Construction of a prognostic model for triple-negative breast cancer based on immune-related genes, and associations between the tumor immune microenvironment and immunological therapy.

BACKGROUND: Triple-negative breast cancer (TNBC) is the subtype of breast cancer with the worst prognosis, and it is highly heterogeneous. There is growing evidence that the tumor immune microenvironment (TIME) plays a crucial role in tumor development, maintenance, and treatment responses. Notably however, the full effects of the TIME on prognosis, TIME characteristics, and immunotherapy responses in TNBC patients have not been fully elucidated. METHODS: Gene Expression Omnibus and The Cancer Genome Atlas data were used to data analysis. Single-cell sequencing and tissue microarray analysis were used to investigate gene expression. The concentrations and distributions of immune cell types were determined and analyzed using the CIBERSORT strategy. Tumor immune dysfunction and exclusion score and the IMvigor210 cohort were used to estimate the sensitivity of TNBC patients with different prognostic statuses to immune checkpoint treatment. RESULTS: Five immune-related genes associated with TNBC prognosis (IL6ST, NR2F1, CKLF, TCF7L2, and HSPA2) was identified and a prognostic evaluation model was constructed based on those genes. The respective areas under the curve of the prognostic nomogram model at 3 and 5 years were 0.791 and 0.859. The group with a lower nomogram score, with a better prognosis survival status and clinical treatment benefit rate. CONCLUSION: A prognostic model for TNBC that was closely related to the immune landscape and therapeutic responses was constructed. This model may help clinicians to make more precise and personalized treatment decisions pertaining to TNBC patients.

BMI-1 promotes breast cancer proliferation and metastasis through different mechanisms in different subtypes.

Breast cancer is among the most common malignant cancers in women. B-cell-specific Moloney murine leukemia virus integration site 1 (BMI-1) is a transcriptional repressor that has been shown to be involved in tumorigenesis, the cell cycle, and stem cell maintenance. In our study, increased expression of BMI-1 was found in both human triple negative breast cancer and luminal A-type breast cancer tissues compared with adjacent tissues. We also found that knockdown of BMI-1 significantly suppressed cell proliferation and migration in vitro and in vivo. Further mechanistic research demonstrated that BMI-1 directly bound to the promoter region of CDKN2D/BRCA1 and inhibited its transcription in MCF-7/MDA-MB-231. More importantly, we discovered that knockdown of CDKN2D/BRCA1 could promote cell proliferation and migration after repression by PTC-209. Our results reveal that BMI-1 transcriptionally suppressed BRCA1 in TNBC cell lines whereas, in luminal A cell lines, CDKN2D was the target gene. This provides a reference for the precise treatment of different types of breast cancer in clinical practice.

Availability of donor milk improves enteral feeding but has limited effect on body growth of infants with very-low birthweight: Data from a historic cohort study.

Compare with preterm formula, donor human milk (DM) is associated with a lower risk of mortality and morbidity in preterm infants. It is thus deemed superior to preterm formula as the sole diet or supplement to own mother's milk (OMM) for preterm infants, especially for those with very low birthweight (VLBW). This historic cohort study investigated the relationship between DM availability, and enteral feeding, body growth of VLBW infants by comparing two cohorts before and after the establishment of a human milk bank. A sub-analysis was also conducted between small-for-gestational-age (SGA) and non-SGA infants in our cohorts. Our results showed that DM availability was associated with earlier initiation and faster advancement of enteral feeding, earlier attainment of full enteral feeding, and a higher proportion of OMM in enteral feeding. DM availability was also associated with earlier regain of birthweight, but not with better body growth. SGA and non-SGA infants responded differently to DM availability with only the non-SGA group showing improved enteral feeding associated with DM availability. The poor growth of VLBW infants with fortified DM warrants further investigations on better fortification strategies to further improve body growth. Studies are also needed on long-term effects of DM feeding on the development of VLBW infants.

Antenatal corticosteroids affecting enteral feeding and growth of preterm infants: A retrospective cohort study.

BACKGROUND: Treatment of antenatal corticosteroids (ACSs) to women at risk of preterm labor can decrease neonatal mortality and morbidity. However, effect of ACS exposure on enteral feeding and body growth of preterm infants remains elusive. METHODS: This retrospective study collected information of eligible singleton infants born between 22+0 and 36+6 weeks' gestation from 2017 to 2019. Logistic regression and multivariate linear regression were adopted to examine the associations of the ACS exposure with various outcomes of enteral feeding and growth considering potential confounders. Stratified analysis was performed based on gestational age (GA) (<34 vs ≥34 weeks). RESULTS: Of the 1694 preterm infants included, 1222 (72.1%) were exposed to ACSs. Infants with ACS exposure had a higher incidence of feeding intolerance (odds ratio 1.51; 95% CI, 1.05 to 2.20; P = .03), slower advancement of enteral feeding (ß coefficient -0.86; 95% CI, -1.48 to -0.25; P = .01), and lower delta body-weight z-scores (ß coefficient-0.13; 95% CI, -0.18 to -0.08; P < .001). Unlike in infants with GA <34 weeks, ACS exposure was associated with slower advancement of enteral feeding, longer time to regain birth weight, and lower delta body-weight z-scores in the ones with GA ≥34 weeks. CONCLUSION: ACS exposure is associated with poorer enteral feeding process and body growth in our study population, which is more prominent in late preterm infants. A multicenter prospective study and mechanistic studies using animal models are required.

