Absolute Quantitative Lipidomics Reveals Different Granule-Associated Surface Lipid Roles in the Digestibility and Pasting of Waxy, Normal, and High-Amylose Rice Starches.

Granule-associated surface lipids (GASLs) and internal lipids showed different lipid-amylose relationships, contents, and distributions, suggesting their differing biological origins and functions, among waxy, normal, and high-amylose rice starch. The GASL content mainly depended on the pore size, while internal lipids regulated starch biosynthesis, as indicated by correlations of internal lipids with the chain length distribution of amylopectin and amylose content. Of the 1346 lipids detected, 628, 562, and 408 differentially expressed lipids were observed between normal-waxy, high-amylose-waxy, and normal-high-amylose starch, respectively. After the removal of GASLs, the higher lysophospholipid content induced greater decreases in the peak and breakdown viscosity and swelling power, while the highest digestibility increase was found with the highest triacylglycerol content. Thus, different GASL compositions led to different digestibility, swelling, and pasting outcomes. This study sheds new light on the mechanism of the role of GASLs in the structure and properties of starch, as well as in potential modifications and amyloplast membrane development.

Construction of glutathione-responsive paclitaxel prodrug nanoparticles for image-guided targeted delivery and breast cancer therapy.

Paclitaxel (PTX) remains an essential drug in the treatment of breast cancer. To improve metabolic stability and real-time monitoring of drug location, we develop a visualized nano-prodrug. Novel hyaluronic acid (HA)-coated glutathione (GSH)-sensitive chitosan (CS)-based nano-prodrug (HA/TPE-CS-SS-PTX NPs) with aggregation-induced emission effects (AIE) were accomplished. The prodrug NPs (drug loading 29.32%, particle size 105 nm, regular sphericity) exhibit excellent fluorescence stability. The prodrug NPs could target tumor cells with high expression of CD44 and decompose in the presence of high concentrations of glutathione. In vitro evaluations revealed that the prodrug NPs have significant cytotoxicity on 4T1 cells, and due to their excellent AIE characteristics, their position in cells can be tracked. Moreover, the prodrug NPs also shown superior anti-tumor effects in vivo experimental. Overall, the HA/TPE-CS-SS-PTX NPs we constructed have excellent bio-imaging capabilities and can be served as a potential nanomedicine for PTX delivery against breast cancer.

Heat-moisture treated waxy highland barley starch: Roles of starch granule-associated surface lipids, temperature and moisture.

Roles of temperature, moisture and starch granule-associated surface lipids (SGASL) during heat-moisture treatment (HMT) of waxy highland barley starch were elucidated. Starch without SGASL showed a higher increase in ratio (1016/993 cm-1) (0.095-0.121), lamellar peak area (88), radius of gyration (Rg1, 0.9-1.8 nm) and power-law exponents (0.19-0.42) than native starch (0.038-0.047, 46, 0.1-0.6 nm, 0.04-0.14), upon the same increase in moisture or temperature. Thus, removing SGASL promoted HMT. However, after HMT (30 % moisture, 120 °C), native starch showed lower relative crystallinity (RC, 11.67 %) and lamellar peak area (165.0), longer lamellar long period (L, 14.99 nm), and higher increase in peak gelatinization temperature (9.2-13.3 °C) than starch without SGASL (12.04 %, 399.2, 14.52 nm, 4.7-6.1 °C). This suggested that the resulting SGASL-amylopectin interaction further destroyed starch structure. Starch with and without SGASL showed similar trends in RC, lamellar peak area, L and Rg1 with increasing temperature, but different trends with increasing moisture, suggesting that removing SGASL led to more responsiveness to the effects of increasing moisture. Removing SGASL resulted in similar trends (RC and lamellar peak area) with increasing moisture and temperature, suggesting that the presence of SGASL induced different effects on moisture and temperature.

Impact of Six Extraction Methods on Molecular Composition and Antioxidant Activity of Polysaccharides from Young Hulless Barley Leaves.

