Development and evaluation of the Newstage system: integrating tumor regression grade and lymph node status for improved prognostication in neoadjuvant treatment of gastric cancer.

BACKGROUND: The predictive correlation of tumor depth of invasion changes after neoadjuvant therapy, and the 8th American Joint Committee on Cancer (AJCC) ypTNM system for gastric cancer may not accurately predict patient prognosis following neoadjuvant therapy. METHODS: A retrospective analysis was conducted on a total of 258 patients who underwent radical surgery for gastric cancer after neoadjuvant therapy. The Newstage system was established based on tumor regression grade and pathological lymph node status. The 3-year survival rates of patients classified by the Newstage system were compared with those classified by the AJCC ypTNM system. RESULTS: In a cohort of 258 patients, the 3-year overall survival rates based on the Newstage system were: (I) 94.6%, (II) 79.3%, (III) 54.5%, and (IV) 30.2%. The Newstage system exhibited a lower Akaike information criterion value (902.57 vs. 912.03). Additionally, the area under the ROC curve (0.756 vs. 0.733) and the C-index (0.731 vs. 0.718) was higher than the AJCC ypTNM system. Furthermore, a multivariate analysis indicated that the Newstage system was an independent prognostic factor (p = 0.001). CONCLUSION: The Newstage system exhibits superior predictive performance in estimating survival rates for neoadjuvant therapy in gastric cancer. It also functions as an independent prognostic factor.

2, 2-dimethylthiazolidine hydrochloride protects against experimental contrast-induced acute kidney injury via inhibition of tubular ferroptosis.

Contrast-induced acute kidney injury (CI-AKI) has become the third leading cause of AKI acquired in hospital, lacking of effective interventions. In the study, we identified the renal beneficial role of 2, 2-dimethylthiazolidine hydrochloride (DMTD), a safer compound which is readily hydrolyzed to cysteamine, in the rodent model of CI-AKI. Our data showed that administration of DMTD attenuated the impaired renal function and tubular injury induced by the contrast agent. Levels of MDA, 4-hydroxynonenal, ferrous iron and morphological signs showed that contrast agent induced ferroptosis, which could be inhibited in the DMTD group. In vitro, DMTD suppressed ferroptosis induced by ioversol in the cultured tubular cells. Treatment of DMTD upregulated glutathione (GSH) and glutathione peroxidase 4 (GPX4). Moreover, we found that DMTD promoted the ubiquitin-mediated proteasomal degradation of Keap1, and thus increased the activity of nuclear factor erythroid 2-related factor 2 (Nrf2). Mechanistically, increase of the ubiquitylation degradation of Keap1 mediates the upregulated effect of DMTD on Nrf2. Consequently, activated Nrf2/Slc7a11 results in the increase of GSH and GPX4, and therefore leads to the inhibition of ferroptosis. Herein, we imply DMTD as a potential therapeutic agent for the treatment of CI-AKI.

The effects of bone morphogenetic protein 2 and thrombopoietin treatment on angiogenic properties of endothelial cells derived from the lung and bone marrow of young and aged, male and female mice.

With an aging world population, there is an increased risk of fracture and impaired healing. One contributing factor may be aging-associated decreases in vascular function; thus, enhancing angiogenesis could improve fracture healing. Both bone morphogenetic protein 2 (BMP-2) and thrombopoietin (TPO) have pro-angiogenic effects. The aim of this study was to investigate the effects of treatment with BMP-2 or TPO on the in vitro angiogenic and proliferative potential of endothelial cells (ECs) isolated from lungs (LECs) or bone marrow (BMECs) of young (3-4 months) and old (22-24 months), male and female, C57BL/6J mice. Cell proliferation, vessel-like structure formation, migration, and gene expression were used to evaluate angiogenic properties. In vitro characterization of ECs generally showed impaired vessel-like structure formation and proliferation in old ECs compared to young ECs, but improved migration characteristics in old BMECs. Differential sex-based angiogenic responses were observed, especially with respect to drug treatments and gene expression. Importantly, these studies suggest that NTN1, ROBO2, and SLIT3, along with angiogenic markers (CD31, FLT-1, ANGPT1, and ANGP2) differentially regulate EC proliferation and functional outcomes based on treatment, sex, and age. Furthermore, treatment of old ECs with TPO typically improved vessel-like structure parameters, but impaired migration. Thus, TPO may serve as an alternative treatment to BMP-2 for fracture healing in aging owing to improved angiogenesis and fracture healing, and the lack of side effects associated with BMP-2.

