The application of phthalocyanines in photothermal therapy has attracted increasing interest in recent years. In this review, the design considerations for enhancing the photothermal effect of ...phthalocyanines are highlighted.
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•Recent progresses made in the use of phthalocyanines as contrast agents for photothermal therapy are outlined.•The main design considerations for enhancing the photothermal effect of phthalocyanine-based contrast agents are discussed.•The perspectives and challenges for the application of phthalocyanines as contrast agents for PTT are discussed.
Phthalocyanine, as a type of organic photothermal agent, has advantages including a definite chemical structure, repeatable synthesis, strong absorption in the near-infrared region, tunable photophysical and photochemical properties, and inherent biodegradability. This review focuses on the recent progress made in the application of phthalocyanines as contrast agents for photothermal therapy (PTT). The present review not only discusses the molecular and/or supramolecular design considerations for enhancing the PTT effect of phthalocyanines, but also provides the perspectives and challenges of the use of phthalocyanines as contrast agents for PTT.
Organic loading rate (OLR) disturbances were introduced into a mesophilic anaerobic digester treating food waste (FW) to induce stable and deteriorative phases. The microbial community of each phase ...was investigated using 454-pyrosequencing. Results show that the relative abundance of acid-producing bacteria and syntrophic volatile fatty acid (VFA) oxidizers increased dramatically at deteriorative phase, while the dominant methanogens did not shift from acetoclastic to hydrogenotrophic groups. The mismatching between bacteria and methanogens may partially be responsible for the process deterioration. Moreover, the succession of predominant hydrogenotrophic methanogens reduced the consumption efficiency of hydrogen; meanwhile, the dominant Methanosaeta with low acetate degradation rate, and the increase of inhibitors concentrations further decreased its activity, which may be the other causes for the process failure. These results improve the understanding of the microbial mechanisms of process instability, and provide theoretical basis for the efficient and stable operation of anaerobic digester treating FW.
GOALS:We aim to characterize the fungal microbiota in the intestinal mucosa and feces in patients with Crohn’s disease (CD).
BACKGROUND:Fungi represent a diverse microbial community in the human ...intestine and might play a role in the pathogenesis of CD; however, little is known about the structure and composition of the fungal microbiota especially adhering to the intestinal mucosa in CD patient.
STUDY:Nineteen patients with active CD and 7 healthy individuals were recruited in this study. The mucosa-associated and fecal fungal microbiotas in CD patients were analyzed using culture-independent community fingerprint techniques.
RESULTS:The fungal richness and diversity were significantly elevated in the inflamed mucosa compared with the noninflamed mucosa. The predominant fungal composition in the inflamed mucosa was strikingly altered, mainly characterized by expansion in the proportions of Candida spp., Gibberella moniliformis, Alternaria brassicicola, and Cryptococcus neoformans. The fecal fungal community was perturbed in CD patients as accompanied by increased fungal diversity and prevalence in Candida albicans, Aspergillus clavatus, and C. neoformans. The species richness and diversity of the mucosal fungal community were associated with the expression of TNF-α, IFN-γ, or IL-10 (P<0.05). The diversity of the fecal fungal microbiota positively correlated with serum C-reactive protein and CD activity index (P<0.05).
CONCLUSIONS:This study first demonstrates that the fungal microbiota in the inflamed mucosa is distinguishable from that of the noninflamed area. Shifts of gut fungal microbiota composition may be associated with mucosal inflammation and disease activity of CD. Our data would provide novel insights into understanding the potential of gut fungal microbiota in the pathogenesis of CD.
Radiotherapy is commonly used for abdominal or pelvic cancer, and patients receiving radiotherapy have a high risk developing to an acute radiation-induced diarrhea. Several previous studies have ...discussed the effect of probiotics on prevention of radiation-induced diarrhea, but the results are still inconsistent.
We performed a meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy of probiotic supplementation for prevention the radiation-induced diarrhea.
Relevant RCTs studies assessing the effect of probiotic supplementation on clinical outcomes compared with placebo were searched in PubMed, EMBASE, and the Cochrane Library databases (up to March 30 2016). Heterogeneity was assessed with I2 and H2, and publication bias was evaluated using sensitive analysis.
Six trials, a total of 917 participants (490 participants received prophylactic probiotics and 427 participants received placebo), were included in this meta-analysis. Compared with placebo, probiotics were associated with a lower incidence of radiation-induced diarrhea (RR: 0.55; 95% CI: 0.34-0.88; P = 0.01; I2: 87%; 95% CI: 75%-94%; H2: 2.8; 95% CI: 2.0-4.0). However, there is no significant difference in the anti-diarrheal medication use (RR: 0.68; 95% CI: 0.40-1.14; P = 0.14) or bristol scale on stool form (RR: 0.64; 95% CI: 0.35-1.17; P = 0.14).
Probiotics may be beneficial to prevent radiation-induced diarrhea in patients who suffered from abdominal or pelvic cancers during radiotherapy period.