Young hulless barley leaves are gaining recognition for potential health benefits, and the method of extracting polysaccharides from them is critical for potential food industry applications. This study delves into a comparative analysis of six distinct fiber extraction techniques: hot water extraction; high-pressure steam extraction; alkaline extraction; xylanase extraction; cellulase extraction; and combined xylanase and cellulase extraction. This analysis included a thorough comparison of polysaccharide-monosaccharide composition, structural properties, antioxidant activities (DPPH, ABTS, and FRAP), and rheological properties among fibers extracted using these methods. The results underscore that the combined enzymatic extraction method yielded the highest extraction yield (22.63%), while the rest of the methods yielded reasonable yields (~20%), except for hot water extraction (4.11%). Monosaccharide composition exhibited divergence across methods; alkaline extraction yielded a high abundance of xylose residues, whereas the three enzymatic methods demonstrated elevated galactose components. The extracted crude polysaccharides exhibited relatively low molecular weights, ranging from 5.919 × 104 Da to 3.773 × 105 Da across different extraction methods. Regarding antioxidant activities, alkaline extraction yielded the highest value in the ABTS assay, whereas enzymatically extracted polysaccharides, despite higher yield, demonstrated lower antioxidant capacity. In addition, enzymatically extracted polysaccharides exerted stronger shear thinning behavior and higher initial viscosity.

Oxidative compensation mechanism of Fe-S synergetic inhibition of Cd activity in paddy field during flooding and drainage.

It is known that the transformation of Fe and S forms in soil affects the migration and activity of Cd, but the coordinated regulation of Cd activity by Fe and S under different redox conditions is still unclear. Here, Diffusive gradients in thin films (DGT), an in-situ monitoring technique, is used to explore the difference of the regulation of Cd activity in paddy fields with ferrihydrite (FH) and ferrihydrite coprecipitated by sulfate (FH-S) under the flooding and drainage conditions. The addition of FH-S and FH significantly reduced the activity of Cd (Dissolved, Exchanged, and CDGT-Cd). Compared with pure FH, the adsorption extent of Cd in FH was enhanced by increasing concentrations of SO42- (i.e., S/Fe ratio), which is attributed to the decrease in the crystallinity of FH by sulfate. During soil flooding, the addition of FH-S promoted the production of metal sulfide (CdS and FeS/FeS2). The activity of Cd increased after drainage, while the FH-S treatment groups delayed the release of Cd. After 30 days of drainage, the concentration of Cd in FH-S treatment groups decreased by 28.9-44.1 % compared with the control group. The fresh FeS/FeS2 is not the main adsorbent for fixing Cd, and due to the existence of oxidation compensation mechanism, the preferential oxidation of FeS/FeS2 delays the release of Cd in the drainage stage. Our study shed new light on the mechanism of Fe-S synergistic regulation of Cd and remediation of Cd-contaminated soils.

Interrogation of dynamic glucose-enhanced MRI and fluorescence-based imaging reveals a perturbed glymphatic network in Huntington's disease.

Huntington's disease (HD) is a neurodegenerative disorder that presents with progressive motor, mental, and cognitive impairment leading to early disability and mortality. The accumulation of mutant huntingtin protein aggregates in neurons is a pathological hallmark of HD. The glymphatic system, a brain-wide perivascular network, facilitates the exchange of interstitial fluid (ISF) and cerebrospinal fluid (CSF), supporting interstitial solute clearance including abnormal proteins from mammalian brains. In this study, we employed dynamic glucose-enhanced (DGE) MRI to measure D-glucose clearance from CSF as a tool to assess CSF clearance capacity to predict glymphatic function in a mouse model of HD. Our results demonstrate significantly diminished CSF clearance efficiency in premanifest zQ175 HD mice. The impairment of CSF clearance of D-glucose, measured by DGE MRI, worsened with disease progression. These DGE MRI findings in compromised glymphatic function in HD mice were further confirmed with fluorescence-based imaging of glymphatic CSF tracer influx, suggesting an impaired glymphatic function in premanifest stage of HD. Moreover, expression of the astroglial water channel aquaporin-4 (AQP4) in the perivascular compartment, a key mediator of glymphatic function, was significantly diminished in both HD mouse brain as well as postmortem human HD brain. Our data, acquired using a clinically translatable MRI approach, indicate a perturbed glymphatic network in the HD brain as early as in the premanifest stage. Further validation of these findings in clinical studies should provide insights into potential of glymphatic clearance as a HD biomarker and for glymphatic functioning as a disease-modifying therapeutic target for HD.

