Evaluation of riboflavin concentrations and light intensities on bacteria reduction in platelets using visible light.

Bacterial contamination in platelets has been a major concern over the years. In this study, we showed that treatment with 420 nm visible light with various concentrations of riboflavin in platelets reduced E. coli and S. aureus by 0-1.56 and 0.3-2.02 logs (50 mW/cm2), 2.24-4.77 and 0.73-3.26 logs (75 mW/cm2), and ≥ 5.14 and ≥ 5.27 logs (100 mW/cm2). Treatment with high-intensity light (100 mW/cm2) and high concentrations of riboflavin (400 µM and 500 µM) effectively reduced both bacteria in platelets by over 4 logs. The study also found a positive correlation between bacterial reduction and light intensity, as well as riboflavin concentration in a dose-dependent manner. These results demonstrate the potential of using riboflavin and visible light to reduce the risk of bacterial contamination in platelets, and support the need for further exploration of pathogen reduction using 420 nm visible light and riboflavin.

Radiotherapy plus anti-PD1 versus radiotherapy for hepatic toxicity in patients with hepatocellular carcinoma.

PURPOSE: In this study, we aimed to compare the radiation-induced hepatic toxicity (RIHT) outcomes of radiotherapy (RT) plus antibodies against programmed cell death protein 1 (anti-PD1) versus RT alone in patients with hepatocellular carcinoma (HCC), evaluate prognostic factors of non-classic radiation-induced liver disease (ncRILD), and establish a nomogram for predicting the probability of ncRILD. PATIENTS AND METHODS: Patients with unresectable HCC treated with RT and anti-PD1 (RT + PD1, n = 30) or RT alone (n = 66) were enrolled retrospectively. Patients (n = 30) in each group were placed in a matched cohort using propensity score matching (PSM). Treatment-related hepatotoxicity was evaluated and analyzed before and after PSM. The prognostic factors affecting ncRILD were identified by univariable logistic analysis and Spearman's rank test in the matched cohort to generate a nomogram. RESULTS: There were no differences in RIHT except for increased aspartate aminotransferase (AST) ≥ grade 1 and increased total bilirubin ≥ grade 1 between the two groups before PSM. After PSM, AST ≥ grade 1 occurred more frequently in the RT + PD1 group (p = 0.020), and there were no significant differences in other hepatotoxicity metrics between the two groups. In the matched cohort, V25, tumor number, age, and prothrombin time (PT) were the optimal prognostic factors for ncRILD modeling. A nomogram revealed a good predictive performance (area under the curve = 0.82). CONCLUSIONS: The incidence of RIHT in patients with HCC treated with RT + PD1 was acceptable and similar to that of RT treatment. The nomogram based on V25, tumor number, age, and PT robustly predicted the probability of ncRILD.

IKKα inhibition re-sensitizes acquired adriamycin-resistant triple negative breast cancer cells to chemotherapy-induced apoptosis.

IKKα has been shown to be responsible of multiple pro-tumorigenic functions and therapy resistance independent of canonical NF-κB, but its role in acquired chemotherapy resistance in breast cancer remains unclarified. In this study, we obtained pre-treatment biopsy and post-treatment mastectomy specimens from a retrospective cohort of triple-negative breast cancer (TNBC) patients treated with neoadjuvant chemotherapy(NAC) (n = 43). Immunohistochemical methods were used to detect the expression of IKKα before and after NAC, and the relationship between IKKα and the pathologic response to NAC was examined. In addition, we developed a new ADR-resistant MDA-MB-231 cell line(MDA-MB-231/ADR) and analyzed these cells for changes in IKKα expression, the role and mechanisms of the increased IKKα in promoting drug resistance were determined in vitro and in vivo. We demonstrated that the expression of IKKα in residual TNBC tissues after chemotherapy was significantly higher than that before chemotherapy, and was positively correlated with lower pathological reaction. IKKα expression was significantly higher in ADR-resistant TNBC cells than in ADR-sensitive cells, IKKα knockdown results in apoptotic cell death of chemoresistant cells upon drug treatment. Moreover, IKKα knockdown promotes chemotherapeutic drug-induced tumor cell death in an transplanted tumor mouse model. Functionally, we demonstrated that IKKα knockdown significantly upregulated the expression of cleaved caspase 3 and Bax and inhibited the expression of Bcl-2 upon ADR treatment. Our findings highlighted that IKKα exerts an important and previously unknown role in promoting chemoresistance in TNBC, combining IKKα inhibition with chemotherapy may be an effective strategy to improve treatment outcome in chemoresistant TNBC patients.

