Quantifying chemical short-range order in metallic alloys.

Metallic alloys often form phases-known as solid solutions-in which chemical elements are spread out on the same crystal lattice in an almost random manner. The tendency of certain chemical motifs to be more common than others is known as chemical short-range order (SRO), and it has received substantial consideration in alloys with multiple chemical elements present in large concentrations due to their extreme configurational complexity (e.g., high-entropy alloys). SRO renders solid solutions "slightly less random than completely random," which is a physically intuitive picture, but not easily quantifiable due to the sheer number of possible chemical motifs and their subtle spatial distribution on the lattice. Here, we present a multiscale method to predict and quantify the SRO state of an alloy with atomic resolution, incorporating machine learning techniques to bridge the gap between electronic-structure calculations and the characteristic length scale of SRO. The result is an approach capable of predicting SRO length scale in agreement with experimental measurements while comprehensively correlating SRO with fundamental quantities such as local lattice distortions. This work advances the quantitative understanding of solid-solution phases, paving the way for the rigorous incorporation of SRO length scales into predictive mechanical and thermodynamic models.

Inhibition of EHMT1/2 rescues synaptic damage and motor impairment in a PD mouse model.

Epigenetic dysregulation that leads to alterations in gene expression and is suggested to be one of the key pathophysiological factors of Parkinson's disease (PD). Here, we found that α-synuclein preformed fibrils (PFFs) induced histone H3 dimethylation at lysine 9 (H3K9me2) and increased the euchromatic histone methyltransferases EHMT1 and EHMT2, which were accompanied by neuronal synaptic damage, including loss of synapses and diminished expression levels of synaptic-related proteins. Furthermore, the levels of H3K9me2 at promoters in genes that encode the synaptic-related proteins SNAP25, PSD95, Synapsin 1 and vGLUT1 were increased in primary neurons after PFF treatment, which suggests a linkage between H3K9 dimethylation and synaptic dysfunction. Inhibition of EHMT1/2 with the specific inhibitor A-366 or shRNA suppressed histone methylation and alleviated synaptic damage in primary neurons that were treated with PFFs. In addition, the synaptic damage and motor impairment in mice that were injected with PFFs were repressed by treatment with the EHMT1/2 inhibitor A-366. Thus, our findings reveal the role of histone H3 modification by EHMT1/2 in synaptic damage and motor impairment in a PFF animal model, suggesting the involvement of epigenetic dysregulation in PD pathogenesis.

[Study on methods measuring mechanical properties of arterial wall by macroscopic indentation].

Accurately evaluating the local biomechanics of arterial wall is crucial for diagnosing and treating arterial diseases. Indentation measurement can be used to evaluate the local mechanical properties of the artery. However, the effects of the indenter's geometric structure and the analysis theory on measurement results remain uncertain. In this paper, four kinds of indenters were used to measure the pulmonary aorta, the proximal thoracic aorta and the distal thoracic aorta in pigs, and the arterial elastic modulus was calculated by Sneddon and Sirghi theory to explore the influence of the indenter geometry and analysis theory on the measured elastic modulus. The results showed that the arterial elastic modulus measured by cylindrical indenter was lower than that measured by spherical indenter. In addition, compared with the calculated results of Sirghi theory, the Sneddon theory, which does not take adhesion forces in account, resulted in slightly larger elastic modulus values. In conclusion, this study provides parametric support for effective measurement of arterial local mechanical properties by millimeter indentation technique.

Interstitial Hydrogen Atom to Boost Intrinsic Catalytic Activity of Tungsten Oxide for Hydrogen Evolution Reaction.