Interspecies analysis of MYC targets identifies tRNA synthetases as mediators of growth and survival in MYC-overexpressing cells.

Aberrant MYC oncogene activation is one of the most prevalent characteristics of cancer. By overlapping datasets of Drosophila genes that are insulin-responsive and also regulate nucleolus size, we enriched for Myc target genes required for cellular biosynthesis. Among these, we identified the aminoacyl tRNA synthetases (aaRSs) as essential mediators of Myc growth control in Drosophila and found that their pharmacologic inhibition is sufficient to kill MYC-overexpressing human cells, indicating that aaRS inhibitors might be used to selectively target MYC-driven cancers. We suggest a general principle in which oncogenic increases in cellular biosynthesis sensitize cells to disruption of protein homeostasis.

A novel genomic classification system of gastric cancer via integrating multidimensional genomic characteristics.

BACKGROUND: Gastric cancer (GC) is one of the leading causes of cancer deaths with high heterogeneity. There is currently a paucity of clinically applicable molecular classification system to guide precise medicine. METHODS: A total of 70 Chinese patients with GC were included in this study and whole-exome sequencing was performed. Unsupervised clustering was undertaken to identify genomic subgroups, based on mutational signature, copy number variation, neoantigen, clonality, and essential genomic alterations. Subgroups were characterized by clinicopathological factors, molecular features, and prognosis. RESULTS: We identified 32 significantly mutated genes (SMGs), including TP53, ARID1A, PIK3CA, CDH1, and RHOA. Of these, PREX2, PIEZO1, and FSIP2 have not been previously reported in GC. Using a novel genome-based classification method that integrated multidimensional genomic features, we categorized GC into four subtypes with distinct clinical phenotypes and prognosis. Subtype 1, which was predominantly Lauren intestinal type, harbored recurrent TP53 mutation and ERBB2 amplification, high tumor mutation burden (TMB)/tumor neoantigen burden (TNB), and intratumoral heterogeneity, with a liver metastasis tendency. Subtype 2 tended to occur at an elder age, accompanying with frequent TP53 and SYNE1 mutations, high TMB/TNB, and was associated with poor prognosis. Subtype 3 and subtype 4 included patients with mainly diffuse/mixed type tumors, high frequency of peritoneal metastasis, and genomical stability, whereas subtype 4 was associated with a favorable prognosis. CONCLUSIONS: By integrating multidimensional genomic characteristics, we proposed a novel genomic classification system of GC associated with clinical phenotypes and provided a new insight to facilitate genome-guided risk stratification and disease management.

Small-molecule CaVα1⋠CaVß antagonist suppresses neuronal voltage-gated calcium-channel trafficking.

