Genome-Wide Identification and Expression Analysis Reveal bZIP Transcription Factors Mediated Hormones That Functions during Early Somatic Embryogenesis in Dimocarpus longan.

The basic leucine zip (bZIP) transcription factors (TFs) are a group of highly conserved gene families that play important roles in plant growth and resistance to adversity stress. However, studies on hormonal regulatory pathways and functional analysis during somatic embryogenesis (SE) in Dimocarpus longan is still unavailable. In this study, a total of 51 bZIP family members were systematically identified in the whole genome of longan, a comprehensive bioinformatics analysis of DlbZIP (bZIP family members of D. longan) was performed, and subcellular localization and profiles patterns after transiently transformed DlbZIP60 were analyzed. The combined analysis of RNA-seq, ATAC-seq and ChIP-seq showed that four members have different H3K4me1 binding peaks in early SE and differentially expressed with increased chromatin accessibility. Comparative transcriptome analysis of bZIPs expression in early SE, different tissues and under 2,4-D treatment revealed that DlbZIP family might involved in growth and development during longan early SE. The qRT-PCR results implied that DlbZIP family were subjected to multiple hormonal responses and showed different degrees of up-regulated expression under indole-3-acetic acid (IAA), abscisic acid (ABA) and methyl jasmonate (MeJA) treatments, which indicated that they played an important role in the hormone synthesis pathways associated with the early SE of longan. Subcellular localization showed that DlbZIP60 was located in the nucleus, and the contents of endogenous IAA, MeJA and ABA were up-regulated in transiently DlbZIP60 overexpressed cell lines. These results suggest that DlbZIP60 may mediate hormones pathways that functions the development during early SE in longan.

Incidence trends in prostate cancer among men in the United States from 2000 to 2020 by race and ethnicity, age and tumor stage.

Purpose: To explore whether prostate cancer incidence trends from 2000 to 2020 in the United States differed by race and ethnicity, age and tumor stage; to explore racial differences in prostate cancer incidence change due to the impact of COVID-19 pandemic lockdown in 2020; and to determine if there is any high-risk population that can be targeted for prevention. Methods: We identified 1,098,349 men who were diagnosed with incident prostate cancer at age ≥20 in 2000-2020 in 17 registries of the Surveillance, Epidemiology, and End Results (SEER) program in the United States; of whom, 778,437 were non-Hispanic whites, 155,111 non-Hispanic blacks, 4,200 American Indians and Alaska Natives (AIAN), 55,267 non-Hispanic Asians/Pacific Islanders, and 105,334 Hispanics. Results: Age-adjusted incidence rate of prostate cancer was the highest in blacks (302.6 cases per 100,000 men), followed by whites (186.6), Hispanics (153.2), AIAN (108.5), and Asians (104.9). Age-adjusted prostate cancer incidence rates dramatically decreased from 2000 to 2013 for all ethnic men. However, age-adjusted prostate cancer incidence rates increased from 2014 to 2020, in which the increasing incidence trend looked sharper in blacks and whites, flatter in Asians, and leveled in AIAN and Hispanics. Among men with local or regional stages across all years, prostate cancer incidence rate was significantly higher in blacks, but significantly lower in Hispanics, AIAN, and Asians as compared to whites. Among men in 2007-2013, the risk of distant stage prostate cancer was statistically significantly elevated in blacks (rate-ratio: 2.22, 95% CI: 2.06-2.38) and Hispanics (1.16, 1.06-1.25), not significantly different in AIAN (1.30, 0.92-1.76), but still significantly lower in Asians (0.73, 0.66-0.82) as compared to whites. There was a drop of prostate cancer incidence from 2019 to 2020 likely due to the impact of COVID-19 pandemic lockdown on the access to medical care in 2020. Overall prostate cancer incidence rate decreased by 40.4 cases per 100,000 population from 277.4 in 2019 to 237.0 in 2020 for blacks, 20.9 from 164.2 to 143.3 for whites, 16.8 from 124.8 to 108.0 for Hispanics, 14.9 from 101.7 to 86.8 for AIAN, and 12.6 from 88.4 to 75.8 for Asians. Conclusion: The decreasing trend of prostate cancer incidence from 2000 to 2013 was statistically significant for all ethnic men. There was an increasing prostate cancer incidence from 2014 to 2020. Age-adjusted incidence rate of prostate cancer was the highest in blacks, followed by whites, Hispanics, AIAN, and Asians, regardless of age groups, tumor stages, and time periods. There will also be a need to monitor and investigate the prostate cancer incidence trend during and after COVID-19 pandemic season.

