Recent advances and progress on the design, fabrication and biomedical applications of Gallium liquid metals-based functional materials.

Gallium (Ga) is a well-known liquid metals (LMs) that possesses the features, such as fluidity, low viscosity, high electrical and thermal conductivity, and relative low toxicity. Owing to the weak interactions between Ga atoms, Ga LMs can be adopted for fabrication of various Ga LMs-based functional materials via ultrasonic treatment and mechanical grinding. Moreover, many organic compounds/polymers can be coated on the surface of LMs-based materials through coordination between oxidized outlayers of Ga LMs and functional groups of organic components. Over the past decades, different strategies have been reported for synthesizing Ga LMs-based functional materials and their biomedical applications have been intensively investigated. Although some review articles have published over the past few years, a concise review is still needed to advance the latest developments in biomedical fields. The main context can be majorly divided into two parts. In the first section, various strategies for fabrication of Ga LMs-based functional materials via top-down strategies were introduced and discussed. Following that, biomedical applications of Ga LMs-based functional materials were summarized and design Ga LMs-based functional materials with enhanced performance for cancer photothermal therapy (PTT) and PTT combined therapy were highlighted. We trust this review article will be beneficial for scientists to comprehend this promising field and greatly advance future development for fabrication of other Ga LMs-based functional materials with better performance for biomedical applications.

Light influences the effect of exogenous ethylene on the phenolic composition of Cabernet Sauvignon grapes.

The gaseous phytohormone ethylene (ETH) plays a key role in plant growth and development, and is a major regulator of phenolic biosynthesis. Light has long been known to influence phytohormone signaling transduction. However, whether light influences the effect of ETH on the phenolic composition of grapes (Vitis vinifera L.) is an open question. Here, the accumulation and composition of anthocyanins and non-anthocyanin phenolics were analyzed in Cabernet Sauvignon grapes under four treatments: light exposure with and without ETH treatment, and box-shading with and without ETH treatment. Both light and ETH promoted ripening, decreased the color index (L*, C*, and h*), and accelerated the color change from green to red and purplish red. Sunlight-exposed grapes had the highest contents of most anthocyanins, flavonols, flavan-3-ols, and hydroxybenzoic acids. In addition, light exposure increased the ratios of 3'5'-substituted/3'-substituted anthocyanins and flavonols, but decreased the ratios of methoxylated/non-methoxylated and acylated/non-acylated anthocyanins and flavan-3-ols. Notably, the effects of ETH were influenced by light exposure. Specifically, ETH treatment promoted anthocyanin and non-anthocyanin biosynthesis in light-exposed grapes, and their increasing multiples were remarkably higher under light-exposed conditions. Furthermore, ETH treatment decreased the ratios of methoxylated/non-methoxylated, 3'5'-substituted/3'-substituted, and acylated/non-acylated anthocyanins and flavan-3-ols in light-exposed grapes, each of which was increased by ETH treatment in shaded grapes. Fifteen differential phenolic components were identified through partial least-squares-discriminant analysis (PLS-DA). Among them, cyanidin-3-O-(cis-6-O-coumaryl)-glucoside, petunidin-3-O-(6-O-acetyl)-glucoside, petunidin-3-O-(trans-6-O-coumaryl)-glucoside, petunidin-3-O-glucoside, myricetin-3-O-galactoside, kaempferol-3-O-galactoside, and kaempferol-3-O-glucoside were the main differential components between ETH treatments under different light conditions. This study contributes to the understanding of the impact of ethylene treatment under dark and light conditions on phenolic synthesis in grape berries.

Effects of full shading of clusters from véraison to ripeness on fruit quality and volatile compounds in Cabernet Sauvignon grapes.