Tungsten oxide (WO3 ) is an appealing electrocatalyst for the hydrogen evolution reaction (HER) owing to its cost-effectiveness and structural adjustability. However, the WO3 electrocatalyst displays undesirable intrinsic activity for the HER, which originates from the strong hydrogen adsorption energy. Herein, for effective defect engineering, a hydrogen atom inserted into the interstitial lattice site of tungsten oxide (H0.23 WO3 ) is proposed to enhance the catalytic activity by adjusting the surface electronic structure and weakening the hydrogen adsorption energy. Experimentally, the H0.23 WO3 electrocatalyst is successfully prepared on reduced graphene oxide. It exhibits significantly improved electrocatalytic activity for HER, with a low overpotential of 33 mV to drive a current density of 10 mA cm-2 and ultra-long catalytic stability at high-throughput hydrogen output (200 000 s, 90 mA cm-2 ) in acidic media. Theoretically, density functional theory calculations indicate that strong interactions between interstitial hydrogen and lattice oxygen lower the electron density distributions of the d-orbitals of the active tungsten (W) centers to weaken the adsorption of hydrogen intermediates on W-sites, thereby sufficiently promoting fast desorption from the catalyst surface. This work enriches defect engineering to modulate the electron structure and provides a new pathway for the rational design of efficient catalysts for HER.

Genome-Wide Identification and Analysis of the Plant Cysteine Oxidase (PCO) Gene Family in Brassica napus and Its Role in Abiotic Stress Response.

Plant Cysteine Oxidase (PCO) is a plant O2-sensing enzyme catalyzing the oxidation of cysteine to Cys-sulfinic acid at the N-termini of target proteins. To better understand the Brassica napus PCO gene family, PCO genes in B. napus and related species were analyzed. In this study, 20, 7 and 8 PCO genes were identified in Brassica napus, Brassica rapa and Brassica oleracea, respectively. According to phylogenetic analysis, the PCOs were divided into five groups: PCO1, PCO2, PCO3, PCO4 and PCO5. Gene organization and motif distribution analysis suggested that the PCO gene family was relatively conserved during evolution. According to the public expression data, PCO genes were expressed in different tissues at different developmental stages. Moreover, qRT-PCR data showed that most of the Bna/Bra/BoPCO5 members were expressed in leaves, roots, flowers and siliques, suggesting an important role in both vegetative and reproductive development. Expression of BnaPCO was induced by various abiotic stress, especially waterlogging stress, which was consistent with the result of cis-element analysis. In this study, the PCO gene family of Brassicaceae was analyzed for the first time, which contributes to a comprehensive understanding of the origin and evolution of PCO genes in Brassicaceae and the function of BnaPCO in abiotic stress responses.

The Potential Role of Timosaponin-AIII in Cancer Prevention and Treatment.

Cancer, as one of the leading causes of death worldwide, has challenged current chemotherapy drugs. Considering that treatments are expensive, alongside the resistance of tumor cells to anticancer drugs, the development of alternative medicines is necessary. Anemarrhena asphodeloides Bunge, a recognized and well-known medicinal plant for more than two thousand years, has demonstrated its effectiveness against cancer. Timosaponin-AIII (TSAIII), as a bioactive steroid saponin isolated from A. asphodeloides, has shown multiple pharmacological activities and has been developed as an anticancer agent. However, the molecular mechanisms of TSAIII in protecting against cancer development are still unclear. In this review article, we provide a comprehensive discussion on the anticancer effects of TSAIII, including proliferation inhibition, cell cycle arrest, apoptosis induction, autophagy mediation, migration and invasion suppression, anti-angiogenesis, anti-inflammation, and antioxidant effects. The pharmacokinetic profiles of TSAII are also discussed. TSAIII exhibits efficacy against cancer development. However, hydrophobicity and low bioavailability may limit the application of TSAIII. Effective delivery systems, particularly those with tissue/cell-targeted properties, can also significantly improve the anticancer effects of TSAIII.

Intratumoral PD-1+CD8+ T cells associate poor clinical outcomes and adjuvant chemotherapeutic benefit in gastric cancer.

BACKGROUND: Although PD-1 has been reported to be a marker of T-cell exhaustion in several malignancies, the biological role of PD-1+CD8+ T cells in gastric cancer (GC) remains unclear. Herein, we aimed to investigate the role of PD-1+CD8+ T cells in the tumour microenvironment and its clinical significance in GC. DESIGNS: This study included 441 tumour microarray specimens and 60 Flow cytometry specimens of GC patients from Zhongshan Hospital, and 250 GC patients from the Asian Cancer Research Group. RESULTS: Here, we demonstrated that PD-1+CD8+ T cells functioned as an independent adverse prognosticator in GC. In addition, an abundance of intratumoral PD-1+CD8+ T cells indicated worse chemotherapeutic responsiveness to fluorouracil in Stage III GC patients. Mechanistically, PD-1+CD8+ T cell high infiltration indicated an exhausted phenotype of global CD8+ T cells in GC tissues, which was characterised by elevated immune checkpoint expression including CTLA-4 and TIM-3, whereas decreased expression of perforin. Furthermore, PD-1+CD8+ T cell high-infiltration patients with Stage III GC held elevated activity of several therapeutic signal pathways. CONCLUSIONS: Our study highlighted that PD-1+CD8+ T cell abundance predicts inferior prognosis in GC, and may serve as a novel predictive biomarker to guide therapeutic option.