Differential distribution of surface proteins/lipids between wheat A- and B-starch granule contributes to their difference in pasting and rheological properties.

The distribution of surface proteins/lipids and their effect on physicochemical properties of wheat A- and B-starch were investigated. Small B-starch with higher surface protein (~1.8 %) and lipid (~0.4 %) contents did not differ significantly from specific surface area of large A-starch (~0.2 % protein and ~0.1 % lipid), indicating surface lipids/proteins for starch are characteristic of their biological origin, not directly related to granule size. The surface of A-starch granule was an integrated membrane structure (lipids covered by proteins). B-starch showed a greater decrease in peak and trough viscosity (130 and 82 cP) than A-starch (99 and 52 cP) after removing surface proteins, perhaps because the presence of residual surface lipid as a membrane protected the rigidity of A-starch granule. B-starch showed a greater increase in consistency coefficient (K) (47.01 Pa·sn) than A-starch (20.33 Pa·sn) after removing surface lipids, possibly because the greater loss of surface lipid as complex with amylose in B-starch retarded retrogradation and reduced K. These results show that different distributions and contents of surface proteins/lipids between wheat A- and B-starch granule contribute to the pasting and rheological properties.

Early detection of exon 1 huntingtin aggregation in zQ175 brains by molecular and histological approaches.

Huntingtin-lowering approaches that target huntingtin expression are a major focus for therapeutic intervention for Huntington's disease. When the cytosine, adenine and guanine repeat is expanded, the huntingtin pre-mRNA is alternatively processed to generate the full-length huntingtin and HTT1a transcripts. HTT1a encodes the aggregation-prone and highly pathogenic exon 1 huntingtin protein. In evaluating huntingtin-lowering approaches, understanding how the targeting strategy modulates levels of both transcripts and the huntingtin protein isoforms that they encode will be essential. Given the aggregation-propensity of exon 1 huntingtin, the impact of a given strategy on the levels and subcellular location of aggregated huntingtin will need to be determined. We have developed and applied sensitive molecular approaches to monitor the levels of aggregated and soluble huntingtin isoforms in tissue lysates. We have used these, in combination with immunohistochemistry, to map the appearance and accumulation of aggregated huntingtin throughout the CNS of zQ175 mice, a model of Huntington's disease frequently chosen for preclinical studies. Aggregation analyses were performed on tissues from zQ175 and wild-type mice at monthly intervals from 1 to 6 months of age. We developed three homogeneous time-resolved fluorescence assays to track the accumulation of aggregated huntingtin and showed that two of these were specific for the exon 1 huntingtin protein. Collectively, the homogeneous time-resolved fluorescence assays detected huntingtin aggregation in the 10 zQ175 CNS regions by 1-2 months of age. Immunohistochemistry with the polyclonal S830 anti-huntingtin antibody showed that nuclear huntingtin aggregation, in the form of a diffuse nuclear immunostain, could be visualized in the striatum, hippocampal CA1 region and layer IV of the somatosensory cortex by 2 months. That this diffuse nuclear immunostain represented aggregated huntingtin was confirmed by immunohistochemistry with a polyglutamine-specific antibody, which required formic acid antigen retrieval to expose its epitope. By 6 months of age, nuclear and cytoplasmic inclusions were widely distributed throughout the brain. Homogeneous time-resolved fluorescence analysis showed that the comparative levels of soluble exon 1 huntingtin between CNS regions correlated with those for huntingtin aggregation. We found that soluble exon 1 huntingtin levels decreased over the 6-month period, whilst those of soluble full-length mutant huntingtin remained unchanged, data that were confirmed for the cortex by immunoprecipitation and western blotting. These data support the hypothesis that exon 1 huntingtin initiates the aggregation process in knock-in mouse models and pave the way for a detailed analysis of huntingtin aggregation in response to huntingtin-lowering treatments.

