Hollow CoFe Nanozymes Integrated with Oncolytic Peptides Designed via Machine-Learning for Tumor Therapy.

Developing novel substances to synergize with nanozymes is a challenging yet indispensable task to enable the nanozyme-based therapeutics to tackle individual variations in tumor physicochemical properties. The advancement of machine learning (ML) has provided a useful tool to enhance the accuracy and efficiency in developing synergistic substances. In this study, ML models to mine low-cytotoxicity oncolytic peptides are applied. The filtering Pipeline is constructed using a traversal design and the Autogluon framework. Through the Pipeline, 37 novel peptides with high oncolytic activity against cancer cells and low cytotoxicity to normal cells are identified from a library of 25,740 sequences. Combining dataset testing with cytotoxicity experiments, an 80% accuracy rate is achieved, verifying the reliability of ML predictions. Peptide C2 is proven to possess membranolytic functions specifically for tumor cells as targeted by Pipeline. Then Peptide C2 with CoFe hollow hydroxide nanozyme (H-CF) to form the peptide/H-CF composite is integrated. The new composite exhibited acid-triggered membranolytic function and potent peroxidase-like (POD-like) activity, which induce ferroptosis to tumor cells and inhibits tumor growth. The study suggests that this novel ML-assisted design approach can offer an accurate and efficient paradigm for developing both oncolytic peptides and synergistic peptides for catalytic materials.

Nonlinear dynamics of cavity optomechanical-thermal systems.

Cavity optomechanics is concerned with the interaction between optical cavities and mechanical resonators. Here, we present systematic research on the dynamic behaviors of cavity optomechanical systems incorporating the influence of thermal nonlinearity. A dimensionless theoretical model was established to describe the system and numerical simulations were performed to study the dynamic behaviors. We theoretically identify the staircase effect, which can abruptly alter the system parameters when adiabatically sweeping the pump laser frequency across the optical cavity resonance and driving the mechanical resonator into oscillation. Moreover, we found bistability effects in several detuning intervals when sweeping the laser forward and backward. Both effects are analyzed theoretically and the roots lie in the thermal instability between averaged cavity energy and laser detuning. Our study shows the dynamic behaviors in an optomechanical-thermal system and provides guidance in leveraging the systems for applications in optical frequency comb, phonon laser, etc.

Optical stealth communication based on quantum noise stream ciphered amplified spontaneous emission light.

Amplified spontaneous emission (ASE) light is the most natural optical carrier to hide a message in the existing optical networks at photonic layer. To enhance the anti-intercept ability of the ASE-carried stealth channel, a novel optical stealth communication scheme based on quantum noise stream cipher is proposed. The ASE light is intensity modulated by the cipher-text according to Y-00 protocol, and then transmitted under public optical noise after power attenuation. The expression of quantum noise stream ciphered ASE signal is derived, and numerical simulation is carried out. A proof-of-concept experiment is set up to demonstrate the feasibility of the proposed scheme. The experiment results show that the quantum noise stream ciphered stealth signals can be transmitted over a 25 km single-mode fiber span error-free.

Subnoise optical covert communication based on amplified spontaneous emission light.

Amplified spontaneous emission (ASE) light is a common noise in optical communication systems with optical amplification, and a suitable optical carrier for optical covert communication. To deeply covert the secure signal, an in-band subnoise optical covert communication scheme is proposed and demonstrated by a proof-of-concept experiment. The power spectral density of optical secure channel is 10 dB less than the optical noise in the public channel. The covert signal is hidden in both optical and electrical domain, and can be transmitted with error-free. The trade-off between covertness and availability is discussed.

Sirolimus or Everolimus Improves Survival After Liver Transplantation for Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.

