Saturated fatty acids increase LPI to reduce FUNDC1 dimerization and stability and mitochondrial function.

Ectopic lipid deposition and mitochondrial dysfunction are common etiologies of obesity and metabolic disorders. Excessive dietary uptake of saturated fatty acids (SFAs) causes mitochondrial dysfunction and metabolic disorders, while unsaturated fatty acids (UFAs) counterbalance these detrimental effects. It remains elusive how SFAs and UFAs differentially signal toward mitochondria for mitochondrial performance. We report here that saturated dietary fatty acids such as palmitic acid (PA), but not unsaturated oleic acid (OA), increase lysophosphatidylinositol (LPI) production to impact on the stability of the mitophagy receptor FUNDC1 and on mitochondrial quality. Mechanistically, PA shifts FUNDC1 from dimer to monomer via enhanced production of LPI. Monomeric FUNDC1 shows increased acetylation at K104 due to dissociation of HDAC3 and increased interaction with Tip60. Acetylated FUNDC1 can be further ubiquitinated by MARCH5 for proteasomal degradation. Conversely, OA antagonizes PA-induced accumulation of LPI, and FUNDC1 monomerization and degradation. A fructose-, palmitate-, and cholesterol-enriched (FPC) diet also affects FUNDC1 dimerization and promotes its degradation in a non-alcoholic steatohepatitis (NASH) mouse model. We thus uncover a signaling pathway that orchestrates lipid metabolism with mitochondrial quality.

Characterizing Local Electronic States of Twin Boundaries in Copper.

Grain boundaries (GBs) and twin boundaries (TBs) in copper (Cu) are two major planar defects that influence electrical conductivity due to their complex electron transport characteristics, involving electron scattering and electron concentration. Understanding their local electronic states is crucial for the design of future conductor materials. In this study, we characterized electron behaviors at TBs and GBs within one Cu grain using atomic force microscopy. Our findings revealed that, compared with GBs, TBs exhibit better current transport capability (direct-current mode) and larger electromagnetic loss (high-frequency microwave mode). Both kelvin probe force microscopy and theoretical analysis suggested that TBs with smaller lattice disorder possess lower density of states at the Fermi level. The reduced density of states may result in decreased electron scattering and a lower electron concentration at TBs. The latter can be highlighted by the high-frequency skinning effect, manifested as larger electromagnetic loss and weaker high-frequency conductivity.

A Structure-Guided Genetic Modification Strategy: Developing Seneca Valley Virus Therapy against Nonsensitive Nonsmall Cell Lung Carcinoma.

Numerous studies have illustrated that the Seneca Valley virus (SVV) shows sufficient oncolytic efficacy targeting small cell lung cancer (SCLC). However, the therapeutics of nonsmall cell lung carcinoma (NSCLC, accounts for 85% of lung cancer cases) using oncolytic virus have been resisting due to the filtration of neutralizing antibody and limited reproduction capacity. Here, we employed structural biology and reverse genetics to optimize novel oncolytic SVV mutants (viral receptor-associated mutant SVV-S177A and viral antigenic peptide-related variant SVV-S177A/P60S) with increased infectivity and lower immunogenicity. The results of the NSCLC-bearing athymic mouse model demonstrated that wild-type (wt) SVV-HB extended the median overall survival (mOS) from 11 days in the PBS group to 19 days. Notably, the newly discovered mutations significantly (P < 0.001) prolonged the mOS from 11 days in the control cohort to 23 days in the SVV-S177A cohort and the SVV-S177A/P60S cohort. Taken together, we present a structure-guided genetic modification strategy for oncolytic SVV optimization and provide a candidate for developing oncolytic viral therapy against nonsensitive NSCLC. IMPORTANCE Nonsmall cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer cases (more than 1.85 million cases with 1.48 million deaths in 2020). In the present study, two novel oncolytic SVV mutants modified based on structural biology and reverse genetics (viral receptor-associated mutant SVV-S177A and viral antigenic peptide-related mutant SVV-S177A/P60S) with increased infectivity or lower immunogenicity significantly (P < 0.001) prolonged the mOS from 11 days in the control cohort to 23 days in the SVV-S177A cohort and the SVV-S177A/P60S cohort in the NSCLC-bearing athymic mouse model, which may provide the direction for modifying SVV to improve the effect of oncolysis.

