptosis was detected using TUNEL and immunohistochemistry. Circulatory levels of brain natriuretic peptide (BNP), intestinal permeability markers endotoxin, D-lactate and zonulin, as well as inflammatory cytokines tumor necrosis factor alpha and interleukin-1 beta were measured by Enzyme-linked immunosorbent assay. Expression levels of tight junction (TJ) proteins and hypoxia-inducible factor-1 alpha (HIF-1α) in colon tissue were detected by immunofluorescence, immunohistochemistry and western blotting. Cardiac function indexes and intestinal permeability markers of patients with HF were analyzed before and after 2–4 months of LQF treatment. Results LQF protected cardiac function and alleviated myocardial fibrosis and apoptosis in rats with ventricular remodeling. LQF protected the intestinal barrier integrity in ventricular remodeling rats, including maintaining colonic tissue morphology, preserving the number of goblet cells and normal expression of TJ proteins. Furthermore, LQF upregulated the expression of HIF-1α protein in colon tissue. Intervention with a HIF-1α inhibitor weakened the protective effect of LQF on intestinal barrier integrity. Moreover, a reduction of HIF-1α aggravated ventricular remodeling, which could be alleviated by LQF. Correspondingly, the circulating levels of intestinal permeability markers and BNP in HF patients were significantly decreased, and cardiac function markedly improved following LQF treatment. Conclusions We demonstrated that LQF effectively protected cardiac function by preserving intestinal barrier integrity caused by ventricular remodeling, at least partially through upregulating HIF-1α expression.

Abstract Background Babesia gibsoni is one of the causative agents of canine babesiosis worldwide. Some dogs infected with B. gibsoni show severe clinical signs with progressive anemia, hemoglobinuria and splenomegaly. However, most infected dogs present a state of chronic infection and thereby may be a persistent pathogen carrier, increasing the risk of pathogen spreading. To date, little is known about this pathogen, with genomic and transcriptomic data in particular generally unavailable. This lack of knowledge extensively limits the development of effective diagnostic strategies and vaccines. Methods High-throughput RNA sequencing of total RNA of B. gibsoni asexual stages collected from infected beagles was performed. The unigenes were annotated in seven databases. The genes were sorted according to their fragments per kilobase per million (FPKM) value, which was used as an indicator for expression level. The gene with the highest FPKM value was cloned from the genome of B. gibsoni and further tested for immunogenicity, cellular localization and efficacy as a potential diagnostic candidate for detecting B. gibsoni in sera collected from beagles. Results A total of 62,580,653 clean reads were screened from the 64,336,475 raw reads, and the corresponding 70,134 transcripts and 36,587 unigenes were obtained. The gene with the highest FPKM value was screened from the unigenes; its full length was 1276 bp, and it was named BgP30. The BgP30 gene comprised three exons and two introns, with a 786-bp open reading frame, and encoded 261 amino acids with a predicted molecular weight of 30 kDa. The cellular localization assay confirmed the existence of P30 protein in B. gibsoni parasites. Moreover, P30 was detected in the serum of experimentally B. gibsoni-infected beagles, from 15 days up to 422 days post-infection, suggesting its usefulness as a diagnostic candidate for both acute and chronic infections. Conclusions We sequenced the transcriptome of B. gibsoni asexual stages for the first time. The BgP30 gene was highly expressed in the transcriptome screening experiments, with further studies demonstrating that it could induce immune response in B. gibsoni-infected dogs. These results lead us to suggest that bgP30 may be a good diagnostic candidate marker to detect both acute and chronic B. gibsoni infections. Graphical Abstract