Extracellular calcium flow through neuronal voltage-gated CaV2.2 calcium channels converts action potential-encoded information to the release of pronociceptive neurotransmitters in the dorsal horn of the spinal cord, culminating in excitation of the postsynaptic central nociceptive neurons. The CaV2.2 channel is composed of a pore-forming α1 subunit (CaVα1) that is engaged in protein-protein interactions with auxiliary α2/δ and ß subunits. The high-affinity CaV2.2α1⋅CaVß3 protein-protein interaction is essential for proper trafficking of CaV2.2 channels to the plasma membrane. Here, structure-based computational screening led to small molecules that disrupt the CaV2.2α1⋅CaVß3 protein-protein interaction. The binding mode of these compounds reveals that three substituents closely mimic the side chains of hot-spot residues located on the α-helix of CaV2.2α1 Site-directed mutagenesis confirmed the critical nature of a salt-bridge interaction between the compounds and CaVß3 Arg-307. In cells, compounds decreased trafficking of CaV2.2 channels to the plasma membrane and modulated the functions of the channel. In a rodent neuropathic pain model, the compounds suppressed pain responses. Small-molecule α-helical mimetics targeting ion channel protein-protein interactions may represent a strategy for developing nonopioid analgesia and for treatment of other neurological disorders associated with calcium-channel trafficking.

Human impact on the diversity and virulence of the ubiquitous zoonotic parasite Toxoplasma gondii.

A majority of emerging infectious diseases in humans are zoonoses. Understanding factors that influence the emergence and transmission of zoonoses is pivotal for their prevention and control. Toxoplasma gondii is one of the most widespread zoonotic pathogens known today. Whereas only a few genotypes of T. gondii dominate in the Northern Hemisphere, many genotypes coexist in South America. Furthermore, T. gondii strains from South America are more likely to be virulent than those from the Northern Hemisphere. However, it is not clear what factor(s) shaped modern-day genetic diversity and virulence of T. gondii Here, our analysis suggests that the rise and expansion of farming in the past 11,000 years established the domestic cat/mouse transmission cycle for T. gondii, which has undoubtedly played a significant role in the selection of certain linages of T. gondii Our mathematical simulations showed that within the domestic transmission cycle, intermediately mouse-virulent T. gondii genotypes have an adaptive advantage and eventually become dominant due to a balance between lower host mortality and the ability to superinfect mice previously infected with a less virulent T. gondii strain. Our analysis of the global type II lineage of T. gondii suggests its Old World origin but recent expansion in North America, which is likely the consequence of global human migration and trading. These results have significant implications concerning transmission and evolution of zoonotic pathogens in the rapidly expanding anthropized environment demanded by rapid growth of the human population and intensive international trading at present and in the future.

Next-generation CRISPR/Cas9 transcriptional activation in Drosophila using flySAM.

CRISPR/Cas9-based transcriptional activation (CRISPRa) has recently emerged as a powerful and scalable technique for systematic overexpression genetic analysis in Drosophila melanogaster We present flySAM, a potent tool for in vivo CRISPRa, which offers major improvements over existing strategies in terms of effectiveness, scalability, and ease of use. flySAM outperforms existing in vivo CRISPRa strategies and approximates phenotypes obtained using traditional Gal4-UAS overexpression. Moreover, because flySAM typically requires only a single sgRNA, it dramatically improves scalability. We use flySAM to demonstrate multiplexed CRISPRa, which has not been previously shown in vivo. In addition, we have simplified the experimental use of flySAM by creating a single vector encoding both the UAS:Cas9-activator and the sgRNA, allowing for inducible CRISPRa in a single genetic cross. flySAM will replace previous CRISPRa strategies as the basis of our growing genome-wide transgenic overexpression resource, TRiP-OE.

The Effects of SRT1720 Treatment on Endothelial Cells Derived from the Lung and Bone Marrow of Young and Aged, Male and Female Mice.

