The combination of nanostructures with biomolecules leading to the generation of functional nanosystems holds great promise for biotechnological and biomedical applications. As a naturally occurring ...biomacromolecule, DNA exhibits excellent biocompatibility and programmability. Also, scalable synthesis can be readily realized through automated instruments. Such unique properties, together with Watson-Crick base-pairing interactions, make DNA a particularly promising candidate to be used as a building block material for a wide variety of nanostructures. In the past few decades, various DNA nanostructures have been developed, including one-, two- and three-dimensional nanomaterials. Aptamers are single-stranded DNA or RNA molecules selected by Systematic Evolution of Ligands by Exponential Enrichment (SELEX), with specific recognition abilities to their targets. Therefore, integrating aptamers into DNA nanostructures results in powerful tools for biosensing and bioimaging applications. Furthermore, owing to their high loading capability, aptamer-modified DNA nanostructures have also been altered to play the role of drug nanocarriers for
in vivo
applications and targeted cancer therapy. In this review, we summarize recent progress in the design of aptamers and related DNA molecule-integrated DNA nanostructures as well as their applications in biosensing, bioimaging and cancer therapy. To begin with, we first introduce the SELEX technology. Subsequently, the methodologies for the preparation of aptamer-integrated DNA nanostructures are presented. Then, we highlight their applications in biosensing and bioimaging for various targets, as well as targeted cancer therapy applications. Finally, we discuss several challenges and further opportunities in this emerging field.
We survey advances in biosensing, bioimaging and cancer therapy applications of aptamer-integrated DNA nanostructures in this review.
Steroid‐refractory (SR) acute graft‐versus‐host disease (aGVHD) is one of the leading causes of early mortality after allogeneic hematopoietic stem cell transplantation (allo‐HSCT). We investigated ...the efficacy, safety, prognostic factors, and optimal therapeutic protocol for SR‐aGVHD patients treated with basiliximab in a real‐world setting. Nine hundred and forty SR‐aGVHD patients were recruited from 36 hospitals in China, and 3683 doses of basiliximab were administered. Basiliximab was used as monotherapy (n = 642) or in combination with other second‐line treatments (n = 298). The cumulative incidence of overall response rate (ORR) at day 28 after basiliximab treatment was 79.4% (95% confidence interval CI 76.5%–82.3%). The probabilities of nonrelapse mortality and overall survival at 3 years after basiliximab treatment were 26.8% (95% CI 24.0%–29.6%) and 64.3% (95% CI 61.2%–67.4%), respectively. A 1:1 propensity score matching was performed to compare the efficacy and safety between the monotherapy and combined therapy groups. Combined therapy did not increase the ORR; conversely, it increased the infection rates compared with monotherapy. The multivariate analysis showed that combined therapy, grade III–IV aGVHD, and high‐risk refined Minnesota aGVHD risk score before basiliximab treatment were independently associated with the therapeutic response. Hence, we created a prognostic scoring system that could predict the risk of having a decreased likelihood of response after basiliximab treatment. Machine learning was used to develop a protocol that maximized the efficacy of basiliximab while maintaining acceptable levels of infection risk. Thus, real‐world data suggest that basiliximab is safe and effective for treating SR‐aGVHD.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Hepatitis B virus (HBV) X protein, HBx, interacts with anti-apoptotic Bcl-2 and Bcl-xL proteins through its BH3-like motif to promote HBV replication and cytotoxicity. Here we report the crystal ...structure of HBx BH3-like motif in complex with Bcl-xL where the BH3-like motif adopts a short α-helix to snuggle into a hydrophobic pocket in Bcl-xL via its noncanonical Trp120 residue and conserved Leu123 residue. This binding pocket is ~2 Å away from the canonical BH3-only binding pocket in structures of Bcl-xL with proapoptotic BH3-only proteins. Mutations altering Trp120 and Leu123 in HBx impair its binding to Bcl-xL in vitro and HBV replication in vivo, confirming the importance of this motif to HBV. A HBx BH3-like peptide, HBx-aa113-135, restores HBV replication from a HBx-null HBV replicon, while a shorter peptide, HBx-aa118-127, inhibits HBV replication. These results provide crucial structural and functional insights into drug designs for inhibiting HBV replication and treating HBV patients.