Sunlight exposure of grape clusters is frequently reported to influence grape aromas greatly. Among them, the effects of full shading (FS) of clusters on fruit quality and volatile compounds in grape berries has scarcely been investigated. In the present study, the effects of FS from véraison to ripeness on fruit quality and volatile compounds in Cabernet Sauvignon grapes were studied. The results showed that FS treatment reduced fruit size and berry weight, delayed fruit maturity, and decreased the contents of anthocyanins, phenols, and tannins in grape berries. In addition, volatile compounds in grape berries were analyzed, and 55 and 53 volatile compounds were detected in the control (CK) and FS groups, respectively. The results indicated that the concentrations of straight-chain fatty aldehydes, straight-chain fatty alcohols, straight-chain fatty acids, and branched-chain fatty acids, norisoprenoids, and total concentration of volatile compounds were all higher in FS group than in CK group. Specifically, FS treatment had significant promoting effects on the concentrations of ß-damascenone, terpineol, 2-ethyl-1-hexanol, and 2-hexenal, and remarkably decreased the concentrations of geranial, benzeneacetaldehyde, neral, and ethyl acetate. Partial least squares-discriminant analysis (PLS-DA) revealed a clear separation between the control (CK) and FS groups, and showed that 2-hexenal and hexanal were the main characteristic aroma compounds in the FS group. Moreover, an increase in the intensity of fruity, herbaceous, floral, and mushroom aromas was recorded in FS grapes. This study provides new insights into the effects of the exclusion of sunlight exposure on volatile compound accumulation in grape berries.

One-step synthesis of a dual-functional AIE-active probe for ClO- detection and photodynamic therapy.

An amphiphilic fluorescent probe (BHSMP) with aggregation-induced emission (AIE) features was synthesized via a one-step route. The probe showed high water dispersibility, low toxicity and the ability of selective and sensitive (limit of detection of 0.11 µM) detection of ClO- with fast-response (≤30 s) in aqueous solution and living organisms. Owing to the donor-acceptor (D-A) structure and existence of cationic groups, BHSMP could also generate reactive oxygen species under light-irradiation and potentially be utilized for photodynamic therapy. The strategy described in this work is of great significance for the design and synthesis of multifunctional AIE-active functional materials to facilitate their biomedical applications.

Identification of WUSCHEL-related homeobox gene and truncated small peptides in transformation efficiency improvement in Eucalyptus.

BACKGROUND: The WUSCHEL-related Homeobox (WOX) genes, which encode plant-specific homeobox (HB) transcription factors, play crucial roles in regulating plant growth and development. However, the functions of WOX genes are little known in Eucalyptus, one of the fastest-growing tree resources with considerable widespread cultivation worldwide. RESULTS: A total of nine WOX genes named EgWOX1-EgWOX9 were retrieved and designated from Eucalyptus grandis. From the three divided clades marked as Modern/WUS, Intermediate and Ancient, the largest group Modern/WUS (6 EgWOXs) contains a specific domain with 8 amino acids: TLQLFPLR. The collinearity, cis-regulatory elements, protein-protein interaction network and gene expression analysis reveal that the WUS proteins in E. grandis involve in regulating meristems development and regeneration. Furthermore, by externally adding of truncated peptides isolated from WUS specific domain, the transformation efficiency in E. urophylla × E. grandis DH32-29 was significant enhanced. The transcriptomics data further reveals that the use of small peptides activates metabolism pathways such as starch and sucrose metabolism, phenylpropanoid biosynthesis and flavonoid biosynthesis. CONCLUSIONS: Peptides isolated from WUS protein can be utilized to enhance the transformation efficiency in Eucalyptus, thereby contributing to the high-efficiency breeding of Eucalyptus.

Novel one-pot strategy for fabrication of a pH-Responsive bone-targeted drug self-frame delivery system for treatment of osteoporosis.