BackgroundBrain atrophy represents a final common pathway for pathological processes in patients with cerebral small vessel disease (CSVD) and is now recognized as a strong independent predictor of clinical status and progression. The mechanism underlying brain atrophy in patients with CSVD is not yet fully comprehended. This study aims to investigate the association of morphologic features of intracranial distal arteries (A2, M2, P2 and more distal) with different brain structures [gray matter volume (GMV), white matter volume (WMV), and cerebrospinal fluid volume (CSFV)]. Furthermore, we also examined whether a correlation existed between these cerebrovascular characteristics and GMV in different brain regions.MethodA total of 39 participants were eventually enrolled. The morphologic features of intracranial distal arteries based on TOF-MRA were extracted and quantified using the intracranial artery feature extraction technique (iCafe). The brain 3D-T1 images were segmented into gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) using the “Segment” tool in CAT12 for the voxel-based morphometry (VBM) analysis. Univariable and multivariable linear regression models were used to investigate the relationship between these cerebrovascular features and different brain structures. Partial correlation analysis with a one-tailed method was used to evaluate the relationship between these cerebrovascular features and GMV in different brain regions.ResultsOur findings indicate that both distal artery length and density were positively correlated with GM fraction in CSVD patients, regardless of whether univariable or multivariable linear regression analyses were performed. In addition, distal artery length (β = −0.428, p = 0.007) and density (β = −0.337, p = 0.036) were also found to be negative associated with CSF fraction, although this relationship disappeared after adjusting for potential confounders. Additional adjustment for the effect of WMHs volume did not change these results. In subgroup anasysis, we found that participants in the highest distal artery length tertile had significantly higher GM fraction and lower CSF fraction level than participants in the lowest distal artery length tertile. In partial correlation analysis, we also found that these cerebrovascular characteristics associated with regional GMV, especially subcortical nuclear.ConclusionThe morphologic features of intracranial distal arteries, including artery length, density and average tortuosity, measured from 3D-TOF MRA, are associated with generalized or focal atrophy indexes of CSVD.

Giardia duodenalis is a zoonotic intestinal protozoan parasite that may cause host diarrhea and chronic gastroenteritis, resulting in great economic losses annually and representing a significant public health burden across the world. However, thus far, our knowledge on the pathogenesis of Giardia and the related host cell responses is still extensively limited. The aim of this study is to assess the role of endoplasmic reticulum (ER) stress in regulating G0/G1 cell cycle arrest and apoptosis during in vitro infection of intestinal epithelial cells (IECs) with Giardia. The results showed that the mRNA levels of ER chaperone proteins and ER-associated degradation genes were increased and the expression levels of the main unfolded protein response (UPR)-related proteins (GRP78, p-PERK, ATF4, CHOP, p-IRE1, XBP1s and ATF6) were increased upon Giardia exposure. In addition, cell cycle arrest was determined to be induced by UPR signaling pathways (IRE1, PERK and ATF6) through upregulation of p21 and p27 levels and promotion of E2F1-RB complex formation. Upregulation of p21 and p27 expression was shown to be related to Ufd1-Skp2 signaling. Therefore, the cell cycle arrest was induced by ER stress when infected with Giardia. Furthermore, the apoptosis of the host cell was also assessed after exposure to Giardia. The results indicated that apoptosis would be promoted by UPR signaling (PERK and ATF6), but would be suppressed by the hyperphosphorylation of AKT and hypophosphorylation of JNK that were modulated by IRE1 pathway. Taken together, both of the cell cycle arrest and apoptosis of IECs induced by Giardia exposure involved the activation of the UPR signaling. The findings of this study will deepen our understanding of the pathogenesis of Giardia and the associated regulatory network.

Shared Mobility Systems (SMS) facilitate on-demand journeys using one or more transportation modes such as car-sharing, bike-sharing, or ride-sharing. As a result, SMS often face challenges such as finding suitable facility locations, efficient routing of shared vehicles, matching and re-distributing available resources with dynamic demands. Most existing surveys study how a particular challenge is addressed using artificial intelligence, machine learning, and optimisation techniques. However, these surveys fail to address the crucial “Whole System Design” point of view, which includes the “whole system” of interconnected stakeholders, entities, and subsystems that participate in, impact, and influence the success of each other and system a whole. Such a survey is highly required with the growing demand for flexible SMS that supports autonomous decision-making and offers multi-modal and inter-operable transportation services catered for highly dynamic traffic conditions in urban areas. This paper attempts to fill this gap by categorising the SMS’ interconnected challenges in different transportation modes and reviewing how offered solutions across all modes address these challenges as a unified system.

