Step-by-step desolvation enables high-rate and ultra-stable sodium storage in hard carbon anodes.

Hard carbon is regarded as the most promising anode material for sodium-ion (Na-ion) batteries, owing to its advantages of high abundance, low cost, and low operating potential. However, the rate capability and cycle life span of hard carbon anodes are far from satisfactory, severely hindering its industrial applications. Here, we demonstrate that the desolvation process defines the Na-ion diffusion kinetics and the formation of a solid electrolyte interface (SEI). The 3A zeolite molecular sieve film on the hard carbon is proposed to develop a step-by-step desolvation pathway that effectively reduces the high activation energy of the direct desolvation process. Moreover, step-by-step desolvation yields a thin and inorganic-dominated SEI with a lower activation energy for Na+ transport. As a result, it contributes to greatly improved power density and cycling stability for both ester and ether electrolytes. When the above insights are applied, the hard carbon anode achieves the longest life span and minimum capacity fading rate at all evaluated current densities. Moreover, with the increase in current densities, an improved plateau capacity ratio is observed. This step-by-step desolvation strategy comprehensively enhances various properties of hard carbon anodes, which provides the possibility of building practical Na-ion batteries with high power density, high energy density, and durability.

Both Resilience and Adhesivity Define Solid Electrolyte Interphases for a High Performance Anode.

Solid electrolyte interphases (SEIs) are sought to protect high-capacity anodes, which suffer from severe volume changes and fast degradations. The previously proposed effective SEIs were of high strength yet abhesive, inducing a yolk-shell structure to decouple the rigid SEI from the anode for accommodating the volume change. Ambivalently, the interfacial void-evolved electro-chemo-mechanical vulnerabilities become inherent defects. Here, we establish a new rationale for SEIs that resilience and adhesivity are both requirements and pioneer a design of a resilient yet adhesive SEI (re-ad-SEI), integrated into a conjugated surface bilayer structure. The re-ad-SEI and its protected particles exhibit excellent stability almost free from the thickening of SEI and the particle pulverization during cycling. More promisingly, the dynamically bonded intact SEI-anode interfaces enable a high-efficiency ion transport and provide a unique mechanical confinement effect for structural integrity of anodes. The high Coulombic efficiency (>99.8%), excellent cycling stability (500 cycles), and superior rate performance have been demonstrated in microsized Si-based anodes.

Weak-Interaction Environment in a Composite Electrolyte Enabling Ultralong-Cycling High-Voltage Solid-State Lithium Batteries.

Poly(vinylidene fluoride) (PVDF)-based solid electrolytes with a Li salt-polymer-little residual solvent configuration are promising candidates for solid-state batteries. Herein, we clarify the microstructure of PVDF-based composite electrolyte at the atomic level and demonstrate that the Li+-interaction environment determines both interfacial stability and ion-transport capability. The polymer works as a "solid diluent" and the filler realizes a uniform solvent distribution. We propose a universal strategy of constructing a weak-interaction environment by replacing the conventional N,N-dimethylformamide (DMF) solvent with the designed 2,2,2-trifluoroacetamide (TFA). The lower Li+ binding energy of TFA forms abundant aggregates to generate inorganic-rich interphases for interfacial compatibility. The weaker interactions of TFA with PVDF and filler achieve high ionic conductivity (7.0 × 10-4 S cm-1) of the electrolyte. The solid-state Li||LiNi0.8Co0.1Mn0.1O2 cells stably cycle 4900 and 3000 times with cutoff voltages of 4.3 and 4.5 V, respectively, as well as deliver superior stability at -20 to 45 °C and a high energy density of 300 Wh kg-1 in pouch cells.

Ubiquitylation-independent cotranslational degradation of dihydrofolate reductase and ubiquitin.