Exploring functional genes' correlation with (S)-equol concentration and new daidzein racemase identification.

With its estrogenic activity, (S)-equol plays an important role in maintaining host health and preventing estrogen-related diseases. Exclusive production occurs through the transformation of soy isoflavones by intestinal bacteria, but the reasons for variations in (S)-equol production among different individuals and species remain unclear. Here, fecal samples from humans, pigs, chickens, mice, and rats were used as research objects. The concentrations of (S)-equol, along with the genetic homology and evolutionary relationships of (S)-equol production-related genes [daidzein reductase (DZNR), daidzein racemase (DDRC), dihydrodaidzein reductase (DHDR), tetrahydrodaidzein reductase (THDR)], were analyzed. Additionally, in vitro functional verification of the newly identified DDRC gene was conducted. It was found that approximately 40% of human samples contained (S)-equol, whereas 100% of samples from other species contained (S)-equol. However, there were significant variations in (S)-equol content among the different species: rats > pigs > chickens > mice > humans. The distributions of the four genes displayed species-specific patterns. High detection rates across various species were exhibited by DHDR, THDR, and DDRC. In contrast, substantial variations in detection rates among different species and individuals were observed with respect to DZNR. It appears that various types of DZNR may be associated with different concentrations of (S)-equol, which potentially correspond to the regulatory role during (S)-equol synthesis. This enhances our understanding of individual variations in (S)-equol production and their connection with functional genes in vitro. Moreover, the newly identified DDRC exhibits higher potential for (S)-equol synthesis compared to the known DDRC, providing valuable resources for advancing in vitro (S)-equol production. IMPORTANCE: (S)-equol ((S)-EQ) plays a crucial role in maintaining human health, along with its known capacity to prevent and treat various diseases, including cardiovascular diseases, metabolic syndromes, osteoporosis, diabetes, brain-related diseases, high blood pressure, hyperlipidemia, obesity, and inflammation. However, factors affecting individual variations in (S)-EQ production and the underlying regulatory mechanisms remain elusive. This study examines the association between functional genes and (S)-EQ production, highlighting a potential correlation between the DZNR gene and (S)-EQ content. Various types of DZNR may be linked to the regulation of (S)-EQ synthesis. Furthermore, the identification of a new DDRC gene offers promising prospects for enhancing in vitro (S)-EQ production.

Association between different insulin resistance surrogates and all-cause mortality in patients with coronary heart disease and hypertension: NHANES longitudinal cohort study.

BACKGROUND: Studies on the relationship between insulin resistance (IR) surrogates and long-term all-cause mortality in patients with coronary heart disease (CHD) and hypertension are lacking. This study aimed to explore the relationship between different IR surrogates and all-cause mortality and identify valuable predictors of survival status in this population. METHODS: The data came from the National Health and Nutrition Examination Survey (NHANES 2001-2018) and National Death Index (NDI). Multivariate Cox regression and restricted cubic splines (RCS) were performed to evaluate the relationship between homeostatic model assessment of IR (HOMA-IR), triglyceride glucose index (TyG index), triglyceride glucose-body mass index (TyG-BMI index) and all-cause mortality. The recursive algorithm was conducted to calculate inflection points when segmenting effects were found. Then, segmented Kaplan-Meier analysis, LogRank tests, and multivariable Cox regression were carried out. Receiver operating characteristic (ROC) and calibration curves were drawn to evaluate the differentiation and accuracy of IR surrogates in predicting the all-cause mortality. Stratified analysis and interaction tests were conducted according to age, gender, diabetes, cancer, hypoglycemic and lipid-lowering drug use. RESULTS: 1126 participants were included in the study. During the median follow-up of 76 months, 455 participants died. RCS showed that HOMA-IR had a segmented effect on all-cause mortality. 3.59 was a statistically significant inflection point. When the HOMA-IR was less than 3.59, it was negatively associated with all-cause mortality [HR = 0.87,95%CI (0.78, 0.97)]. Conversely, when the HOMA-IR was greater than 3.59, it was positively associated with all-cause mortality [HR = 1.03,95%CI (1.00, 1.05)]. ROC and calibration curves indicated that HOMA-IR was a reliable predictor of survival status (area under curve = 0,812). No interactions between HOMA-IR and stratified variables were found. CONCLUSION: The relationship between HOMA-IR and all-cause mortality was U-shaped in patients with CHD and hypertension. HOMA-IR was a reliable predictor of all-cause mortality in this population.

