Unconventional tonicity-regulated nuclear trafficking of NFAT5 mediated by KPNB1, XPOT and RUVBL2.

NFAT5 is the only known mammalian tonicity-responsive transcription factor with an essential role in cellular adaptation to hypertonic stress. It is also implicated in diverse physiological and pathological processes. NFAT5 activity is tightly regulated by extracellular tonicity, but the underlying mechanisms remain elusive. Here, we demonstrate that NFAT5 enters the nucleus via the nuclear pore complex. We found that NFAT5 utilizes a unique nuclear localization signal (NFAT5-NLS) for nuclear import. siRNA screening revealed that only karyopherin ß1 (KPNB1), but not karyopherin α, is responsible for the nuclear import of NFAT5 via direct interaction with the NFAT5-NLS. Proteomics analysis and siRNA screening further revealed that nuclear export of NFAT5 under hypotonicity is driven by exportin-T (XPOT), where the process requires RuvB-like AAA-type ATPase 2 (RUVBL2) as an indispensable chaperone. Our findings have identified an unconventional tonicity-dependent nucleocytoplasmic trafficking pathway for NFAT5 that represents a critical step in orchestrating rapid cellular adaptation to change in extracellular tonicity. These findings offer an opportunity for the development of novel NFAT5 targeting strategies that are potentially useful for the treatment of diseases associated with NFAT5 dysregulation.

Super enhancer related gene ANP32B promotes the proliferation of acute myeloid leukemia by enhancing MYC through histone acetylation.

BACKGROUND: Acute myeloid leukemia (AML) is a malignancy of the hematopoietic system, and childhood AML accounts for about 20% of pediatric leukemia. ANP32B, an important nuclear protein associated with proliferation, has been found to regulate hematopoiesis and CML leukemogenesis by inhibiting p53 activity. However, recent study suggests that ANP32B exerts a suppressive effect on B-cell acute lymphoblastic leukemia (ALL) in mice by activating PU.1. Nevertheless, the precise underlying mechanism of ANP32B in AML remains elusive. RESULTS: Super enhancer related gene ANP32B was significantly upregulated in AML patients. The expression of ANP32B exhibited a negative correlation with overall survival. Knocking down ANP32B suppressed the proliferation of AML cell lines MV4-11 and Kasumi-1, along with downregulation of C-MYC expression. Additionally, it led to a significant decrease in H3K27ac levels in AML cell lines. In vivo experiments further demonstrated that ANP32B knockdown effectively inhibited tumor growth. CONCLUSIONS: ANP32B plays a significant role in promoting tumor proliferation in AML. The downregulation of ANP32B induces cell cycle arrest and promotes apoptosis in AML cell lines. Mechanistic analysis suggests that ANP32B may epigenetically regulate the expression of MYC through histone H3K27 acetylation. ANP32B could serve as a prognostic biomarker and potential therapeutic target for AML patients.

Peroxidase-like activity and mechanism of gold nanoparticle-modified Ti3C2 MXenes for the construction of H2O2 and ampicillin colorimetric sensors.

Transition metal carbides modified by Au nanoparticles (Au/Ti3C2) were synthesized and developed as a colorimetric sensor for the determination of H2O2 and ampicillin. The surface electrical properties of Ti3C2 were changed, and Au nanoparticles (AuNPs) and gold growth solution were synthesized simultaneously. Au/Ti3C2 was obtained by seed growth method with AuNPs modified on the surface of transition metal carbides, nitrides or carbon-nitrides (Ti3C2 MXenes). The synthesized AuNPs and Ti3C2 had no peroxidase-like activity, but Au/Ti3C2 had. The peroxidase catalytic mechanism was due to electron transfer. The peroxidase activity of Au/Ti3C2 can be utilized for the determination of H2O2. The linear range of Au/Ti3C2 for H2O2 was 1-60 µM, and the detection limit was 0.12 µM (S/N = 3). A colometric sensor for ampicillin detection based on Au/Ti3C2 was further constructed since S in ampicillin formed an Au-S bond with Au/Ti3C2, leading to the weakening of its peroxidase-like property. The change of peroxidase-like property attenuated oxidation of TMB, and the ampicillin content was inversely proportional to the concentration of oxidized TMB, and the blue color of solution faded, which enabled the determination of ampicillin. The linear range for ampicillin was 0.005-0.5 µg mL- 1, and the detection limit was 1.1 ng mL- 1 (S/N = 3). The sensor was applied to the detection of ampicillin in milk and human serum.

