Identification of blood exosomal metabolomic profiling for high-altitude cerebral edema.

High-altitude cerebral edema (HACE) is a severe neurological condition that can occur at high altitudes. It is characterized by the accumulation of fluid in the brain, leading to a range of symptoms, including severe headache, confusion, loss of coordination, and even coma and death. Exosomes play a crucial role in intercellular communication, and their contents have been found to change in various diseases. This study analyzed the metabolomic characteristics of blood exosomes from HACE patients compared to those from healthy controls (HCs) with the aim of identifying specific metabolites or metabolic pathways associated with the development of HACE conditions. A total of 21 HACE patients and 21 healthy controls were recruited for this study. Comprehensive metabolomic profiling of the serum exosome samples was conducted using ultraperformance liquid chromatography-tandem mass spectrometry (UPLC‒MS/MS). Additionally, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed to identify the metabolic pathways affected in HACE patients. Twenty-six metabolites, including ( +)-camphoric acid, choline, adenosine, adenosine 5'-monophosphate, deoxyguanosine 5'-monophosphate, guanosine, and hypoxanthine-9-ß-D-arabinofuranoside, among others, exhibited significant changes in expression in HACE patients compared to HCs. Additionally, these differentially abundant metabolites were confirmed to be potential biomarkers for HACE. KEGG pathway enrichment analysis revealed several pathways that significantly affect energy metabolism regulation (such as purine metabolism, thermogenesis, and nucleotide metabolism), estrogen-related pathways (the estrogen signaling pathway, GnRH signaling pathway, and GnRH pathway), cyclic nucleotide signaling pathways (the cGMP-PKG signaling pathway and cAMP signaling pathway), and hormone synthesis and secretion pathways (renin secretion, parathyroid hormone synthesis, secretion and action, and aldosterone synthesis and secretion). In patients with HACE, adenosine, guanosine, and hypoxanthine-9-ß-D-arabinofuranoside were negatively correlated with height. Deoxyguanosine 5'-monophosphate is negatively correlated with weight and BMI. Additionally, LPE (18:2/0:0) and pregnanetriol were positively correlated with age. This study identified potential biomarkers for HACE and provided valuable insights into the underlying metabolic mechanisms of this disease. These findings may lead to potential targets for early diagnosis and therapeutic intervention in HACE patients.

Codelivery of CPT and siPHB1 with GSH/ROS Dual-Responsive Hybrid Nanoparticles Based on a [12]aneN3-Derived Lipid for Synergistic Lung Cancer Therapy.

The combination of small-interfering RNA (siRNA)-mediated gene silencing and chemotherapeutic agents for lung cancer treatment has attracted widespread attention in terms of a greater therapeutic effect, minimization of systemic toxicity, and inhibition of multiple drug resistance (MDR). In this work, three amphiphiles, CBN1-CBN3, were first designed and synthesized as a camptothecin (CPT) conjugate and gene condensation agents by the combination of CPT prodrugs and di(triazole-[12]aneN3) through the ROS-responsive phenylborate ester and different lengths of alkyl chains (with 6, 9, 12 carbon chains for CBN1-CBN3, respectively). CBN1-CBN3 were able to be self-assembled into liposomes with an average diameter in the range of 320-240 nm, showing the ability to effectively condense siRNA. Among them, CBN2, with a nine-carbon alkyl chain, displayed the best anticancer efficiency in A549 cells. In order to give nanomedicines a stealth property and PEGylation/dePEGylation transition, a GSH-responsive PEGylated TPE derivative containing a disulfide linkage (TSP) was further designed and prepared. A combination of CBN2/siRNA complexes and DOPE with TSP resulted in GSH/ROS dual-responsive lipid-polymer hybrid nanoparticles (CBN2-DP/siRNA NPs). In present GSH and H2O2, CBN2-DP/siRNA NPs were decomposed, resulting in the controlled release of CPT drug and siRNA. In vitro, CBN2-DP/siPHB1 NPs showed the best anticancer activity for suppression of about 75% of A549 cell proliferation in a serum medium. The stability of CBN2-DP/siRNA NPs was significantly prolonged in blood circulation, and they showed effective accumulation in the A549 tumor site through an enhanced permeability and retention (EPR) effect. In vivo, CBN2-DP/siPHB1 NPs demonstrated enhanced synergistic cancer therapy efficacy and tumor inhibition as high as 71.2%. This work provided a strategy for preparing lipid-polymer hybrid NPs with GSH/ROS dual-responsive properties and an intriguing method for lung cancer therapy.