Removing starch granule-associated surface lipids affects structure of heat-moisture treated hull-less barley starch.

The effects of starch granule-associated surface lipids removal on hull-less barley starch structure formed by heat-moisture treatment were investigated. Removing surface lipids made the peak at 2θ of 13° disappear and resulted in higher lamellar peak intensity after harsh treatment and a lower reduction in mass fractal dimension (from 2.49 to 2.43) and radius of gyration (from 24.3 to 24.0) when temperature increased from 100 to 120 °C at 20 % moisture. Treatment at 25 % moisture and 120 °C decreased relative crystallinity (from 15.73 % to 7.43 %) and Gaussian peak area (from 646.7 to 137.7) of native starch, and decreased relative crystallinity (from 14.24 % to 12.56 %) and Gaussian peak area (from 604.1 to 539.6) for starch without surface lipids. Different trends of change in lamellar thickness, linear crystallinity, peak temperatures, and enthalpy of gelatinization were observed among modified starches with increasing temperature and/or moisture content. These results demonstrate that removing surface lipids changes structure of heat-moisture treated starch.

Mechanisms of S cooperating with Fe and Mn to regulate the conversion of Cd and Cu during soil redox process revealed by LDHs-DGT technology.

The activity changes of Cd and Cu in paddy field were strongly influenced by the transformation of S, Fe and Mn species. However, in the process of soil redox, how S cooperates with Fe/Mn to regulate the law and mechanism of Cd and Cu speciation transformation still needs to be studied. In this study, we used DGT technology based on layer double hydroxides (LDHs) combined with pore water sampling to investigate soil redox changes, rice growth, and the effects of different forms of sulfur (S0, SO42-) on soil Cd and Cu activities. The results showed that the concentrations of CDGT-Cd and Cu in the soil decreased rapidly in the anaerobic stage, but increased slowly in the oxidative stage. Multiple regression analysis showed that the changes of Cu and Cd concentrations mainly depended on the changes of Fe/Mn morphology. Sulfur treatment promoted the dissolution of Fe/Mn oxides in the short term (<48 h), and the activities of CDGT-Fe, Mn, and Cd increased simultaneously, but CDGT-Cu was not affected. However, after long-term anaerobic conditions (>10 d), sulfur addition reduced the activities of CDGT-Cd and Cu, and decreased the uptake of Cd and Cu by rice. During sulfate reduction, the sulfur addition treatment group resulted in a 24.5-50.2 % decrease in CDGT-Fe, indicating that sulfur addition may delay the release of Cd and Cu after rice planting by promoting the formation of FeS/FeS2. In addition, in the anaerobic stage, Cu formed sulfide before Cd and was fixed, and the higher thermodynamic stability of CuS would promote the dissolution of CdS in the oxidation stage. Overall, soil flooding with sulfur to enhance the generation of metal sulfides and secondary iron ores provides an opportunity to use sulfur as an environmentally friendly modifier to coordinate Fe, Mn to improve heavy metal-contaminated soils.

An RNA-targeting CRISPR-Cas13d system alleviates disease-related phenotypes in Huntington's disease models.