The Scar-Hidden Surgery on Gynecomastia: Experiences from a Single-Institutional Large Case Series.

BACKGROUND: To summarize the experiences on the mastoscopic subcutaneous mastectomy for gynecomastia by "nine-step method" based on the "5S" goal and standardize this operation. PATIENTS AND METHODS: Between January 1, 2002, and October 31, 2021, a total of 2035 breasts of 1082 male patients with gynecomastia, of which 129 patients with one side, were underwent mastoscopic subcutaneous mastectomy. The follow-up endpoint was 3 months after surgery. RESULTS: All patients were successfully completed the operation, and none of them was transferred to open operation. The operation time for unilateral breast was 12-28 min, and the average time was 17.7 ± 6.2 min. The amount of bleeding during unilateral operation was very small, about 5-10 ml. The total drainage volume was 5-50 ml after the operation, and the drainage tube was removed in 3-5 days. The epidermal necrosis occurred in 0.3% nipple. 0.2% chest wall had a little ecchymosis in the supero-medial region of the breast. All patients had the normal feeling of nipples and areola, the smoothing and symmetrical chest wall, and the natural contour. There was no recurrence during the follow-up period. CONCLUSIONS: The mastoscopic subcutaneous mastectomy for gynecomastia by "nine-step method" based on the "5S" goal has a short operation time, few surgical complications and good esthetics. It achieves the "5S" goals on the complete removal of glandular tissue (sweeping), small and scar-hidden incision are small (scarless), good symmetry of bilateral chest wall (symmetry), normal chest shape (shape), and smoothing chest wall (smoothing). LEVEL OF EVIDENCE III: The journal asks authors to assign a level of evidence to each article. For a complete description of Evidence-Based Medicine ratings, see the Table of Contents or the online Instructions for Authors at www.springer.com/00266 .

SNHG1, a KLF4-upregulated gene, promotes glioma cell survival and tumorigenesis under endoplasmic reticulum stress by upregulating BIRC3 expression.

Increasing evidence indicates that long noncoding RNAs (lncRNAs) play crucial roles in the resistance to endoplasmic reticulum (ER) stress in many cancers. However, ER stress-regulated lncRNAs are still unknown in glioma. In the present study, we investigated the altered lncRNAs upon ER stress in glioma and found that small nucleolar RNA host gene 1 (SNHG1) was markedly increased in response to ER stress. Increased SNHG1 suppressed ER stress-induced apoptosis and promoted tumorigenesis in vitro and in vivo. Further mechanistic studies indicated that SNHG1 elevated BIRC3 mRNA stability and enhanced BIRC3 expression. We also found that KLF4 transcriptionally upregulated SNHG1 expression and contributed to the ER stress-induced SNHG1 increase. Collectively, the present findings indicated that SNHG1 is a KLF4-regulated lncRNA that suppresses ER stress-induced apoptosis and facilitates gliomagenesis by elevating BIRC3 expression.

Adherence to the World Cancer Research Fund/American Institute for Cancer Research cancer prevention recommendations throughout the life course and risk of colorectal cancer precursors.

BACKGROUND: Despite the increasing incidence in colorectal cancer (CRC) among the young population, the involvement of modifiable early-life exposures is understudied. METHODS: We prospectively investigated the association of lifestyle score, which measures adherence to the 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) cancer prevention recommendations, in adolescence and adulthood with risk of CRC precursors in 34,509 women enrolled in the Nurses' Health Study II. Participants reported adolescent diet in 1998 and subsequently underwent at least one lower gastrointestinal endoscopy between 1999 and 2015. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression for clustered data. RESULTS: During follow-up (1998-2015), 3036 women had at least one adenoma, and 2660 had at least one serrated lesion. In multivariable analysis, per unit increase in adolescent WCRF/AICR lifestyle score was not associated with risk of total adenoma or serrated lesions, in contrast to adult WCRF/AICR lifestyle score (OR = 0.92, 95% CI: 0.87-0.97, Ptrend = 0.002 for total adenoma; and OR = 0.86, 95% CI: 0.81-0.92, Ptrend < 0.001 for total serrated lesions). CONCLUSION: Adherence to the 2018 WCRF/AICR recommendations during adulthood but not during adolescence was associated with a lower risk of CRC precursors.