Angiogenesis is critical for successful fracture healing. Age-related alterations in endothelial cells (ECs) may cause impaired bone healing. Therefore, examining therapeutic treatments to improve angiogenesis in aging may enhance bone healing. Sirtuin 1 (SIRT1) is highly expressed in ECs and its activation is known to counteract aging. Here, we examined the effects of SRT1720 treatment (SIRT1 activator) on the growth and function of bone marrow and lung ECs (BMECs and LECs, respectively), derived from young (3-4 month) and old (20-24 month) mice. While aging did not alter EC proliferation, treatment with SRT1720 significantly increased proliferation of all LECs. However, SRT1720 only increased proliferation of old female BMECs. Vessel-like tube assays showed similar vessel-like structures between young and old LECs and BMECs from both male and female mice. SRT1720 significantly improved vessel-like structures in all LECs. No age, sex, or treatment differences were found in migration related parameters of LECs. In males, old BMECs had greater migration rates than young BMECs, whereas in females, old BMECs had lower migration rates than young BMECs. Collectively, our data suggest that treatment with SRT1720 appears to enhance the angiogenic potential of LECs irrespective of age or sex. However, its role in BMECs is sex- and age-dependent.

Molecular Detection, Multilocus Genotyping, and Population Genetics of Enterocytozoon bieneusi in Pigs in Southeastern China.

Enterocytozoon bieneusi is an important opportunistic pathogen widely distributed in humans and animals that causes diarrhea or fatal diarrhea in immunocompromised hosts. To examine the infection status and molecular characteristics of E. bieneusi in pigs, 725 fecal samples were collected from pigs in six areas of Fujian Province. The E. bieneusi genotypes were identified based on the internal transcribed spacer (ITS) regions of the ribosomal RNA (rRNA) gene by nested PCR, and its population genetics were analyzed by multilocus sequence typing (MLST). The results showed that the infection rate of E. bieneusi was 24.4% (177/725), and 11 known genotypes (EbpC, EbpA, CHN-RR2, KIN-1, CHG7, CHS5, CM11, CHG23, G, PigEBITS, and D) and 2 novel genotypes (FJF and FJS) were identified. All the genotypes were found to be clustered into zoonotic Group 1. Moreover, 52 positive samples were successfully amplified at minisatellite and microsatellite loci and formed 48 distinct multilocus genotypes (MLGs). Further population structure analyses showed strong genetic linkage disequilibrium (LD) and several recombination events (Rm), indicating that E. bieneusi has a clonal population structure. This study is the first to investigate the prevalence and molecular characteristics of E. bieneusi in Fujian Province and could provide baseline data to control E. bieneusi infection in pigs and humans and deepen our understanding of the zoonotic risk of E. bieneusi and its distribution in China.

Influence of microcirculation load on FFR in coronary artery stenosis model.

BACKGROUND: The coronary artery hemodynamics are impacted by both the macrocirculation and microcirculation. Whether microcirculation load impact the functional assessment of a coronary artery stenosis is unknown. The purpose of this study is to investigate the effect of porous media of the microcirculation on fractional flow reserve (FFR) in stenotic coronary artery model. METHODS: A three dimensional computational simulation of blood flow in coronary artery symmetric stenotic model was constructed. The computational fluid dynamics (CFD) model was developed with Fluent 16.0. Blood was modeled as a shear thinning, non-Newtonian fluid with the Carreau model. A seepage outlet boundary condition and transient inlet conditions were imposed on the model. Coronary physiologica diagnostic parameter such as pressure, velocity and fractional flow reserve (FFR) were investigated in the model and compared with the microcirculation load (ML) and constant pressure load (PL) condition. RESULTS: The present study showed the different hemodynamics in the ML and PL condition. The pre-stenotic pressure is almost the same in the two model. However the pressure in the post-stenotic artery domain is much lower in the PL model. The fluctuation range of the pressures is much higher in ML model than those in PL model. The velocity flow was more steady and lower in the ML model. For the PL model with 75% artery stenosis the FFR was 0.776, while for the ML model with the same stenosis, the FFR was 0.813. CONCLUSIONS: This study provides evidence that FFR increased in the presentation of ML condition. There is a strong hemodynamic effect of microcirculation on coronary artery stenosis.

Optimized strategy for in vivo Cas9-activation in Drosophila.