Experimental Quantum Homomorphic Encryption Using a Quantum Photonic Chip.

A fully homomorphic encryption system enables computation on encrypted data without the necessity for prior decryption. This facilitates the seamless establishment of a secure quantum channel, bridging the server and client components, and thereby providing the client with secure access to the server's substantial computational capacity for executing quantum operations. However, traditional homomorphic encryption systems lack scalability, programmability, and stability. In this Letter, we experimentally demonstrate a proof-of-concept implementation of a homomorphic encryption scheme on a compact quantum chip, verifying the feasibility of using photonic chips for quantum homomorphic encryption. Our work not only provides a solution for circuit expansion, addressing the longstanding challenge of scalability while significantly reducing the size of quantum network infrastructure, but also lays the groundwork for the development of highly sophisticated quantum fully homomorphic encryption systems.

H2B Lys34 Ubiquitination Induces Nucleosome Distortion to Stimulate Dot1L Activity.

Ubiquitination-dependent histone crosstalk plays critical roles in chromatin-associated processes and is highly associated with human diseases. Mechanism studies of the crosstalk have been of the central focus. Here our study on the crosstalk between H2BK34ub and Dot1L-catalyzed H3K79me suggests a novel mechanism of ubiquitination-induced nucleosome distortion to stimulate the activity of an enzyme. We determined the cryo-electron microscopy structures of Dot1L-H2BK34ub nucleosome complex and the H2BK34ub nucleosome alone. The structures reveal that H2BK34ub induces an almost identical orientation and binding pattern of Dot1L on nucleosome as H2BK120ub, which positions Dot1L for the productive conformation through direct ubiquitin-enzyme contacts. However, H2BK34-anchored ubiquitin does not directly interact with Dot1L as occurs in the case of H2BK120ub, but rather induces DNA and histone distortion around the modified site. Our findings establish the structural framework for understanding the H2BK34ub-H3K79me trans-crosstalk and highlight the diversity of mechanisms for histone ubiquitination to activate chromatin-modifying enzymes.

Serum 8-Hydroxydeoxyguanosine Is a Potential Indicator for the Severity and Prognosis in Patients with Community-Acquired Pneumonia: A Prospective Cohort Study.

Previous studies have demonstrated that 8-hydroxydeoxyguanosine (8-OHdG) exerted key roles in various pulmonary diseases, but the evidence for its role in community-acquired pneumonia (CAP) was lacking. The goal of this research was to evaluate the correlations of serum 8-OHdG with the severity and prognosis among patients with CAP through a prospective cohort study. A total of 239 patients with CAP and 239 healthy participants were enrolled. Fasting blood samples were collected. 8-OHdG and inflammatory cytokines were measured by ELISA. On admission, serum 8-OHdG was significantly increased in patients with CAP compared with control subjects. Besides, serum 8-OHdG was incrementally increased in line with CAP severity scores. Pearson correlative analysis found that serum 8-OHdG was correlated with clinical characteristics and inflammatory cytokines in patients with CAP. Linear and logistic regression analysis showed that serum 8-OHdG was positively associated with CAP severity scores. Furthermore, the prognostic outcomes were tracked. Higher serum 8-OHdG on admission increased the risks for intensive care unit admission, mechanical ventilation, vasoactive agent usage, death, and longer hospital stay among patients with CAP. Serum 8-OHdG combination with confusion, respiratory rate, blood pressure, and age ≥65 y or pneumonia severity index had stronger predictive powers for death than single 8-OHdG, CAP severity scores, or several inflammatory cytokines in patients with CAP. These results indicated that serum 8-OHdG is positively associated with the severity and poor prognosis in patients with CAP, demonstrating that 8-OHdG may be involved in the pathophysiology process of CAP.