Spatial pilot-aided fast-adapted framework for stable image transmission over long multi-mode fiber.

Multi-mode fiber (MMF) has emerged as a promising platform for spatial information transmission attributed to its high capacity. However, the scattering characteristic and time-varying nature of MMF pose challenges for long-term stable transmission. In this study, we propose a spatial pilot-aided learning framework for MMF image transmission, which effectively addresses these challenges and maintains accurate performance in practical applications. By inserting a few reference image frames into the transmitting image sequence and leveraging a fast-adapt network training scheme, our framework adaptively accommodates to the physical channel variations and enables online model update for continuous transmission. Experimented on 100 m length unstable MMFs, we demonstrate transmission accuracy exceeding 92% over hours, with pilot frame overhead around 2%. Our fast-adapt learning scheme requires training of less than 2% of network parameters and reduces the computation time by 70% compared to conventional tuning approaches. Additionally, we propose two pilot-insertion strategies and elaborately compare their applicability to a wide range of scenarios including continuous transmission, burst transmission and transmission after fiber re-plugging. The proposed spatial pilot-aided fast-adapt framework opens up the possibility for MMF spatial transmission in practical complicated applications.

A circular RNA produced by LRBA promotes cirrhotic mouse liver regeneration through facilitating the ubiquitination degradation of p27.

BACKGROUND AND AIMS: Accumulating circular RNAs (circRNAs) play important roles in tissue repair and organ regeneration. However, the biological effects of circRNAs on liver regeneration remain largely unknown. This study aims to systematically elucidate the functions and mechanisms of circRNAs derived from lipopolysaccharide-responsive beige-like anchor protein (LRBA) in regulating liver regeneration. METHODS: CircRNAs derived from mouse LRBA gene were identified using CircBase. In vivo and in vitro experiments were conducted to confirm the effects of circLRBA on liver regeneration. RNA pull-down and RNA immunoprecipitation assays were used to investigate the underlying mechanisms. Clinical samples and cirrhotic mouse models were used to evaluate the clinical significance and transitional value of circLRBA. RESULTS: Eight circRNAs derived from LRBA were registered in CircBase. The circRNA mmu_circ_0018031 (circLRBA) was significantly upregulated in the liver tissues after 2/3 partial hepatectomy (PHx). Adeno-associated virus serotype 8 (AAV8)-mediated knockdown of circLRBA markedly inhibited mouse liver regeneration after 2/3 PHx. In vitro experiments confirmed that circLRBA exerted its growth-promoting function mainly through liver parenchymal cells. Mechanistically, circLRBA acted as a scaffold for the interaction between E3 ubiquitin-protein ligase ring finger protein 123 and p27, facilitating the ubiquitination degradation of p27. Clinically, circLRBA was lowly expressed in cirrhotic liver tissues and negatively correlated with perioperative levels of total bilirubin. Furthermore, overexpression of circLRBA enhanced cirrhotic mouse liver regeneration after 2/3 PHx. CONCLUSIONS: We conclude that circLRBA is a novel growth promoter in liver regeneration and a potential therapeutic target related to deficiency of cirrhotic liver regeneration.

GSDMD-Mediated Cardiomyocyte Pyroptosis Promotes Myocardial I/R Injury.

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A comprehensive review on the properties, production, and applications of functional glucobioses.