Nascent proteins are degraded during or immediately after synthesis, a process called cotranslational protein degradation (CTPD). Although CTPD was observed decades ago, it has never been fully explored mechanistically and functionally. We show here that dihydrofolate reductase (DHFR) and ubiquitin (Ub), two stable proteins widely used in protein degradation studies, are actually subject to CTPD. Unlike canonical posttranslational protein degradation, CTPD of DHFR and Ub does not require prior ubiquitylation. Our data also suggest that protein expression level and N-terminal folding pattern may be two critical determinants for CTPD. Thus, this study reveals that CTPD plays a role in regulating the homeostasis of long-lived proteins and provides insights into the mechanism of CTPD.

Electrolyte Sieving Chemistry in Suppressing Gas Evolution of Sodium-Metal Batteries.

The sodium (Na)-metal batteries hold great promise as a sustainable technology owing to the high element abundance and low cost. However, the generally used carbonate electrolytes remain highly reactive towards Na metal, leading to flammable gas evolution. Here, we propose an electrolyte sieving strategy to separate anion-mediated ion-pairs from dilute electrolytes by introducing a 3A zeolite molecular sieve film. The anion-mediated ion-pair firstly weakens the electron-withdrawing property of the cation, which effectively suppresses the gassing. In addition, the sieved electrolyte promotes the formation of robust inorganic-dominated solid electrolyte interphases. Therefore, it contributes to stable Na plating/stripping in Na|Al half cells with Coulombic efficiency maintaining at 98.5 % and a long service life of 800 cycles in full cells. Moreover, the electrode stability is well preserved even under harsh conditions of high temperature and ester-based electrolytes with higher reactivity.

ZIF-67-derived N-enriched porous carbon doped with Co, Fe and CoS for electrocatalytic hydrogen evolution reaction.

Hybrid composites based on transition metal-doped materials exhibit excellent performance and stability as electrocatalysts for the hydrogen evolution reaction (HER). Thus, they could easily replace HER catalysts based on noble metals. To demonstrate this, we fabricated Co, Fe, and CoS doped N-enriched porous carbon materials (CoFeS/NC) using a simple, straightforward and quick method (involving absorption, pyrolysis and sulfidation steps), which used ZIF-67 metal-organic framework (MOF) material as a precursor. The fabricated CoFeS/NC showed excellent HER performance and long-term stability: it achieved a low potential (equal to 176 mV) at 10 mA cm-2 current density and a small Tafel slope (equal to 67.8 mV dec-1) in 1.0 KOH. Such outstanding HER performance was attributed to the synergistic effect of the CoFeS/NC components, including unique mesoporosity. All these properties ensured the presence of numerous active sites and high conductivity provided by the carbon matrix. The excellent CoFeS/NC electrocatalytic activity makes it a promising material for H2 production on an industrial scale. Our work demonstrated a simple way of its preparation, which could be applied to other material groups.

Chirality-Dependent Second-Order Nonlinear Optical Effect in 1D Organic-Inorganic Hybrid Perovskite Bulk Single Crystal.

The introduction of chirality into organic-inorganic hybrid perovskites (OIHPs) is expected to achieve excellent photoelectric and nonlinear materials related to circular dichroism. Owing to the existence of asymmetric center and intrinsic chirality in the chiral OIHPs, the different efficiencies of second harmonic generation (SHG) signal occurs when the circularly polarized light (CPL) with different phases passes through the chiral crystal, which is defined as second harmonic generation circular dichroism (SHG-CD). Here, the SHG-CD effect is developed in bulk single crystals of chiral one-dimensional (1D) [(R/S)-3-aminopiperidine]PbI4 . It is the first time that CPL is distinguished using chirality-dependent SHG-CD effect in OIHPs bulk single crystals. Such SHG-CD technology extends the detection range to near infrared region (NIR). In this way, the anisotropy factor (gSHG-CD ) through SHG-CD signal is as high as 0.21.

A Corrosion-Resistant and Dendrite-Free Zinc Metal Anode in Aqueous Systems.