Parallel beam splitting and controlling system based on cascaded acousto-optic modulators.

In recent years, ultrashort pulse lasers (lasers) have been already widely used for providing excellent laser machining quality for the electronics industry, replication tools, and other applications. However, the major drawback of this processing is low efficiency, especially for a large number of laser ablation demands. In this paper, a beam-splitting approach based on cascaded acousto-optic modulators (AOMs) is proposed and analyzed in detail. The cascaded AOMs can split a laser beam into several beamlets with the same propagation direction. These beamlets can be switched on and off individually, and the beam pitch can be changed independently. At the same time, the experimental setup of three cascaded AOM beam splittings is built up to verify the capability of the high-speed control (switching rate:1 MHz), high-energy utilization rate (>96% at three AOMs), and high-energy splitting uniformity (nonuniformity: 3.3%). This scalable approach enables the processing of arbitrary surface structures with high quality and efficiency.

Angiotensin-II stimulating vs. inhibiting antihypertensive drugs and the risk of Alzheimer's disease or related dementia in a large cohort of older patients with colorectal cancer.

Background: Several previous studies showed that patients who received angiotensin II-stimulating antihypertensive medications had a lower incident dementia rate than those angiotensin II-inhibiting antihypertensive users, but no study has been conducted in long-term cancer survivors. Objectives: To determine the risk of Alzheimer's disease (AD) and related dementia (ADRD) associated with the types of antihypertensive medications in a large cohort of survivors with colorectal cancer in 2007-2015 with follow-up from 2007 to 2016. Methods: We identified 58,699 men and women with colorectal cancer aged 65 or older from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database in 17 SEER areas in 2007-2015 with follow-up to 2016, who were free of any diagnosed ADRD at the baseline (within 12 months prior to and 12 months after the date of diagnosis for colorectal cancer). All patients who were defined as having hypertension by ICD diagnosis code or received antihypertensive drugs during this baseline 2-year period were classified into 6 groups based on whether they received angiotensin-II stimulating or inhibiting antihypertensive drugs. Results: Crude cumulative incidence rates of AD and ADRD were similar between those who received angiotensin II-stimulating antihypertensive medications (4.3% and 21.7%) and those receiving angiotensin II-inhibiting antihypertensive medications (4.2% and 23.5%). As compared to patients who received angiotensin II-stimulating antihypertensive drugs, those who received angiotensin II-inhibiting antihypertensives were significantly more likely to develop AD (adjusted hazard ratio: 1.15, 95% CI: 1.01-1.32), vascular dementias (1.27, 1.06-1.53), and total ADRD (1.21, 1.14-1.28) after adjusting for potential confounders. These results remained similar after adjusting for medication adherence and considering death as a competing risk. Conclusions: The risk of AD and ADRD in patients with hypertension who received angiotensin II-inhibiting antihypertensive medications was higher than in those receiving angiotensin II-stimulating antihypertensive drugs in patients with colorectal cancer.

Incidence trends in triple-negative breast cancer among women in the United States from 2010 to 2019 by race/ethnicity, age and tumor stage.