Author Correction: EWS-FLI1 increases transcription to cause R-loops and block BRCA1 repair in Ewing sarcoma.

In this Letter, the sentence beginning "This work was funded…." in the Acknowledgements should have read "CPRIT (RP140105) to J.C.R." rather than "CPRIT (RP150445) to J.C.R." This error has been corrected online.

EWS-FLI1 increases transcription to cause R-loops and block BRCA1 repair in Ewing sarcoma.

Ewing sarcoma is an aggressive paediatric cancer of the bone and soft tissue. It results from a chromosomal translocation, predominantly t(11;22)(q24:q12), that fuses the N-terminal transactivation domain of the constitutively expressed EWSR1 protein with the C-terminal DNA binding domain of the rarely expressed FLI1 protein. Ewing sarcoma is highly sensitive to genotoxic agents such as etoposide, but the underlying molecular basis of this sensitivity is unclear. Here we show that Ewing sarcoma cells display alterations in regulation of damage-induced transcription, accumulation of R-loops and increased replication stress. In addition, homologous recombination is impaired in Ewing sarcoma owing to an enriched interaction between BRCA1 and the elongating transcription machinery. Finally, we uncover a role for EWSR1 in the transcriptional response to damage, suppressing R-loops and promoting homologous recombination. Our findings improve the current understanding of EWSR1 function, elucidate the mechanistic basis of the sensitivity of Ewing sarcoma to chemotherapy (including PARP1 inhibitors) and highlight a class of BRCA-deficient-like tumours.

Potential Approach to Quantifying the Volume of the Ischemic Core in Truncated Computed Tomography Perfusion Scans: A Preliminary Study.

OBJECTIVE: This study aimed to provide an alternative approach for quantifying the volume of the ischemic core (IC) if truncation of computed tomography perfusion (CTP) occurs in clinical practice. METHODS: Baseline CTP and follow-up diffusion-weighted imaging (DWI) data from 88 patients with stroke were retrospectively collected. CTP source images (CTPSI) from the unenhanced phase to the peak arterial phase (CTPSI-A) or the peak venous phase (CTPSI-V) were collected to simulate the truncation of CTP in the arterial or venous phases, respectively. The volume of IC on CTPSI-A (V CTPSI-A ) or CTPSI-V (V CTPSI-V ) was defined as the volume of the brain tissue with >65% reduction in attenuation compared with that of the normal tissue. The volume of IC on the baseline CTP (V CTP ) was defined as a relative cerebral blood flow of <30% of that in the normal tissue. The volume of the posttreatment infarct on the follow-up DWI (V DWI ) image was manually delineated and calculated. One-way analysis of variance, Bland-Altman plots, and Spearman correlation analyses were used for the statistical analysis. RESULTS: V CTPSI-A was significantly higher than V DWI ( P < 0.001); however, no significant difference was observed between V CTP and V DWI ( P = 0.073) or between V CTPSI-V and V DWI ( P > 0.999). The mean differences between V DWI and V CTPSI-V , V DWI and V CTP , and V DWI and V CTPSI-A were 1.70 mL (limits of agreement [LoA], -56.40 to 59.70), 8.30 mL (LoA, -40.70 to 57.30), and -68.10 mL (LoA, -180.90 to 44.70), respectively. Significant correlations were observed between V DWI and V CTP ( r = 0.68, P < 0.001) and between V DWI and V CTPSI-V ( r = 0.39, P < 0.001); however, no significant correlation was observed between V DWI and V CTPSI-A ( r = 0.20, P = 0.068). CONCLUSIONS: V CTPSI-V may be a promising method for quantifying the volume of the IC if truncation of CTP occurs.