Rechargeable aqueous zinc (Zn) ion-based energy storage systems have been reviving recently because of their low cost and high safety merits; however, they still suffer from the problems of corrosion and dendrite growth on Zn metal anodes that cause gas generation and early battery failure. Unfortunately, the corrosion problem has not received sufficient attention until now. Here, it is pioneeringly demonstrated that decorating the Zn surface with a dual-functional metallic indium (In) layer, acting as both a corrosion inhibitor and a nucleating agent, is a facile but effective strategy to suppress both drastic corrosion and dendrite growth. Symmetric cells assembled with the treated Zn electrodes can sustain up to 1500 h of plating/stripping cycles with an ultralow voltage hysteresis (54 mV), and a 5000 cycle-life is achieved for a prototype full cell. This work will instigate the further development of aqueous metal-based energy storage systems.

Designing a Multifunctional Separator for High-Performance Li-S Batteries at Elevated Temperature.

The practical applications of lithium-sulfur (Li-S) batteries are seriously limited by the undesirable polysulfide shuttling and lithium dendrite growth. Herein, a multifunctional membrane is designed and prepared by coating a lithiated Nafion (Li@Nafion) layer and an Al2 O3 layer on the two sides of a routine polymer membrane (polypropylene/polyethylene/polypropylene, PEP). The Li@Nafion layer faced to the sulfur cathode builds a "polysulfide-phobic" surface to restrain the shuttle effect via Coulomb repulsion, while the Al2 O3 layer with a uniform porous structure aids in regulating homogeneous Li+ fluxes to achieve stable Li electrodeposition. As a result, the Li//Li symmetric cell with a Li@Nafion/PEP/Al2 O3 (LNPA) separator realizes stable Li plating/striping even after 1000 h at a high current density (5 mA cm-2 ). Moreover, the Li-S batteries incorporating LNPA separators not only can achieve excellent outstanding cyclic stability at an ultrahigh sulfur loading (7.6 mg cm-2 ), but also exhibit impressive electrochemical performance at an elevated temperature (60 °C). The rational design of the LNPA separator presents new insights to develop high-performance Li-S batteries.

Satisfaction of psychiatric inpatients in China: clinical and institutional correlates in a national sample.

BACKGROUND: Surveying patients' satisfaction is essential to improve patient-centered care, however, studies on satisfaction and their correlates among psychiatric inpatients are rare in China. This study aimed to measure satisfaction levels of psychiatric inpatients in a national sample and to examine individual and institutional correlates. METHODS: As part of the National Survey for the Evaluation of Psychiatric Hospital Performance, psychiatric inpatients from 32 tertiary psychiatric hospitals in 29 Chinese provinces were interviewed on the day of discharge by trained research staff. Satisfaction was assessed using a five-item questionnaire. Patients' sociodemographic and clinical information were manually retrieved from medical records and institutional data were provided by participating hospitals. Multilevel linear regression was used to assess factors associated with level of satisfaction. RESULTS: Among 1663 inpatients, the reported satisfaction levels were high, with a mean score of 23.3 ± 2.4 out of 25. Education level was positively associated with global satisfaction, satisfaction with costs, and satisfaction with privacy protection. Treatment response was associated with global satisfaction and with the doctor-patient communication subscore. The number of psychotherapy sessions was positively associated with the privacy protection subscore (coefficient = 0.0, P = 0.046). The Global Assessment of Function score was positively associated with the doctor-patient communication subscore (coefficient = 0.0, P = 0.003). Total satisfaction scores and all five subscores were positively associated with hospital-level factors, and patients discharged from hospitals with better staffing and resources reported significantly higher levels of satisfaction. CONCLUSION: Overall, psychiatric inpatients in China were satisfied with the services they received. To further improve patient satisfaction, mental health professionals should optimize their patients' treatment response as much as possible before discharge and provide more psychological treatment during the hospitalization. The government should also provide more resources to increase the number of mental health professionals (nurses, psychologists, and psychiatrists) working in psychiatric hospitals.