There were substantial ethnic disparities in the incidence rates of triple-negative breast cancer, but few studies were conducted on the incidence trend of triple-negative breast cancer by race/ethnicity. This study aimed to address the longer trends in the incidence of triple-negative breast cancer by race/ethnicity in women from 2010 to 2019, examine the incidence trends by patient age, tumor stage and time periods, and explore the changing proportions of three component receptors over time for triple-negative breast cancer. Our study identified 573,168 women with incident breast cancer at age ≥20 years between 2010 and 2019 in 18 SEER (Surveillance, Epidemiology, and End Results) registries. Of them, 62,623 (10.9%) were incident triple-negative breast cancer and 510,545 were non-triple negative breast cancer cases. The denominator of population included 320,117,009 women aged ≥20 in the same SEER areas. The study found that overall age-adjusted incidence rate of triple-negative breast cancer in women aged ≥20 years was 18.3 cases per 100,000 women. Age-adjusted incidence rate of triple-negative breast cancer was the highest in black women (33.8 cases per 100,000 women), followed by white (17.5), American Indian and Alaska Native (AIAN) (14.7), Hispanic (14.7), and Asian women (12.4). The significantly higher age-adjusted incidence of triple-negative breast cancer in black women as compared to white women appeared to be limited in younger women aged 20-44 only. Annual percentage changes in age-adjusted incidence of triple-negative breast cancer slightly decreased insignificantly in white, black and Asian women aged 20-44 and 45-54 years. There was a statistically significant annual percentage increase in age-adjusted incidence of triple-negative breast cancer in Asian and black women aged ≥55 years. In conclusion, there was a significantly higher incidence of triple-negative breast cancer in black women aged 20-44 years. From 2010 to 2019, there were no significant annual percentage changes in age-adjusted incidence of triple-negative breast cancer in all ethnic groups of women aged <55 years, with the exception of a significant decrease among AIAN women aged 45-54 years. However, there was a statistically significant annual percentage increase in age-adjusted incidence of triple-negative breast cancer in Asian and black women aged ≥55 years.

Biological evaluation of a novel stable peptide PET molecular probe [18F]AlF-NOTA-DVAP targeting to tumor cell surface GRP78.

BACKGROUNDS: Glucose-Regulated Protein 78 (GRP78) is an attractive anticancer target for its selective anchoring on the surface of tumor cells and cancer endothelial cells rather than normal cells. Cell-surface GRP78 overexpression of tumor indicates that GRP78 is a crucial target for relative tumor imaging and clinical treatment. Herein, we report the design and preclinical evaluation of a new D peptide ligand [18F]AlF-NOTA-DVAP recognizing GRP78 expressed on the cell surface of breast cancer. METHODS: Radiochemical synthesis of [18F]AlF-NOTA-DVAP was achieved via a one-pot labeling process by heating NOTA-DVAP in the presence of in situ prepared [18F]AlF for 15 min at 110 °C and purified through HPLC. RESULTS: The radiotracer showed high in vitro stability in rat serum at 37 °C over 3 h. Both biodistribution studies and in vivo micro-PET/CT imaging studies in BALB/c mice bearing 4 T1 tumor showed [18F]AlF-NOTA-DVAP had a rapid and high uptake in tumor, as well as a long residence time. The high hydrophilicity of the radiotracer enables its fast clearance from most normal tissues and thus improves the tumor-to-normal tissue ratios (4.40 at 60 min) which is better than [18F]FDG (1.31 at 60 min). Pharmacokinetic studies showed the average in vivo mean residence time of the radiotracer was just 0.6432 h and indicated that this hydrophilic radiotracer was quickly eliminated from the body to reduce the distribution of non-target tissues. CONCLUSIONS: These results suggest that [18F]AlF-NOTA-DVAP is a very promising PET probe for tumor-specific imaging of cell-surface GRP78-positive tumor.

Genome-wide analysis of the GLP gene family and overexpression of GLP1-5-1 to promote lignin accumulation during early somatic embryo development in Dimocarpus longan.

Longan (Dimocarpus longan Lour.) is an economically important subtropical fruit tree. Its fruit quality and yield are affected by embryo development. As a plant seed germination marker gene, the germin-like protein (GLP) gene plays an important role in embryo development. However, the mechanism underlying the role of the GLP gene in somatic embryos is still unclear. Therefore, we conducted genome-wide identification of the longan GLP (DlGLP) gene and preliminarily verified the function of DlGLP1-5-1. Thirty-five genes were identified as longan GLP genes and divided into 8 subfamilies. Based on transcriptome data and qRT‒PCR results, DlGLP genes exhibited the highest expression levels in the root, and the expression of most DlGLPs was upregulated during the early somatic embryogenesis (SE) in longan and responded to high temperature stress and 2,4-D treatment; eight DlGLP genes were upregulated under MeJA treatment, and four of them were downregulated under ABA treatment. Subcellular localization showed that DlGLP5-8-2 and DlGLP1-5-1 were located in the cytoplasm and extracellular stroma/chloroplast, respectively. Overexpression of DIGLP1-5-1 in the globular embryos (GEs) of longan promoted the accumulation of lignin and decreased the H2O2 content by regulating the activities of ROS-related enzymes. The results provide a reference for the functional analysis of DlGLPs and related research on improving lignin accumulation in the agricultural industry through genetic engineering.