The effects of mammalian target of rapamycin (mTOR) inhibitors (sirolimus [SRL] and everolimus [EVL]) on survival in liver transplantation (LT) recipients with hepatocellular carcinoma (HCC) remain the subject of intense research. Therefore, we performed this systematic review and meta-analysis to investigate the potential survival benefits of mTOR inhibitors (mTORis). Embase, PubMed, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for all randomized controlled trials (RCTs) and cohort studies investigating effects of SRL or EVL on LT recipients for HCC. The primary outcomes were 1-, 2-, 3-, and 5-year overall survival (OS), and the secondary outcomes were 1-, 2-, and 3-year recurrence-free survival (RFS) and adverse effects. Pooled relative risks (RRs) with 95% confidence interval (CI) were calculated by a fixed or random effects model with Mantel-Haenszel weighting. Subgroup analyses were performed according to crucial clinical characteristics. We also conducted sensitivity analyses to assess the reliability of our findings. A total of 17 studies were included. OS was improved in both RCTs (1 year: RR, 1.04; 95% CI, 1.00-1.08; 2 years: RR, 1.09; 95% CI, 1.02-1.16; 3 years: RR, 1.13; 95% CI, 1.04-1.24; 5 years: RR, 1.13; 95% CI, 1.02-1.26) and cohort studies (1 year: RR, 1.13; 95% CI, 1.06-1.20; 2 years: RR, 1.24; 95% CI, 1.16-1.32; 3 years: RR, 1.24; 95% CI, 1.15-1.34; 5 years: RR, 1.17; 95% CI, 1.10-1.24), with a lower risk of renal toxicity (RR, 0.75; 95% CI, 0.60 to 0.93). The 1-, 2-, and 3-year RFS were also improved. Current evidence indicates that SRL- or EVL-based immunosuppression improves OS and RFS with a lower risk of renal toxicity compared with mTORi-free immunosuppression. Nevertheless, results must be interpreted with caution.

Quantum noise ciphered optical stealth communication based on equivalent spectral encoding.

To provide secure and covert transmission for optical communication system at the same time, a quantum-noise stream ciphered optical stealth communication approach is proposed for the first time. In the proposed system, the optical pulses are time spread by a chromatic dispersion device and then phase modulated with optical codes at chip rate to realize an equivalent spectral encoding. Binary optical codes are converted to multiple level phase-shift keying signal according to Y-00 protocol. The encoded optical signals are attenuated to mesoscopic coherent states and sent to a public channel. The ciphered signals are stealthy transmitted under public channel noise. The availability and covertness of the optical stealth channel is verified by system simulations.

The epidemiological trends of biliary tract cancers in the United States of America.

BACKGROUND: Biliary tract cancers (BTCs) are a series of heterogeneous malignancies that are broadly grouped based on the anatomical site where they arise into subtypes including intrahepatic cholangiocarcinoma (ICC), extrahepatic cholangiocarcinoma (ECC), gallbladder cancer (GBC), and ampulla of Vater cancer (AVC). METHODS AND RESULTS: The present study provides an overview of the epidemiology of the various BTCs based on data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database from 2000 to 2018. Distinct differences in both incidence and mortality rates were observed for these BTCs as a function of age, sex, ethnicity, and calendar year. In 2018, BTCs emerged as the fifth most prevalent form of alimentary tract cancer in the USA. While the incidence and mortality of ICC appear to be increasing, the incidence rates of GBC, ECC, and AVC have remained stable, as have the corresponding mortality rates. The most common and deadliest BTCs in 2018 were ICC and GBC among males and females, respectively. The ethnic groups exhibiting the highest incidence rates of these different BTCs were American Indians and Alaska Natives for GBC, and Asian and Pacific Islanders for ICC, ECC, and AVC. The incidence of all of these forms of BTC rose with age. There were some variations in BTCs in terms of staging, locoregional surgical treatments, adjuvant therapies, and prognostic outcomes from 2000 to 2018. CONCLUSIONS: The epidemiological characteristics, staging, locoregional surgical treatments, adjuvant therapies, and prognostic outcomes were distinct for each of these BTCs.

Contributions of Escherichia coli and Its Motility to the Formation of Dual-Species Biofilms with Vibrio cholerae.