While several large-scale resources are available for in vivo loss-of-function studies in Drosophila, an analogous resource for overexpressing genes from their endogenous loci does not exist. We describe a strategy for generating such a resource using Cas9 transcriptional activators (CRISPRa). First, we compare a panel of CRISPRa approaches and demonstrate that, for in vivo studies, dCas9-VPR is the most optimal activator. Next, we demonstrate that this approach is scalable and has a high success rate, as >75% of the lines tested activate their target gene. We show that CRISPRa leads to physiologically relevant levels of target gene expression capable of generating strong gain-of-function (GOF) phenotypes in multiple tissues and thus serves as a useful platform for genetic screening. Based on the success of this CRISRPa approach, we are generating a genome-wide collection of flies expressing single-guide RNAs (sgRNAs) for CRISPRa. We also present a collection of more than 30 Gal4 > UAS:dCas9-VPR lines to aid in using these sgRNA lines for GOF studies in vivo.

Prevalence of gastrointestinal parasites in free-range yaks (Bos grunniens) in Gansu Province, Northwest China.

BACKGROUND: Little information about the prevalence of gastrointestinal parasites in yaks (Bos grunniens) in northwest China is available. Therefore, the objective of the study was to quantify faecal egg counts of gastrointestinal parasites (helminths and coccidia) in free-range yaks from Gannan Tibetan Autonomous Prefecture, Gansu Province, Northwest China. RESULTS: Parasites were detected in 290 of 733 (39.56%) faecal samples. The results showed that Strongylidae, Trichuris spp. and Eimeria spp. were detected all year round, Strongyloides papillosus was detected in autumn and summer, and Nematodirus spp. was detected in both autumn and spring. In contrast, Fasciola spp. was only detected in spring. The prevalence rates of parasitic infections in different seasons were significantly different. CONCLUSIONS: To our knowledge, this is the first investigation of gastrointestinal parasites in yaks (Bos grunniens) in Gansu, China. The results demonstrated a high prevalence of gastrointestinal parasitic infections, specifically GN infections, in yaks in GTAP and these infections can cause economic losses to the local cattle industry.

Occurrence of Enterocytozoon bieneusi in Chinese Tan sheep in the Ningxia Hui Autonomous Region, China.

Enterocytozoon bieneusi is a zoonotic parasite which is considered to be an opportunistic pathogen of humans and animals. A number of studies have reported E. bieneusi infection in various animals. However, no information is available on the occurrence of E. bieneusi in Tan sheep, a unique indigenous sheep species in the Ningxia Hui Autonomous Region, China. The objectives of the present study were to examine the prevalence and identify the genotypes of E. bieneusi in Tan sheep in China. A total of 1014 fecal specimens of Tan sheep from six farms in the Ningxia Hui Autonomous Region were examined by nested PCR amplification of the internal transcribed spacer (ITS) of nuclear ribosomal DNA. The total prevalence of E. bieneusi was 12.2% (124/1014), ranging from 0.5 to 22.2% on six farms. Sequence analysis identified 10 genotypes of E. bieneusi, including three known genotypes, BEB6, COS-I, and CHG13, and seven novel genotypes designated as NX1 to NX7, which all belonged to group 2 by phylogenetic analysis. This is the first report describing the prevalence of E. bieneusi in Tan sheep, and the new genotypes identified in the current study expand the genotype distribution of E. bieneusi. These findings provide baseline data and have implications for the epidemiology and control of E. bieneusi infection in Tan sheep.

Small molecules inhibit ex vivo tumor growth in bone.

Bone is a common site of metastasis for breast, prostate, lung, kidney and other cancers. Bone metastases are incurable, and substantially reduce patient quality of life. To date, there exists no small-molecule therapeutic agent that can reduce tumor burden in bone. This is partly attributed to the lack of suitable in vitro assays that are good models of tumor growth in bone. Here, we take advantage of a novel ex vivo model of bone colonization to report a series of pyrrolopyrazolone small molecules that inhibit cancer cell invasion and ex vivo tumor growth in bone at single-digit micromolar concentration. We find that the compounds modulated the expression levels of genes associated with bone-forming osteoblasts, bone-destroying osteoclasts, cancer cell viability and metastasis. Our compounds provide chemical tools to uncover novel targets and pathways associated with bone metastasis, as well as for the development of compounds to prevent and reverse bone tumor growth in vivo.