TIM3+ cells in gastric cancer: clinical correlates and association with immune context.

BACKGROUND: T cell immunoglobulin and mucin domain-containing protein 3 (TIM3) is a crucial immune checkpoint and is considered as an emerging target for cancer treatment. However, the clinical significance and immune-related role of TIM3+ cells in gastric cancer remain unknown. This study aimed to investigate the clinical significance of tumour-infiltrating TIM3+ cells and their association with immune contexture in gastric cancer. METHODS: This study enrolled three cohorts, including 436 tumour tissue microarray specimens and 58 fresh tumour tissues of gastric cancer patients from Zhongshan Hospital, and 330 transcriptional data from The Cancer Genome Atlas. TIM3+ cells and their association with CD8+ T cells were evaluated by immunohistochemistry and flow cytometry analyses. Kaplan-Meier curves, Cox model and interaction test were performed to assess clinical outcomes. RESULTS: Tumour-infiltrating TIM3+ cells' high subgroups experienced poorer overall survival and disease-free survival and predicted inferior therapeutic responsiveness to fluorouracil-based adjuvant chemotherapy. TIM3 indicated CD8+ T cell dysfunction, which impeded chemotherapeutic responsiveness. Besides, HAVCR2 messenger RNA expression was associated with specific molecular characteristics. CONCLUSIONS: The abundance of tumour-infiltrating TIM3+ cells could identify an immunoevasive subtype gastric cancer with CD8+ T cell dysfunction, suggesting that TIM3 might serve as a promising target for immunotherapy in gastric cancer.

Poor Clinical Outcomes and Immunoevasive Contexture in Intratumoral IL-10-Producing Macrophages Enriched Gastric Cancer Patients.

OBJECTIVE: To investigate the clinical significance of IL-10+ tumor-associated macrophages (TAMs) in gastric cancer. BACKGROUND: Due to the plasticity and diversity of TAMs, it is necessary to phenotypically and functionally classify subsets of TAMs to better understand the critical role of TAMs in cancer progression. TAMs expressing interleukin-10 (IL-10) have been found to facilitate immune evasion in many malignancies, but the role of IL-10+ TAMs in gastric cancer remains obscure. METHODS: Four hundred and sixty-eight tumor tissue microarray specimens, 52 fresh tumor tissue samples of gastric cancer patients from Zhongshan Hospital, and data of 298 gastric cancer patients from the Cancer Genome Atlas (TCGA) were analyzed. IL-10+ TAM level and immune contexture were examined by CIBERSORT, immunohistochemistry, and flow cytometry. Clinical outcomes were analyzed by Kaplan-Meier curves and Cox model. RESULTS: Gastric cancer patients with high IL-10+ TAM infiltration exhibited poor prognosis and inferior therapeutic responsiveness to fluorouracil-based adjuvant chemotherapy. IL-10+ TAM infiltration yielded an immunoevasive tumor microenvironment featured by regulatory T cell infiltration and CD8+ T cell dysfunction. The combinational analysis of IL-10+ TAM and CD8+ T cell infiltration stratified patients into distinct risk groups with different clinical outcomes. Moreover, IL-10+ TAM infiltration was correlated with tumor-intrinsic characteristics including EBV status, PD-L1 expression, and genome stability in gastric cancer. CONCLUSIONS: This study revealed that IL-10+ TAMs might drive an immunoevasive microenvironment and determine poor prognosis and inferior therapeutic responsiveness to fluorouracil-based adjuvant chemotherapy, indicating IL-10+ TAMs could be applied as a potential target for immunotherapeutic approach in gastric cancer.