Glucobiose is a range of disaccharides consisting of two glucose molecules, generally including trehalose, kojibiose, sophorose, nigerose, laminaribiose, maltose, cellobiose, isomaltose, and gentiobiose. The difference glycosidic bonds of two glucose molecules result in the diverse molecular structures, physiochemical properties and physiological functions of these glucobioses. Some glucobioses are abundant in nature but have unconspicuous roles on health like maltose, whereas some rare glucobioses display remarkable biological effects. It is unpractical process to extract these rare glucobioses from natural resources, while biological synthesis is a feasible approach. Recently, the production and application of glucobiose have attracted considerable attention. This review provides a comprehensive overview of glucobioses, including their natural sources and physicochemical properties like structure, sweetness, digestive performance, toxicology, and cariogenicity. Specific enzymes used for the production of various glucobioses and fermentation production processes are summarized. Additionally, their versatile functions and broad applications are also introduced.

Rapid Simulation of Decade-Scale Charcoal Aging in Soil: Changes in Physicochemical Properties and Their Environmental Implications.

In situ aging can change biochar properties, influencing their ecosystem benefits or risks over time. However, there is a lack of field verification of laboratory methods that attempt simulation of long-term natural aging of biochar. We exploited a decade-scale natural charcoal (a proxy for biochar) aging event to determine which lab-aging methods best mimicked field aging. We oxidized charcoal by ultraviolet A radiation (UVA), H2O2, or monochloramine (NH2Cl), and compared it to 10-year field-aged charcoal. We considered seven selected charcoal properties related to surface chemistry and organic matter release, and found that oxidation with 30% H2O2 most representatively simulated 10-year field aging for six out of seven properties. UVA aging failed to approximate oxidation levels while showing a distinctive dissolved organic carbon (DOC) release pattern. NH2Cl-aged charcoal was the most different, showing an increased persistent free radical (PFR) concentration and lower hydrophilicity. All lab oxidation techniques overpredicted polycyclic aromatic hydrocarbon release. The O/C ratio was well-correlated with DOC release, PFR concentration, surface charge, and charcoal pH, indicating the possibility to accurately predict biochar aging with a reduced suite of physicochemical properties. Overall, our rapid and verified lab-aging methods facilitate research toward derisking and enhancing long-term benefits of biochar application.

Ultrasonographic characteristics, genetic features, and maternal and fetal outcomes in fetuses with omphalocele in China: a single tertiary center study.

BACKGROUND: Patients with omphalocele, a midline abdominal wall defect at the umbilical cord base, have a low survival rate. However, the long-term outcomes of fetuses with prenatally diagnosed omphalocele have scarcely been studied. Therefore, we investigated the ultrasonographic features, genetic characteristics, and maternal and fetal outcomes of fetuses with omphalocele and provided a reference for the perinatal management of such cases. METHODS: A total of 120 pregnant females with fetal omphalocele were diagnosed using prenatal ultrasonography at the Fujian Provincial Maternity and Child Health Hospital from January 2015 to March 2022. Amniotic fluid or cord blood samples were drawn at different gestational weeks for routine karyotype analysis, chromosomal microarray analysis (CMA) detection, and whole exome sequencing (WES). The maternal and fetal outcomes were followed up. RESULTS: Among the 120 fetuses, 27 were diagnosed with isolated omphalocele and 93 with nonisolated omphalocele using prenatal ultrasonography. Cardiac anomalies were the most observed cause in 17 fetuses. Routine karyotyping and CMA were performed on 35 patients, and chromosomal abnormalities were observed in five patients, trisomy 18 in three, trisomy 13 in one, and chromosome 8-11 translocation in one patient; all were non-isolated omphalocele cases. Six nonisolated cases had normal CMA results and conventional karyotype tests, and further WES examination revealed one pathogenic variant and two suspected pathogenic variants. Of the 120 fetuses, 112 were successfully followed up. Eighty of the 112 patients requested pregnancy termination. Seven of the cases died in utero. A 72% 1-year survival rate was observed from the successful 25 live births. CONCLUSION: The prognosis of fetuses with nonisolated omphalocele varies greatly, and individualized analysis should be performed to determine fetal retention carefully. Routine karyotyping with CMA testing should be provided for fetuses with omphalocele. WES is an option if karyotype and CMA tests are normal. If the fetal karyotype is normal and no associated abnormalities are observed, fetuses with omphalocele could have a high survival rate, and most will have a good prognosis.

Effects of Nursing Care Using a Fast-Track Surgery Approach in 49 Patients with Early-Stage Hepatocellular Carcinoma Undergoing First-Line Treatment with Radiofrequency Ablation: A Retrospective Study.