Predictive value of serum albumin levels on cancer survival: a prospective cohort study.

Background: Serum albumin levels and cancer mortality are closely related, yet large-sample studies encompassing a broad spectrum of cancer types are lacking. Methods: This study encompassed patients diagnosed with cancer across the continuous 10 cycles of NHANES surveys from 1999 to 2018. The study population was stratified into two groups based on median albumin levels (≤ 4.2g/dL and > 4.2 g/dL) or cancer aggressiveness (well-survived cancers and poorly-survived cancers). Survival rates were estimated using the Kaplan-Meier method. The Cox proportional hazards model was employed to evaluate the association between serum albumin levels and cancer mortality. Restricted cubic spline (RCS) analysis was conducted to assess the nonlinear relationship between serum albumin levels and the risk of cancer mortality. Results: Kaplan-Meier curves demonstrated that patients with albumin levels ≤ 4.2 g/dL exhibited lower survival rates compared to those with levels > 4.2 g/dL, irrespective of cancer aggressiveness. Following adjustment for confounders, decreased albumin levels were associated with an elevated risk of cancer mortality across all groups [all cancers, HR (95%CI) = 2.03(1.73, 2.37); well survived cancers, HR (95%CI) = 1.78(1.38, 2.32); and poorly survived cancers, HR (95%CI) = 1.99(1.64, 2.42)]. RCS analyses revealed a stable nonlinear negative association between albumin levels and cancer mortality in all groups, regardless of confounder adjustment. Conclusion: Low serum albumin levels predict higher cancer mortality. Furthermore, a nonlinear negative association was observed between serum albumin levels and the risk of cancer mortality.

RSPSSL: A novel high-fidelity Raman spectral preprocessing scheme to enhance biomedical applications and chemical resolution visualization.

Raman spectroscopy has tremendous potential for material analysis with its molecular fingerprinting capability in many branches of science and technology. It is also an emerging omics technique for metabolic profiling to shape precision medicine. However, precisely attributing vibration peaks coupled with specific environmental, instrumental, and specimen noise is problematic. Intelligent Raman spectral preprocessing to remove statistical bias noise and sample-related errors should provide a powerful tool for valuable information extraction. Here, we propose a novel Raman spectral preprocessing scheme based on self-supervised learning (RSPSSL) with high capacity and spectral fidelity. It can preprocess arbitrary Raman spectra without further training at a speed of ~1 900 spectra per second without human interference. The experimental data preprocessing trial demonstrated its excellent capacity and signal fidelity with an 88% reduction in root mean square error and a 60% reduction in infinite norm ([Formula: see text]) compared to established techniques. With this advantage, it remarkably enhanced various biomedical applications with a 400% accuracy elevation (ΔAUC) in cancer diagnosis, an average 38% (few-shot) and 242% accuracy improvement in paraquat concentration prediction, and unsealed the chemical resolution of biomedical hyperspectral images, especially in the spectral fingerprint region. It precisely preprocessed various Raman spectra from different spectroscopy devices, laboratories, and diverse applications. This scheme will enable biomedical mechanism screening with the label-free volumetric molecular imaging tool on organism and disease metabolomics profiling with a scenario of high throughput, cross-device, various analyte complexity, and diverse applications.

Coffee Consumption and Incidence of Cardiovascular and Microvascular Diseases in Never-Smoking Adults with Type 2 Diabetes Mellitus.