Integration of phospholipid-complex nanocarrier assembly with endogenous N-oleoylethanolamine for efficient stroke therapy.

BACKGROUND: Leading to more and more deaths and disabilities, stroke has become a serious threat to human health. What's more, few effective drugs are available in clinic till now. RESULTS: In this research, we prepared a novel neuroprotective nanoformation (OEA-SPC NPs) via the combination of the nanoparticle drug delivery system with the endogenous N-oleoylethanolamine (OEA). By forming hydrogen bond between OEA and the carrier-soybean phosphatidylcholine (SPC), the form of OEA was turned into amorphus state when loading to the nanoparticles, which greatly improved its bioavailability. Then the following systematic experiments revealed the efficient neuroprotective effect of OEA-SPC NPs in vivo. Compared with the MCAO group, the cerebral infarct volume was reduced by 81.1%, and the edema degree by 78.4% via the oral administration of OEA-SPC NPs. And the neurological deficit scores illustrated that the MCAO rats treated with OEA-SPC NPs exhibited significantly less neurological dysfunction. The Morris water maze test indicated that the spatial learning and memory of cerebral ischemia model rats were almost recovered to the normal level. Besides, the OEA-SPC NPs could inhibit the inflammation of reperfusion to a very slight level. CONCLUSIONS: These results suggest that the OEA-SPC NPs have a great chance to be a potential anti-stroke formation for clinic application and actually bring hope to thousands of stroke patients.

The influence of basic public health service project on maternal health services: an interrupted time series study.

BACKGROUND: Reducing maternal mortality remains a global priority. In 2000, the United Nations Member States pledged to work towards a series of Millennium Development Goals (MDGs), in which the fifth target was to reduce maternal mortality ratio by 75% from 1990 to 2015. The Chinese government introduced Basic Public Health Service project in 2009 to the further improvement of maternal health services and reduction in maternal mortality. China had achieved the goal of MDG5 1 year ahead of the schedule in 2014, but the effects of the project on reducing maternal mortality were rarely evaluated with robust methods. METHODS: We conducted a longitudinal study on maternal mortality ratio by extracting mortality data from the National Maternal Mortality Surveillance System (1991-2016) and maternal health services measures from the China health statistic yearbook (2001-2016). We utilized the segmented linear regression model to assess changes and trends of maternal mortality ratio and maternal health services before and after the introduction of Basic Public Health Service project. Pearson correlation analysis was conducted to measure the strength of association between the maternal mortality ratio and maternal health services. RESULTS: The yearly trend change of national maternal mortality ratio was - 1.76 (p < 0.01) after the introduction of Basic Public Health Service project in 2009, while the yearly trend change of maternal health record establish rate, prenatal examination rate, postpartum visit rate was 0.77 (p < 0.01), 0.61 (p < 0.01) and 0.83 (p < 0.01) separately. The negative correlations were also found between national maternal mortality ratio and prenatal examination rate (r = - 0.95, p < 0.01), maternal health record establish rate (r = - 0.93, p < 0.01) and postpartum visit rate (r = - 0.92, p < 0.01). CONCLUSIONS: The Basic Public Health Service project was found to be associated with the improvements in the maternal health services and reduction in maternal mortality. The design and implementation of the project may serve as a positive example for other developing countries. Continued monitoring and assessment of project effects should be stressed.

Job satisfaction and associated factors among psychiatric nurses in tertiary psychiatric hospitals: Results from a nationwide cross-sectional study.