Biofilm formation is important in both the environmental and intestinal phases of the Vibrio cholerae life cycle. Nevertheless, most studies of V. cholerae biofilm formation focus on monospecies cultures, whereas nearly all biofilm communities found in nature consist of a variety of microorganisms. Multispecies biofilms formed between V. cholerae and other bacteria in the environment and the interactions that exist between these species are still poorly understood. In this study, the influence of Escherichia coli on the biofilm formation of V. cholerae was studied in the context of both in vitro coculture and in vivo coinfection. To understand the underlying synergistic mechanisms between these two species and to investigate the role of E. coli in V. cholerae biofilm formation, different pathotypes of E. coli and corresponding deletion mutants lacking genes that influence flagellar motility, curli fibers, or type I pili were cocultured with V. cholerae. Our findings demonstrate that the presence of commensal E. coli increases biofilm formation at the air-liquid interface in vitro and the generation of biofilm-like multicellular clumps in mouse feces. Examination of laboratory E. coli flagellar-motility ΔfliC and ΔmotA mutants in dual-species biofilm formation suggests that flagellar motility plays an important role in the synergistic interaction and coaggregation formation between V. cholerae and E. coli. This study facilitates a better understanding of how V. cholerae resides in harsh environments and colonizes the intestine. IMPORTANCE Biofilms play an important role in the V. cholerae life cycle. Until now, only monospecies biofilm formation of V. cholerae has been well studied. However, in nature, bacteria live in complex microbial communities, where biofilm is mostly composed of multiple microbial species that interact to cooperate with or compete against each other. Uncovering how V. cholerae forms multispecies biofilms is critical for furthering our understanding of how V. cholerae survives in the environment and transitions to infecting the human host. In this work, the dual-species biofilm containing V. cholerae and Escherichia coli was investigated. We demonstrate that the presence of commensal E. coli increased overall biofilm formation. Furthermore, we demonstrate that the motility of E. coli flagella is important for V. cholerae and E. coli to form coaggregation clumps in a dual-species biofilm. These results shed light on a new mechanism for understanding the survival and pathogenesis of V. cholerae.

Comparison of Carotid Plaque Characteristics Between Men and Women Using Magnetic Resonance Vessel Wall Imaging: A Chinese Atherosclerosis Risk Evaluation Study.

BACKGROUND: Carotid vulnerable plaque is a major cause of stroke and differs between men and women. Few studies have investigated the differences in carotid plaque features between sexes in a Chinese population. PURPOSE: To compare carotid atherosclerotic plaque features between men and women in a Chinese population using magnetic resonance imaging. STUDY TYPE: Cross-sectional. SUBJECTS: A total of 567 patients (mean age: 61.5 ± 10.1 years; 404 men) who had recent stroke or transient ischemia attack and atherosclerotic plaque in at least one carotid artery. FIELD STRENGTH: A 3.0 T. SEQUENCE: T1- and T2-weighted turbo spin echo, three-dimensional time-of-flight (TOF) fast field echo and magnetization-prepared rapid acquisition gradient echo sequences. ASSESSMENT: Plaque characteristics including lumen area (LA), wall area (WA), total vessel area (TVA), mean wall thickness (MWT), and mean normalized wall index (NWI); presence of calcification, lipid-rich necrotic core (LRNC), intraplaque hemorrhage (IPH), and fibrous cap rupture (FCR); and percent composition area (%area) were evaluated and compared between men and women. STATISTICAL TESTS: Independent-sample t test, Mann-Whitney U test, chi-square test, and multiple linear and logistic regressions. RESULTS: In symptomatic arteries, men had significantly greater LA (46.2 ± 15.6 mm2 vs. 40.7 ± 12.9 mm2 , P < 0.05), WA (33.9 ± 11.5 mm2 vs. 26.3 ± 7.5 mm2 , P < 0.05), and TVA (80.1 ± 20.4 mm2 vs. 67.0 ± 18.0 mm2 , P < 0.05); higher MWT (1.2 ± 0.4 mm vs. 1.0 ± 0.2 mm, P < 0.05); and higher prevalence of LRNC (72.3% vs. 46.0%, P < 0.05) and IPH (18.6% vs. 4.9%, P < 0.05) compared with women. In asymptomatic arteries, men had significantly greater LA (48.3 ± 16.9 mm2 vs. 42.1 ± 12.6 mm2 , P < 0.05), WA (32.9 ± 11.0 mm2 vs. 25.8 ± 6.1 mm2 , P < 0.05), and TVA (81.2 ± 22.1 mm2 vs. 67.9 ± 16.5 mm2 , P < 0.05); higher MWT (1.2 ± 0.3 mm vs. 1.0 ± 0.2 mm, P < 0.05); higher prevalence of LRNC (67.8% vs. 42.9%, P < 0.05), IPH (14.9% vs. 1.2%, P < 0.05), and FCR (6.4% vs. 1.2%, P < 0.05); and higher %LRNC area (24.8 ± 17.2% vs. 17.8 ± 14.1%, P < 0.05) compared with women. DATA CONCLUSION: Men have similar plaque burden but more vulnerable atherosclerotic plaques compared with women in both symptomatic and asymptomatic carotid arteries in a Chinese population. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 3.