Tanshinone IIA reverses gefitinib resistance in EGFR-mutant lung cancer via inhibition of SREBP1-mediated lipogenesis.

BACKGROUND AND AIM: Gefitinib resistance is an urgent problem to be solved in the treatment of non-small cell lung cancer (NSCLC). Tanshinone IIA (Tan IIA) is one of the main active components of Salvia miltiorrhiza, which exhibits significant antitumor effects. The aim of this study is to explore the reversal effect of Tan IIA on gefitinib resistance in the epidermal growth factor receptor (EGFR)-mutant NSCLC and the underlying mechanism. EXPERIMENTAL PROCEDURE: CCK-8, colony formation assay, and flow cytometry were applied to detect the cytotoxicity, proliferation, and apoptosis, respectively. The changes in lipid profiles were measured by electrospray ionization-mass spectrometry (MS)/MS. Western blot, real-time q-PCR, and immunohistochemical were used to detect the protein and the corresponding mRNA levels. The in vivo antitumor effect was validated by the xenograft mouse model. KEY RESULTS: Co-treatment of Tan IIA enhanced the sensitivity of resistant NSCLC cells to gefitinib. Mechanistically, Tan IIA could downregulate the expression of sterol regulatory element binding protein 1 (SREBP1) and its downstream target genes, causing changes in lipid profiles, thereby reversing the gefitinib-resistance in EGFR-mutant NSCLC cells in vitro and in vivo. CONCLUSIONS AND IMPLICATIONS: Tan IIA improved gefitinib sensitivity via SREBP1-mediated lipogenesis. Tan IIA could be a potential candidate to enhance sensitivity for gefitinib-resistant NSCLC patients.

A Crowd Movement Analysis Method Based on Radar Particle Flow.

Crowd movement analysis (CMA) is a key technology in the field of public safety. This technology provides reference for identifying potential hazards in public places by analyzing crowd aggregation and dispersion behavior. Traditional video processing techniques are susceptible to factors such as environmental lighting and depth of field when analyzing crowd movements, so cannot accurately locate the source of events. Radar, on the other hand, offers all-weather distance and angle measurements, effectively compensating for the shortcomings of video surveillance. This paper proposes a crowd motion analysis method based on radar particle flow (RPF). Firstly, radar particle flow is extracted from adjacent frames of millimeter-wave radar point sets by utilizing the optical flow method. Then, a new concept of micro-source is defined to describe whether any two RPF vectors originated from or reach the same location. Finally, in each local area, the internal micro-sources are counted to form a local diffusion potential, which characterizes the movement state of the crowd. The proposed algorithm is validated in real scenarios. By analyzing and processing radar data on aggregation, dispersion, and normal movements, the algorithm is able to effectively identify these movements with an accuracy rate of no less than 88%.

Hybrid dual-mode tunable polarization conversion metasurface based on graphene and vanadium dioxide.

We present and numerically verify a functionally hybrid dual-mode tunable polarization conversion metasurface based on graphene and vanadium dioxide (VO2). The tunable polarization converter consists of two patterned graphene layers separated by grating which is composed of gold and VO2. Due to the existence of phase change material VO2, the polarization conversion mode can be switched flexibly between the transmission and reflection modes. Theoretical calculations show the proposed polarization conversion metasurface can obtain giant asymmetric transmission (AT) at 0.42 and 0.77 THz when VO2 is in the insulating state. Conversely, when VO2 is in the metallic state, the converter switches to the reflection mode, demonstrating broadband polarization conversion for both forward and backward incidences. Furthermore, the conductivity of graphene can be modulated by changing the gate voltage, which allows dynamic control polarization conversion bandwidth of the reflection mode as well as the AT of the transmission mode. The robustness of the metasurface has also been verified, the high polarization conversion efficiency and AT can be maintained over wide incidence angles up to 65° for both the xoz plane and yoz plane. These advantages make the proposed hybrid tunable polarization conversion metasurface a promising candidate for THz radiation switching and modulation.