Plasma Metabolomics to Evaluate Progression of Necrotising Enterocolitis in Preterm Pigs.

Necrotising enterocolitis (NEC) is a microbiome-dependent gut disease in preterm infants in early life. Antibiotic treatment is a common intervention for NEC. How NEC lesions, with or without antibiotics, affect plasma metabolome was explored in this study. Formula-fed preterm pigs were used as a model for human NEC and treated with saline, parenteral or oral antibiotics (n = 15-17) for four days after delivery. Gut tissues were collected for evaluation of NEC-like lesions and plasma for metabolomic analysis by proton nuclear magnetic resonance spectroscopy (1H-NMR). Metabolites were annotated, quantified and subjected to statistical modelling to delineate the effects of NEC and antibiotic treatment. Presence of severe NEC lesions, not antibiotic treatment, was the main drive for plasma metabolite changes. Relative to other pigs, pigs with severe NEC lesions had higher levels of alanine, histidine and myo-inositol, and lower levels of 3-hydroxybutyric acid and isobutyric acid. Across NEC lesion states (healthy, mild, severe), antibiotics directly affected only a few metabolites (tryptophan, 3-phenyllactic acid). Together and independently, NEC and antibiotic treatment affected circulating metabolites in preterm pigs. Amino acids and plasma metabolites, partly related to the gut microbiome, may be helpful to monitor progression of NEC lesions after proper validation.

Early Protein Markers of Necrotizing Enterocolitis in Plasma of Preterm Pigs Exposed to Antibiotics.

Background: Most hospitalized preterm infants receive antibiotics in the first days of life to prevent or treat infections. Short-term, early antibiotic treatment may also prevent the microbiota-dependent gut inflammatory disorder, necrotizing enterocolitis (NEC). It remains a challenge to predict NEC, and a few early blood diagnostic markers exist. Using preterm pigs as model for infants, blood parameters and plasma proteins affected by early progression of NEC were profiled in preterm pigs subjected to oral, systemic, or no antibiotics after preterm birth. Methods: Preterm newborn pigs were treated with saline (CON) or antibiotics (ampicillin, gentamicin, and metronidazole) given enterally (ENT) or parenterally (PAR), and fed formula for 4 days to induce variable microbiome-dependent sensitivities to NEC. The gut was collected for macroscopic scoring of NEC lesions and blood for hematology, blood biochemistry, and LC/MS-based plasma proteomics. Statistical modeling was applied to detect plasma proteins affected by NEC and/or antibiotics. Results: Analyzed across different antibiotic regimens, NEC progression was associated with altered blood parameters and abundance of 89 plasma proteins that were functionally involved in extracellular membrane destruction, lipid metabolism, coagulopathy, and acute phase response. Large NEC-related changes were observed in abundance of RBP4, FGA, AHSG, C5, PTPRG, and A-1-antichymotrypsin 2, indicating potential serving as early markers of NEC. Conversely, antibiotic treatment, independent of NEC, affected only 4 proteins with main differences found between ENT and CON pigs. Conclusion: Early postnatal development of NEC lesions is associated with marked plasma protein changes that may be used for early NEC diagnosis.

Ultra-thin and broadband tunable metamaterial graphene absorber.

A broadband tunable metamaterial graphene absorber is investigated in this paper. The unit cell of the proposed metamaterial graphene absorber is composed of four patch resonators. By tuning the chemical potential of graphene and the geometric size of each patch, the simulated total reflectivity is less than -10 dB from 22.02 to 36.61 THz and with the total thickness of 0.76 um (only 0.09λ at the lowest frequency). The analysis of the surface current, magnetic field and power flow distributions has been performed to better understand the absorption mechanism. Moreover, this proposed absorber achieves its bandwidth tunable characteristics through a voltage biasing of the graphene's Fremi level. This proposed metamaterial graphene absorber (MGA) could be used as smart absorbers, photovoltaic devices and tunable sensors.

A 90° fair circular waveguide bend.

We propose a synthesis method to design a 90° bent fair circular waveguide TE01 mode transition based on the non-uniform rational B-spline technique. The transition by this method has advantages of small geometry, high transmission with wide band and high profile fairness. An example of design of such a transition is presented. The simulation shows that the transition exhibits a transmission as high as 99.3% at the central frequency 35 GHz and has a bandwidth of 16.7% when keeping the transmission over 95%. Furthermore, the profile is extremely fair, which meets the requirements to decrease the geometry errors between actual device and its design, to reduce the machining difficulty in the machining process. The hot test data indicate that good transmission of the TE01 mode is obtained.