Huntington's disease (HD) is a fatal, dominantly inherited neurodegenerative disorder caused by CAG trinucleotide expansion in exon 1 of the huntingtin (HTT) gene. Since the reduction of pathogenic mutant HTT messenger RNA is therapeutic, we developed a mutant allele-sensitive CAGEX RNA-targeting CRISPR-Cas13d system (Cas13d-CAGEX) that eliminates toxic CAGEX RNA in fibroblasts derived from patients with HD and induced pluripotent stem cell-derived neurons. We show that intrastriatal delivery of Cas13d-CAGEX via an adeno-associated viral vector selectively reduces mutant HTT mRNA and protein levels in the striatum of heterozygous zQ175 mice, a model of HD. This also led to improved motor coordination, attenuated striatal atrophy and reduction of mutant HTT protein aggregates. These phenotypic improvements lasted for at least eight months without adverse effects and with minimal off-target transcriptomic effects. Taken together, we demonstrate proof of principle of an RNA-targeting CRISPR-Cas13d system as a therapeutic approach for HD, a strategy with implications for the treatment of other dominantly inherited disorders.

A new DGT technique based on nano-sized Mg2Al layered double hydroxides with DTPA for sampling of eight anionic and cationic metals.

In this work, a new resin gel incorporated with layered double hydroxide nanoparticles modified with diethylenetriaminepentaacetic acid is developed for application in diffusive gradients in thin-film devices (abbreviated as LDHs DGT) to monitor eight anions and cations (such as Fe, Mn, Co, Ni, Cu, Cd, Pb, and As) in natural waters and soils. The accumulated anions and cations were quantitatively recovered by one-step elution using 0.5 mol·L-1 HNO3 with an optimized elution time of 30 min. The performance of the LDHs DGT was independent of solution pH (5-8) and ionic strengths (5-100 mmol·L-1). The capacities of the LDHs DGT for Mn(II), Fe(II), Co(II), Ni(II), Cu(II), As(V), Cd(II), and Pb(II) individually are determined to be 202.9, 363.6, 246.9, 88.8, 99.5, 75.3, 159.8, and 671.7 µg·cm-2. During the field deployments in a nature river, LDHs DGT measured concentrations of cations and anions were almost like those measured by the traditional sampling method (except Fe(II), Cd(II), and Co(II)). In addition, bioavailable Cd measured by LDHs DGT correlated well with Cd in rice grains (R2 = 0.55), indicating that LDHs DGT is a reliable tool for assessing the risk of Cd.

Mechanism of mercapto-modified palygorskite in reducing soil Cd activity.

Mercapto-modified palygorskite (MP) is an efficient novel amendment with superior ability to decrease soil Cd bioavailability, but the unclear immobilization mechanism has become the bottleneck of its performance improvement and precise application. In order to clarify the Cd reducing mechanism of MP, long-term and short-term soil incubation with three types of soils (paddy soil, alluvial soil and yellow mountain soil) and sorption verification experiments were conducted to investigate the dynamic process of soil labile Cd impacted by MP and the synergetic effects on labile Fe, Mn, S and dissolved organic carbon via in-situ diffusive gradients in thin-films and soil solution sampling techniques. MP with four dosages rapidly and continuously decreased soil labile Cd contents by 14.50 % ∼ 89.16 % in long-term incubation, meanwhile low-dosage MP reduced soil labile Fe and Mn contents, but high-dosage MP increased their contents. With MP dosages increased, the effects of Fe-Mn oxides on soil labile Cd content gradually weakened. MP effectively promoted the reduction of Fe adsorbed by clay minerals and enhanced their ability to adsorb Cd. Short-term incubation showed that MP could decline soil labile Cd by 7.17 % ∼ 44.74 %, especially at the dosage 0.4 %. MP was a reduction catalyst to facilitate Fe reduction, which profited for clay minerals adsorbing Cd. The sorption experiments indicated that 0.30 % MP could adsorb 73.34 % Cd2+, promote the release of Fe2+ from the soil, and stimulate the ability of clay minerals to adsorb Cd. The results revealed that MP decreased soil labile Cd content within 2 d, and MP made soil Cd activity change out of the influence of soil Fe/Mn redox system. The mechanism will be beneficial for the large-scale application of MP in safe utilization of Cd contaminated soil.

Physicochemical properties of A- and B-type granules isolated from waxy and normal hull-less barley starch.

