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ABSTRACT: The addition of Bifidobacterium to goat milk has dual effects on health, for which various inherent nutrients of goat milk are retained and live probiotics are provided. We explored the effect of Bifidobacterium animalis ssp. lactis Probio-M8 (Probio-M8) on fermentation characteristics, formation of organic acid, sensory properties, and storage characteristics of fermented goat milk (with added 4.0% sucrose). Addition of Probio-M8 decreased the fermentation time and significantly increased the content of functional organic acids, such as acetic acid, and functional long-chain unsaturated fatty acids, including linoleic acid, α-linolenic acid, and docosahexaenoic acid. Furthermore, the contents of medium-chain and short-chain fatty acids, which are related to “goaty” flavor, were significantly lower in the Probio-M8 treatment compared with the control. The number of living Probio-M8 decreased from 8.27 log cfu/mL (1.80 × 108 cfu/mL) to 7.94 log cfu/mL (0.79 × 108 cfu/mL) after 28 d of storage. Titratable acidity and pH value did not differ between the control group and experimental group (containing Probio-M8). Sensory evaluation indicated a lower goaty flavor and odor in the Probio-M8 fermented milk. Our results suggest that the addition of the probiotic Probio-M8 could improve the sensory, physicochemical, and functional properties of fermented goat milk.

Stroke is one of the leading causes of death. (D-ala2, D-leu5) enkephalin (DADLE) is a synthetic peptide and highly selective delta opioid receptor (δOR) agonist that has exhibited protective properties in ischemia. However, the specific target and mechanism are still unclear. The present study explores the expression of δOR on brain microvascular endothelial cells (BMECs) and whether DADLE could relieve I/R-induced injury by reducing apoptosis. A lateral ventricular injection of DADLE for pretreatment, the neurofunctional behavior score, and TTC staining, were used to evaluate the protective effect of DADLE. Immunofluorescence technology was used to label different types of cells with apoptosis-positive signals to test co-localization status. Primary cultured BMECs were separated and treated with DADLE, accompanied by OGD/R. The CCK-8 test was conducted to evaluate cell viability and TdT-mediated dUTP Nick-end Labelling (TUNEL) staining to test apoptosis levels. The levels of apoptosis-related proteins were analyzed by Western blotting. The co-localization results showed that BMECs, but not astrocytes, microglia, or neurons, presented mostly TUNEL-positive signals, especially in the Dentate gyrus (DG) area of the hippocampus. Either activation of δORs on rats’ brains or primary BMECs mainly reduce cellular apoptosis and relieve the injury. Interference with the expression δOR could block this effect. DADLE also significantly increased levels of Bcl-2 and reduced levels of Bax. δOR’s expressions can be detected on the BMECs, but not on the HEK293 cells, by Western blotting and IFC. Therefore, DADLE exerts a cytoprotective effect, primarily under hypoxia-ischemic injury/reperfusion conditions, by targeting BMECs to inhibit apoptosis.

Abstract Background Cancer immunotherapy with immune checkpoint blockade (CKB) is now standard of care for multiple cancers. The clinical response to CKB is associated with T cell immunity targeting cancer-induced mutations that generate novel HLA-binding epitopes (neoepitopes). Methods Here, we developed a rapid bioinformatics pipeline and filtering strategy, EpitopeHunter, to identify and prioritize clinically relevant neoepitopes from the landscape of somatic mutations. We used the pipeline to determine the frequency of neoepitopes from the TCGA dataset of invasive breast cancers. We predicted HLA class I-binding neoepitopes for 870 breast cancer samples and filtered the neoepitopes based on tumor transcript abundance. Results We found that the total mutational burden (TMB) was highest for triple-negative breast cancer, TNBC, (median = 63 mutations, range: 2–765); followed by HER-2(+) (median = 39 mutations, range: 1–1206); and lowest for ER/PR(+)HER-2(−) (median = 32 mutations, range: 1–2860). 40% of the nonsynonymous mutations led to the generation of predicted neoepitopes. The neoepitope load (NEL) is highly correlated with the mutational burden (R2 = 0.86). Conclusions Only half (51%) of the predicted neoepitopes are expressed at the RNA level (FPKM≥2), indicating the importance of assessing whether neoepitopes are transcribed. However, of all patients, 93% have at least one expressed predicted neoepitope, indicating that most breast cancer patients have the potential for neo-epitope targeted immunotherapy.