Non-classic radiation-induced liver disease after intensity-modulated radiotherapy for Child-Pugh grade B patients with locally advanced hepatocellular carcinoma.

BACKGROUND: The incidence of classic radiation-induced liver disease (cRILD) has been significantly reduced. However, non-classic radiation-induced liver disease (ncRILD) remains a major concern following radiotherapy in patients with hepatocellular carcinoma (HCC). This study evaluated the incidence of ncRILD following intensity-modulated radiotherapy (IMRT) for Child-Pugh grade B (CP-B) patients with locally advanced HCC and established a nomogram for predicting ncRILD probability. METHODS: Seventy-five CP-B patients with locally advanced HCC treated with IMRT between September 2014 and July 2021 were included. The max tumor size was 8.39 cm ± 5.06, and the median prescribed dose was 53.24 Gy ± 7.26. Treatment-related hepatotoxicity was evaluated within three months of completing IMRT. A nomogram model was formulated to predict the probability of ncRILD, using univariate and multivariate analysis. RESULTS: Among CP-B patients with locally advanced HCC, ncRILD occurred in 17 (22.7%) patients. Two patients (2.7%) exhibited a transaminase elevation of ≥ G3, fourteen (18.7%) exhibited a Child-Pugh score increase of ≥ 2, and one (1.3%) demonstrated both a transaminase elevation of ≥ G3 and a Child-Pugh score increase of ≥ 2. No cRILD cases were observed. A mean dose to the normal liver of ≥ 15.1 Gy was used as the cutoff for ncRILD. Multivariate analysis revealed that the prothrombin time before IMRT, tumour number, and mean dose to the normal liver were independent risk factors for ncRILD. The nomogram established on the basis of these risk factors displayed exceptional predictive performance (AUC = 0.800, 95% CI 0.674-0.926). CONCLUSIONS: The incidence of ncRILD following IMRT for CP-B patients with locally advanced HCC was acceptable. A nomogram based on prothrombin time before IMRT, tumour number, and mean dose to the normal liver accurately predicted the probability of ncRILD in these patients.

Prognostic value of a nomogram based on peripheral blood immune parameters in unresectable hepatocellular carcinoma after intensity-modulated radiotherapy.

BACKGROUND: For patients with unresectable hepatocellular carcinoma (uHCC), intensity-modulated radiotherapy (IMRT) has become one of the options for clinical local treatment. Immune parameters, including platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR) and systemic immune inflammatory (SII), predict survival in various cancers. This study aimed to determine whether peripheral immune parameters can predict survival in patients with uHCC undergoing IMRT and establish a clinically useful prognostic nomogram for survival prediction. METHODS: The clinical data of 309 HCC patients were retrospectively analyzed and randomly divided into training (n = 216) and validation (n = 93) cohorts. PLR, NLR and SII were collected before and after IMRT. Univariate and multivariate Cox analyses were performed to identify independent prognostic factors affecting survival, which were used to generate a nomogram. RESULTS: The median survival was 16.3 months, and significant increases in PLR, NLR, and SII were observed after IMRT (P < 0.001). High levels of immune parameters were associated with poor prognosis (P < 0.001); enlarged spleen, Barcelona clinic liver cancer stage (B and C), post-SII, and delta-NLR were independent risk factors for survival and were included in the nomogram, which accurately predicted 3- and 5-year survival. The nomogram was well verified in the validation cohort. CONCLUSIONS: High levels of immune parameters are associated with poor prognosis in uHCC patients receiving IMRT. Our nomogram accurately predicts the survival of patients with uHCC receiving IMRT.