Spatially correlated MIMO for exploiting the capacity of NLOS ultraviolet turbulent channels.

In order to break through the inherent limitation of channel capacity, we employ a correlated multiple input multiple output (MIMO) framework over non-line-of-sight (NLOS) ultraviolet (UV) turbulent channels. Subsequently, a method of segmented correlation is proposed to define the spatial correlation of UV MIMO structures. Furthermore, the correlation and channel capacity are studied with varying elevation angle, turbulence intensity, signal-to-noise ratio (SNR) and number of transceiver in pairs (NTPs). The results show that this correlated MIMO framework can obtain higher channel capacity by reducing the elevation angle of the transceivers or increasing turbulence intensity or NTPs. Moreover, channel capacity increases with the SNR. But at low SNR, a larger gain of channel capacity can be provided. Therefore, this paper develops the capacity of UV turbulent channels and provides a guide for optimal parameter configuration of correlated UV MIMO.

Carotid Artery Remodeling Is Segment Specific: An In Vivo Study by Vessel Wall Magnetic Resonance Imaging.

OBJECTIVE: Early atherosclerosis is often undetected due in part to compensatory enlargement of the outer wall, termed positive remodeling. Variations in hemodynamic conditions and clinical factors influence the patterns of remodeling. The carotid artery provides an opportunity to examine these variations because of the unique geometry of the carotid bulb. This study aimed to determine differences in remodeling of the common, internal, and bifurcation segments of the carotid using magnetic resonance imaging. APPROACH AND RESULTS: Carotid arteries of 525 subjects without history of cardiovascular disease were imaged by magnetic resonance imaging. The carotid artery was divided into 3 segments: common carotid artery; bifurcation; and internal carotid artery. Remodeling patterns were characterized using linear regression analysis of lumen and total vessel areas (dependent variables) compared with maximum wall thickness (independent variable) for each segment, adjusted for age, sex, and height. The common carotid artery demonstrated a pattern consistent with positive remodeling, whereas the bifurcation demonstrated negative remodeling. The internal carotid artery demonstrated a mixed pattern of outer wall expansion and lumen constriction. Females and subjects with diabetes mellitus showed more positive remodeling, hypertension was associated with attenuated positive remodeling, and those with hypercholesterolemia showed more negative remodeling. CONCLUSIONS: In this cohort of 55- to 80-year-old individuals without history of cardiovascular disease, the pattern of early carotid artery remodeling was segment specific and appeared to be associated with sex and clinical characteristics. These findings provide the groundwork for longitudinal studies to define local and systemic factors such as hemodynamic and clinical conditions on carotid artery remodeling.

Psychosocial and functional contributors to personal recovery in serious mental illness.

Background: Although recovery-oriented services have been conceptualized to improve personal recovery, related research often focuses on measures of clinical recovery. Identifying the relationships between personal recovery, clinical recovery, and psychosocial variables will inform service components and outcome measurement in recovery-oriented services. Aims: This study sought to determine the connection between personal recovery and two sets of potential contributors: psychosocial variables (i.e., empowerment, resilience, and consumer involvement) and functional indicators of clinical recovery. Method: These relationships were examined by analyzing survey data collected from 266 consumers who are receiving public mental health services in the United States. Results: Empowerment, resilience and psychological involvement were associated with personal recovery. Clinical recovery did not uniquely contribute to personal recovery once psychosocial factors were accounted for. Interactions revealed that the relationship between psychological involvement and personal recovery was stronger for those who had been recently hospitalized, and for those with relatively greater resilience. Conclusions: Results indicate that personal recovery is an essential outcome measure for recovery-oriented services that cannot be replaced by clinical recovery outcome measurement. Additionally, empowerment, resilience, and consumer involvement are key components of recovery, which suggests that services and outcome measures should prioritize incorporation of these constructs.