Osteoporosis (OP) is a systemic metabolic orthopedic disorder prevalent in elderly people, that is characterized by a decrease in bone mass. Although many therapeutics have been adopted for OP treatment, many of them are still not well satisfied clinical requirements and therefore development of novel therapeutics is of great significance. In this work, a novel bone-targeting drug self-frame delivery system (DSFDS) with high drug loading efficiency and pH responsive drug release was fabricated by condensation of curcumin (Cur), amino group terminated polyethylene glycol (NH2-PEG), and alendronate (ALN) using hexachlorocyclotriphosphonitrile (HCCP) as the linker. The final product named as HCCP-Cur-PEG-ALN (HCPA NPs) displayed excellent water dispersity with small size (181.9 â€‹± â€‹25.9 â€‹nm). Furthermore, the drug loading capacity of Cur can reach 25.8%, and Cur can be released from HCPA NPs under acidic environment. Owing to the introduction of ALN, HCPA NPs exhibited strong binding to HAp in vitro and excellent bone-targeting effect in vivo. Results from cellular and biochemical analyses revealed that HCPA NPs could effectively inhibit the formation and differentiation function of osteoclasts. More importantly, we also demonstrated that HCPA NPs could effectively reduce bone loss in OVX mice with low toxicity to major organs. The above results clearly demonstrated that HCPA NPs are promising for OP treatment. Given the simplicity and well designability of fabrication strategy, explicit therapy efficacy and low toxicity of HCPA NPs, we believe that this work should be of great interest for fabrication of various DSFDS to deal with many diseases.

Significantly enhanced lithium-ion conductivity of solid-state electrolytes via flower-like structured lamellar metal-organic frameworks with open metal sites.

Solid-state electrolytes (SSEs) are a frontier topic in battery technology with the potential to solve the safety problem of lithium ion batteries (LIBs). Metal organic frameworks (MOFs) are regarded as promising candidates for a new type of solid-state ion conductor, but the low ionic conductivity and unstable interface contact still seriously hinder the application of MOF based solid state electrolytes (SSEs). Herein, a HKUST-1 based solid-state electrolyte (SSE) was designed and prepared, which possess both a flower-like lamellar structure and sufficient accessible open metal sites (OMSs). These sites could capture anions and release free lithium ions (Li+), and the ultra-thin thickness shortened the Li+ transmission path. The lamellar HKUST-1 exhibits an ionic conductivity of 1.6 × 10-3 S cm-1 at 25 °C with an activation energy of 0.12 eV, Li-ion transference number of 0.73 and electrochemical stability window of 0-5.5 V. The MOF based electrolyte has been assessed with Li|MOFs|LiFePO4 cells at 25 °C, which showed a high capacity retention of 93% at 0.1C after 100 cycles and excellent rate capability. It also exhibited excellent cycle stability in Li symmetric cells. This Li+ conduction strategy of modulating the morphology and modifying pore walls provides a new research idea for designing advanced SSEs.

Geographic-genomic and geographic-phenotypic differentiation of the Aquilegia viridiflora complex.

How species diverge into different lineages is a central issue in evolutionary biology. Despite the increasing evidence indicating that such divergences do not need geographic isolation, the correlation between lineage divergence and the adaptive ecological divergence of phenotype corresponding to distribution is still unknown. In addition, gene flow has been widely detected during and through such diverging processes. We used one widely distributed Aquilegia viridiflora complex as a model system to examine genomic differentiation and corresponding phenotypic variations along geographic gradients. Our phenotypic analyses of 20 populations from northwest to northeast China identified two phenotypic groups along the geographic cline. All examined traits are distinct from each other, although a few intermediate individuals occur in their contacting regions. We further sequenced the genomes of representative individuals of each population. However, four distinct genetic lineages were detected based on nuclear genomes. In particular, we recovered numerous genetic hybrids in the contact regions of four lineages. Gene flow is widespread and continuous between four lineages but much higher between contacting lineages than geographically isolated lineages. Gene flow and natural selection might result in inconsistency between heredity and phenotype. Moreover, many genes with fast lineage-specific mutations were identified to be involved in local adaptation. Our results suggest that both geographic isolation and local selection exerted by the environment and pollinators may together create geographic distributions of phenotypic variations as well as the underlying genomic divergences in numerous lineages.

A Strategy to Enhance the Ferroelectric Behavior of MOF-802(Hf) via Doping Zr4+ Ions.