AIMS: To investigate the job satisfaction among psychiatric nurses in China and to explore its associated factors. DESIGN: A cross-sectional survey among a nationwide sample from 32 tertiary psychiatric hospitals in 29 provincial capitals in China. METHODS: Nurses (N = 9.907) were targeted for this survey in December 2017. In all, 8,493 responded (response rate = 85.7%) and 7,881 (79.5%) were included in the analysis. An online questionnaire was used to collect demographics and factors related to the work environment. The short version of the Minnesota Satisfaction Questionnaire was used to assess job satisfaction. Multilevel regression was used to examine the association between job satisfaction and these factors. RESULTS: The mean job satisfaction score was 73.7. The multiple regression analysis indicated that self-rated health, monthly income, medical liability insurance coverage, perceived respect from patients, social recognition, nurse-physician collaboration, and trust were significantly associated with higher job satisfaction scores, while age, work hours, and directly experiencing patient-initiated violence were negatively associated with job satisfaction (p < .05). CONCLUSION: Overall, Chinese psychiatric nurses are closer to satisfied than neutral and some demographics and factors related to stressful work environments were associated with nurses' job satisfaction scores. IMPACT: This study examined factors associated with the job satisfaction of Chinese psychiatric nurses in a nationwide sample and indicated that to improve nurses' job satisfaction, the government and hospital administrators could consider ways to promote nurses' personal health and to modify the stressful work environments, such as improving income, reducing work hours, promoting the psychiatric nursing specialty in ways that increase the public's respect for it, increasing awareness of medical liability insurance coverage, and protecting nurses from patients' violence.

Intrastriatal transplantation of stem cells from human exfoliated deciduous teeth reduces motor defects in Parkinsonian rats.

BACKGROUND: This study explored the neural differentiation and therapeutic effects of stem cells from human exfoliated deciduous teeth (SHED) in a rat model of Parkinson's disease (PD). METHODS: The SHED were isolated from fresh dental pulp and were induced to differentiate to neurons and dopamine neurons by inhibiting similar mothers against dpp (SMAD) signaling with Noggin and increase conversion of dopamine neurons from SHED with CHIR99021, Sonic Hedgehog (SHH) and FGF8 in vitro. The neural-primed SHED were transplanted to the striatum of 6-hydroxydopamine (6-OHDA)-induced PD rats to evaluate their neural differentiation and functions in vivo. RESULTS: These SHED were efficiently differentiated to neurons (62.7%) and dopamine neurons (42.3%) through a newly developed method. After transplantation, the neural-induced SHED significantly improved recovery of the motor deficits of the PD rats. The grafted SHED were differentiated into neurons (61%), including dopamine neurons (22.3%), and integrated into the host rat brain by forming synaptic connections. Patch clamp analysis showed that neurons derived from grafted SHED have the same membrane potential profile as dopamine neurons, indicating these cells are dopamine neuron-like cells. The potential molecular mechanism of SHED transplantation in alleviating motor deficits of the rats is likely to be mediated by neuronal replacement and immune-modulation as we detected the transplanted dopamine neurons and released immune cytokines from SHED. CONCLUSION: Using neural-primed SHED to treat PD showed significant restorations of motor deficits in 6-OHDA-induced rats. These observations provide further evidence that SHED can be used for cell-based therapy of PD.

Biosynthesis of flower-shaped Au nanoclusters with EGCG and their application for drug delivery.

BACKGROUND: In the last decade, the biosynthesis of metal nanoparticles using organisms have received more and more considerations. However, the complex composition of organisms adds up to a great barrier for the characterization of biomolecules involved in the synthesis process and their biological mechanisms. RESULTS: In this research, we biosynthesized a kind of flower-shaped Au nanoclusters (Au NCs) using one definite component-epigallocatechin gallate (EGCG), which was the main biomolecules of green tea polyphenols. Possessing good stability for 6 weeks and a size of 50 nm, the Au NCs might be a successful candidate for drug delivery. Hence, both methotrexate (MTX) and doxorubicin (DOX) were conjugated to the Au NCs through a bridge of cysteine (Cys). The introduction of MTX provided good targeting property for the Au NCs, and the conjugation of DOX provided good synergistic effect. Then, a novel kind of dual-drug loaded, tumor-targeted and highly efficient drug delivery system (Au-Cys-MTX/DOX NCs) for combination therapy was successfully prepared. The TEM of HeLa cells incubated with Au-Cys-MTX/DOX NCs indicated that the Au-Cys-MTX/DOX NCs could indeed enter and kill cancer cells. The Au-Cys-MTX/DOX NCs also possessed good targeting effect to the FA-receptors-overpressed cancer cells both in vitro and in vivo. Importantly, the Au-Cys-MTX/DOX NCs resulted in an excellent anticancer activity in vivo with negligible side effects. CONCLUSIONS: These results suggest that the biosynthesized Au-Cys-MTX/DOX NCs could be a potential carrier with highly efficient anticancer properties for tumor-targeted drug delivery.