The Fructose-Specific Phosphotransferase System of Klebsiella pneumoniae Is Regulated by Global Regulator CRP and Linked to Virulence and Growth.

Klebsiella pneumoniae is an opportunistic pathogen, and its hypervirulent variants cause serious invasive community-acquired infections. A genomic view of K. pneumoniae NTUH-2044 for the carbohydrate phosphotransferase system (PTS) found a putative fructose PTS, namely, the Frw PTS gene cluster. The deletion mutant and the complemented mutant of frwC (KP1_1992), which encodes the putative fructose-specific enzyme IIC, were constructed, and the phenotypes were characterized. This transmembrane PTS protein is responsible for fructose utilization. frwC deletion can enhance biofilm formation and capsular polysaccharide (CPS) biosynthesis but decreases the growth rate and lethality in mice. frwC expression was repressed in the cyclic AMP receptor protein (CRP) mutant. Electrophoretic mobility shift assay showed that CRP can directly bind to the promoter of frwC These results indicated that frwC expression is controlled by CRP directly and that such regulation contributes to bacterial growth, CPS synthesis, and the virulence of the Δcrp strain. The findings help elucidate fructose metabolism and the CRP regulatory mechanism in K. pneumoniae.

Microbial Degradation of Pesticide Residues and an Emphasis on the Degradation of Cypermethrin and 3-phenoxy Benzoic Acid: A Review.

Nowadays, pesticides are widely used in preventing and controlling the diseases and pests of crop, but at the same time pesticide residues have brought serious harm to human's health and the environment. It is an important subject to study microbial degradation of pesticides in soil environment in the field of internationally environmental restoration science and technology. This paper summarized the microbial species in the environment, the study of herbicide and pesticides degrading bacteria and the mechanism and application of pesticide microbial degrading bacteria. Cypermethrin and other pyrethroid pesticides were used widely currently, while they were difficult to be degraded in the natural conditions, and an intermediate metabolite, 3-phenoxy benzoic acid would be produced in the degradation process, causing the secondary pollution of agricultural products and a series of problems. Taking it above as an example, the paper paid attention to the degradation process of microorganism under natural conditions and factors affecting the microbial degradation of pesticide. In addition, the developed trend of the research on microbial degradation of pesticide and some obvious problems that need further solution were put forward.

Analytical link bandwidth model based square array reception for non-line-of-sight ultraviolet communication.

An analytical model is presented firstly in this paper to formulate the link bandwidth of non-line-of-sight (NLOS) ultraviolet (UV) channel. The link bandwidth is characterized by three geometrical parameters including transmitter (Tx) elevation angle, receiver (Rx) field of view (FOV), and transceiver separation distance, and further expressed as a closed-form through software-aided numerical fitting. Comparison with the link bandwidth obtained via a Monte Carlo model is done to verify the feasibility of this model. Based on this model, we investigate the diversity reception on the NLOS UV communication from a new perspective. A spatially squared distributed Rx array is customized for the NLOS UV channel. Lower temporal broadening is enabled, leading to a higher link bandwidth. Numerical results suggest that over 100% improvement of the link bandwidth is predicted by the square array reception and the ratio grows rapidly with the narrowing of Tx beam divergence. Therefore, this paper provides a guide for link analysis and receiver design for NLOS UV communication.

Diagnostic value of gadobutrol versus gadopentetate dimeglumine in enhanced MRI of brain metastases.