MOF ferroelectrics, as a crucial member of molecular ferroelectrics, have shown intriguing advantages owing to the designability of structures and tunability of physicochemical properties, which make them an appealing group of ferroelectric materials. However, the weak ferroelectric property still is a huge challenge for further development. Here, a series of Zr-doped MOF-802(Hf)s were successfully synthesized through doping Zr4+ ions into the parent MOF-802(Hf) to improve ferroelectric properties. The well-shaped P-E hysteresis loops of Zr-doped MOF-802(Hf)s illustrate their ferroelectricity, and ferroelectric properties are effectively enhanced compared with the parent MOF-802(Hf). What's more, remanent polarization reaches 0.511 µC/cm2 when the concentration of Zr4+ ions is 5%, which is 5 times higher than that of the parent MOF-802(Hf) and is on par with some perovskite ferroelectrics. The increased ferroelectric performance is attributed to the enhanced polarity of the whole structure triggered by lattice distortion when Hf4+ ions of the parent MOF-802(Hf) are substituted by Zr4+ ions. As far as we know, this is the first report on Hf-MOF exhibiting improved ferroelectric behaviors through doping metal ions into lattice nodes. This work demonstrates that introducing the second metal ions into lattice nodes of MOFs is an efficacious approach for exploiting MOF ferroelectrics with superior performance.

[Retracted] MicroRNA­329 serves a tumor suppressive role in colorectal cancer by directly targeting transforming growth factor beta­1.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the cell migration and invasion assay data shown in Figs. 2C and 5C were strikingly similar to data appearing in different form in other articles by different authors at different research institutes. Owing to the fact that the contentious data in the above article were already under consideration for publication prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 16: 3825­3832, 2017; DOI: 10.3892/mmr.2017.7077].

A dual-function probe with aggregation-induced emission feature for Cu2+ detection and chemodynamic therapy.

Herein, a fluorescent probe (named TPACP) with aggregation-induced emission (AIE) feature was developed and utilized for the selective detection of Cu2+ with high sensitivity and fast-response. The resultant TPACP@Cu2+ complexes from coordination of TPACP with Cu2+ can also be potentially applied for chemodynamic and photodynamic therapy.

Effective Enhancement of the Ferroelectric Performance of Polar Co-Gallate MOF by Doping M2+ Ions (M = Mg, Mn, Ni) into Framework Nodes.

MOF ferroelectrics have been demonstrated to be a promising candidate owing to various structures and controllable properties. However, weak ferroelectricity hampers their boom. Herein, a convenient strategy, doping metal ions into the framework nodes of parent MOF, is adopted to enhance ferroelectric performance. A series of M-doped Co-Gallate (M = Mg, Mn, Ni) were synthesized to improve ferroelectric properties. The electrical hysteresis loop demonstrated its ferroelectric behaviors, exhibiting obviously improved ferroelectric properties compared with the parent Co-Gallate. The remanent polarization was enhanced by two times for Mg-doped Co-Gallate, six times for Mn-doped Co-Gallate, and four times for Ni-doped Co-Gallate. The promoted ferroelectric performances are ascribed to the enhanced polarity of the overall structure triggered by framework distortion. Intriguingly, ferroelectric behaviors increase in the order Mg < Ni < Mn, displaying the same tendency as the difference value in the ionic radius between Co2+ ions and M2+ metal ions (M = Mg, Mn, Ni). These results demonstrate doping of metal ions is a valid strategy to enhance ferroelectric performances, which may serve as a guide in modulating ferroelectric behaviors.

Genome-Wide Analysis of the FBA Subfamily of the Poplar F-Box Gene Family and Its Role under Drought Stress.

F-box proteins are important components of eukaryotic SCF E3 ubiquitin ligase complexes, which specifically determine protein substrate proteasomal degradation during plant growth and development, as well as biotic and abiotic stress. It has been found that the FBA (F-box associated) protein family is one of the largest subgroups of the widely prevalent F-box family and plays significant roles in plant development and stress response. However, the FBA gene family in poplar has not been systematically studied to date. In this study, a total of 337 F-box candidate genes were discovered based on the fourth-generation genome resequencing of P. trichocarpa. The domain analysis and classification of candidate genes revealed that 74 of these candidate genes belong to the FBA protein family. The poplar F-box genes have undergone multiple gene replication events, particularly in the FBA subfamily, and their evolution can be attributed to genome-wide duplication (WGD) and tandem duplication (TD). In addition, we investigated the P. trichocarpa FBA subfamily using the PlantGenIE database and quantitative real-time PCR (qRT-PCR); the results showed that they are expressed in the cambium, phloem and mature tissues, but rarely expressed in young leaves and flowers. Moreover, they are also widely involved in the drought stress response. At last, we selected and cloned PtrFBA60 for physiological function analysis and found that it played an important role in coping with drought stress. Taken together, the family analysis of FBA genes in P. trichocarpa provides a new opportunity for the identification of P. trichocarpa candidate FBA genes and elucidation of their functions in growth, development and stress response, thus demonstrating their utility in the improvement of P. trichocarpa.