Objectives
To evaluate the clinical efficacy of a high‐efficiency air purifier in patients with allergic rhinitis.
Design
We conducted a randomised, double‐blind, clinical controlled trial with ...active and inactive versions of an air purifier. Our study included patients with allergic rhinitis who were sensitive to Artemisia pollen and treatment of the indoor environment using air filtration at night. We evaluated the clinical efficacy of indoor air filtration during the Artemisia pollen scattering season in Yulin City in Shanxi Province, China.
Setting
The First Hospital of Yulin (Yulin City, Shanxi Province, China).
Participants
A total of 90 patients with allergic rhinitis who were sensitive to allergens of Artemisia pollen were randomly assigned to one of two groups in equal numbers.
Main outcome measures
The primary outcome measure was the difference in visual analogue scale scores from baseline. Secondary outcomes were changes from baseline in nasal symptoms, allergy symptom scores, responses to the Rhinoconjunctivitis Quality of Life Questionnaire, Epworth Sleepiness Scale scores and tolerability scores for the air purifier.
Results
Based on the allergy symptom score, we found significant differences in rhinitis symptoms between the groups who used the active versus the inactive air purifier.
Conclusions
The results of our investigation demonstrated the health benefits of particle filtration.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Phthalic acid esters (PAEs) are a group of recalcitrant and hazardous organic compounds that pose a great threat to both ecosystem and human beings. A novel endophytic strain YJB3 that could utilize ...a wide range of PAEs as the sole carbon and energy sources for cell growth was isolated from Canna indica root tissue. It was identified as Bacillus megaterium based on morphological characteristics and 16S rDNA sequence homology analysis. The degradation capability of the strain YJB3 was investigated by incubation in mineral salt medium containing di-n-butyl-phthalate (DBP), one of important PAEs under different environmental conditions, showing 82.5% of the DBP removal in 5days of incubation under the optimum conditions (acetate 1.2g·L−1, inocula 1.8%, and temperature 34.2°C) achieved by two-step sequential optimization technologies. The DBP metabolites including mono-butyl phthalate (MBP), phthalic acid (PA), protocatechuic acid (PCA), etc. were determined by GC–MS. The PCA catabolic genes responsible for the aromatic ring cleavage of PCA in the strain YJB3 were excavated by whole-genome sequencing. Thus, a degradation pathway of DBP by the strain YJB3 was proposed that MBP was formed, followed by PA, and then the intermediates were further utilized till complete degradation. To our knowledge, this is the first study to show the biodegradation of PAEs using endophyte. The results in the present study suggest that the strain YJB3 is greatly promising to act as a competent inoculum in removal of PAEs in both soils and crops.
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•This is the first study on the biodegradation of PAEs using endophyte.•A novel endophytic Bacillus megaterium YJB3 capable of degrading PAEs was isolated.•PAEs catabolic genes in the stain YJB3 were excavated by whole genome analysis.•The strain YJB3 is equipped with a complete degradation pathway of DBP.•The strain YJB3 is an ideal candidate for in situ removal of PAEs in soil and crop.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Allergic rhinitis (AR) is a worldwide health problem. Allergen avoidance is strongly recommended for AR patients. Air purification can reduce concentrations of particles in indoor air, including ...those of allergens. Air purifiers have been recommended by clinicians for AR patients, but few studies have focused on the removal of airborne allergens from home environments. Such studies have been limited by a lack of blinding, small samples, or a failure to measure allergen levels, disease activity, or a combination of these factors. This study investigates the efficacy of a high-efficiency air purifier in reducing disease activity in the homes of AR patients sensitive to the allergens produced by Artemisia (mugwort) pollen.
This is a randomized, double-blind, clinical controlled trial that will test active and inactive versions of an air purifier (Atmosphere®; Amway China). Sixty AR patients sensitive to the allergens produced by Artemisia pollen will be assigned randomly to two groups of equal numbers. All patients will undergo a 4-week treatment period and a 4-week observation period. Evaluation will be conducted at baseline (day 0) and on days 7, 14, 21, 28, and 56. The primary outcome measure will be the difference in visual analog scale scores from baseline. Secondary outcomes will be changes from baseline in nasal symptoms, allergy symptom scores, responses to the Rhinoconjunctivitis Quality of Life Questionnaire, Epworth Sleepiness Scale scores, and tolerability scores for the air purifier. Side effects of treatment will be recorded.