PURPOSE: To compare gadobutrol and gadopentetate dimeglumine (Gd-DTPA) contrast-enhanced magnetic resonance imaging (MRI) at 3T for visualizing brain metastases. MATERIALS AND METHODS: The present randomized study included 60 consecutive patients with known or suspected brain metastases from systemic malignancies. Two enhanced cerebral MR scans were performed in each patient within an interval of 2-5 days using different contrast agents (gadobutrol or Gd-DTPA) at 3T. The dose of the contrast agents (0.1 mmol/kg Gd) was also identical. The axial T1 FLAIR images at 3, 7, and 10 minutes after the injection of the contrast agent were obtained for evaluation. Two experienced radiologists performed subjective evaluation of the image quality, made the choice of the optimal images, and performed an objective evaluation including: signal-to-noise ratio (SNR) of the brain metastases, contrast-to-noise ratio (CNR), contrast enhancement (CE), contrast-to-brain ratio (CBR), and contrast enhancement ratio (CER) of the brain metastases. RESULTS: Subjective evaluation showed that at 3, 7, and 10 minutes gadobutrol elicited higher scores (margin score: 3.56 ± 0.74 vs. 3.33 ± 0.93, 3.68 ± 0.57 vs. 3.45 ± 0.81, 3.58 ± 0.71 vs. 3.43 ± 0.76; interior score: 2.83 ± 0.42 vs. 2.63 ± 0.61, 2.86 ± 0.38 vs. 2.73 ± 0.52, 2.80 ± 0.42 vs. 2.69 ± 0.53; and overall score: 4.42 ± 0.98 vs. 4.09 ± 1.19, 4.57 ± 0.75 vs. 4.26 ± 1.05, 4.48 ± 0.83 vs. 4.21 ± 1.03, respectively) in displaying the details and overall lesions than Gd-DTPA (repeated measures analysis of variance [ANOVA], margin score: P = 0.001, < 0.0001, 0.006; interior score: P < 0.0001, 0.004, 0.009; and overall score: P = 0.001, < 0.0001, < 0.0001, respectively). Subjective optimal image evaluation showed that the percentage of image assessed as "gadobutrol was better than Gd-DTPA (41.2-44.1%)" was greater than that assessed as "Gd-DTPA was better than gadobutrol (5.9-26.5%)." Objective evaluation showed that at 3, 7, and 10 minutes the SNR (214.17 ± 85.70 vs. 199.57 ± 85.08, 214.80 ± 86.03 vs. 199.19 ± 84.74, and 213.83 ± 82.46 vs. 193.68 ± 79.59, respectively), CNR (68.64 ± 50.18 vs. 57.88 ± 51.06, 75.42 ± 53.19 vs. 63.74 ± 53.91, and 77.13 ± 51.86 vs. 63.21 ± 51.71, respectively), CE (101.76 ± 63.31 vs. 87.61 ± 64.85, 99.85 ± 61.56 vs. 85.08 ± 64.98, and 100.33 ± 58.63 vs. 82.73 ± 61.73, respectively), CBR (0.48 ± 0.32 vs. 0.40 ± 0.33, 0.54 ± 0.34 vs. 0.46 ± 0.35, and 0.56 ± 0.34 vs. 0.47 ± 0.34, respectively), and CER (0.99 ± 0.69 vs. 0.88 ± 0.81, 0.97 ± 0.68 vs. 0.86 ± 0.84, and 0.98 ± 0.65 vs. 0.85 ± 0.80, respectively) were all higher when using gadobutrol compared with Gd-DTPA in the enhanced MR (repeated measures ANOVA, all P < 0.0001). On Gd-DTPA enhanced images, 289, 292, and 292 lesions at 3, 7, and 10 minutes were detected by the two radiologists, while 295, 301, and 301 lesions were detected on gadobutrol-enhanced images, respectively. CONCLUSION: Using a 3T T1 FLAIR sequence, gadobutrol (0.1 mmol/kg body weight)-enhanced MR resulted in more conspicuous brain metastases, and more metastases compared with the same dose of Gd-DTPA. A delay time of 7 minutes for postcontrast MRI in patients with brain metastases is suggested in clinical practice. LEVEL OF EVIDENCE: 2 J. MAGN. RESON. IMAGING 2017;45:1827-1834.