The relationship between coffee consumption and diabetes-related vascular complications remains unclear. To eliminate confounding by smoking, this study assessed the relationships of coffee consumption with major cardiovascular disease (CVD) and microvascular disease (MVD) in never-smokers with type 2 diabetes mellitus (T2DM). Included were 9964 never-smokers with T2DM from the UK Biobank without known CVD or cancer at baseline (7781 were free of MVD). Participants were categorized into four groups according to daily coffee consumption (0, 0.5-1, 2-4, ≥5 cups/day). CVD included coronary heart disease (CHD), myocardial infarction (MI), stroke, and heart failure (HF). MVD included retinopathy, peripheral neuropathy, and chronic kidney disease (CKD). Cox regression models were used to estimate hazard ratios (HRs) and 95% confidential intervals (CIs) of total CVD and MVD and the component outcomes associated with coffee consumption. During a median of 12.7 years of follow-up, 1860 cases of CVD and 1403 cases of MVD were identified. Coffee intake was nonlinearly and inversely associated with CVD (P-nonlinearity = 0.023) and the component outcomes. Compared with no coffee intake, HRs (95% CIs) associated with a coffee intake of 2 to 4 cups/day were 0.82 (0.73, 0.93) for CVD, 0.84 (0.73, 0.97) for CHD, 0.73 (0.57, 0.92) for MI, 0.76 (0.57, 1.02) for stroke, and 0.68 (0.55, 0.85) for HF. Higher coffee intake (≥5 cups/day) was not significantly associated with CVD outcomes. Coffee intake was linearly and inversely associated with risk of CKD (HR for ≥5 vs. 0 cups/day = 0.64; 95% CI: 0.45, 0.91; P-trend = 0.0029) but was not associated with retinopathy or peripheral neuropathy. Among never-smoking individuals with T2DM, moderate coffee consumption (2-4 cups/day) was associated with a lower risk of various CVD outcomes and CKD, with no adverse associations for higher consumption.

[12]aneN3-modified camptothecin and PEGylated AIEgens co-assembly into core-shell nanoparticles with ROS/NTR dual-response for enhanced cancer therapy.

A novel dual-responsive nanoparticle (NP) system was aimed to be developed for the co-delivery of camptothecin (CPT) and plasmid encoding TNF-related apoptosis-inducing ligand (pTRAIL) DNA in cancer therapy. The combination of the prodrug CPT and the nucleic acid condensing di-(triazole-[12]aneN3) unit with 4-nitrobenzyl ester through alkyl chains resulted in three nitroreductase (NTR) responsive amphiphiles, CNN1-CNN3 (with 5, 8, and 11 carbon chains, respectively). Among them, CNN2 was the most effective in inhibiting the proliferation of HeLa cells in the presence of fusogenic lipid DOPE. The NPs composed of CNN2, pDNA, and DOPE were further co-assembled with ROS-responsive thioketal-linked amphiphilic polymer (TTP) to afford the core-shell NPs (CNN2-DT/pDNA) with an average size of 118 nm, which exhibited high drug-loading capacity, excellent serum tolerance, and good biocompatibility. In the presence of ROS, NTR, and NADH, the core-shell NPs were decomposed, leading to the efficient release of 80% CPT and abundant pDNA. The self-assembly and delivery process of CNN2-DT NPs and DNA were clearly observed through the AIE fluorescent imaging. In vitro and in vivo results demonstrated that the CNN2-DT/pTRAIL NPs synergistically promoted 68% apoptosis of tumor cells and inhibited tumor growth with negligible toxic side effects. This study showed that the combination of prodrug and nucleic acid through dual-responsive core-shell NPs provide a spatially and temporally-controlled strategy for cancer therapy.

Cardiac macrophages undergo dynamic changes after coxsackievirus B3 infection and promote the progression of myocarditis.