IntroductionMeningitis caused by oral anaerobic bacteria is rare, especially when complicated with an infected intracranial aneurysm. This paper has described an extremely rare case of bacterial meningitis caused by a mixed infection of oral microflora dominated by anaerobes, which developed cerebral infarcts, brain abscess, intracranial aneurysm, and severe hydrocephalus during treatment.Case reportWe describe a 65-year-old male patient who was presented with fever and headache as the initial symptoms and then developed left ophthalmoplegia, right hemiplegia, and disturbance of consciousness. Brain imaging showed that intracranial lesions were increased progressively, and cerebral infarcts, brain abscesses, intracranial aneurysm, and severe hydrocephalus were appeared gradually. Eventually, we diagnosed it as anaerobic meningitis by making deoxyribonucleic acid sequencing from the brain abscess pus. After using an anti-microbial regimen that can sufficiently cover anaerobes, the patient's condition was effectively controlled.ConclusionAnaerobic meningitis can cause a series of intracranial complications. Among them, the intracranial aneurysm is extremely rare. When evidence shows that the infection originates from oral flora, physicians should consider the possibility of this type of encephalitis. An early diagnosis and timely treatment are crucial to improving the prognosis.

Heart failure is the terminal stage of cardiovascular diseases. In the population-aging trend, it remains a serious social problem with high morbidity, mortality, and rehospitalization rates. Traditional Chinese medicine has long been used to treat heart failure. LuQi Formula was modified by Professor Zhou Hua of Shuguang Hospital, Shanghai, based on years of clinical experience and the concept of the “heart-kidney intersection.” It has been proven effective in the treatment of heart failure, and is beneficial in inhibiting myocardial fibrosis, decreasing collagen deposition and brain natriuretic peptide levels, improving heart function in rats with acute myocardial infarction, and affecting adenosine triphosphate production. In this review, we summarized the clinical and laboratory research on LuQi Formula, and the mechanism of the cardioprotective effect of each medicine in this recipe. This review offers a theoretical basis and research direction for further mechanistic studies on LuQi Formula to foster its development into new cardiovascular drugs.

Cardiovascular disease poses a significant threat to the quality of human life. Metabolic abnormalities caused by excessive caloric intake have been shown to lead to the development of cardiovascular diseases. Ceramides are structural molecules found in biological membranes; they are crucial for cell survival and lipid metabolism, as they maintain barrier function and membrane fluidity. Increasing evidence has demonstrated that ceramide has a strong correlation with cardiovascular disease progression. Nevertheless, it remains a challenge to develop sphingolipids as therapeutic targets to improve the prognosis of cardiovascular diseases. In this review, we summarize the three synthesis pathways of ceramide and other intermediates that are important in ceramide metabolism. Furthermore, mechanistic studies and therapeutic strategies, including clinical drugs and bioactive molecules based on these intermediates, are discussed.

Abstract Background The thrombospondin-related anonymous protein (TRAP) was first discovered in the sporozoite of Plasmodium falciparum and TRAP family proteins are secreted by micronemes and transported to the parasite surface to participate in the invasion process. Various TRAP proteins have been identified in apicomplexan protozoans, but there have been few reports about TRAP proteins in Babesia orientalis. Methods The functional domain of TRAP2 in B. orientalis was cloned, sequenced, characterized and compared to the TRAP sequences of related apicomplexan parasites. The functional domain of BoTRAP2 was truncated, named BoTRAP2-1, and then cloned into the pET-28a expression vector. Rabbit anti-rBoTRAP2-1 polyclonal antibody was produced by immunizing three rabbits. Western blot analysis was used to identify the native form and immunogenicity of BoTRAP2. The localization of BoTRAP2 was identified by indirect fluorescence assay (IFA). Results The amplified genes of BoTRAP2 are 2817 bp in length, encoding a functional domain of about 938 aa with two vWFA domains, one TSP domain and one transmembrane domain. The amino acid sequence of BoTRAP2 has a high similarity with that of B. bovis and B. gibsoni. The predicted tertiary structure of truncated BoTRAP2-1 confirmed that BoTRAP2 contains two vWFA domains and a TSP domain, the main functional areas of the protein. The native BoTRAP2 was identified from B. orientalis lysate by using rabbit polyclonal anti-rBoTRAP2-1. A band corresponding to rBoTRAP2-1 was detected by reaction with serum from a B. orientalis-infected water buffalo, indicating that the protein has a high immunogenicity. IFA showed that BoTRAP2 is mainly localized on the apical end of parasites by rabbit anti-rBoTRAP2-1 polyclonal serum. Conclusions The rBoTRAP2 could differentiate serum from B. orientalis-infected water buffalo and normal water buffalo, implicating that BoTRAP2 has high immunogenicity and could serve as a candidate antigen for diagnosis of B. orientalis infection in buffalo.