This study reviews the latest progress in research on climate change and water resources in the arid region of Northwest China, analyzes the cause of water resource changes within the region from the ...perspective of climate change and human activities, and summarizes future likely changes in water resources and associated adaptation strategies. The research shows that the climate in the region has experienced warming and wetting with the most significant warming in winter and the highest increase in summer precipitation since 1961. Areas with the most significant warming trends include the Qaidam Basin, the Yili River Valley, and Tacheng. Spatially, the increasing trend in precipitation becomes increasingly significant from the southeast to the northwest, and northern Xinjiang experienced the highest increase. Studies have shown a decrease in headwater of Shiyang River because runoff is mainly based on precipitation which shows a decrease trend. But an increase in western rivers was observed such as Tarim River and Shule River as well as Heihe River due to rapid glacier shrinkage and snowmelt as well as precipitation increase in mountain area. Meanwhile unreasonable human activities resulted in decrease of runoff in the middle and lower reaches of Haihe River, Shiyang River and Kaidu River. Finally, recommendations for future studies are suggested that include characteristics of changes in extreme weather events and their impacts on water resources, projections of future climate and water resource changes, climate change attribution, the selection of adaptation strategies relating to climate change and social economic activities, and use of scientific methods to quantitatively determine water resource allocation.
Receptor mediated transcytosis (RMT) is a common mechanism used for nanotherapeutics to traverse the blood–brain barrier (BBB). However, the transcytosis of ligand modified nanoparticles via RMT is ...likely to be trapped within brain capillary endothelial cells due to the high binding affinity of ligand with receptors, which greatly reduces the amount of nanoparticles across BBB. Here, P‐aminophenyl‐α‐D‐mannopyranoside (MAN) decorated doxorubicin‐loaded dendrigraft poly‐l‐lysine with acid‐cleavable transferrin (Tf) coating outside (DD‐MCT) is proposed. The DD‐MCT is engineered to specifically recognize the Tf receptor (TfR) on the luminal side of BBB endothelium. Then the DD‐MCT undergoes an acid‐responsive cleavage of Tf, leading to the separation of MAN‐decorated DGL‐DOX (DD‐M) from the Tf–TfR complex in endo/lysosomes. The detached DD‐M is more prone to escape from endo/lysosomes and can further be exocytosed into brain parenchyma via the mediation of glucose transporter located on the abluminal endothelial membrane. Moreover, the DD‐M in brain parenchyma can target glioma cells. Significantly, the DD‐MCT enters into brain parenchyma in greater amounts, resulting in enhanced accumulation at glioma site and thus improved antiglioma therapeutic outcome. This strategy pioneers a new path for reducing the trapping of nanotherapeutics within BBB endothelium but increasing their transcytosis into brain parenchyma.
Acid‐cleavable transferrin and P‐aminophenyl‐α‐D‐mannopyranoside co‐modified doxorubicin‐tethered dendrigraft poly‐l‐lysine are successfully designed and synthesized. The functional nanoparticles undergo a four‐step journey within endothelial cells for programmed targeting delivery to glioma cells. The nanoparticles exhibit increased transcytosis across blood–brain barriers and precise glioma targeting effect, as well as improved chemotherapeutic outcome.
The trade-off between strength and ductility of particulate reinforced metal matrix composites (PRMMCs) has been a longstanding puzzle. Here we propose an effective strategy to surmount the inverse ...relationship between strength and ductility of an A356 Al alloy based PRMMC by in situ synthesizing novel reinforcing particulates with a special core-shell (CS) structure. Such structure features a Ti core inside a dual-layer shell: the inner layer has a nano-grained (~130 nm) heterogeneous structure, and the outer layer possesses a composite structure composed of a (Al,Si)3Ti substrate with dense dispersion of nanoparticles. As a result, the obtained composite reinforced with such CS reinforcing particulates (CS composite) achieves an unprecedented tensile elongation to failure of 8.3 ± 0.8% and a uniform elongation of 7.1 ± 0.6%, which nearly triples that of the same alloy based composite reinforced with monolithic (Al,Si)3Ti particulates (monolithic composite) and equivalent to corresponding matrix alloy while maintaining high ultimate tensile strength of 373 ± 8.8 MPa and yield strength of 268 ± 7.9 MPa, equivalent to monolithic composite simultaneously. This special architecture of shell renders itself a high capability of stress bearing and good toughness, and the nanoparticles in outer layer further slower crack development, which significantly postpone crack formation in shell. Subsequent propagation of cracks in Ti core is also constrained remarkably by the transformation-induced plasticity effect occurred ahead of crack tips resulting from stress-induced phase transformation of hcp-Ti into fcc-Ti. These factors lead to highest work hardening rate that undergoes a long plateau and thus overcome the strength-ductility trade-off of A356 alloy based PRMMC.