Although most patients with acute viral myocarditis recover spontaneously, some patients progress to heart failure. Perturbations in innate immunity may partially explain the heterogeneity of clinical outcomes. As the most abundant immune cells in the heart, cardiac macrophages have heterogeneous origins, including embryonic-derived resident macrophages (ResMϕs) and monocyte-derived macrophages (MoMFs). However, the time course change and role of cardiac macrophage subsets has not been fully explored. In the present study, we found that BALB/c mice had prolonged MoMF accumulation and low proportions of ResMϕs that could not be restored to normal levels. MoMFs of BALB/c mice generally exhibit an M1-dominant functional phenotype. Moreover, the preferential depletion of MoMF by a C-C chemokine receptor type 2 (CCR2) inhibitor resulted in improved acute myocarditis and chronic fibrosis, as well as the recovery of ResMϕs number and reduced CD4+ T cell expansion. Hence, immunomodulatory therapy that targets the balance among cardiac macrophages and modulates their function is expected to prevent the progression of cardiac injury to overt heart failure and improve adverse outcomes.

Nickel -supported PdM (M = Au and Ag) nanodendrites as formate oxidation (electro)catalytic anodes for direct fuel cells and hydrogen generation at room temperature.

The study provides a proof of concept for the first time that unique palladium-gold (PdAu) and palladium-silver (PdAg) nanodendrites are bifunctional catalytic active sites for formate oxidation reactions (FORs) and formate dehydrogenation reactions (FDRs). The unique nanodendritic structure was developed via a simple galvanic displacement reaction for the direct growth of PdAu and PdAg nanodendrites on a nickel foam (PdAu/NiNF and PdAg/NiNF). These PdAu/NiNF and PdAg/NiNF electrodes exhibited 2.32 and 1.59 times higher specific activity than that of the commercial Pd/C electrode and promising stability toward FORs. Moreover, the PdAu/NiNF and PdAg/NiNF nanodendrites were also highly active and selective catalysts for hydrogen generation from a formate solution with turnover frequency (TOF) values of 311 h-1 and 287 h-1 respectively. Impressively, a passive air-breathing formate fuel cell with PdAu/NiNF used as an anode can yield an open-circuit voltage of 1.12 V and a peak power density of 21.7 mW cm-2, which outperforms most others reported in the literature. PdAu and PdAg nanodendritic catalysts supported on a nickel foam demonstrate an open structure and uniform catalyst distribution and offer a promising nanoalloy for air-breathing formate fuel cells and on-site chemical hydrogen production systems.

Distribution and accumulation of cadmium in soil under wheat-cultivation system and human health risk assessment in coal mining area of China.

The soil contamination caused by the discharge of cadmium (Cd) from coal mining activities has aroused continuous attention due to the detrimental effects on the human health. This study aimed to investigate the characteristics on distribution of Cd in soils and its accumulation in wheat grains under wheat-cultivation system, and further assess the human health risks to adults and children. 58 soils and wheat samples in pairs from Linhuan coal mining area, Anhui Province were collected and analyzed. Results showed that the concentrations of Cd in 17.24% of soil samples exceeded the limit value established by the Ministry of Ecology and Environment. The ordinary kriging interpolation displayed that the spatial variability of Cd concentrations in soils was mainly influenced by coal mining activities. The transfer capacity of Cd from soils to wheat roots was greater than that from the wheat roots to grains. Multiple linear regression model clarified that soil pH and exchangeable Cd fraction in soils were the critical factors affecting the Cd accumulation in wheat grains. The carcinogenic risk of Cd levels in our studied wheat grains was a concern but still within the acceptable range, while their non-carcinogenic hazard was negligible for adults and children. The calculation results were in accord with the uncertainty analysis conclusion based on Monte Carlo simulation. The study was expected to promote the source management and control strategy of reducing tailing discharge, and providing scientific references for current soil remediation and land degradation prevention.

Successful management of Stanford type A aortic dissection with severe scoliosis in the setting of Marfan syndrome: a case report.