BACKGROUND Fast-track surgery (FTS), also known as enhanced recovery after surgery (ERAS), includes a coordinated perioperative approach to patient care that aims to facilitate postoperative recovery. The role of nursing care is central to the concept of FTS. This retrospective study aimed to evaluate the effects of nursing care using an FTS approach in 49 patients with early-stage hepatocellular carcinoma (HCC) undergoing first-line treatment with radiofrequency ablation (RFA). MATERIAL AND METHODS A retrospective analysis was made of 49 patients with early-stage hepatocellular carcinoma who underwent first-line treatment with radiofrequency ablation in the Department of Hepatobiliary Surgery in our hospital from January 2020 to December 2021. The nurses have been nursing the patients in accordance with the requirements of FTS from 2021. Compared with the data of patients receiving traditional nursing, the detailed differences in postoperative recovery, pain score, complication rate, liver and kidney function, and nursing satisfaction were analyzed. RESULTS After applying the FTS nursing model, the patients had significantly shorter time to first flatus, infusion, postoperative hospital stay, and lower total hospitalization expenses (P<0.05). Moreover, the Numerical Pain Rating Scale score was lower than that in the control group, the postoperative complications in the 2021 group were lower than those in the 2020 group, and the nursing satisfaction was also better than that of the 2020 group (P<0.05). CONCLUSIONS Nursing care using a fast-track surgery approach with early-stage hepatocellular carcinoma patients undergoing first-line treatment with radiofrequency ablation is better than conventional nursing, and improves recovery of patients.

Biodegradation of asphaltenes by an indigenous bioemulsifier-producing Pseudomonas stutzeri YWX-1 from shale oil in the Ordos Basin: Biochemical characterization and complete genome analysis.

Crude oil pollution is environmentally ubiquitous and has become a global public concern about its impact on human health. Asphaltenes are the key components of heavy crude oil (HCO) that are underutilized due to their high viscosity and density, and yet, the associated information about biodegradation is extremely limited in the literature. In the present study, an indigenous bacterium with effective asphaltene-degrading activity was isolated from oil shale and identified as Pseudomonas stutzeri by a polyphasic taxonomic approach, named YWX-1. Supplemented with 75 g L-1 heavy crude oil as the sole carbon source for growth in basic mineral salts liquid medium (MSM), strain YWX-1 was able to remove 49% of asphaletene fractions within 14 days, when it was cultivated with an initial inoculation size of 1%. During the degradation process, the bioemulsifier produced by strain YWX-1 could emulsify HCO obviously into particles, as well as it had the ability to solubilize asphaletenes. The bioemulsifier was identified to be a mixture of polysaccharide and protein through Fourier transform infrared spectroscopy (FT-IR). The genome of strain YWX-1 contains one circular chromosome of 4488441 bp with 63.98% GC content and 4145 protein coding genes without any plasmid. Further genome annotation indicated that strain YWX-1 possesses a serial of genes involved in bio-emulsification and asphaltenes biodegradation. This work suggested that P. stutzeri YWX-1 could be a promising species for bioremediation of HCO and its genome analysis provided insight into the molecular basis of asphaltene biodegradation and bioemulsifier production.

The effects of dual antiplatelet therapy (DAPT) adherence on survival in patients undergoing revascularization and the determinants of DAPT adherence.