Reducing exposure to allergens can reduce the risk of conditions such as AR. We hypothesise that AR patients sensitive to the allergens produced by Artemisia pollen will not suffer symptoms in a pollen-free environment. AR patients can remove pollen from their homes using air purifiers, decreasing the risk of symptoms. We expect that our study results will provide reliable evidence for determining the effects of air-purification therapy.
ChiCTR-INR-17012481 . (Retrospectively registered 26 August 2017).
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Purpose
To evaluate the incidence, type and risk factors of cement leakage (CL) with cement-augmented pedicle screw instrumentation (CAPSI) in degenerative lumbosacral disease.
Methods
Two hundred ...and two patients using a total of 950 cement-augmented screws were enrolled. CL was classified into three types: type S: leakage via segmental veins; type B: leakage via basivertebral veins; and type I: leakage via pedicle screw instrumentation to paravertebral soft tissue. The age, gender, operation stage (primary or later stage), body mass index, bone mineral density, the number and type of augmented screw, the position of the tip of screw (lateral or internal part of vertebral body), the position of screw (left or right side), the volume of bone cement, location of the augmented vertebra (lumbar or sacrum), the type of CL and complications were recorded. Binary logistic regression correlation was used to analyze risk factors of veins leakage (type S and type B).
Results
The CL was observed in 165 patients (81.68%) and 335 screws (35.26%), leakage types of S, B and I were seen in 255 (76.12%), 77 (22.99%), and 30 (8.96%) of screws, respectively. Besides, double or multiple routes of leakage were seen in 27 screws. Number of augmented screw was a risk factor for vein leakage (OR 0.58; 95% CI 0.44–0.77;
P
= 0.000). Furthermore, the doses of cement (OR 0.79; 95% CI 0.61–0.99;
P
= 0.038) and the position of screw (OR 0.39; 95% CI 0.29–0.53;
P
= 0.000) were identified as risk factors for type S, and the doses of bone cement (OR 0.37; 95% CI 0.25–0.54;
P
= 0.000) and the position of the tip of screw (OR 0.07; 95% CI 0.04–0.13;
P
= 0.000) were risk factors for type B.
Conclusions
CAPSI bears a high risk of asymptomatic CL, with a higher rate of leakage into segmental veins and basivertebral veins. As is known, more augmented screws and larger doses of cement are risk factors for veins leakage (type S and type B), while the tip of screw approaching to the midline of the vertebral body is another risk factor to type B. Thus, the CL could be reduced by the amelioration of operative techniques and procedures.
Graphical abstract
These slides can be retrieved under Electronic Supplementary Material.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
High-Sr/Y granitoids in continental settings are sometimes erroneously regarded as the products derived from partial melting of thickened/delaminated mafic lower curst under relatively higher ...pressures (>1.5 GPa) in a collisional orogenic setting. In fact, multiple magmatic processes in the
-crustal magma system, such as recycling of antecrysts, crustal assimilation, and fractional crystallization, can create or modify the primary “adakitic” signature. As a result, the generation of adakitic magmas in continental settings remains controversial from a bulk-rock perspective. Here, we address the origin of adakitic plutonic rocks through geochemical and textural characterization of rock-forming minerals in the pyroxene-bearing Zhuyuan granodiorite, West Qinling, China. The Zhuyuan granodiorite formed in a post-collisional setting and primarily consists of resorbed orthopyroxene, three types of clinopyroxene, amphibole, two types of plagioclases, K-feldspar, biotite, and quartz. Type-1 Cpx has high X
(70.0–81.7). Type-2 Cpx displays normal zoning and decreasing X
(80.9 to 71.5) from the core to rim. Type-3 Cpx is reversely zoned, where the rims have higher X
(75.5–86.9), Ni, Cr, suggesting a recharge event. Orthopyroxene has high-Ni and -Cr contents, as well as high X
(80.9–82.8), indicative of antecrysts that grew in mafic magma reservoirs. The injection of magmas from different sources is supported by sieve-textured plagioclase and crystal size distributions of non-poikilitic amphibole. Finally, non-sieve textured plagioclase, biotite, K-feldspar, and quartz are late-crystallized phases, indicative of an orthocrystic origin. The melts in equilibrium with these orthocrysts display significantly higher Sr/Y values than the magma batches that crystallized other mafic phases (i.e., amphibole, clinopyroxene, and orthopyroxene). Thus, we propose that the system involved an initial high-Sr/Y melts in equilibrium with the orthocryst assemblage was generated by water-fluxed melting of intermediate to felsic sources. The addition of low Sr/Y non-orthocrysts (e.g., amphibole and pyroxene) and associated melt diluted the original “adakitic signal” in the magma reservoir and drove the bulk composition to more mafic values. Consequently, the Zhuyuan pyroxene-bearing granodiorite represents a mixture of crystals with diverse origins and distinct magma batches of various compositions (from felsic to mafic compositions). Our study emphasizes that the origin of adakitic granitoids cannot be clearly deciphered without geochemical analysis of the constituent minerals. We also suggest that Sr/Y values in plutons should be cautiously used in paleo-crustal thickness estimates in collisional settings because of possible open system scenarios as described here.