Background: Marfan syndrome (MFS) is a connective tissue disorder involving multiple organs. The most severe complications include aortic root dilatation and dissection. In the present report, we provide an uncommon case of acute aortic Stanford type A dissection (AADA) repair with severe scoliosis in an MFS patient and it is even more rare for such surgical treatment to be successfully completed along with holistic management that enables the patient to recover successfully. We offer a reference for future surgical therapy since the specific surgical treatment methods in this case have not been reported in the literature. Case Description: A 40-year-old Chinese female with MFS was rushed to our surgical clinic due to the sudden onset of intense chest pain. Physical examination revealed a diastolic murmur at the aortic valve area, increased arm and pectus carinatum deformity, severe scoliosis, acromicria, arachnodactyly, and planovalgus foot. Subsequently, AADA was discovered through computed tomography scan. In addition, echocardiogram revealed moderate aortic regurgitation and hydropericardium in small amount. Based on revised Ghent criteria, the patient was diagnosed with MFS complicated with aortic dissection. Emergency surgery was successfully performed for repair of the patient's aortic dissection and the diseased aortic valve. Postoperatively, the patient presented with a degree of respiratory insufficiency. However, the respiratory function was not greatly impaired, with good early intervention, such as taking deep breaths and coughing fully, active sputum suction, effective analgesia, ambulation and treadmill exercise. The patient finally recovered completely and was discharged 3 weeks later. Conclusions: We reported on a patient with severe scoliosis who successfully underwent surgical repair of AADA. Our report shows that the application of standard median sternotomy for repairing AADA offers the feasibility of implementation, on the basis of effectively solving various practical problems in the surgery brought about by scoliosis. It has been thoroughly assessed and addressed how the postoperative condition of such patients affects subsequent respiratory function and postoperative recovery. This report further provides a successful clinical reference for the implementation of this type of surgery and the postoperative management of respiratory function.

Speciation, bioaccessibility and human health risk assessment of chromium in solid wastes from an ultra-low emission coal-fired power plant, China.

Chromium (Cr) in solid wastes from ultra-low emission (ULE) coal-fired power plants (CFPPs) could engender adverse effects on environment and human health. Hence, solid waste samples containing bottom ash, fly ash, gypsum and sludge were collected from a typical ULE CFPP in China to study the distribution, speciation, bioaccessibility and human health risk of Cr. The results showed that Cr was depleted in gypsum, whereas significantly enriched in bottom ash, fly ash and sludge comparing with feed coal. The ratios of Cr(VI) to total Cr in solid wastes were relatively low, but the increase of flow fractions in Cr chemical binding forms implied the deterioration of environmental stability. Based on the in vitro simulated digestion methods of solubility bioavailability research consortium (SBRC) and physiologically based extraction test (PBET), the bioaccessibility of Cr in the gastric and intestinal phases reached the highest values in either gypsum or sludge. After incorporating bioaccessibility in human health risk assessment, the carcinogenic risk (CR) within acceptable limits of Cr in solid wastes to adults and children was concluded, with the non-carcinogenic hazard quotient (HQ) was all within the safety threshold. The Monte Carlo model was applied to evaluate the uncertainty analysis of human health risk assessment at 5% and 95% confidence interval, and the fitting results were consistent with the calculation results of the carcinogenic and non-carcinogenic risk for adults and children. This study is expected to provide insights for the integration of bioaccessibility into the health risk assessment of Cr in solid wastes from ULE CFPPs, thus is conducive to the disposal of solid wastes and human health protection.

Thermodynamics-Kinetics-Balanced Metal-Organic Framework for In-Depth Radon Removal under Ambient Conditions.