Design, Synthesis, and Bioevaluation of Pyrido[2,3-d]pyrimidin-7-ones as Potent SOS1 Inhibitors.

The use of small molecular modulators to target the guanine nucleotide exchange factor SOS1 has been demonstrated to be a promising strategy for the treatment of various KRAS-driven cancers. In the present study, we designed and synthesized a series of new SOS1 inhibitors with the pyrido[2,3-d]pyrimidin-7-one scaffold. One representative compound 8u showed comparable activities to the reported SOS1 inhibitor BI-3406 in both the biochemical assay and the 3-D cell growth inhibition assay. Compound 8u obtained good cellular activities against a panel of KRAS G12-mutated cancer cell lines and inhibited downstream ERK and AKT activation in MIA PaCa-2 and AsPC-1 cells. In addition, it displayed synergistic antiproliferative effects when used in combination with KRAS G12C or G12D inhibitors. Further modifications of the new compounds may give us a promising SOS1 inhibitor with favorable druglike properties for use in the treatment of KRAS-mutated patients.

Effectiveness of a Protocol Intervention for Aspiration Pneumonia Prevention in Patients With Esophageal Cancer During Concurrent Chemoradiotherapy: A Randomized Control Trial.

BACKGROUND: Dysphagia is a leading cause of aspiration pneumonia and negatively affects tolerance of chemoradiotherapy in patients with esophageal cancer. OBJECTIVE: This study aimed to assess a protocol for preventing the occurrence of aspiration pneumonia for adult patients with esophageal cancer experiencing swallowing dysfunction. METHODS: This study tested a dysphagia intervention that included high-risk patients confirmed by the Eating Assessment Tool questionnaire and Water Swallowing Test. A protocol guide (Interventions for Esophageal Dysphagia [IED]) to prevent aspiration pneumonia during chemoradiotherapy was also implemented. Thirty participants were randomly assigned to an intervention or control group. The study period was 50 days; participants were visited every 7 days for a total of 7 times. Instruments for data collection included The Eating Assessment Tool, Water Swallowing Test, and personal information. The IED was administered only to the experimental group. All data were managed using IBM SPSS statistics version 21.0. RESULTS: The IED significantly reduced the occurrence of aspiration pneumonia (P = .012), delayed the onset of aspiration pneumonia (P = .005), and extended the survival time (P = .007) in the experimental group. CONCLUSION: For patients with esophageal cancer undergoing chemoradiotherapy, this protocol improved swallowing dysfunction and reduced aspiration pneumonia. IMPLICATION FOR PRACTICE: The IED protocol should be included in continuous educational training for clinical nurses to help them become familiar with these interventions and to provide these strategies to patients.

Efficacy and safety of janagliflozin monotherapy in Chinese patients with type 2 diabetes mellitus inadequately controlled on diet and exercise: A multicentre, randomized, double-blind, placebo-controlled, Phase 3 trial.