RIP140-Mediated NF-κB Inflammatory Pathway Promotes Metabolic Dysregulation in Retinal Pigment Epithelium Cells.

Metabolic dysregulation of the retinal pigment epithelium (RPE) has been implicated in age-related macular degeneration (AMD). However, the molecular regulation of RPE metabolism remains unclear. RIP140 is known to affect oxidative metabolism and mitochondrial biogenesis by negatively controlling mitochondrial pathways regulated by PPAR-γ co-activator-1 α(PGC-1α). This study aims to disclose the effect of RIP140 on the RPE metabolic program in vitro and in vivo. RIP140 protein levels were assayed by Western blotting. Gene expression was tested using quantitative real-time PCR (qRT-PCR), ATP production, and glycogen concentration assays, and the release of inflammatory factors was analyzed by commercial kits. Mice photoreceptor function was measured by electroretinography (ERG). In ARPE-19 cells, RIP140 overexpression changed the expression of the key metabolic genes and lipid processing genes, inhibited mitochondrial ATP production, and enhanced glycogenesis. Moreover, RIP140 overexpression promoted the translocation of NF-κB and increased the expression and production of IL-1ß, IL-6, and TNF-α in ARPE-19 cells. Importantly, we also observed the overexpression of RIP140 through adenovirus delivery in rat retinal cells, which significantly decreased the amplitude of the a-wave and b-wave measured by ERG assay. Therapeutic strategies that modulate the activity of RIP140 could have clinical utility for the treatment of AMD in terms of preventing RPE degeneration.

Murine diabetic models for dengue virus infection.

Dengue virus (DENV) is a critical public health concern in tropical and subtropical regions worldwide. Thus, immunocompetent murine models of DENV infection with robust viremia are required for vaccine studies. Diabetes is highly prevalent worldwide, making it frequent comorbidity in patients with dengue fever. Therefore, murine models are needed to understand viral pathogenesis and disease progression. Acquired-induced and inherently diabetic C57BL/6 and db/db mice were inoculated with DENV-3 via the tail vein. After infection, both the diabetic C57BL/6 and db/db mice showed obvious weight loss with clinical manifestations. Quantitative reverse-transcription polymerase chain reaction revealed robust and replicable viremia in the two types of diabetic mice. Immunohistochemical detection showed persistent DENV-3 infection in the liver. Enzyme-linked immunosorbent assay for cytokine detection revealed that diabetic mice showed more severe inflammatory responses than did nondiabetic mice, and significant histological alterations were observed in diabetic mice. Thus, the diabetic mice were more susceptible to DENV infection than the nondiabetic mice. Taken together, we established two types of immunocompetent diabetic mice for DENV infection, which can be used to further study the mechanisms of dengue pathogenesis in diabetes and to develop antiviral pharmaceuticals and treatments.

Effect of Network-Based Positive Psychological Nursing Model Combined With Elemene Injection on Negative Emotions, Immune Function and Quality of Life in Lung Cancer Patients Undergoing Chemotherapy in the Era of Big Data.