Height dissatisfaction and loneliness among adolescents: the chain mediating role of social anxiety and social support.

Previous research on body dissatisfaction has mainly focused on the dissatisfaction with weight and appearance. Limited research has examined the dissatisfaction with another major body feature that is important to our social relationships and personal well-being, namely, body height. We hypothesized that height dissatisfaction would predict more intense loneliness among adolescents, and that this relationship is mediated by greater social anxiety and reduced social support. Participants of this study were 515 Chinese high school students. The Shortness subscale of the Negative Physical Self Scale, Social Anxiety Scale for Adolescents, Perceived Social Support Scale, and ULS-8 were integrated into a paper-and-pencil survey. The results revealed that adolescents with high levels of height dissatisfaction reported higher levels of loneliness. A chain mediation model showed that the relationship between height dissatisfaction and loneliness could be both sequentially mediated by social anxiety and social support, and mediated by social anxiety. However, no mediating role of social support was found. We also found that body height did not predict social anxiety or social support, but can predict loneliness. The current findings provide novel insights into the occurrence of loneliness among adolescents, and indicate that negative self-perceptions of body height and the resulting social anxiety can lead to loneliness.

Metallic-semiconducting transition and spin polarized-unpolarized transition in a single molecule with a negative Poisson's ratio.

Different from conventional materials, structures with a negative Poisson's ratio (NPR) contract/expand laterally under a longitudinal compressive/tensile strain, usually exhibiting peculiar features. Through first-principles calculations, we investigate the electronic and transport properties of Pd9B16 molecules. Its Poisson's ratio is found to be negative under uniaxial strain along a specific direction. By contacting with Au nanowires, atomic Au chains and atomic C chain electrodes, two kinds of transitions for transmission states could be realized by the modulation of the strain and the contacting site, i.e., metallic-semiconducting transition and spin polarized-unpolarized transition. Further analysis shows that it is the suppression and shifting of density of states, caused by the strain or contacting electrodes, that trigger the transitions. Those findings combine NPR and spintronics at the single-molecule level, which may throw light on the development of nanoelectronic devices.

First Report of Lecanicillium aphanocladii causing rot of Morchella sextelata in China.

Morel mushroom (Morchella spp.) is a rare edible fungus with high nutritional and medicinal value. In China they are cultivated in sandy soils in greenhouses and production of fresh mushrooms reached 10,000 tons in 2019. However, from 2019 to 2020, a serious rot disease with 30% natural incidence was observed on M. sextelata at a mushroom farm in Pinghu (N30°39', E121°2'), Zhejiang province of China. The symptoms mainly occurred after the first flush in the early February. First, a small white mold-like symptoms appeared on the surface or the pinnacle of pileus. Then the lesion developed to encircle the pileus and spread gradually to the stipe. The lesions expanded rapidly at high temperature (>20 °C) and humidity (>70%). In the final stages of infection, the fruiting bodies became soft with white molds. The pathogen was isolated from the margin of the lesions by plating onto potato dextrose agar (PDA) and incubated at 25 °C in the dark. Colonies on PDA grew fast, reaching 60 mm in 7 days at 25 °C, and were white to cream in color, while the back of colonies appeared red to brick-red gradually. Conidiogenous cell was solitary or in whorls of 2-4, flask-shaped in the beginning, and tapered into a thread-like neck. Conidia were borne at the tips of conidiogenous cells, were oval to sub-globose, and ranged from 1.2-2.0 µm in width and 3.2-4.3 µm in length. All these characteristics were consistent with those of Lecanicillium aphanocladii (Zare R and Gams W. 2001). To confirm the identity of the pathogen (L. aphanocladii strain G1), the genomic fragments for the internal transcribed spacer (ITS) and RNA polymerase II second largest subunit (RPB2) gene of the isolate were amplified by PCR (White et al. 1990; Zhou et al. 2020). The resulting sequence was deposited in GenBank with accession No. OL629617 and No. ON005041, respectively. BLAST results showed >99% identity with those of L. aphanocladii (MG593981.1 and KM283853.1, respectively). Concatenated sequences of the two genes in L. aphanocladii strain G1 were used to conduct a phylogenetic analysis using Bayesian inference (BI) and maxium likelihood (ML) methods in MEGA6 (Tamura et al. 2013). The pathogen was grown in PDB medium at 25 °C, 200 r/min for 14 days, and after which conidial suspension (1×107conidia/mL) was prepared by filtration with four layers of sterile gauze. A pathogenicity test was performed by spraying on ten fruit bodies of M. sextelata and cultured in 20 °C and 90 to 95% relative humidity for 7 days. The test results showed that the pathogen infected the pileus and developed into white mold-like lesion, gradually spread to the stipe, and eventually the whole fruiting body became soft with white molds. The pathogen was re-isolated from infected fruiting bodies and was confirmed to be L. aphanocladii, based on morphological characteristics and the ITS, RPB2 sequence. Meanwhile,the control M. sextelata was sprayed with PDB medium and grew normally without any symptoms. L. aphanocladii has been reported on cultivated fungi such as Agaricus bisporus and A. bitorquis in Europe (Zare & Gams 2001) as well as more recently on Tremella fuciformis in China (Liu et al 2018). To our knowledge, this is the first report of L. aphanocladii causing rot of M. sextelata. According to the disease observation in the farm of Pinghu, this rot disease breaks out and spreads fast, and is getting worse ever year, resulting in a huge loss of yield and commodity value. It is a big concern to producers of this edible fungus.