Latency-associated Peptide Identifies Immunoevasive Subtype Gastric Cancer With Poor Prognosis and Inferior Chemotherapeutic Responsiveness.

OBJECTIVE: To examine the clinical significance of LAP to predict survival outcomes and chemotherapeutic responsiveness in gastric cancer. BACKGROUND: LAP has been shown to possess significant immunoregulatory roles in several malignancies. However, the role and clinical significance of LAP in gastric cancer still remains unknown. METHODS: Four hundred and fifty-six tumor tissue microarray specimens, 80 fresh tumor tissue samples of gastric cancer patients from Zhongshan Hospital, Fudan University and transcriptomic and clinical data of 328 gastric cancer patients from the Cancer Genome Atlas were analyzed. LAP expression and immune contexture were examined by immunohistochemistry, CIBERSORT, and flow cytometry. Clinical outcomes of patient subgroups were compared by Kaplan-Meier curves, Cox model and interaction test. RESULTS: High LAP expression predicted poor overall survival (P < 0.001, P < 0.001, and P = 0.022) and inferior therapeutic responsiveness to fluorouracil-based adjuvant chemotherapy (P = 0.008 for interaction) in gastric cancer. LAP was associated with immunoevasive tumor microenvironment featured by dysfunctional CD8+ T cells infiltration (P < 0.001). The LAP-associated dysfunctional CD8+ T cells had an exhausted phenotype with decreased effector molecules such as interferon-γ, granzyme B, and perforin, but also elevated programmed cell death protein-1, which resulted in poor prognosis and inferior therapeutic responsiveness. CONCLUSIONS: This study revealed that LAP could identify immunoevasive subtype gastric cancer, indicating LAP might be a potential immunotherapeutic target and facilitate patient counseling on individualized adjuvant therapy and follow-up scheduling in gastric cancer.

Intratumoral Foxp3+RORγt+ T cell infiltration determines poor prognosis and immunoevasive contexture in gastric cancer patients.

BACKGROUND: Foxp3+RORγt+ T cells possess both characteristics of regulatory T cells and T helper 17 cells and show significant immunoregulatory functions in autoimmune diseases. However, the role and clinical significance of Foxp3+RORγt+ T cells in gastric cancer remains unclear. METHODS: We enrolled 452 gastric cancer tissue microarray samples and 60 fresh tumor tissue samples from Zhongshan Hospital. The infiltration of Foxp3+RORγt+ T cells and immune contexture were examined by immunohistochemistry and flow cytometry. Survival analyses of patient subgroups were conducted by Kaplan-Meier curves, log-rank test and Cox proportional model. RESULTS: High infiltration of Foxp3+RORγt+ T cells predicted poor overall survival (P = 0.0222 and 0.0110) and inferior therapeutic response (P = 0.003 for interaction) in gastric cancer. Foxp3+RORγt+ T cells were associated with impaired effective function of CD8+ T cells featured by decreased interferon-γ, granzyme B and CD107a expression. Co-evaluation of Foxp3+RORγt+ T cells and CD8+ T cells could predict survival outcomes and chemotherapeutic responsiveness more precisely. CONCLUSIONS: We found that Foxp3+RORγt+ T cells could potentially attenuate effective functions of CD8+ T cells and led to adverse survival outcomes and inferior chemotherapeutic responsiveness. Moreover, the novel co-evaluation system might be useful for prognosis prediction for appropriate treatment in gastric cancer. NOVELTY AND IMPACT STATEMENTS: Clinical significance of Foxp3+RORγts+ T cells has not been studied in gastric cancer. Herein, we investigated the prognostic value of Foxp3+RORγt+ T cells in 452 patients. We demonstrated that intratumoral Foxp3+RORγt+ T cell infiltration was a prognostic biomarker for overall survival and the identification of patients might benefit from post-gastrectomy 5-fluorouracil. These findings allow a more precise stratification upon the co-evaluation with CD8+ T cells to better clinical management for patients who would benefit from 5-fluorouracil.

Lymphocyte-activation gene 3 expression associates with poor prognosis and immunoevasive contexture in Epstein-Barr virus-positive and MLH1-defective gastric cancer patients.