Background: With the development of big data, big data interpenetrate in every person's life. Health care is no exception to this trend, especially in regard to nursing analytics. The data that is analyzed and leveraged in this field is gathered from a variety of sources, including electronic health records (EHRs), medical histories, provider notes and mobile applications, creating an accumulation of personalized health information around each individual. Objective: To explore the effect of the network-based positive psychological nursing model combined with elemene injection on negative emotions, immune function and quality of life (QOL) in patients with lung cancer (LC) undergoing chemotherapy. Methods: The clinical data of 90 LC patients who underwent chemotherapy in our hospital from December 2020 to December 2021 were retrospectively analyzed, and the patients were equally split into experimental group (EG) and control group (CG) according to the order of enrollment. The patients in CG received routine nursing intervention during chemotherapy, while those in EG received the network-based positive psychological nursing model combined with elemene injection to compare negative emotions, immune function and quality of life (QOL) between the two groups. Results: Compared with CG, EG had notably higher immune function indexes (P < 0.001), lower serum VEGF and MMP-2 levels (P < 0.001), lower HAMA and HAMD scores (P < 0.05), and higher scores of PTGI, physiological function, psychological function, social function and physical function (P < 0.001). Conclusion: The network-based positive psychological nursing model combined with elemene injection is a reliable method to enhance the immune function and QOL of LC patients undergoing chemotherapy and alleviate their negative emotions, which has a high clinical application value.

CIRKIL Exacerbates Cardiac Ischemia/Reperfusion Injury by Interacting With Ku70.

BACKGROUND: Ku70 participates in several pathological processes through mediating repair of DNA double-strand breaks. Our previous study has identified a highly conserved long noncoding RNA cardiac ischemia reperfusion associated Ku70 interacting lncRNA (CIRKIL) that was upregulated in myocardial infarction. The study aims to investigate whether CIRKIL regulates myocardial ischemia/reperfusion (I/R) through binding to Ku70. METHODS: CIRKIL transgenic and knockout mice were subjected to 45-minute ischemia and 24-hour reperfusion to establish myocardial I/R model. RNA pull-down and RNA immunoprecipitation assay were used to detect the interaction between CIRKIL and Ku70. RESULTS: The expression of CIRKIL was increased in I/R myocardium and H2O2-treated cardiomyocytes. Overexpression of CIRKIL increased the expression of γH2A.X, a specific marker of DNA double-strand breaks and aggravated cardiomyocyte apoptosis, whereas knockdown of CIRKIL produced the opposite changes. Transgenic overexpression of CIRKIL aggravated cardiac dysfunction, enlarged infarct area, and worsened cardiomyocyte damage in I/R mice. Knockout of CIRKIL alleviated myocardial I/R injury. Mechanistically, CIRKIL directly bound to Ku70 to subsequently decrease nuclear translocation of Ku70 and impair DNA double-strand breaks repair. Concurrent overexpression of Ku70 mitigated CIRKIL overexpression-induced myocardial I/R injury. Furthermore, knockdown of human CIRKIL significantly suppressed cell damage induced by H2O2 in adult human ventricular cardiomyocytes and human induced pluripotent stem cell-derived cardiomyocytes. CONCLUSIONS: CIRKIL is a detrimental factor in I/R injury acting via regulating nuclear translocation of Ku70 and DNA double-strand breaks repair. Thus, CIRKIL might be considered as a novel molecular target for the treatment of cardiac conditions associated with I/R injury.

Novel Dietary and Lifestyle Inflammation Scores Directly Associated with All-Cause, All-Cancer, and All-Cardiovascular Disease Mortality Risks Among Women.

BACKGROUND: Exogenous exposures collectively may contribute to chronic, low-grade inflammation and increase risks for major chronic diseases and mortality. We previously developed, validated, and reported a novel, FFQ-based and lifestyle questionnaire-based, inflammation biomarker panel-weighted, predominantly whole foods-based 19-component dietary inflammation score (DIS) and 4-component lifestyle inflammation score (LIS; comprising physical activity, alcohol intake, BMI, and current smoking status). Both scores were more strongly associated with circulating biomarkers of inflammation in 3 populations than were previously reported dietary inflammation indices. Associations of the DIS and LIS with mortality risk have not been reported. OBJECTIVES: To investigate separate and joint associations of the DIS and LIS with all-cause, all-cancer, and cardiovascular disease (CVD) mortality risks in the prospective Iowa Women's Health Study (1986-2012; n = 33,155 women, ages 55-69 years, of whom 17,431 died during follow-up, including 4379 from cancer and 6574 from CVD). METHODS: We summed each study participant's scores' components, weighted by their published weights, to yield the participant's inflammation score; a higher score was considered more pro-inflammatory. We assessed DIS and LIS mortality associations using multivariable Cox proportional hazards regression. RESULTS: Among participants in the highest relative to the lowest DIS and LIS quintiles, the adjusted HRs for all-cause mortality were 1.11 (95% CI: 1.05-1.16) and 1.60 (95% CI: 1.53-1.68), respectively; for all-cancer mortality were 1.07 (95% CI: 0.97-1.17) and 1.51 (95% CI: 1.38-1.66), respectively; and for CVD mortality were 1.12 (95% CI: 1.03-1.21) and 1.79 (95% CI: 1.66-1.94), respectively (all Ptrend values < 0.01). Among those in the highest relative to the lowest joint LIS/DIS quintiles, the HRs for all-cause, all-cancer, and all-CVD mortality were 1.88 (95% CI: 1.71-2.08), 1.82 (95% CI: 1.50-2.20), and 1.92 (95% CI: 1.64-2.24), respectively. CONCLUSIONS: More pro-inflammatory diets and lifestyles, separately but especially jointly, may be associated with higher all-cause, all-cancer, and all-CVD mortality risks among women.