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Depression is the most significant risk factor for suicide, yet the causes are complex and disease mechanism remains unclear. The incidence and disability rate of depression are very high and the ...efficacy of some traditional antidepressants is not completely satisfactory. Recently, some studies have found that benzofurans have anti-oxidation and anti-monoamine oxidase properties, which are related to depression. Euparin is a monomer compound of benzofuran, previous work by our team found that it improves the behavior of depressed mice. However, additional antidepressant effects and mechanisms of Euparin have not been reported. In this study, the Chronic Unpredictable Mild Stress (CUMS) model of mice was used to further investigate the effect and mechanism of Euparin on depression. Results showed that Euparin (8, 16 and 32 mg/kg) reduced depression-like behavior in mice compared with the model group. Meanwhile, all doses of Euparin were found to increase the contents of monoamine neurotransmitter and decrease monoamine oxidase and reactive oxygen species (ROS) levels in brain of depression mice. Additionally, Euparin restored CUMS-induced decrease of Spermidine/Spermine N1-Acetyltransferase 1 (SAT1), N-methyl-D-aspartate receptor subtype 2B (NMDAR2B) and brain derived neurotrophic factor (BDNF) expression. These findings demonstrate that Euparin has antidepressant properties, and its mechanism involves the SAT1/NMDAR2B/BDNF signaling pathway.
Objective
To evaluate long‐term safety/tolerability of brivaracetam at individualized doses ≤200 mg/d (primary) and maintenance of efficacy over time (secondary) in adults with focal seizures or ...primary generalized seizures (PGS) enrolled in phase 3, open‐label, long‐term follow‐up trial N01199 (NCT00150800).
Methods
Patients ≥16 years of age who had completed double‐blind, placebo‐controlled adjunctive brivaracetam trials NCT00175825, NCT00490035, NCT00464269, or NCT00504881 were eligible. Outcomes included safety, efficacy, and quality of life.
Results
The safety set included 667 patients (focal seizures, 97.8%; PGS, 2.2%); the efficacy set included 648 patients with focal seizures and 15 patients with PGS. Overall, 49.2% of patients had ≥48 months of exposure. Treatment‐emergent adverse events (TEAEs) occurred in 91.2% of all patients (91.3% of focal seizures group), brivaracetam discontinuation due to TEAEs in 14.8%, drug‐related TEAEs in 56.7%, and serious TEAEs in 22.8%. The most common TEAEs in the focal seizures group (≥15%) were headache (25.3%) and dizziness (21.9%). Mean changes from baseline in Hospital Anxiety and Depression Scale scores at last value during 2‐year evaluation were −0.7 (standard deviation SD = 4.3) and −0.2 (SD = 4.4) overall. In the focal seizures group, median reduction from baseline in focal seizure frequency/28 days was 57.3%, 50% responder rate was 55.6%, and 6‐month and 12‐month seizure freedom rates were 30.3% and 20.3%, respectively. Efficacy outcomes improved by exposure duration cohort and then stabilized through the 108‐month cohort. Mean improvement from baseline in Patient‐Weighted Quality of Life in Epilepsy Inventory total score (efficacy set) was 5.7 (SD = 16.1, Cohen's d = 0.35) at month 12 and 6.5 (SD = 18.0, Cohen's d = 0.36) at month 24.
Significance
Adjunctive brivaracetam was well tolerated, with a good safety profile in long‐term use in adults with epilepsy at individualized doses. Approximately half of the patients remained in the trial at 4 years. Brivaracetam reduced focal seizure frequency versus baseline. Efficacy improved with increasing exposure duration and remained stable through the 9‐year cohort.
Aims
Many patients taking risperidone for the treatment of psychiatric disorders experience substantial body weight gain. Researchers have speculated that risperidone induces obesity by modulating ...central signals; however, the precise central mechanisms involved remain to be fully elucidated.
Methods
Twenty‐four C57BL/6J mice were divided into four groups: a control group; a risperidone‐treated group; a lorcaserin‐treated group; and a combined risperidone + lorcaserin‐treated group. The mice were received the corresponding treatments for 4 weeks, and their brains were collected for in situ hybridization analysis. A subset of C57BL/6J mice was administrated with risperidone or placebo, and brains were collected 60 minutes post‐treatment for determination of c‐fos activity. In addition, brains of NPY‐GFP mice treated with or without risperidone were collected to perform colocalization of NPY and c‐fos, as well as NPY and 5‐HT2c receptor using immunohistochemistry.
Results
There was significantly elevated c‐fos expression in the hypothalamic arcuate nucleus (Arc) of risperidone‐treated mice. More than 68% c‐fos‐positive neurons were NPY‐expressing neurons. Furthermore, in situ hybridization revealed that Arc NPY mRNA expression was significantly increased in the risperidone‐treated group compared with control group. Moreover, we identified that 95% 5‐HT2c receptors were colocalized with NPY positive neurons, and increased Arc NPY mRNA expression induced by risperidone was markedly reduced by cotreatment with lorcaserin, a specific 5‐HT2c receptor agonist.
Conclusion
Our findings provide critical insight into the mechanisms underlying antipsychotic‐induced obesity, which may assist the development of therapeutic strategies to address metabolic side effects of risperidone.
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