Babesia orientalis, a major infectious agent of water buffalo hemolytic babesiosis, is transmitted by Rhipicephalus haemaphysaloides. However, no effective vaccine is available. Essential antigens that are involved in parasite invasion of host red blood cells (RBCs) are potential vaccine candidates. Therefore, the identification and the conduction of functional studies of essential antigens are highly desirable. Here, we evaluated the function of B. orientalis merozoite surface antigen 2c1 (BoMSA-2c1), which belongs to the variable merozoite surface antigen (VMSA) family in B. orientalis. We developed a polyclonal antiserum against the purified recombinant (r)BoMSA-2c1 protein. Immunofluorescence staining results showed that BoMSA-2c1 was expressed only on extracellular merozoites, whereas the antigen was undetectable in intracellular parasites. RBC binding assays suggested that BoMSA-2c1 specifically bound to buffalo erythrocytes. Cytoadherence assays using a eukaryotic expression system in vitro further verified the binding and inhibitory ability of BoMSA-2c1. We found that BoMSA-2c1 with a GPI domain was expressed on the surface of HEK293T cells that bound to water buffalo RBCs, and that the anti-rBoMSA2c1 antibody inhibited this binding. These results indicated that BoMSA-2c1 was involved in mediating initial binding to host erythrocytes of B. orientalis. Identification of the occurrence of binding early in the invasion process may facilitate understanding of the growth characteristics, and may help in formulating strategies for the prevention and control of this parasite.

Abstract Background The apicomplexan parasite Babesia orientalis, the causative agent of water buffalo babesiosis in China, is widespread in central and south China, resulting in a huge economic loss annually. Currently, there is no effective vaccine or drug against this disease. Babesia bovis and Plasmodium falciparum were reported to possess an apicoplast which contains the methylerythritol phosphate (MEP) pathway inhibitable by fosmidomycin, suggesting that the pathway could serve as a drug target for screening new drugs. However, it remains unknown in B. orientalis. Methods Primers were designed according to the seven MEP pathway genes of Babesia microti and Babesia bovis. The genes were cloned, sequenced and analyzed. The open reading frames (ORFs) of the first two enzyme genes, 1-deoxy-D-xylulose 5-phosphate synthase (BoDXS) and 1-Deoxy-D-xylulose 5-phosphate reductoisomerase (BoDXR), were cloned into the pET-32a expression vector and expressed as a Trx-tag fusion protein. Rabbit anti-rBoDXS and rabbit anti-rBoDXR antibodies were generated. Western blot was performed to identify the native proteins of BoDXS and BoDXR in B. orientalis. Fosmidomycin and geranylgeraniol were used for inhibition assay and rescue assay, respectively, in the in vitro cultivation of B. orientalis. Results The seven enzyme genes of the B. orientalis MEP pathway (DXS, DXR, IspD, IspE, IspF, IspG and IspH) were cloned and sequenced, with a full length of 2094, 1554, 1344, 1521, 654, 1932 and 1056 bp, respectively. BoDXS and BoDXR were expressed as Trx-tag fusion proteins, with a size of 95 and 67 kDa, respectively. Western blot identified a 77 kDa band for the native BoDXS and a 49 kDa band for the native BoDXR. The drug assay results showed that fosmidomycin could inhibit the growth of B. orientalis, and geranylgeraniol could reverse the effect of fosmidomycin. Conclusions Babesia orientalis has the isoprenoid biosynthesis pathway, which could be a potential drug target for controlling and curing babesiosis. Considering the high price and instability of fosmidomycin, further studies should focus on the screening of stable and cheap drugs.