Involvement of lncR-30245 in Myocardial Infarction-Induced Cardiac Fibrosis Through Peroxisome Proliferator-Activated Receptor-γ-Mediated Connective Tissue Growth Factor Signalling Pathway.

BACKGROUND: Long noncoding RNAs (lncRNAs) are emerging as important mediators of cardiac pathophysiology. The aim of the present study is to investigate the effects of lncR-30245, an lncRNA, on cardiac fibrogenesis and the underlying mechanism. METHODS: Myocardial infarction (MI) and transforming growth factor (TGF)-ß1 were used to induce fibrotic phenotypes. Cardiac fibrosis was detected by Masson's trichrome staining. Cardiac function was evaluated by echocardiography. Western blot, quantitative reverse transcription-polymerase chain reaction, and pharmacological approaches were used to investigate the role of lncR-30245 in cardiac fibrogenesis. RESULTS: Expression of lncR-30245 was significantly increased in MI hearts and TGF-ß1-treated cardiac fibroblasts (CFs). LncR-30245 was mainly located in the cytoplasm. Overexpression of lncR-30245 promoted collagen production and CF proliferation. Knockdown of lncR-30245 significantly inhibited TGF-ß1-induced collagen production and CF proliferation. LncR-30245 overexpression inhibited the antifibrotic role of peroxisome proliferator-activated receptor (PPAR)-γ and increased connective tissue growth factor (CTGF) expression, whereas lncR-30245 knockdown exerted the opposite effects. Rosiglitazone, a PPAR-γ agonist, significantly inhibited lncR-30245-induced CTGF upregulation and collagen production in CFs. In contrast, T0070907, a PPAR-γ antagonist, attenuated the inhibitory effects of lncR-30245 small interfering RNA (siRNA) on TGF-ß1-induced CTGF expression and collagen production. LncR-30245 knockdown significantly enhanced ejection fraction and fractional shortening and attenuated cardiac fibrosis in MI mice. CONCLUSION: Our study indicates that the lncR-30245/PPAR-γ/CTGF pathway mediates MI-induced cardiac fibrosis and might be a therapeutic target for various cardiac diseases associated with fibrosis.

An extended research of crossmodal correspondence between color and sound in psychology and cognitive ergonomics.

Based on the existing research on sound symbolism and crossmodal correspondence, this study proposed an extended research on cross-modal correspondence between various sound attributes and color properties in a group of non-synesthetes. In Experiment 1, we assessed the associations between each property of sounds and colors. Twenty sounds with five auditory properties (pitch, roughness, sharpness, tempo and discontinuity), each varied in four levels, were used as the sound stimuli. Forty-nine colors with different hues, saturation and brightness were used to match to those sounds. Result revealed that besides pitch and tempo, roughness and sharpness also played roles in sound-color correspondence. Reaction times of sound-hue were a little longer than the reaction times of sound-lightness. In Experiment 2, a speeded target discrimination task was used to assess whether the associations between sound attributes and color properties could invoke natural cross-modal correspondence and improve participants' cognitive efficiency in cognitive tasks. Several typical sound-color pairings were selected according to the results of Experiment 1. Participants were divided into two groups (congruent and incongruent). In each trial participants had to judge whether the presented color could appropriately be associated with the sound stimuli. Result revealed that participants responded more quickly and accurately in the congruent group than in the incongruent group. It was also found that there was no significant difference in reaction times and error rates between sound-hue and sound-lightness. The results of Experiment 1 and 2 indicate the existence of a robust crossmodal correspondence between multiple attributes of sound and color, which also has strong influence on cognitive tasks. The inconsistency of the reaction times between sound-hue and sound-lightness in Experiment 1 and 2 is probably owing to the difference in experimental protocol, which indicates that the complexity of experiment design may be an important factor in crossmodal correspondence phenomena.