Radon (Rn), a ubiquitous radioactive noble gas, is the main source of natural radiation to human and one of the major culprits for lung cancer. Reducing ambient Rn concentration by porous materials is considered as the most feasible and energy-saving option to lower this risk, but the in-depth Rn removal under ambient conditions remains an unresolved challenge, mainly due to the weak van der Waals (vdW) interaction between inert Rn and adsorbents and the extremely low partial pressure (<1.8 × 10-14 bar, <106 Bq/m3) of Rn in air. Adsorbents having either favorable adsorption thermodynamics or feasible diffusion kinetics perform poorly in in-depth Rn removal. Herein, we report the discovery of a metal-organic framework (ZIF-7-Im) for efficient Rn capture guided by computational screening and modeling. The size-matched pores in ZIF-7-Im abide by the thermodynamically favorable principle and the exquisitely engineered quasi-open apertures allow for feasible kinetics with little sacrifice of sorption thermodynamics. The as-prepared material can reduce the Rn concentration from hazardous levels to that below the detection limit of the Rn detector under ambient conditions, with an improvement of at least two orders of amplitude on the removal depth compared to the currently best-performing and only commercialized material activated charcoal.

Current Status and Future Directions of Bacteria-Based Immunotherapy.

With the in-depth understanding of the anti-cancer immunity, immunotherapy has become a promising cancer treatment after surgery, radiotherapy, and chemotherapy. As natural immunogenicity substances, some bacteria can preferentially colonize and proliferate inside tumor tissues to interact with the host and exert anti-tumor effect. However, further research is hampered by the infection-associated toxicity and their unpredictable behaviors in vivo. Due to modern advances in genetic engineering, synthetic biology, and material science, modifying bacteria to minimize the toxicity and constructing a bacteria-based immunotherapy platform has become a hotspot in recent research. This review will cover the inherent advantages of unedited bacteria, highlight how bacteria can be engineered to provide greater tumor-targeting properties, enhanced immune-modulation effect, and improved safety. Successful applications of engineered bacteria in cancer immunotherapy or as part of the combination therapy are discussed as well as the bacteria based immunotherapy in different cancer types. In the end, we highlight the future directions and potential opportunities of this emerging field.

Multifunctional amphiphilic peptide dendrimer as nonviral gene vectors for effective cancer therapy via combined gene/photodynamic therapies.

Gene therapy holds great promise for treatment of gene-associated diseases. However, safe and successful clinical application urgently requires further advancement of constructing efficient delivery systems. Herein, three amphiphilic peptide dendrimers (TTC-L-KRR/KKK/KHH), containing the natural amino acid residues (lysine K, arginine R, and histidine H) and AIE-based photosensitizer (tetraphenylethenethiophene modified cyanoacrylate, TTC) modified with alkyl chain (L), have been designed and prepared for improving therapeutic potency via the combination of gene therapy (GT) and photodynamic therapy (PDT). All three compounds possessed typical aggregation-induced emission (AIE) characteristics and ultralow critical micelle concentrations (CMCs). The liposomes consisting of amphiphilic peptide dendrimers and dioleoylphosphatidylethanolamine (DOPE) can effectively bind DNA into nanoparticles with appropriate sizes, regular morphology and good biocompatibility. Among them, liposomes TTC-L-KKK/DOPE exhibited the highest transfection efficiency up to 5.7-fold as compared with Lipo2000 in HeLa cells. Meanwhile, rapid endocytosis, successful endo/lysosomal escape, gene release and rapid nuclear delivery of DNA revealed the superiority of liposomes TTC-L-KKK/DOPE during gene delivery process. More importantly, efficient reactive oxygen species (ROS) generation by TTC-L-KKK/DOPE led to effective PDT, thus improving therapeutic potency via combining with p53 mediated-gene therapy. Our work brought novel insight and direction for the construction of bio-safe and bio-imaging liposome as the multifunctional nonviral gene vectors for the effective combined gene/photodynamic therapies.

The abnormal distribution of peripheral B1 cells and transition B cells in patients with idiopathic dilated cardiomyopathy: a pilot study.