Insufficient cement distribution (ICD) in the fractured area has been advocated to be responsible for unsatisfied pain relief after percutaneous vertebroplasty (PVP) for osteoporotic vertebral ...compression fractures (OVCFs). However, little is known about risk factors for the occurrence of ICD.
The present study aimed to identify independent risk factors of the emergence of ICD.
A retrospective cohort study.
Department of spinal surgery, an affiliated hospital of a medical university.
Patients who underwent PVP for single-level OVCF from January 2012 to September 2014 and met this study's inclusion criteria were retrospectively reviewed. Associations of ICD with co-variates (age, gender, bone mass density with a T-score, amount of injected cement, cement leakage, fracture level, fracture age, fracture severity grade, and location of the fractured area) and the influence of ICD on pain relief were analyzed.
A total of 225 patients were included. ICD was found in 26 (11.6%) patients. Fractured area located in the superior portion of the index vertebra was significantly associated with occurrence of ICD. No further significant associations between the studied co-variates and emergence of ICD were seen in the adjusted analysis. In addition, patients with ICD had significantly higher immediate postoperative visual analog scale scores of back pain compared with those with sufficient cement distribution in the fractured area.
Location of the fractured area and cement distribution in the fractured area could not be evaluated quantitatively.
The incidence of ICD is higher in patients with the fractured area located in the superior portion of the index vertebra and ICD might be responsible for unsatisfied pain relief after PVP for OVCFs.
Percutaneous vertebroplasty, insufficient cement distribution, fractured area, risk factor, osteoporosis, vertebral compression fracture, spine, unsatisfied pain relief, cement augmentation.
This study aimed to investigate the therapeutic potential of monoclonal antibody (mAb) against HBV as a novel treatment approach to chronic hepatitis B (CHB) in mouse models.
Therapeutic effects of ...mAbs against various epitopes on viral surface protein were evaluated in mice mimicking persistent HBV infection. The immunological mechanisms of mAb-mediated viral clearance were systematically investigated.
Among 11 tested mAbs, a novel mAb E6F6 exhibited the most striking therapeutic effects in several HBV-persistent mice. Single-dose administration of E6F6 could profoundly suppress the levels of hepatitis B surface antigen (HBsAg) and HBV DNA for several weeks in HBV-transgenic mice. E6F6 regimen efficiently prevented initial HBV infection, and reduced viral dissemination from infected hepatocytes in human-liver-chimeric mice. E6F6-based immunotherapy facilitated the restoration of anti-HBV T-cell response in hydrodynamic injection (HDI)-based HBV carrier mice. Immunological analyses suggested that the Fcγ receptor-dependent phagocytosis plays a predominant role in E6F6-mediated viral suppression. Molecular analyses suggested that E6F6 recognises an evolutionarily conserved epitope (GPCK(R)TCT) and only forms a smaller antibody-viral particle immune complex with limited interparticle crosslinking when it binds to viral particles. This unique binding characteristic of E6F6 to HBV was possibly associated with its effective in vivo opsonophagocytosis for viral clearance.
These results provided new insight into understanding the therapeutic role and mechanism of antibody against persistent viral infection. The E6F6-like mAbs may provide a novel immunotherapeutic agent against human chronic HBV infection.
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