Lymphocyte activation gene 3 (LAG-3) is a transmembrane immune checkpoint that facilitates immune escape via suppressing T-cell-mediated anti-tumor immunity. The role of LAG-3 in gastric cancer is little known. Consequently, we assessed the clinical significance of LAG-3 in gastric cancer. In our study, patients with gastric cancer from Zhongshan Hospital (n = 464) and data from the Asian Cancer Research Group (n = 300) were analyzed. LAG-3+ cell infiltration and other immune contexture in gastric cancer were detected by immunohistochemistry. Kaplan-Meier curves and log-rank test were used for survival analyses. Intratumoral LAG-3+ cells mainly accumulated in Epstein-Barr virus (EBV)-positive (EBV subtype) and MLH1-defective (dMLH1 subtype) gastric cancer. Furthermore, LAG-3+ cell infiltration was strongly associated with inferior clinical outcomes in patients with these two subtypes of gastric cancer. Moreover, we found intratumoral LAG-3+ cell high infiltration was associated with an immunoevasive contexture featured by decreased IFN-γ+ cells and perforin-1+ cells, but increased regulatory T cells and M2-like macrophages in EBV/dMLH1 subtype of gastric cancer. LAG-3 was a poor prognostic factor and might be a potential immunotherapeutic target in EBV-positive and MLH1-defective gastric cancer.

CD47 expression in gastric cancer clinical correlates and association with macrophage infiltration.

BACKGROUND: CD47 has been identified as an innate immune checkpoint and found to be associated with inferior survival in various types of cancer. However, the critical role of CD47 in gastric cancer and its association with tumor associated macrophages remain unclear. METHODS: Tumor tissues of gastric cancer from Zhongshan Hospital and data from GSE62254, GSE84437 and TCGA datasets were analyzed. Immunohistochemistry was performed to detect the expression of CD47, CD11c, CD163 and CD68 in gastric cancer tissues. Kaplan-Meier curves and Cox model were used for comparing the clinical outcomes of patients belonging to different subgroups. RESULTS: Gastric cancer patients with high CD47 expression exhibited poor prognosis and inferior therapeutic responsiveness to fluorouracil-based adjuvant chemotherapy (ACT). A positive correlation was found between M1-polarized macrophage infiltration and CD47 expression in gastric cancer; however, the prognostic value of M1-polarized macrophages was attenuated in CD47-high gastric cancer patients. Moreover, we found that CD47 mRNA level was enriched in microsatellite-instable (MSI) subtype of gastric cancer and associated with ARID1A mutation and FGFR2 signaling pathway activation. CONCLUSIONS: Aberrant CD47 expression represented an independent predictor for adverse survival outcome and ACT resistance in gastric cancer. Targeting CD47 might be a promising strategy for gastric cancer patients.

Clinical Outcomes and Immune Metrics in Intratumoral Basophil-Enriched Gastric Cancer Patients.

BACKGROUND: Accumulation of basophils has been reported in several malignancies. In gastric cancer, the relation between tumor-infiltrating basophils and patient overall survival and chemotherapeutic responsiveness still remains obscure. OBJECTIVE: We aimed to investigate the postoperative prognostic and predictive significance of basophils to survival outcomes and chemotherapeutic responsiveness in resectable gastric cancer. METHODS: The study enrolled two independent patient data sets with 448 gastric cancer patients overall. Basophils were evaluated with the use of immunohistochemistry (IHC) staining, and the correlation with clinicopathological characteristics, survival outcomes, and responsiveness to fluorouracil-based adjuvant chemotherapy (ACT) were investigated. Additionally, IHC was applied to characterize immune contexture in gastric cancer. RESULTS: In either the discovery or validation data sets, accumulated basophils indicated poorer prognosis, and tumor-infiltrating basophils were identified as an independent adverse prognostic factor by multivariate analysis. Furthermore, tumor-infiltrating basophils determined significantly inferior therapeutic responsiveness to fluorouracil-based ACT in patients with stage III tumors. In addition, the abundance of basophils was correlated with an immunoevasive contexture characterized by M2-polarized macrophage infiltration. Moreover, our findings indicated elevated interleukin-4 expression but decreased interferon-γ expression in the high-basophils subgroup. CONCLUSIONS: Tumor-infiltrating basophils in gastric cancer were identified as an independent adverse prognosticator, and also predicted inferior chemotherapeutic responsiveness, which identified those patients in need of much more individualized postoperative adjuvant therapy and more stringent follow-up. Furthermore, the infiltration of basophils was associated with immunoevasive tumor microenvironment, which might be a potential immunotherapeutic target for gastric cancer.