Abstract Background The spherical body, a membrane bound organelle localized in the apical organelle complex, is unique to Babesia and Theileria spp. The spherical body proteins (SBPs) secreted by spherical bodies include SBP1, SBP2, SBP3 and SBP4. Up to now, only SBP3 has been characterized in Babesia orientalis. Methods The BoSBP4 gene was amplified from cDNA and gDNA and cloned into the pGEX-6P-1 vector by homologous recombination, sequenced and analyzed by bioinformatics tools. The amino acid (aa) sequence of BoSBP4 was compared with that of Babesia bovis and Babesia bigemina as well as SBP3 of B. orientalis. The immunoreactivity was evaluated by incubating recombinant BoSBP4 (rBoSBP4) with the serum of B. orientalis-infected water buffalo. The native form of BoSBP4 was identified by incubating lysate of B. orientalis-infected water buffalo erythrocytes with the anti-rBoSBP4 mouse serum. The cellular localization of BoSBP4 was determined by indirect immunofluorescence assay. Results The full length of the BoSBP4 gene was estimated to be 945 bp without introns, encoding a 314 aa polypeptide with a predicted molecular weight of 37 kDa. The truncated recombinant protein was expressed from 70 to 945 bp as a GST fusion protein with a practical molecular weight of 70 kDa. BoSBP4 shared a 40% and 30% identity with B. bovis and B. bigemina, respectively. Furthermore, it was 31% identical to SBP3 of B. orientalis. BoSBP4 was identified in the lysate of B. orientalis-infected water buffalo erythrocytes with a molecular weight of 37 kDa, corresponding to the expected molecular mass of BoSBP4. The result of rBoSBP4 with positive serum revealed that BoSBP4 can elicit an immune response to B. orientalis-infected water buffalo. The cellular localization of BoSBP4 was detected to be adjacent to the merozoite nucleus in the intracellular phase, followed by the diffusion of the fluorescence of BoSBP4 into the cytoplasm of B. orientalis-infected erythrocytes as puncta-like specks and a gradual increase of the fluorescence. Conclusions In this study, SBP4 in B. orientalis was characterized for the first time. It may play a key role in interaction with the host cell by being secreted into the cytoplasm of the B. orientalis-infected erythrocytes to facilitate parasite growth and reproduction.

Abstract Background The spherical body is a distinct organelle only existing in Babesia and Theileria. Spherical body proteins (SBPs) are secreted from spherical bodies and incorporated into the cytoplasm of infected erythrocytes during invasion and post-invasion stages. Four different SBP homologues (SBP1, SBP2, SBP3 and SBP4) have been identified in Babesia bovis and Babesia bigemina. So far, there has been no report available about the identification of SBPs in Babesia orientalis. Methods The SBP3-like in B. orientalis (BoSBP3-like) was cloned, sequenced, characterized and compared to the SBP3 sequences of B. bovis and B. bigemina by bioinformatics analyses. The BoSBP3-like gene was truncated into three fragments: BoSBP3-like-1 (915 bp), BoSBP3-like-2 (1311 bp) and BoSBP3-like-3 (1011 bp), which were amplified and cloned into the expression vector pET-28a and expressed as three truncated recombinant (His-fusion) proteins. The immunogenicity, native forms and localization of BoSBP3-like were identified by western blot and indirect immunofluorescence assay (IFA). Results The BoSBP3-like gene was intronless with an open reading frame (ORF) of 3237 bp, encoded a 1079 amino acid polypeptide with a predicted size of 135 kDa, and contained a cysteine-rich region, three dispersing FAINT domains and a signal peptide (1–16 aa) at the N-terminus. The amino acid sequence of BoSBP3-like was 61.6 and 35.0% identical to that of B. bovis and B. bigemina, respectively. BoSBP3-like was identified as 135 kDa in the parasite lysate by rabbit antiserum against the truncated recombinant BoSBP3-like-1 (rBoSBP3-like-1). Three specific bands corresponding to rBoSBP3-like-1 (1–305 aa, 43 kDa), rBoSBP3-like-2 (306–742 aa, 58 kDa) and rBoSBP3-like-3 (743–1079 aa, 52 kDa) were detected by reaction with serum from B. orientalis-infected buffalo. The BoSBP3-like was not only localized in the spherical body of B. orientalis but also in the cytoplasm of infected erythrocytes of buffalo as puncta-like protein specks at both single and paired parasite development stages. Conclusions Through secretion into the cytoplasm of infected erythrocytes, BoSBP3-like may play a significant role in adaptation, interaction, and modification related to the host environment to benefit the growth and survival of Babesia. BoSBP3-like could react with the serum from B. orientalis-infected buffalo, but not healthy buffalo, implicating that BoSBP3-like is highly antigenic and may serve as a candidate diagnostic antigen for the detection of B. orientalis.