AIMS: To evaluate the efficacy and safety of janagliflozin, a selective renal sodium-glucose cotransporter-2 inhibitor, as monotherapy in drug-naive Chinese patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: This Phase 3 trial included a 24-week, multicentre, randomized, double-blind, placebo-controlled period, followed by a 28-week extension period. A total of 432 patients with glycated haemoglobin (HbA1c) levels ≥7.0% (53 mmol/mol) and ≤10.5% (91 mmol/mol) were randomized (1:1:1) to receive once-daily placebo, 25 mg or 50 mg janagliflozin. After 24 weeks, patients on placebo were switched and re-randomized (1:1) to 25 mg or 50 mg janagliflozin, whereas patients on janagliflozin maintained the initial therapy. The primary endpoint was change from baseline in HbA1c after 24 weeks. RESULTS: At Week 24, the placebo-adjusted least squares mean changes in HbA1c were -0.80% (95% confidence interval [CI] -0.98% to -0.62%)/-8.7 mmol/mol (95% CI -10.7 mmol/mol to -6.8 mmol/mol) and -0.88% (95% CI -1.06% to -0.70%)/-9.6 mmol/mol (95% CI -11.6 mmol/mol to -7.7 mmol/mol), respectively (P < 0.001 for both). A higher proportion of patients achieved HbA1c <7.0% (53 mmol/mol) with janagliflozin 25 mg and janagliflozin 50 mg compared with placebo (47.2%, 49.3%, and 23.5%, respectively). Both janagliflozin doses significantly decreased fasting plasma glucose, 2-hour postprandial glucose, body weight and systolic blood pressure, as well as increased high-density lipoprotein (HDL) cholesterol and insulin sensitivity compared with placebo (P < 0.05 for all). The trends in improvement of these variables were sustained during the 28-week extension period. Overall incidences of adverse events were 67.8%, 71.5% and 60.7% with janagliflozin 25 mg, janagliflozin 50 mg and placebo, respectively. The incidence of urinary tract infections and genital fungal infections was low. No severe hypoglycaemia or ketoacidosis occurred. CONCLUSIONS: Janagliflozin 25 mg and 50 mg monotherapy once-daily effectively improved glycaemic control, reduced body weight and blood pressure, improved HDL cholesterol and insulin sensitivity, and was generally well tolerated.

Updated Confirmatory Diagnosis for Mucopolysaccharidoses in Taiwanese Infants and the Application of Gene Variants.

Mucopolysaccharidosis (MPS) is a lysosomal storage disease caused by genetic defects that result in deficiency of one specific enzyme activity, consequently impairing the stepwise degradation of glycosaminoglycans (GAGs). Except for MPS II, the other types of MPS have autosomal recessive inheritance in which two copies of an abnormal allele must be present in order for the disease to develop. In this study, we present the status of variant alleles and biochemistry results found in infants suspected of having MPS I, II, IVA, and VI. A total of 324 suspected infants, including 12 for MPS I, 223 for MPS II, 72 for MPS IVA, and 17 for MPS VI, who were referred for MPS confirmation from newborn screening centers in Taiwan, were enrolled. In all of these infants, one specific enzyme activity in dried blood spot filter paper was lower than the cut-off value in the first blood sample, as well asin a second follow-up sample. The confirmatory methods used in this study included Sanger sequencing, next-generation sequencing, leukocyte enzyme fluorometric assay, and GAG-derived disaccharides in urine using tandem mass spectrometry assays. The results showed that five, nine, and six infants had MPS I, II, and IVA, respectively, and all of them were asymptomatic. Thus, a laboratory diagnosis is extremely important to confirm the diagnosis of MPS. The other infants with identified nucleotide variations and reductions in leukocyte enzyme activities were categorized as being highly suspected cases requiring long-term and intensive follow-up examinations. In summary, the final confirmation of MPS depends on the most powerful biomarkers found in urine, i.e., the quantification of GAG-derived disaccharides including dermatan sulfate, heparan sulfate, and keratan sulfate, and analysis of genetic variants can help predict outcomes and guide treatment.

Newborn Screening Program for Mucopolysaccharidosis Type II and Long-Term Follow-Up of the Screen-Positive Subjects in Taiwan.