Identification and validation of an immunogenic subtype of gastric cancer with abundant intratumoural CD103+CD8+ T cells conferring favourable prognosis.

BACKGROUND: Intratumoural CD103+CD8+ T cells have been linked to prolonged survival in several malignancies. However, the clinical significance of CD103+CD8+ T cells in gastric cancer remains unexplored. METHODS: Gastric cancer tissues from Zhongshan Hospital and data from Gene Expression Omnibus were obtained and analysed. Immunohistochemistry and flow cytometry were performed to detect the number and phenotypical characteristics of CD103+CD8+ T cells. The effect of programmed cell death protein-1 (PD-1) blockade on CD103+CD8+ T cells was evaluated with the use of an in vitro study based on fresh tumour tissues. RESULTS: CD103+CD8+ T cells predicted superior overall survival and provided better prognostic power than total CD8+ T cells in gastric cancer. Patients with high CD103+CD8+ T cell infiltration also gained more benefit from adjuvant chemotherapy. Flow cytometry analysis showed that CD103+CD8+ T cells exerted superior anti-tumour effects with stronger retention capacity and cytotoxicity. Moreover, an in vitro study showed that CD103+CD8+ T cells were more functionally restored after PD-1 blockade than CD103-CD8+ T cells. CONCLUSIONS: CD103+CD8+ T cells might be a useful marker to predict prognosis and therapeutic efficacy for gastric cancer patients. Efforts to increase intratumoural CD103+CD8+ T cell frequency might be a novel therapeutic strategy in gastric cancer.

Lauren classification identifies distinct prognostic value and functional status of intratumoral CD8+ T cells in gastric cancer.

With dichotomous etiology and pathogenesis, intestinal type and diffuse type gastric cancers vary in their clinical and molecular features to the point of representing distinct entities. However, the differences of tumor-infiltrating immune cells within the two types of gastric cancer have not been well researched. This study was aimed to evaluate the functional impact of Lauren classification on immune contexture in gastric cancer patients. Tumor tissues of gastric cancer patients from Zhongshan Hospital and gastric cancer data from The Cancer Genome Atlas (TCGA) cohort were analyzed. By immunohistochemistry and flow cytometry, we found that intratumoral CD8+ T cells were more abundant but less functional in diffuse type as compared with those in intestinal type tumor tissues. Survival analysis indicated that CD8+ T cells yielded favorable prognosis only in intestinal type patients other than diffuse type cancer patients. Moreover, such diffuse type-associated CD8+ T cell dysfunction was featured by elevated expression of immunosuppressive factors including interleukin-10 (IL-10), transforming growth factor-ß1 (TGF-ß1) and indoleamine 2,3-dioxygenase 1 (IDO1). In summary, we found that the density, prognostic significance and functional status of intratumoral CD8+ T cells varied with Lauren subtypes in gastric cancer. These results further indicated Lauren classification might be a potential therapeutic marker, and should be considered in therapeutic decisions, especially immunotherapeutic eligibility.

Synergistic effects of predation and parasites on the overwinter survival of root voles.

Predators and parasites have been important extrinsic factors influencing the fluctuation of small mammal populations. They can have non-additive effects on a shared group of preys or hosts, which can have important consequences for population dynamics. However, experimental studies incorporating the interactions between predation and parasites are scarce in small mammal populations. Here we systematically examined the synergistic effects of predators and coccidian parasites interaction on overwinter survival and likely mechanisms underlying the synergistic effects in the root vole (Microtus oeconomus). Our aim was to test the general hypothesis that predators and coccidia interact synergistically to decrease overwinter survival of root voles through mediating vole's physiological traits and body conditions. We carried out a factorial experimental design, by which we manipulated the predator exclusion in combination with the parasitic removal in enclosures, and then measured fecal corticosterone metabolite (FCM) levels, immunocompetence, and body conditions in captured animals via repeated live trapping. We found a strong negative synergistic effect of predators and coccidia on survival. Importantly, we found that predators increased both the prevalence and intensity of coccidian infection in voles through immune suppression induced by predation stress, while increased coccidian infection reduced plasma protein and hematocrit level of voles, which may impair anti-predator ability of voles and lead to an increase in predation. Our finding showed when voles are exposed to both predation risk and infection, their synergistic effects greatly reduce overwinter survival and population density. This may be an important mechanism influencing population dynamics in small mammals.