Large A-type and small B-type starch granules separated from waxy and normal hull-less barley starches were investigated for their physicochemical properties. Hull-less barley starch granules were covered by a membrane composed mainly of phospholipids. Channels of waxy A- and B-type granules were rich in proteins and phospholipids. Compared with A-type starch, B-type starch exhibited higher specific surface area, volume and average diameter of mesopores. Waxy A-type granules exhibited the higher peak, breakdown, final and setback viscosity than did B-type granules, while normal A-type granules showed the lower peak, breakdown, final viscosity and the higher setback viscosity than did B-type granules. B-type starch gels with lower storage modulus exhibited a less elastic gel network structure and retrograded more slowly. Moreover, in vitro hydrolysis of starch showed that the B-type granules exhibited a higher hydrolysis extent and rate than the A-type granules in the first stage, which was consistent with higher initial α-amylase binding ability of B-type granules. The study showed that the A-type and B-type starch separated from waxy and normal hull-less barley exhibited very different physicochemical properties.

Chemical Characterization and In Vitro Anti-Cancer Activities of a Hot Water Soluble Polysaccharide from Hulless Barley Grass.

Hulless barley grass may confer many health benefits attributed to its bioactive functional components, such as polysaccharides. Here, a hot water soluble polysaccharide was extracted from hulless barley grass, and its chemical characterization and in vitro anti-cancer activities were investigated. The yield of hulless barley grass polysaccharide (HBGP) was 2.3%, and the purity reached 99.1% with a polydispersity index (PDI) of 1.11 after purification by a diethylaminoethyl cellulose (DE-32) column and an S-400 high resolution (HR) column. The molecular weight and number-average molecular weight of HBGP were 3.3 × 104 and 2.9 × 104 Da, respectively. The monosaccharide composition of HBGP included 35.1% galactose, 25.6% arabinose, 5.5% glucose, and 5.3% xylose. Based on infrared spectrum analysis, HBGP possessed pyranose and galactose residues. In addition, this water-soluble polysaccharide showed significant cell proliferation inhibitory effects against cancer cell lines HT29, Caco-2, 4T1, and CT26.WT in a dose-dependent manner, especially for HT29 (the half-inhibitory concentration IC50 value = 2.72 mg/mL). The results provide a basis for the development and utilization of hulless barley grass in functional foods to aid in preventing cancer.

Multi-scale structure of A- and B-type granules of normal and waxy hull-less barley starch.

The multi-scale structure of combined (A- and B- type granules), A-type, and B-type granules from normal (NHB) and waxy hull-less barley (WHB) starch was studied, including crystalline structure, molecular branching, nanostructural and fractal characteristics. Particle size distribution was applied to determine the separation purity (>95%), and micrography was used to distinguish between the A-type and B-type granules. Lacking amylose, WHB had higher relative crystallinity, gelatinization temperature, enthalpy, level of scattering intensity and uniformity of orientation of double helices than NHB starch. Generally, B-type granules had higher gelatinization temperature, lower enthalpy, greater relative crystallinity, higher ratio of crystalline to amorphous region, more fa chains in amylopectin, and thicker semi-crystalline lamellae than A-type and combined granules. The results showed that the multi-scale structure of A-type and B-type granules differed greatly, and the characteristics of combined granules were not the same as those of its two constituent granule fractions.

Microwave treatment alters the fine molecular structure of waxy hull-less barley starch.

Waxy hull-less barley kernels and their isolated starches were exposed to different microwave conditions (power 640, 720, and 800 W, time 60, 120 and 180 s) and changes in morphology, particle size, digestibility, rheological properties, and molecular structure were measured and analyzed. Microwave treatment caused roughness and deformation of granular surfaces, and an increase in granule size. After treatment, the in vitro digestibility of starch was increased, i.e., the RDS increased, but the RS decreased. Microwave treatment decreased the K values of the in-kernel MWI WHBS. Dynamic rheological results showed that the in-kernel MWI WHBS pastes had lower TG'max, and higher G'max, G'90°C, G'25°C, G'0.1Hz and G'20Hz after treatment. The chain-length distribution did not significantly change after microwave treatment. However, the results for molecular size distributions showed that the peaks of amylopectin (Rh = ~100 nm) shifted left and right, indicating that the molecular volume might become smaller or larger under different processing conditions. The primary effects of microwave treatment may be loosening the molecular structure and cutting main chains of amylopectin.