MOF@Polydopamine-incorporated membrane with high permeability and mechanical property for efficient fouling-resistant and oil/water separation.

Metal organic frameworks (MOFs) have demonstrated great potential for their favorable impacts on the performance of water treatment membranes. Herein, the novel nanoparticles based on both nanoporous MOFs and organic PDA layer was exploited as a novel dopant for the fabrication of PES ultrafiltration (UF) membranes. The PDA was synthesized via oxidative self-polymerization under alkaline conditions and formed adhesive coatings on dispersed MOF. The properties of resulting membranes on the porosity, membrane morphology, hydrophilicity, permeability and anti-fouling performance were adequately investigated. The membranes incorporated with MOF@PDA exhibited exceptionally high permeability (209.02 L m-2·h-1), which is approximately 6 times higher than that of the pure PES membrane, and high BSA rejection (99.12%). Notably, the mechanical property and hydrophilicity of the PES membrane were both enhanced by MOF@PDA, and it has been demonstrated that greater hydrophilicity prevents fouling under practical conditions, which results in significant improvements in flux recovery ratio (FRR) (82%). In addition, the modified PES membranes were used to purify the oil/water emulsion, and the results indicates that the membranes have high permeability and rejection of oil/water emulsion, showing its great promise in practical oily sewage remediation.

Assessing the Clinical Impact of Percutaneous Coronary Intervention in Patients with Acute Myocardial Infarction.

Background: Percutaneous coronary intervention (PCI) has emerged as a pivotal intervention in reducing mortality among ST-segment elevation myocardial infarction (STEMI) patients. Objective: This study aimed to evaluate the clinical effectiveness of PCI in the management of acute myocardial infarction (AMI). Design: A retrospective study design was adopted. Setting: The study was conducted at the Affiliated Taizhou People's Hospital of Nanjing Medical University. Participants: A total of 126 AMI patients were selected and categorized into two groups based on their treatment regimen: the study group (n=76) underwent PCI, while the control group (n=50) received standard drug therapy. Interventions: The control group was managed with conventional drug treatment, while the study group underwent PCI. Primary Outcome Measures: The primary outcome measures included (1) N-terminal pro-B-type natriuretic peptide levels, (2) cardiac function, (3) total clinical effectiveness, (4) incidence of adverse cardiovascular events, and (5) quality of life. Results: After treatment, both groups exhibited a reduction in N-terminal pro-B-type natriuretic peptide levels, with a more significant decrease observed in the study group compared to the control group (P < .05). Post-treatment left ventricular end-diastolic and end-systolic volumes decreased, while left ventricular ejection fraction increased in both groups. The study group exhibited more substantial improvements in these parameters compared to the control group (P < .05). The study group also demonstrated a higher total clinical effectiveness rate (χ2 = 9.95, P < 0.05) and a lower incidence of adverse cardiovascular events during follow-up (P < .05). Additionally, both groups reported an increase in quality-of-life scores, with the study group experiencing a more significant improvement (P < .05). Conclusions: This study suggests that PCI, when applied in the clinical management of AMI patients, can significantly reduce N-terminal pro-B-type natriuretic peptide levels, enhance cardiac function, lower the occurrence of cardiovascular adverse events, and improve patients' overall quality of life.

Human Activity Recognition Method Based on FMCW Radar Sensor with Multi-Domain Feature Attention Fusion Network.