Noninvasively Imaging Subcutaneous Tumor Xenograft by a Handheld Raman Detector, with the Assistance of an Optical Clearing Agent.

A handheld Raman detector with operational convenience, high portability, and rapid acquisition rate has been applied in clinics for diagnostic purposes. However, the inherent weakness of Raman scattering and strong scattering of the turbid tissue restricts its utilization to superficial locations. To extend the applications of a handheld Raman detector to deep tissues, a gold nanostar-based surface-enhanced Raman scattering (SERS) nanoprobe with robust colloidal stability, a fingerprint-like spectrum, and extremely high sensitivity (5.0 fM) was developed. With the assistance of FPT, a multicomponent optical clearing agent (OCA) efficiently suppressing light scattering from the turbid dermal tissues, the handheld Raman detector noninvasively visualized the subcutaneous tumor xenograft with a high target-to-background ratio after intravenous injection of the gold nanostar-based SERS nanoprobe. To the best of our knowledge, this work is the first example to introduce the optical clearing technique in assisting SERS imaging in vivo. The combination of optical clearing technology and SERS is a promising strategy for the extension of the clinical applications of the handheld Raman detector from superficial tissues to subcutaneous or even deeper lesions that are usually "concealed" by the turbid dermal tissue.

Lead-Free KNbO3:xZnO Composite Ceramics.

It is a tough issue to develop dense and water resistant KNbO3 ceramics due to high evaporation and hygroscopicity of K2O. Here, KNbO3:xZnO composite ceramics were used to successfully solve this problem, where ZnO particles were randomly distributed into a KNbO3 matrix. The addition of ZnO hardly affects the phase structure of KNbO3, and moreover, the enhancement of electrical properties, thermal stability, and aging characteristics was observed in KNbO3:xZnO composite ceramics. The composites possessed the maximum d33 of 120 ± 5 pC/N, which is superior to that of pure KNbO3 (d33 = 80 pC/N). More importantly, a strong water resistance and an aging-free characteristic were observed in KNbO3:0.4ZnO. This is the first time for KNbO3 ceramics to simultaneously improve electrical properties and resolve the water-absorbing properties. We believe that these composite ceramics are promising for practical applications.

Cholesterol Retards Senescence in Bone Marrow Mesenchymal Stem Cells by Modulating Autophagy and ROS/p53/p21Cip1/Waf1 Pathway.

In the present study, we demonstrated that bone marrow mesenchymal stem cells (BMSCs) of the 3rd passage displayed the senescence-associated phenotypes characterized with increased activity of SA-ß-gal, altered autophagy, and increased G1 cell cycle arrest, ROS production, and expression of p53 and p21Cip1/Waf1 compared with BMSCs of the 1st passage. Cholesterol (CH) reduced the number of SA-ß-gal positive cells in a dose-dependent manner in aging BMSCs induced by H2O2 and the 3rd passage BMSCs. Moreover, CH inhibited the production of ROS and expression of p53 and p21Cip1/Waf1 in both cellular senescence models and decreased the percentage of BMSCs in G1 cell cycle in the 3rd passage BMSCs. CH prevented the increase in SA-ß-gal positive cells induced by RITA (reactivation of p53 and induction of tumor cell apoptosis, a p53 activator) or 3-MA (3-methyladenine, an autophagy inhibitor). Our results indicate that CH not only is a structural component of cell membrane but also functionally contributes to regulating cellular senescence by modulating cell cycle, autophagy, and the ROS/p53/p21Cip1/Waf1 signaling pathway.