Dual-drug loaded nanoneedles with targeting property for efficient cancer therapy.

BACKGROUND: Since the anticancer drugs have diverse inhibited mechanisms to the cancer cells, the use of two or more kinds of anticancer agents may achieve excellent therapeutic effects, especially to the drug-resistant tumors. RESULTS: In this study, we developed a kind of dual drug [methotrexate (MTX) and 10-hydroxycamptothecine (HCPT)] loaded nanoneedles (DDNDs) with pronounced targeting property, high drug loading and prolonged drug release. The anti-solvent precipitation of the HCPT and MTX modified PEG-b-PLGA (PEG-b-PLGA-MTX, PPMTX) leads to nucleation of nanoneedles with nanocrystalline HCPT as the core wrapped with PPMTX as steric stabilizers. In vitro cell uptake studies showed that the DDNDs revealed an obviously targeting property and entered the HeLa cells easier than the nanoneedles without MTX modification. The cytotoxicity tests illustrated that the DDNDs possessed better killing ability to HeLa cells than the individual drugs or their mixture in the same dose, indicating its good synergistic effect and targeting property. The in vivo studies further confirmed these conclusions. CONCLUSIONS: This approach led to a promising sustained drug delivery system for cancer diagnosis and treatment.

Expression of Dlx-5 and Msx-1 in Craniofacial Skeletons and Ilia of Rats Treated With Zoledronate.

PURPOSE: Because of the different embryologic origins of the craniofacial skeleton and ilium, differences in gene expression patterns have been observed between the jaw bones and ilium. Distal-less homeobox (Dlx) genes and Msh homeobox genes, particularly Dlx-5 and Msx-1, play major roles in cell differentiation and osteogenesis. The purpose of this study was to investigate the effects of zoledronate (ZOL) on the craniofacial skeleton and ilium by detecting changes in Dlx-5 and Msx-1 expression at both the protein and messenger RNA levels. MATERIALS AND METHODS: A total of 24 female Sprague-Dawley rats were randomly divided into 2 groups: ZOL group (n = 12), in which the rats were injected intraperitoneally with zoledronic acid for 12 weeks, and control group (n = 12), in which the rats were injected with saline solution for 12 weeks. By use of immunohistochemistry, Western blotting, and real-time reverse transcription polymerase chain reaction, the expression levels of Dlx-5 and Msx-1 in the craniofacial skeleton (including the maxilla, mandible, and parietal bone) and ilium were examined. RESULTS: Dlx-5 expression in the maxilla and mandible was increased at the protein and messenger RNA levels in the ZOL group compared with the control group (P < .01). In addition, Msx-1 expression in the maxilla and mandible was decreased in the ZOL group (P < .01). Furthermore, Dlx-5 and Msx-1 expression in the ilium was decreased in the ZOL group (P < .05). However, no significant difference in Dlx-5 or Msx-1 expression in the parietal bone was observed between the 2 groups (P > .05). CONCLUSIONS: Site-specific differences in the effects of ZOL on the craniofacial skeleton and ilium could be explained by differently altered tendencies in Dlx-5 and Msx-1 expression. The jaw bones were more susceptible to the effects of ZOL than the parietal bone and ilium.