BACKGROUND: The aberrant distribution of peripheral B cell subsets is associated with the pathogenesis of a variety of inflammatory and autoimmune diseases. However, the distribution of peripheral B cell subsets in patients with idiopathic dilated cardiomyopathy (DCM) remains to be elucidated. METHODS: Twenty-seven patients with idiopathic DCM (DCM group), 18 control patients with heart failure (HF group) and 21 healthy individuals (HC group) were included in this study. Peripheral B cell subsets were analysed using multicolour flow cytometry. The plasma ß1 adrenergic receptor (ß1-AR) autoantibody titre was determined using ELISA. Additionally, clinical features were also collected. RESULTS: Compared with the HF and HC groups, the percentage of B1 cells was significantly decreased, whereas the percentage of transitional B cells (Tr) was significantly increased in the DCM group. Notably, the percentage of B1 cells was significantly lower in patients with ß1-AR autoantibody-positive DCM than in ß1-AR autoantibody-negative patients. The correlation analysis showed that the percentage of B1 cells was negatively correlated with N-terminal pro-brain natriuretic peptide (NT-proBNP) levels and positively correlated with the left ventricular ejection fraction in patients with DCM. CONCLUSION: As shown in the present study, the percentage of B1 cells in the peripheral blood of patients with idiopathic DCM is abnormally decreased, especially in ß1-AR autoantibody-positive patients, while the percentage of Tr cells is significantly increased, indicating that B1 cells and Tr cells may be implicated in the pathogenesis of idiopathic DCM. The decrease in the percentage of B1 cells is directly related to the severity of DCM.

[12]aneN3-Conjugated AIEgens with two-photon imaging properties for synergistic gene/photodynamic therapy in vitro and in vivo.

Six amphiphiles (TTC-L-M-1/2/3/4/5/6), each consisting of hydrophilic macrocyclic polyamine triazole-[12]aneN3 (M) and a hydrophobic photosensitizer tetraphenylethenethiophene modified cyanoacrylate (TTC) moiety linked with alkyl chains (L), have been designed and synthesized for synergetic anticancer gene therapy and photodynamic therapy (PDT). These amphiphiles showed strong AIE fluorescence emissions around 600 nm with large Stokes shifts up to 168 nm in an aqueous solution. They were able to condense DNA into nanoparticles with appropriate sizes, positive charges, reversible release, and good biocompatibility. Quantitative and qualitative gene transfection studies indicated that TTC-L-M-4 with a 12 carbon alkyl chain exhibited the best transfection efficiency in HeLa cells, and its transfection efficiency was 4.5-fold that of Lipo2000 in the presence of DOPE. The detailed and efficient delivery process of DNA by TTC-L-M-4 was clearly observed through one- and two-photon fluorescence imaging. Simultaneously, TTC-L-M-4/DOPE was able to deliver siRNA and gene silencing was better than that of Lipo2000. Furthermore, TTC-L-M-4 was able to efficiently generate reactive oxygen species (ROS) for PDT upon light irradiation. It was further demonstrated that combined p53 gene therapy and PDT significantly enhanced cancer therapy in vitro and in vivo. This study provides novel one-for-all organic agents with multiple therapeutic modalities.

Element partitioning, emissions, and relative risk during disposal processes of diverse litters, fruit tree branches, and crop straws: dry distillation, incomplete combustion, and sufficient combustion.

This study reports the release behaviors, enrichment characteristics, contamination level, and health risk of twenty-one elements in biomass, when dry distillation, incomplete combustion, and sufficient combustion. Results indicate that the element concentration in different kinds of biomass varies greatly. Even for the same kind of biomass, concentration in three products of dry distillation, incomplete combustion, and sufficient combustion is also different: fifteen elements (K, Ca, Mg, Al, Fe, Mn, B, Cu, Zn, Mo, Cd, Cr, Pb, Sb, Sn) have no significant difference in concentration but other six elements (As, Co, Ni, V, Na, P) are the opposite. Multivariate statistical approaches were used to assess five significant factors which affect element concentration, suggesting the contributes from biomass type, moisture content, soil, biomass age or organ, and disposal methods. Disposal methods and biomass type result in significant differences in element enrichment factor. More elements will release during sufficient combustion rather than dry distillation. The increasing of supplied oxygen during disposal process may increase the overall toxicity from elements release. The data of excess lifetime cancer risk (ELCR) suggests that Cr, Ni, Co, Cd, and Pb are the largest contributors to cancer risks during biomass application.