BACKGROUND: The prevalence and burden of coronary heart disease (CHD) has increased substantially in India, accompanied with increasing need for percutaneous coronary interventions (PCI). Although a large government-funded insurance scheme in Maharashtra, India covered the cost of PCI for low-income patients, the high cost of post-PCI treatment, especially Dual Antiplatelet Therapy (DAPT), still caused many patients to prematurely discontinue the secondary prevention. Our study aimed to investigate the effectiveness of DAPT adherence on all-cause mortality among post-PCI patients and explore the potential determinants of DAPT adherence in India. METHOD: We collected clinical data of 4,595 patients undergoing PCI in 110 participating medical centers in Maharashtra, India from 2012 to 2015 by electronic medical records. We surveyed 2527 adult patients who were under the insurance scheme by telephone interview, usually between 6 to 12 months after their revascularization. Patients reporting DAPT continuation in the telephone survey were categorized as DAPT adherence. The outcome of the interest was all-cause mortality within 1 year after the index procedure. Multivariate Cox proportional hazard (PH) model with adjustment of potential confounders and standardization were used to explore the effects of DAPT adherence on all-cause mortality. We further used a multivariate logistic model to investigate the potential determinants of DAPT adherence. RESULTS: Out of the 2527 patients interviewed, 2064 patients were included in the analysis, of whom 470 (22.8%) discontinued DAPT prematurely within a year. After adjustment for baseline confounders, DAPT adherence was associated with lower one-year all-cause mortality compared to premature discontinuation (less than 6-month), with an adjusted hazard ratio (HR) of 0.52 (95% Confidence Interval (CI) = (0.36, 0.67)). We also found younger patients (OR per year was 0.99 (0.97, 1.00)) and male (vs. female, OR of 1.30 (0.99, 1.70)) had higher adherence to DAPT at one year as did patients taking antihypertensive medications (vs. non medication, OR of 1.57 (1.25, 1.95)). CONCLUSION: These findings suggest the protective effects of DAPT adherence on 1-year mortality among post-PCI patients in a low-income setting and indicate younger age, male sex and use of other preventive treatments were predictors of higher DAPT adherence.

Isolation of Peptide Inhibiting SGC-7901 Cell Proliferation from Aspongopus chinensis Dallas.

Aspongopus chinensis Dallas is used as a traditional Chinese medicine as well as an edible insect. Although its anti-tumor effects have been observed, the anti-tumor active component(s) in the hemolymph of A. chinensis remains unknown. In this study, a combination usage of ultrafiltration, gel filtration chromatography, FPLC and RP-HPLC to separate and purify active peptides was performed based on the proliferation of the human gastric cancer SGC-7901 cell line treated with candidates. One peptide (MW = 2853.3 Da) was isolated from the hemolymph of A. chinensis. A total of 24 amino acid residues were continuously determined for the active peptide: N'-ECGYCAEKGIRCDDIHCCTGLKKK-C'. In conclusion, a peptide that can inhibit the proliferation of gastric cancer SGC-7901 cells in the hemolymph of A. chinensis was purified in this study, which is homologous to members of the spider toxin protein family. These results should facilitate further works for this peptide, such as the cloning of genes, expression in vitro by prokaryotic or eukaryotic systems, more specific tests of anti-tumor activity, and so on.

Removal of Antimony in Wastewater by Antimony Tolerant Sulfate-Reducing Bacteria Isolated from Municipal Sludge.

Antimony (Sb), a global and priority controlled pollutant, causes severe environmental issues. Bioremediation by microbial communities containing sulfate-reducing bacteria (SRB) is considered to be among the safest, economical, and environmentally friendly methods to remove Sb from wastewater. However, the roles of SRB species in these communities remain uncertain, and pure cultures of bacteria that may be highly efficient have not yet been developed for Sb removal. In this study, an Sb tolerant community was enriched from municipal sludge, and molecular ecological analysis showed that Escherichia (40%) and Desulfovibrio (15%) were the dominant bacteria. Further isolation and identification showed that the enriched SRB strains were closely related to Cupidesulfovibrio oxamicus, based on the molecular analyses of 16S rRNA and dsrB genes. Among them, a strain named SRB49 exhibited the highest activity in removal of Sb(V). SRB49 was able to remove 95% of Sb(V) at a concentration of 100 mg/L within 48 h under optimum conditions: a temperature of 37-40 °C, an initial pH value of 8, 4 mM of sulfate, and an initial redox potential of 145-229 mV. SEM-EDX analysis showed that SRB49 did not adsorb Sb(V) but reduced and precipitated Sb(V) via the formation of Sb2S3. The results demonstrated the potential roles that pure cultures of SRB species may play in Sb removal and the use of Sb-tolerant SRB strains for Sb remediation.

Novel immune-related genes in the tumor microenvironment with prognostic value in breast cancer.