Babesia microti, a tick-borne intraerythrocytic zoonotic protozoan, causes most of human babesiosis in the world, and patients usually experience intermittent fever, fatigue, and chills, followed by a combination of additional symptoms and even death in severe cases. Unfortunately, there is no curable drug or effective vaccine available, and the mechanism of related virulence factors in invasion to host cells during the merozoite stage is unclear. Here, we evaluated a secreted protein annotated as B. microti surface antigen 1 (BmSA1) and identified from in vitro culture supernatant by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). BmSA1 fragment was expressed in Escherichia coli to prepare polyclonal antiserum. Western blot analysis revealed the existence of BmSA1 in the lysate of the parasites and the hemolysate of infected red blood cells (iRBCs). Laser confocal microscopy confirmed BmSA1 as a secreted protein with diffuse distribution around the parasites in red blood cells (RBCs). The adhesion capacity of BmSA1 against the host RBCs was tested by RBC binding assays using the recombinant BmSA1 protein (rBmSA1), which was shown to specifically bind to host RBCs. Further in vitro antiserum-neutralization test demonstrated that the growth of parasites could be significantly inhibited by the anti-BmSA1 antiserum. These results indicate that BmSA1 is a crucial factor for B. microti invasion into host RBCs with an important role in host-parasite interactions during the merozoite stage and has the potential use as a vaccine candidate due to its high secretion amount.

A number of studies have demonstrated that Babesia orientalis (B. orientalis) can only infect water buffalo (Bubalus bubalis) and not dairy cattle (Bos taurus) or beef cattle (Bos taurus), even though all three belong to the tribe Bovini and have close evolutionary relationships. In addition, Babesia species are intracellular protozoans that obligately parasitize in erythrocytes. This may indicate that the infection specificity is due to differences in erythrocyte proteins. Totals of 491, 1,143, and 1,145 proteins were identified from water buffalo, beef cattle, and dairy cattle, respectively, by searching the Uniprot and NCBI databases. The number of proteins identified for water buffalo was far lower than for beef cattle and dairy cattle, particularly in the range from 15 to 25 kDa. Remarkably, 290 identified proteins were unique to water buffalo, of which putative gamma-globin and putative epsilon-globin had a significant possibility of being relevant to the survival of B. orientalis only in water buffalo. A total of 2,222 proteins were annotated in terms of molecular function, biological process, and cellular component according to GO annotation. The number of proteins of water buffalo in oxygen binding was far higher than for beef cattle and dairy cattle. This is the first time that the protein profiles of water buffalo, beef cattle, and dairy cattle have been comparatively analyzed. The uniquely expressed proteins in water buffalo obtained in this study may provide new insights into the mechanism of B. orientalis infection exclusivity in water buffalo and may be a benefit for the development of strategies against B. orientalis.

Human babesiosis caused by Babesia microti is an emerging threat for severe illness and even death, with an increasing impact worldwide. Currently, the regimen of atovaquone and azithromycin is considered as the standard therapy for treating human babesiosis, which, however, may result in drug resistance and relapse, suggesting the necessity of developing new drugs to control B. microti. In this regard, natural products are promising candidates for drug design against B. microti due to their active therapeutic efficacy, lower toxicity, and fewer adverse reactions to host. Here, the potential inhibitors against B. microti were preliminarily screened from 133 natural products, and 47 of them were selected for further screening. Gossypol (Gp) and xanthohumol (Xn) were finally shown to effectively inhibit the growth of B. microti with IC50 values of 8.47 μm and 21.40 μm, respectively. The cytotoxicity results showed that Gp and Xn were non-toxic to erythrocytes at a concentration below 100 μm. Furthermore, both of them were confirmed to be non-toxic to different types of cells in previous studies. Our findings suggest the potential of Gp and Xn as effective drugs against B. microti infection.

This paper presents a novel leaky-wave antenna based on the Half-Mode Substrate Integrated Waveguide (HMSIW) structure with low side lobe level. The effect of the structural parameters of the LWAs on the radiation performances is studied. Using beam-forming technique, the leakage loss factor α along the radiation aperture is designed in a tapered way by controlling the aperture depth along the structure. This controls the radiated power along the antenna aperture and finally achieves the radiation pattern with low SLL. Furthermore, the antenna structure is optimized to get an even lower SLL.

The article discusses research which examined the seroprevalence of neutralizing antibodies against hand, foot and mouth disease (HFMD) associated enteroviruses among health individuals in Shanghain, China. The study observed different trends in the seroprevalence of four serotypes of coxsackieviruses in different age groups. It analyzed the seroprevalence of protective and high-level neutralizing antibodies (NtAb) titers and the seroprotection rates of coxsackieviruses.