A comparison of arterial spin labeling perfusion MRI and DCE-MRI in human prostate cancer.

Perfusion MRI has the potential to provide pathophysiological biomarkers for the evaluating, staging and therapy monitoring of prostate cancer. The objective of this study was to explore the feasibility of noninvasive arterial spin labeling (ASL) to detect prostate cancer in the peripheral zone and to investigate the correlation between the blood flow (BF) measured by ASL and the pharmacokinetic parameters K(trans) (forward volume transfer constant), kep (reverse reflux rate constant between extracellular space and plasma) and ve (the fractional volume of extracellular space per unit volume of tissue) measured by dynamic contrast-enhanced (DCE) MRI in patients with prostate cancer. Forty-three consecutive patients (ages ranging from 49 to 86 years, with a median age of 74 years) with pathologically confirmed prostate cancer were recruited. An ASL scan with four different inversion times (TI = 1000, 1200, 1400 and 1600 ms) and a DCE-MRI scan were performed on a clinical 3.0 T GE scanner. BF, K(trans), kep and ve maps were calculated. In order to determine whether the BF values in the cancerous area were statistically different from those in the noncancerous area, an independent t-test was performed. Spearman's bivariate correlation was used to assess the relationship between BF and the pharmacokinetic parameters K(trans), kep and ve. The mean BF values in the cancerous areas (97.1 ± 30.7, 114.7 ± 28.7, 102.3 ± 22.5, 91.2 ± 24.2 ml/100 g/min, respectively, for TI = 1000, 1200, 1400, 1600 ms) were significantly higher (p < 0.01 for all cases) than those in the noncancerous regions (35.8 ± 12.5, 42.2 ± 13.7, 53.5 ± 19.1, 48.5 ± 13.5 ml/100 g/min, respectively). Significant positive correlations (p < 0.01 for all cases) between BF and the pharmacokinetic parameters K(trans), kep and ve were also observed for all four TI values (r = 0.671, 0.407, 0.666 for TI = 1000 ms; 0.713, 0.424, 0.698 for TI = 1200 ms; 0.604, 0.402, 0.595 for TI = 1400 ms; 0.605, 0.422, 0.548 for TI = 1600 ms). It can be seen that the quantitative ASL measurements show significant differences between cancerous and benign tissues, and exhibit strong to moderate correlations with the parameters obtained using DCE-MRI. These results show the promise of ASL as a noninvasive alternative to DCE-MRI.

Transcriptome and proteome analyses reveal the mechanisms involved in polystyrene nanoplastics disrupt spermatogenesis in mice.

Nanoplastics have been demonstrated to be reproductively toxic to mammals. However, the mechanisms of nanoplastics induce reproductive damage in mammals, especially their effects on spermatogenesis, remain elusive. Herein, we explored the effects and underlying mechanisms of polystyrene nanoplastics (PS-NPs) on the testicular development of male mice after 28 days of exposure, representing the first systematic study of PS-NPs-induced male reproductive injury by integrating histomorphology, transcriptomics and proteomics. PS-NPs decreased the sperm concentration, sperm motility, and disrupted the structure of the seminiferous tubules of the mice. Besides, transcriptome and proteome analyses revealed that PS-NPs disrupted spermatogenesis by inhibiting the transcription of Prm3/Tnp1/Aurkc/Mea1/Mettl14 and the expression of Pmfbp1/Ggn/Fsip2. Furthermore, PS-NPs enabled Hsd3b5 protein expression to reduce dihydrotestosterone levels, and affected sperm flagellar assembly by decreasing the expression of Dnah8/Tekt5/Rsph6a. Moreover, PS-NPs induced testicular cell apoptosis by up-regulating the expression of cathepsins (B/F/H). In addition, PS-NPs destroyed tight junctions by reducing the expression of the Claudin family (3/5/15). In conclusion, PS-NPs can disrupt spermatogenesis by altering the expression patterns of transcriptome and proteome, inducing testicular cell apoptosis and destroying tight junctions.

A Customized Biohybrid Presenting Cascade Responses to Tumor Microenvironment.