From O2- to HO2- : Reducing By-Products and Overpotential in Li-O2 Batteries by Water Addition.

The development of aprotic Li-O2 batteries, which are promising candidates for high gravimetric energy storage devices, is severely limited by superoxide-related parasitic reactions and large voltage hysteresis. The fundamental reaction pathway of the aprotic Li-O2 battery can be altered by the addition of water, which changes the discharge intermediate from superoxide (O2- ) to hydroperoxide (HO2- ). The new mechanism involving HO2- intermediate realizes the two-electron transfer through a single step, which significantly suppresses the superoxide-related side reactions. Moreover, addition of water also triggers a solution-based pathway that effectively reduces the voltage hysteresis. These discoveries offer a possible solution for desirable Li-O2 batteries free of aggressive superoxide species, highlighting the design strategy of modifying the reaction pathway for Li-O2 electrochemistry.

Mutations in the glucocerebrosidase gene are common in patients with Parkinson's disease from Eastern Canada.

BACKGROUND: Mutations in the ß-glucocerebrosidase gene (GBA) have been implicated as a risk factor for Parkinson's disease (PD). However, GBA mutations in PD patients of different ethnic origins were reported to be inconsistent. METHODS: We sequenced all exons of the GBA gene in 225 PD patients and 110 control individuals from Eastern Canada. RESULT: Two novel GBA variants of c.-119 A/G and S(-35)N, five known GBA mutations of R120W, N370S, L444P, RecNciI and RecTL mutation (del55/D409H/RecNciI) as well as two non-pathological variants of E326K and T369M were identified from PD patients while only one mutation of S13L and two non-pathological variants of E326K and T369M were found in the control individuals. The frequency of GBA mutations within PD patients (4.4%) is 4.8 times higher than the 0.91% observed in control individuals (X(2) = 2.91, p = 0.088; odds ratio = 4.835; 95% confidence interval = 2.524-9.123). The most common mutations of N370S and L444P accounted for 36.0% (9/25) of all the GBA mutations in this Eastern Canadian PD cohort. The frequency (6.67%) of E326K and T369M in PD patients is comparable to 7.27% in control individuals (X(2) = 0.042, p = 0.8376), further supporting that these two variants have no pathological effects on PD. Phenotype analysis showed that no significant difference in family history, age at onset and cognitive impairment was identified between the GBA mutation carriers and non-GBA mutation carriers. CONCLUSION: GBA mutations were found to be a common genetic risk factor for PD in Eastern Canadian patients.

Bacillus-shape design of polymer based drug delivery systems with janus-faced function for synergistic targeted drug delivery and more effective cancer therapy.

The particle shape of the drug delivery systems had a strong impact on their in vitro and in vivo performance, but there was limited availability of techniques to produce the specific shaped drug carriers. In this article, the novel methotrexate (MTX) decorated MPEG-PLA nanobacillus (MPEG-PLA-MTX NB) was prepared by the self-assembly technique followed by the extrusion through SPG membrane with high N2 pressure for targeted drug delivery, in which Janus-like MTX was not only used as a specific anticancer drug but could also be served as a tumor-targeting ligand. The MPEG-PLA-MTX NBs demonstrated much higher in vitro and in vivo targeting efficiency compared to the MPEG-PLA-MTX nanospheres (MPEG-PLA-MTX NSs) and MPEG-PLA nanospheres (MPEG-PLA NSs). In addition, the MPEG-PLA-MTX NBs also displayed much more excellent in vitro and in vivo antitumor activity than the MPEG-PLA-MTX NSs and free MTX injection. To our knowledge, this work provided the first example of the integration of the shape design (which mediated an early phase tumor accumulation and a late-phase cell internalization) and Janus-faced function (which mediated an early phase active targeting effect and a late-phase anticancer effect) on the basis of nanoscaled drug delivery systems. The highly convergent and cooperative drug delivery strategy opens the door to more drug delivery systems with new shapes and functions for cancer therapy.