Characterization of the complete mitochondrial genome of Marshallagia marshalli and phylogenetic implications for the superfamily Trichostrongyloidea.

Marshallagia marshalli (Nematoda: Trichostrongylidae) infection can lead to serious parasitic gastroenteritis in sheep, goat, and wild ruminant, causing significant socioeconomic losses worldwide. Up to now, the study concerning the molecular biology of M. marshalli is limited. Herein, we sequenced the complete mitochondrial (mt) genome of M. marshalli and examined its phylogenetic relationship with selected members of the superfamily Trichostrongyloidea using Bayesian inference (BI) based on concatenated mt amino acid sequence datasets. The complete mt genome sequence of M. marshalli is 13,891 bp, including 12 protein-coding genes, 22 transfer RNA genes, and 2 ribosomal RNA genes. All protein-coding genes are transcribed in the same direction. Phylogenetic analyses based on concatenated amino acid sequences of the 12 protein-coding genes supported the monophylies of the families Haemonchidae, Molineidae, and Dictyocaulidae with strong statistical support, but rejected the monophyly of the family Trichostrongylidae. The determination of the complete mt genome sequence of M. marshalli provides novel genetic markers for studying the systematics, population genetics, and molecular epidemiology of M. marshalli and its congeners.

Small Molecules Engage Hot Spots through Cooperative Binding To Inhibit a Tight Protein-Protein Interaction.

Protein-protein interactions drive every aspect of cell signaling, yet only a few small-molecule inhibitors of these interactions exist. Despite our ability to identify critical residues known as hot spots, little is known about how to effectively engage them to disrupt protein-protein interactions. Here, we take advantage of the ease of preparation and stability of pyrrolinone 1, a small-molecule inhibitor of the tight interaction between the urokinase receptor (uPAR) and its binding partner, the urokinase-type plasminogen activator uPA, to synthesize more than 40 derivatives and explore their effect on the protein-protein interaction. We report the crystal structure of uPAR bound to previously discovered pyrazole 3 and to pyrrolinone 12. While both 3 and 12 bind to uPAR and compete with a fluorescently labeled peptide probe, only 12 and its derivatives inhibit the full uPAR·uPA interaction. Compounds 3 and 12 mimic and engage different hot-spot residues on uPA and uPAR, respectively. Interestingly, 12 is involved in a π-cation interaction with Arg-53, which is not considered a hot spot. Explicit-solvent molecular dynamics simulations reveal that 3 and 12 exhibit dramatically different correlations of motion with residues on uPAR. Free energy calculations for the wild-type and mutant uPAR bound to uPA or 12 show that Arg-53 interacts with uPA or with 12 in a highly cooperative manner, thereby altering the contributions of hot spots to uPAR binding. The direct engagement of peripheral residues not considered hot spots through π-cation or salt-bridge interactions could provide new opportunities for enhanced small-molecule engagement of hot spots to disrupt challenging protein-protein interactions.

Small molecules inhibit STAT3 activation, autophagy, and cancer cell anchorage-independent growth.