Intrinsic characteristics of microorganisms, including non-specific metabolism sites, toxic byproducts, and uncontrolled proliferation constrain their exploitation in medical applications such as tumor therapy. Here, the authors report an engineered biohybrid that can efficiently target cancerous sites through a pre-determined metabolic pathway to enable precise tumor ablation. In this system, DH5α Escherichia coli is engineered by the introduction of hypoxia-inducible promoters and lactate oxidase genes, and further surface-armored with iron-doped ZIF-8 nanoparticles. This bioengineered E. coli can produce and secrete lactate oxidase to reduce lactate concentration in response to hypoxic tumor microenvironment, as well as triggering immune activation. The peroxidase-like functionality of the nanoparticles extends the end product of the lactate metabolism, enabling the conversion of hydrogen peroxide (H2O2) into highly cytotoxic hydroxyl radicals. This, coupled with the transformation of tirapazamine loaded on nanoparticles to toxic benzotriazinyl, culminates in severe tumor cell ferroptosis. Intravenous injection of this biohybrid significantly inhibits tumor growth and metastasis.

Effect of dietary supplementation with recombinant human lysozyme on growth performance, antioxidative characteristics, and intestinal health in broiler chickens.

Lysozyme is often used as a feed additive to act as an antibacterial protein that boosts the immune system of livestock and poultry while protecting against pathogens. To investigate the effects of recombinant human lysozyme (rhLYZ) from Pichia pastoris and chlortetracycline on broiler chicken's production performance, antioxidant characteristics, and intestinal microbiota, a total of 200, 1-d-old male Arbor Acres broiler chickens (46.53 ±â€…0.42 g) were selected for a 42-d experiment. Dietary treatments included a basal diet of corn-soybean meal supplemented with either 0 mg/kg (CON), 50 mg/kg aureomycin (ANT), 20 mg/kg rhLYZ (LOW), 60 mg/kg rhLYZ (MEDIUM), or 180 mg/kg rhLYZ (HIGH). Compared with CON, MEDIUM diet increased (P < 0.05) average daily gain (67.40 g) of broilers from day 22 to 42. In the early (1.29) and overall phases (1.69), MEDIUM led to a reduction (P < 0.05) in the feed conversion ratio of broiler chickens. Furthermore, in comparison to the CON and ANT, MEDIUM exhibited reduced (P < 0.05) levels of INF-γ and tumor necrosis factor-α in the serum. In the cecum, the abundance of Monoglobus and Family_XIII_AD3011_group was lower (P < 0.05) in the MEDIUM treatment compared to CON. Overall, supplementation of 60 mg/kg of rhLYZ improved growth performance, nutrient utilization efficiency, and serum immune function, while also influencing the composition of intestinal microbiota. This suggests lysozyme's potential to replace antibiotic additives in feed.

The aim of this study was to explore the effects of recombinant human lysozyme (rhLYZ) produced from Pichia pastoris and chlortetracycline on broiler chicken performance, antioxidant properties, and gut microbiota. A 42-d experiment was conducted, involving 200 1-d-old male Arbor Acres broiler chickens. We provided different diets: a standard diet (CON), a diet with 50 mg/kg aureomycin (ANT), a diet with 20 mg/kg rhLYZ (LOW), a diet with 60 mg/kg rhLYZ (MEDIUM), or a diet with 180 mg/kg rhLYZ (HIGH). The results showed that, compared to the control group, the MEDIUM group significantly increased the average daily gain of broilers to 67.40 g from day 22 to 42. Additionally, the MEDIUM group exhibited a reduced feed conversion ratio during both the early and overall growth stages of the chickens. Furthermore, serum levels of INF-γ and tumor necrosis factor-α were lower in the MEDIUM group compared to both the CON and ANT groups. In the cecum, the abundance of Monoglobus and Family_XIII_AD3011_group was also lower in the MEDIUM treatment compared to the CON group. Overall, supplementation with 60 mg/kg of rhLYZ improved growth performance, nutrient utilization efficiency, and serum immune function in broiler chickens while also influencing the composition of their intestinal microbiota. This suggests the potential of lysozyme as a replacement for antibiotic additives in feed.