BACKGROUND: Mucopolysaccharidosis II (MPS II) is an X-linked disorder resulting from a deficiency in lysosomal enzyme iduronate-2-sulfatase (IDS), which causes the accumulation of glycosaminoglycans (GAGs) in the lysosomes of many tissues and organs, leading to progressive cellular dysfunction. An MPS II newborn screening program has been available in Taiwan since 2015. The aim of the current study was to collect and analyze the long-term follow-up data of the screen-positive subjects in this program. METHODS: From August 2015 to April 2022, 548,624 newborns were screened for MPS II by dried blood spots using tandem mass spectrometry, of which 202 suspected infants were referred to our hospital for confirmation. The diagnosis of MPS II was confirmed by IDS enzyme activity assay in leukocytes, quantitative determination of urinary GAGs by mass spectrometry, and identification of the IDS gene variant. RESULTS: Among the 202 referred infants, 10 (5%) with seven IDS gene variants were diagnosed with confirmed MPS II (Group 1), 151 (75%) with nine IDS gene variants were classified as having suspected MPS II or pseudodeficiency (Group 2), and 41 (20%) with five IDS gene variants were classified as not having MPS II (Group 3). Long-term follow-up every 6 months was arranged for the infants in Group 1 and Group 2. Intravenous enzyme replacement therapy (ERT) was started in four patients at 1, 0.5, 0.4, and 0.5 years of age, respectively. Three patients also received hematopoietic stem cell transplantation (HSCT) at 1.5, 0.9, and 0.6 years of age, respectively. After ERT and/or HSCT, IDS enzyme activity and the quantity of urinary GAGs significantly improved in all of these patients compared with the baseline data. CONCLUSIONS: Because of the progressive nature of MPS II, early diagnosis via a newborn screening program and timely initiation of ERT and/or HSCT before the occurrence of irreversible organ damage may lead to better clinical outcomes. The findings of the current study could serve as baseline data for the analysis of the long-term effects of ERT and HSCT in these patients.

Fabrication of chitosan based luminescent nanoprobe with aggregation-induced emission feature through ultrasonic treatment.

Chitosan is an abundant natural polysaccharide that contains a lot of amino and hydroxyl groups. It possesses great potential for biomedical applications owing to its low toxicity, biodegradability and low cost. Herein, a novel chitosan-based fluorescent copolymer (WS-CS-TPA) was designed and synthesized via nucleophilic substitution of hexachlorocyclotriphosphazene (HCCP), water-soluble chitosan (WS-CS) and an aggregation-induced emission (AIE) fluorogen (AIEgen) triphenylamine derivative (TPA-NH2). Under ultrasonic treatment, 1.16 g TPA-NH2 and 1.1 g WS-CS can be conjugated by 0.7 g HCCP at room temperature. The obtained copolymer shows amphiphilic property and could assemble into nanoparticles with size about 100 nm. After self-assembly, TPA-NH2 was aggregated in the core, thus exhibiting superb AIE feature with intense green fluorescence emission in aqueous media. On the other hand, hydrophilic WS-CS was coated on the surface of nanoparticles and endowed their high water dispersibility. Results from preliminary biological assays suggested that WS-CS-TPA can be internalized by cells and exhibits low cytotoxicity, suggesting their great potential for biological imaging and intracellular drug delivery.

PeTGA1 enhances disease resistance against Colletotrichum gloeosporioides through directly regulating PeSARD1 in poplar.

Basic leucine zipper (bZIP) proteins play important roles in responding to biotic and abiotic stresses in plants. However, the molecular mechanisms of plant resistance to pathogens remain largely unclear in poplar. The present study isolated a TGACG-binding (TGA) transcription factor, PeTGA1, from Populus euphratica. PeTGA1 belongs to subgroup D of the bZIP family and was localized to the nucleus. To study the role PeTGA1 plays in response to Colletotrichum gloeosporioides, transgenic triploid white poplars overexpressing PeTGA1 were generated. Results showed that poplars with overexpressed PeTGA1 showed a higher effective defense response to C. gloeosporioides than the wild-type plants. A yeast one-hybrid assay and an electrophoretic mobility shift assay revealed that PeTGA1 could directly bind to the PeSARD1 (P. euphratica SYSTEMIC ACQUIRED RESISTANCE DEFICIENT 1) promoter, an important regulator for salicylic acid biosynthesis. The transactivation assays indicated that PeTGA1 activated the expression of PeSARD1, and PR1 (PATHOGENESIS-RELATED 1), a SA marker gene involved in SA signaling. Subsequently, we observed that the PeTGA1 overexpression lines showed elevated SA levels, thereby resulting in the increased resistance to C. gloeosporioides. Taken together, our results indicated that PeTGA1 may exert a key role in plant immunity not only by targeting PeSARD1 thus participating in the SA biosynthesis pathway but also by involving in SA signaling via activating the expression of PR1.