Primary care clinicians in rural China are required to balance their immediate duty of care to their patients with patient expectations for antibiotics, financial pressures, and their wider responsibilities to public health. The clinicians in our sample appear to make greater efforts in managing immediate clinical risks and personal reputation than in considering the long-term consequences of their actions as potentially contributing to antimicrobial resistance. This paper employs Bourdieu's theory of capital to examine the perspectives and practices of Chinese primary care clinicians prescribing antibiotics at low-level health facilities in rural Anhui province, China. We examine the institutional context and clinical realities of these rural health facilities and identify how these influence the way clinicians utilize antibiotics in the management of common upper respiratory tract infections. Confronted with various official regulations and institutional pressures to generate revenues, informants' desire to maintain good relations with patients coupled with their concerns for patient safety result in tensions between their professional knowledge of “rational” antibiotic use and their actual prescribing practices. Informants often deferred responsibility for antimicrobial stewardship to the government or upper echelons of the healthcare system and drew on the powerful public discourse of “suzhi” (human quality) to legitimize their liberal prescribing of antibiotics in an imagined socioeconomic hierarchy. The demands of both practitioners' and patients' social, cultural, and economic forms of capital help to explain patterns of antibiotic prescribing in rural Chinese health facilities.

Abstract Background Elevated PD-L1 expression on tumor cells, a context associated with an adaptive immune response, has been linked to the total burden of copy number variants (CNVs) in aneuploid tumors, to microsatellite instability (MSI), and to specific genomic driver lesions, including loss of PTEN, MYC amplification, and activating mutations in driver oncogenes such as KRAS and PIK3CA. Triple-negative breast cancers (TNBCs) typically have high levels of CNVs and diverse driver lesions in their genomes. Thus, there is significant interest in exploiting genomic data to develop predictive immunotherapy biomarkers for patients with TNBC. Methods Whole tissue samples from 55 resected TNBCs were screened by immunohistochemistry (IHC) for PD-1 and PD-L1 by using validated antibodies and established scoring methods for staining of tumor and non-tumor cells. In parallel, we interrogated biopsies from each resection with DNA content flow cytometry and sorted the nuclei of diploid, tetraploid, and aneuploid cell populations. CNVs were mapped with CNV oligonucleotide arrays by using purified (>95%) tumor populations. We generated whole exome data for 12 sorted tumor samples to increase the resolution within loci of interest and to incorporate somatic mutations into our genomic signatures. Results and Conclusions PD-L1 staining was detected on tumor cells in 29 out of 54 (54%) evaluable cases and was associated with increased overall survival (P = 0.0024). High levels of PD-1 and PD-L1 (IHC ≥4) were present in 11 out of 54 (20%) and 20 out of 54 (37%) cases with staining of PD-L1 primarily on tumor cells for 17 out of 20 (85%) cases. The latter included tumors with both high (>50) and low (

Introduction This study aims to investigate patterns of antibiotic treatment-seeking, describe current levels of and drivers for antibiotic use for common infections (respiratory tract and urinary tract infections) and test the feasibility of determining the prevalence and epidemiology of antimicrobial resistance (AMR) in rural areas of Anhui province, in order to identify potential interventions to promote antibiotic stewardship and reduce the burden of AMR in China.Methods and analysis We will conduct direct observations, structured and semistructured interviews in retail pharmacies, village clinics and township health centres to investigate treatment-seeking and antibiotic use. Clinical isolates from 1550 sputum, throat swab and urine samples taken from consenting patients at village and township health centres will be analysed to identify bacterial pathogens and ascertain antibiotic susceptibilities. Healthcare records will be surveyed for a subsample of those recruited to the study to assess their completeness and accuracy.Ethics and dissemination The full research protocol has been reviewed and approved by the Biomedical Ethics Committee of Anhui Medical University (reference number: 20170271). Participation of patients and doctors is voluntary and written informed consent is sought from all participants. Findings from the study will be disseminated through academic routes including peer-reviewed publications and conference presentations, via tailored research summaries for health professionals, health service managers and policymakers and through an end of project impact workshop with local and regional stakeholders to identify key messages and priorities for action.