Five new species of Eimeria Schneider, 1875 from the endangered Tibetan antelope Pantholops hodgsonii (Abel) (Artiodactyla: Bovidae: Caprinae) in the Hoh Xil Nature Reserve Area of Qinghai Province, China.

We examined faeces of 76 endangered Tibetan antelopes Pantholops hodgsonii (Abel) in May 2017, from the Hoh Xil Nature Reserve, Qinghai Province, China, and found 62/76 (82%) discharging oöcysts representing five new species of Eimeria Schneider, 1875. Oöcysts of Eimeria pantholopensis n. sp., found in 54/76 (71%) chiru, are subspheroidal/ellipsoidal, 15-22 × 12-19 (18.6 × 16.1) µm, with a length/width (L/W) ratio of 1.0-1.3 (1.2); micropyle cap and 1-3 polar granules are present, but oöcyst residuum is absent. Sporocysts are ovoidal, 7-11 × 4-6 (9.2 × 5.3) µm, with a L/W ratio of 1.6-2.0 (1.7); Stieda body and sporocyst residuum of small, scattered granules are present; each sporozoite contains 2 refractile bodies. Oöcysts of Eimeria wudaoliangensis n. sp. found in 52/76 (68%) chiru, are pyriform, 21-29 × 17-21 (24.9 × 19.0) µm, with a L/W ratio of 1.1-1.5 (1.3); micropyle, micropyle cap and 1-4 polar granules are present, but oöcyst residuum is absent. Sporocysts are ovoidal, 9-13 × 5-8 (11.7 × 6.7) µm, with a L/W ratio of 1.4-2.7 (1.7); Stieda body and sporocyst residuum of disbursed granules are present; sporozoites have a single large refractile body. Oöcysts of Eimeria hodgsonii n. sp. found in 20/76 (26%) chiru, are elongate-ellipsoidal, 25-32 × 18-21 (28.9 × 19.8) µm, with a L/W ratio of 1.2-1.7 (1.5); micropyle, micropyle cap and 1-3 polar granules are present, but oöcyst residuum is absent. Sporocysts are ovoidal, 11-14 × 6-7 (12.3 × 6.8) µm, with a L/W ratio of 1.7-2.1 (1.8); Stieda body and sporocyst residuum as group of large granules lying along the interface between intertwined sporozoites are present; sporozoites have 2 refractile bodies. Oöcysts of Eimeria schalleri n. sp. found in 49/76 (64.5%) chiru, are ellipsoidal, 26-36 × 19-25 (30.4 × 23.2) µm, with a L/W ratio of 1.2-1.5 (1.3); micropyle with micropyle cap and polar granules appearing as many diffuse tiny bodies are present, but oöcyst residuum is absent. Sporocysts are ovoidal, 12-16 × 7-9 (14.2 × 7.8) µm, with a L/W ratio of 1.6-2.1 (1.8); Stieda body and sporocyst residuum are present, the latter as a group of small dispersed granules between intertwined sporozoites; sporozoites with 2 refractile bodies. Oöcysts of Eimeria sui n. sp. found in 4/76 (5%) chiru, are ovoidal, 32-38 × 26-30 (36.6 × 28.6) µm, with a L/W ratio of 1.0-1.4 (1.3); micropyle and micropyle cap and 1-3 polar granules are present, but oöcyst residuum is absent. Sporocysts are ovoidal, 15-18 × 8-10 (16.7 × 8.9) µm, with a L/W ratio of 1.7-2.1 (1.9); Stieda body and sporocyst residuum are present, the latter as a group of dispersed small granules; sporozoites with 2 refractile bodies. Five of 62 faecal samples in which oöcysts were detected (8%) had a single species infection, 13 of 62 (21%) had two species, 28 of 62 (45%) had three species and 16 of 62 (26%) had four species.