Triple-negative breast cancers (TNBCs) lack the signature targets of other breast tumors, such as HER2, estrogen receptor, and progesterone receptor. These aggressive basal-like tumors are driven by a complex array of signaling pathways that are activated by multiple driver mutations. Here we report the discovery of 6 (KIN-281), a small molecule that inhibits multiple kinases including maternal leucine zipper kinase (MELK) and the non-receptor tyrosine kinase bone marrow X-linked (BMX) with single-digit micromolar IC50s. Several derivatives of 6 were synthesized to gain insight into the binding mode of the compound to the ATP binding pocket. Compound 6 was tested for its effect on anchorage-dependent and independent growth of MDA-MB-231 and MDA-MB-468 breast cancer cells. The effect of 6 on BMX prompted us to evaluate its effect on STAT3 phosphorylation and DNA binding. The compound's inhibition of cell growth led to measurements of survivin, Bcl-XL, p21WAF1/CIP1, and cyclin A2 levels. Finally, LC3B-II levels were quantified following treatment of cells with 6 to determine whether the compound affected autophagy, a process that is known to be activated by STAT3. Compound 6 provides a starting point for the development of small molecules with polypharmacology that can suppress TNBC growth and metastasis.

Feasibility and diagnostic performance of dual-tracer-guided sentinel lymph node biopsy in cT1-2N0M0 gastric cancer: a systematic review and meta-analysis of diagnostic studies.

BACKGROUND: Dual-tracer-guided sentinel lymph node (SLN) biopsy may provide a promising diagnostic tool to assess accurately the status of lymph node metastasis in the surgical operation and assure the oncologic safety of the function or stomach preserving surgery. The diagnostic performance of this technology in recent studies varied. Thus, we conducted this meta-analysis. METHODS: This systematic review and meta-analysis was registered at the PROSPERO. Eligible studies were searched in the PubMed, EMBASE, Web of Knowledge, and Cochrane Library databases. A random-effect model was used to pool the data. Summary receiver operator characteristic curves, analysis for publication bias, meta-regression, and subgroup analysis were also performed. RESULTS: The pooled SLN identification rate and sensitivity were 0.97 and 0.89. 99mTc-human serum albumin with indocyanine green (ICG), 99mTc-antimony sulfur colloid with ICG, performing SLN biopsy ≥15 min after dye injection, an SLN ≥5, the basin dissection, laparoscopic surgery, in studies conducted in Japan and studies published after 2012, were associated with higher sensitivity. CT1 stage, performing SLN biopsy ≥15 min after dye injection, in studies conducted in Japan and studies published after 2012, were related with a higher identification rate. CONCLUSIONS: Dual tracer is promising in SLN biopsy in gastric cancer, and the clinical application of SLN biopsy should be limited to the patients of cT1N0M0 gastric cancer. The combination of 99mTc-human serum albumin and ICG as well as the combination of 99mTc-antimony sulfur colloid and ICG may be the optimal tracer combination. However, it seems not justified to put this technique into routine clinical application recently. Some factors that might enhance diagnostic value are identified.

Seroprevalence and Risk Factors of Fascioliasis in Yaks, Bos grunniens, from Three Counties of Gansu Province, China.

The aim of this study was to determine the seroprevalence and risk factors of fascioliasis in yaks, Bos grunniens, from 3 counties of Gansu Province in China. A total of 1,584 serum samples, including 974 samples from white yaks from Tianzhu, 464 from black yaks from Maqu, and 146 from black yaks from Luqu County, were collected and analyzed using ELISA to detect IgG antibodies against Fasciola hepatica. The overall F. hepatica seroprevalence was 28.7% (454/1,584), with 29.2% in white yaks (284/974) and 27.9% in black yaks (170/610). The seroprevalence of F. hepatica in yaks from Tianzhu, Luqu, and Maqu was 29.2%, 22.6%, and 29.5%, respectively. Female yaks (30.9%) had higher F. hepatica seroprevalence than male yaks (23.4%). Also, F. hepatica seroprevalence varied by different age group from 24.1% to 33.8%. Further, the seroprevalence ranged from 21.8% to 39.1% over different seasons. Interestingly, the season and age of yaks were associated with F. hepatica infection in yaks in the investigated areas. These findings provided a basis for further studies on this disease in yaks from 3 counties of Gansu Province in northwestern China, which may ultimately support the development of effective control strategies of fascioliasis in these areas.