BACKGROUND: Breast cancer is one of the most frequently diagnosed cancers among women worldwide. Alterations in the tumor microenvironment (TME) have been increasingly recognized as key in the development and progression of breast cancer in recent years. To deeply comprehend the gene expression profiling of the TME and identify immunological targets, as well as determine the relationship between gene expression and different prognoses is highly critical. METHODS: The stromal/immune scores of breast cancer patients from The Cancer Genome Atlas (TCGA) were employed to comprehensively evaluate the TME. Then, TME characteristics were assessed, overlapping genes of the top 3 Gene Ontology (GO) terms and upregulated differentially expressed genes (DEGs) were analyzed. Finally, through combined analyses of overall survival, time-dependent receiver operating characteristic (ROC), and protein-protein interaction (PPI) network, novel immune related genes with good prognosis were screened and validated in both TCGA and GEO database. RESULTS: Although the TME did not correlate with the stages of breast cancer, it was closely associated with the subtypes of breast cancer and gene mutations (CDH1, TP53 and PTEN), and had immunological characteristics. Based on GO functional enrichment analysis, the upregulated genes from the high vs low immune score groups were mainly involved in T cell activation, the external side of the plasma membrane, and receptor ligand activity. The top GO terms of the upregulated DEGs from the high vs low immune score groups exhibited better prognosis in breast cancer; 15 of them were related to good prognosis in breast cancer, especially CD226 and KLRC4-KLRK1. CONCLUSIONS: High CD226 and KLRC4-KLRK1 expression levels were identified and validated to correlate with better overall survival in specific stages or subtypes of breast cancer. CD226, KLRC4-KLRK1 and other new targets seem to be promising avenues for promoting antitumor targeted immunotherapy in breast cancer.

Social Support and Tinnitus Distress: The Importance of Developing Positive Psychological Qualities in Patients with Chronic Tinnitus.

INTRODUCTION: The role of social support in the relief of tinnitus distress and related mechanisms remains unclear. This study aimed to confirm a hypothesis that the influence of social support on tinnitus distress is mediated by resilience and self-esteem. METHODS: The Social Support Rating Scale, Connor-Davidson Resilience Scale, Positive Version of Rosenberg Self-Esteem Scale, and Tinnitus Handicap Inventory were used to assess 296 patients who experience chronic subjective tinnitus. The collected data were subjected to correlational analysis, mediating effect testing, and structural equation model analysis using R 3.3.1 with the mediate and lavaan packages. RESULTS: The result showed that social support had significant positive correlations with resilience and self-esteem, while resilience and self-esteem had significant negative correlations with tinnitus distress. Furthermore, social support indirectly affected tinnitus distress through the full mediating effects of resilience and self-esteem and could indirectly affect resilience through the partial mediating effects of self-esteem. CONCLUSION: These results suggested that the key to social support for alleviating tinnitus distress lies in the development of patients' resilience and self-esteem. Promoting the development of positive psychological quality of tinnitus patients and improving their perception of social support may become the new approaches of clinical management of tinnitus.

In Vivo Experimental and Analytical Studies for Bevacizumab Diffusion Coefficient Measurement in the Rabbit Vitreous Humor.

In order to measure the effective diffusion coefficient D of Bevacizumab (Avastin, Genentech) in the vitreous humor, a new technique is developed based on the "contour method" and in vivo optical coherence tomography measurements. After injection of Bevacizumab-fluorescein conjugated compound solution into the rabbit eye, the contours of drug concentration distribution at the subsurface of injection were tracked over time. The 2D contours were extrapolated to 3D contours using reasonable assumptions and a numerically integrated analytical model was developed for the theoretical contours for the irregularly shaped drug distribution in the experimental result. By floating the diffusion coefficient, different theoretical contours were constructed and the least-squares best fit to the experimental contours was performed at each time point to get the best fit solution. The approach generated consistent diffusion coefficient values based on the experiments on four rabbit eyes over a period of 3 h each, which gave D = 1.2 ± 0.6 × 10 - 6 cm 2 / s , and the corresponding theoretical contours matched well with the experimental contours. The quantitative measurement of concentration using optical coherence tomography and fluorescein labeling gives a new approach for the "noncontact" in vivo drug distribution measurement within vitreous.