Prognostic and Predictive Value of O6-methylguanine Methyltransferase for Chemotherapy in Patients with Muscle-Invasive Bladder Cancer.

PURPOSE: DNA repair genes are potential biomarkers for chemotherapy in muscle-invasive bladder cancer (MIBC). O6-methylguanine methyltransferase (MGMT) is involved in DNA repair and is found to affect the efficacy of platinum-based chemotherapy. However, the prognostic or predictive value of MGMT expression in chemotherapy for MIBC is unknown. MATERIALS AND METHODS: Immunohistochemical staining for MGMT was performed in paraffin-embedded tumor tissue of high-grade MIBC patients who underwent cystectomy in two independent cohorts [n = 74 for Fudan University Shanghai Cancer Center (FUSCC) cohort and n = 115 for Zhongshan Hospital (ZS) cohort]. MGMT messenger RNA (mRNA) analysis was conducted using patients' clinical and fragments per kilobase of exon model per million mapped fragments mRNA data from The Cancer Genome Atlas (TCGA) database (n = 245). RESULTS: In our cohorts, high MGMT expression was significantly correlated with shorter overall survival (OS) in patients with platinum-based adjuvant chemotherapy [hazard ratio (HR) 2.386, p = 0.048; HR 2.920, p = 0.007; HR 2.324, p = 0.004, respectively, in FUSCC, ZS, and combination sets], but not in patients without chemotherapy. These findings were corroborated by the TCGA set (HR 1.952 and 0.697 for patients with and without chemotherapy, respectively). The chemotherapy-MGMT interaction for OS was significant in both the surgery set (p = 0.045) and TCGA set (p = 0.034). CONCLUSIONS: We demonstrated that high MGMT expression is an independent poor prognostic factor in MIBC patients with platinum-based adjuvant chemotherapy, but not in patients without chemotherapy. MGMT expression may be a potential predictor for administration of adjuvant chemotherapy.

B4GALT1 expression predicts prognosis and adjuvant chemotherapy benefits in muscle-invasive bladder cancer patients.

BACKGROUND: The expression alterations of B4GALT1 have been noted in some types of cancer and they are related to cancer cell proliferation, invasiveness, metastasis, and drug resistance. We aimed to establish the expression of B4GALT1 in bladder cancer and its connection to patient outcomes, as well as forecasting the advantages of adjuvant chemotherapy (ACT) in patients with muscle-invasive bladder cancer (MIBC). METHODS: There were 142 and 112 MIBC patients who were consecutively recruited and treated via radical cystectomy from 2008 to 2012 in Shanghai Zhongshan Hospital and Fudan University Shanghai Cancer Center (FUSCC), respectively. Tissue microarrays (TMAs) were constructed in triplicate from specimens that had been fixed in formalin and embedded in paraffin samples. Immunohistochemistry was conducted to evaluate B4GALT1 expression in tumor cores, the connection between B4GALT1 expression and patients' clinical characteristics, and clinical results. RESULTS: B4GALT1 expression was not connected to clinical prognosis markers, but it was linked to overall survival (OS) (P = 0.013 and P = 0.010, respectively) in the two groups. Moreover, the high levels of B4GALT1 expression were independent indicators of poor OS (P = 0.026 and P = 0.046, respectively). Inclusion of B4GALT1 in the prognostic model revealed a greater predictive accuracy than the primary models. In addition, no differences were observed between B4GALT1 expression (low vs. high) and CD8+ T cell infiltration density (number/cm2) within tumor cores, but there was a positive Pearson correlation between B4GALT1 expression and expression of inhibitory receptor ligands, such as PD-L1 and CTLA4. Most significantly, the advantage of ACT noted in pT3/4 or N+ bladder cancer patients with low B4GALT1 expression was greater than in patients with a high B4GALT1 expression. CONCLUSIONS: Our evaluation indicated that B4GALT1 may be a possible prognosticator of MIBC, and it may be a predictive marker for the choice of ACT in pT3/4 or N+ patients.