H2O2-Responsive amphiphilic polymer with aggregation-induced emission (AIE) for DOX delivery and tumor therapy.

Stimuli-responsive drug delivery systems (DDSs) based on amphiphilic polymers have attracted much attention. In this study, we reported an innovative H2O2-responsive amphiphilic polymer (TBP), bearing a H2O2-sensitive phenylboronic ester, AIE fluorophore tetraphenylethene (TPE) hydrophobic, and polyethylene glycol hydrophilic (PEG) moieties. TBP could self-assemble into micelles with an encapsulation efficiency as high as 74.9% for doxorubicin (DOX) in aqueous solution. In the presence of H2O2, TBP micelles was decomposed by oxidation, hydrolysis and rearrangement, leading to almost 80% DOX release from TBP@DOX micelles. TBP and the corresponding degradation products were biocompatible, while TBP@DOX micelles only displayed obvious toxicity toward cancer cells. Drug delivery process was clearly monitored by confocal laser scanning microscopic (CLSM) and flow cytometry (FCM) analysis. Moreover, in vivo anticancer study showed that TBP@DOX micelles were accumulated in tumor region of nude mice and effectively inhibited tumor growth. The results suggested that the reported H2O2-responsive amphiphilic polymer displayed great potential in drug delivery and tumor therapy.

Study on the inhibitory effect of selective estrogen receptor modulators on Streptococcus mutans.

OBJECTIVES: To screen small-molecule antibacterial drugs and investigate the antibacterial effect and mechanism of selective estrogen receptor modulators (SERMs) against Streptococcus mutans (S.mutans). METHODS: The minimum inhibitory concentration of 426 Food and Drug Administration (FDA)-approved small-molecule drugs against S. mutans was determined using the microdilution method, and the target of SERMs acting on S. mutans was explored by employing a random transposon mutant library. RESULTS: Among the 426 FDA-approved SERMs, toremiphene, tamoxifen, clomiphene, and raloxifene exhibited excellent antibacterial effects against S.mutans. Results of mutant library screening showed that the two mutant strains were resistant to clomiphene. The gene sequence of the resistant strains showed that the transposon insertion sites were located in the genes of smu_546 and smu_874. CONCLUSIONS: SERMs, such as toremifene, tamoxifen, clomiphene, and raloxifene, exerted obvious antibacterial effects on S. mutans, and their targets may be proteins expressed by smu_546 and smu_874 gene.

Degradable cationic polyesters via ring-opening copolymerization of valerolactones as nanocarriers for the gene delivery.

The development of cationic polymers as non-viral gene vectors has been hurdled by their high toxicity, thus degradable and biocompatible polymers are urgently demanded. Herein, five polyesters (B3a-B3e) were synthesized based on the ring-opening copolymerization between α-allyl-δ-valerolactone and δ-valerolactone derivatives decorated with alkyl or alkoxyl chains of different lengths, followed by the modification with 1,5,9-triazacyclododecyl ([12]aneN3) through thiol-ene click reactions. The five polyesters effectively condensed DNA into nanoparticles. Of them, B3a with a shorter alkyl chain and B3d with more positive charged units showed stronger DNA condensing performance and can completely retard the migration of DNA at N/P = 1.6 in the presence of DOPE. B3b/DOPE with a longer alkyl chain exhibited the highest transfection efficiency in HeLa cells with 1.8 times of 25 kDa PEI, while B3d/DOPE with more positive charged units exhibited highest transfection efficiency in A549 cells with 2.3 times of 25 kDa PEI. B3b/DOPE and B3d/DOPE successfully delivered pEGFP into zebrafish, which was superior to 25 kDa PEI (1.5 folds and 1.1 folds, respectively). The cytotoxicity measurements proved that the biocompatibility of these polyesters was better than 25 kDa PEI, due to their degradable property in acid environment. The results indicated that these cationic polyesters can be developed as potential non-viral gene vectors for DNA delivery.