In vivo antiviral effect of plant essential oils against avian infectious bronchitis virus.

BACKGROUND: Infectious bronchitis virus (IBV) leads to huge economic losses in the poultry industry worldwide. The high levels of mutations of IBV render vaccines partially protective. Therefore, it is urgent to explore an effective antiviral drug or agent. The present study aimed to investigate the in vivo anti-IBV activity of a mixture of plant essential oils (PEO) of cinnamaldehyde (CA) and glycerol monolaurate (GML), designated as Jin-Jing-Zi. RESULTS: The antiviral effects were evaluated by clinical signs, viral loads, immune organ indices, antibody levels, and cytokine levels. The infection rates in the PEO-M (middle dose) and PEO-H (high dose) groups were significantly lower than those in the prevention, positive drug, and PEO-L (low dose) groups. The cure rates in the PEO-M and PEO-H groups were significantly higher than those in the prevention, positive drug, and PEO-L groups, and the PEO-M group had the highest cure rate of 92.31%. The symptom scores and IBV mRNA expression levels were significantly reduced in the PEO-M group. PEO significantly improved the immune organ indices and IBV-specific antibody titers of infected chickens. The anti-inflammatory factor levels of IL-4 and IFN-γ in the PEO-M group maintained high concentrations for a long time. The IL-6 levels in the PEO-M group were lower than those in prevention, positive drug, and PEO-L groups. CONCLUSION: The PEO had remarkable inhibition against IBV and the PEO acts by inhibiting virus multiplication and promoting immune function, suggesting that the PEO has great potential as a novel anti-IBV agent for inhibiting IBV infection.

Perceived Importance of Breast Cancer Risk Factors: A Survey on 386 Physicians in China.

There are varying definitions of women at high risk of breast cancer across different institutions, and there are reports suggesting that the breast cancer risk assessment tools have not been well integrated into clinical practice. In this study, we tried to investigate the perceived importance of different breast cancer risk factors by physicians in China. A cross-sectional survey involving 386 anonymous physicians was conducted using a 20-item, 5-point Likert scale questionnaire. The Kruskal-Wallis test and post-hoc pairwise comparisons were used to compare the differences in response. Most of the respondents were either breast surgeons/specialists (n=161; 41.7%) or medical oncologists (n=151; 39.1%), and the results showed that the breast cancer risk factors were not perceived as equally important. The weighting of each risk factor also varied depending on the physician's medical specialty, location of practice, and the number of years of clinical experience.  This study provides a more updated insight into the perceptions of physicians in China toward the breast cancer risk factors, as well as underlines the potential improvements in breast cancer risk assessment strategies that can be done.