This paper proposes a human activity recognition (HAR) method for frequency-modulated continuous wave (FMCW) radar sensors. The method utilizes a multi-domain feature attention fusion network (MFAFN) model that addresses the limitation of relying on a single range or velocity feature to describe human activity. Specifically, the network fuses time-Doppler (TD) and time-range (TR) maps of human activities, resulting in a more comprehensive representation of the activities being performed. In the feature fusion phase, the multi-feature attention fusion module (MAFM) combines features of different depth levels by introducing a channel attention mechanism. Additionally, a multi-classification focus loss (MFL) function is applied to classify confusable samples. The experimental results demonstrate that the proposed method achieves 97.58% recognition accuracy on the dataset provided by the University of Glasgow, UK. Compared to existing HAR methods for the same dataset, the proposed method showed an improvement of about 0.9-5.5%, especially in the classification of confusable activities, showing an improvement of up to 18.33%.

Fast DOA Estimation Algorithms via Positive Incremental Modified Cholesky Decomposition for Augmented Coprime Array Sensors.

This paper proposes a fast direction of arrival (DOA) estimation method based on positive incremental modified Cholesky decomposition atomic norm minimization (PI-CANM) for augmented coprime array sensors. The approach incorporates coprime sampling on the augmented array to generate a non-uniform, discontinuous virtual array. It then utilizes interpolation to convert this into a uniform, continuous virtual array. Based on this, the problem of DOA estimation is equivalently formulated as a gridless optimization problem, which is solved via atomic norm minimization to reconstruct a Hermitian Toeplitz covariance matrix. Furthermore, by positive incremental modified Cholesky decomposition, the covariance matrix is transformed from positive semi-definite to positive definite, which simplifies the constraint of optimization problem and reduces the complexity of the solution. Finally, the Multiple Signal Classification method is utilized to carry out statistical signal processing on the reconstructed covariance matrix, yielding initial DOA angle estimates. Experimental outcomes highlight that the PI-CANM algorithm surpasses other algorithms in estimation accuracy, demonstrating stability in difficult circumstances such as low signal-to-noise ratios and limited snapshots. Additionally, it boasts an impressive computational speed. This method enhances both the accuracy and computational efficiency of DOA estimation, showing potential for broad applicability.

Adenoviral Vector for Enhanced Prostate Cancer Specific Transferrin Conjugated Drug Targeted Therapy.

Prostate cancer (PCa) is one of the leading causes of death for men worldwide. Unlike some other types of cancer, there is a lack of targeted therapy for prostate cancer patients that can kill cancer cells but do much less damage to the normal tissue. In this paper, we report on an adenoviral vector enhanced prostate cancer specific transferrin conjugated drug targeted therapy. In particular, a functional PCa-specific gene probe is introduced to drive and up-regulate the transferrin receptor expression on the PCa via adenoviral vector. As a result, significantly enhanced accumulation of nanoscale transferrin-doxorubicin (Tf-DOX) protein drug conjugates and concomitant notably elevated PCa tumor inhibition are observed. This conceptual strategy provides the proof-of-concept for the targeted therapy of PCa that is highly desired but not yet developed.

Amphiphilic Grafted Polymers Based on Citric Acid and Aniline Used to Enhance the Antifouling and Permeability Properties of PES Membranes.

Water treatment technology based on ultrafiltration (UF) faces the problem of severe membrane fouling due to its inherent hydrophobicity. The use of amphiphilic polymers that possess both hydrophobic and hydrophilic chain segments can be advantageous for the hydrophilic modification of UF membranes due to their excellent combination in the membrane matrix. In the present study, we examined a novel amphiphilic CA-g-AN material, constructed by grafting citric acid (CA) to aniline (AN), as a modified material to improve the hydrophilicity of a PES membrane. This material was more compatible with the polymer membrane matrix than a pure hydrophilic modified material. The polyethersulfone (PES) membranes modified by amphiphilic CA-g-AN demonstrated a higher water flux (290.13 L·m-2·h-1), which was more than eight times higher than that of the pure PES membrane. Furthermore, the flux recovery ratio (FRR) of the modified membrane could reach 83.24% and the value of the water contact angle (WCA) was 76.43°, demonstrating the enhanced hydrophilicity and antifouling ability of the modified membranes. With this study, we aimed to develop a new amphiphilic polymer to improve the antifouling property and permeability of polymer-based UF membranes to remove organic pollutants from water.