Octenyl succinic anhydride modification alters blending effects of waxy potato and waxy rice starches.

This study compared blending effects of native and octenyl succinic anhydride (OSA) modified blends (waxy rice and waxy potato starch). OSA groups were observed to be present primarily in the outer layer of waxy potato starch granule, but throughout the whole waxy rice granule. A high linear correlation with blending ratio was observed for trough viscosity and final viscosity of native blends, but for peak viscosity (PV) and breakdown viscosity (BD) of esterified blends. PV and BD of esterified blends showed weaker non-additive effects than those of native blends. Consistency coefficient in downward curve, flow behavior index in downward curve, and loss tangent mainly showed non-additive effects in native blends, but additive effects in esterified blends. OSA modification affects interaction between molecules on the outer surfaces of two starch granules by altering molecular structures on the outer surfaces, resulting in different blending effects between native and esterified waxy starch blends.

Removal of starch granule associated proteins alters the physicochemical properties of annealed rice starches.

The effect of removal of starch granule associated proteins (SGAPs), annealing and dual-treatment on physicochemical properties of three rice starches with different amylose content (AC) was investigated. SGAPs removal reduced stability of starch granules, thus increasing amylose leaching, swelling power, solubility, and pseudoplasticity of Qiuguang (15.6% AC) and Luhui (22.1% AC) rice starches, decreasing pseudoplasticity of Yangfunuo (1.56% AC) starch, and decreasing To, Tp, and Tc, pasting viscosity and storage modulus of all three rice starches. Annealing decreased amylose leaching of the three starches, and pasting properties, pseudoplastic and storage modulus of Yangfunuo starch, but increased swelling power of the three starches, ΔH and To of Qiuguang starch, and pasting properties and pseudoplasticity of Qiuguang and Luhui starches. The effect of dual-treatment was generally the sum of effect of SGAPs removal and annealing treatment. But an interaction effect of the dual-treatment was observed for some parameters. The effect of annealing was closely related to the variety and composition of the starch.

Huntingtin silencing delays onset and slows progression of Huntington's disease: a biomarker study.

Huntington's disease is a dominantly inherited, fatal neurodegenerative disorder caused by a CAG expansion in the huntingtin (HTT) gene, coding for pathological mutant HTT protein (mHTT). Because of its gain-of-function mechanism and monogenic aetiology, strategies to lower HTT are being actively investigated as disease-modifying therapies. Most approaches are currently targeted at the manifest stage, where clinical outcomes are used to evaluate the effectiveness of therapy. However, as almost 50% of striatal volume has been lost at the time of onset of clinical manifest, it would be preferable to begin therapy in the premanifest period. An unmet challenge is how to evaluate therapeutic efficacy before the presence of clinical symptoms as outcome measures. To address this, we aim to develop non-invasive sensitive biomarkers that provide insight into therapeutic efficacy in the premanifest stage of Huntington's disease. In this study, we mapped the temporal trajectories of arteriolar cerebral blood volumes (CBVa) using inflow-based vascular-space-occupancy (iVASO) MRI in the heterozygous zQ175 mice, a full-length mHTT expressing and slowly progressing model with a premanifest period as in human Huntington's disease. Significantly elevated CBVa was evident in premanifest zQ175 mice prior to motor deficits and striatal atrophy, recapitulating altered CBVa in human premanifest Huntington's disease. CRISPR/Cas9-mediated non-allele-specific HTT silencing in striatal neurons restored altered CBVa in premanifest zQ175 mice, delayed onset of striatal atrophy, and slowed the progression of motor phenotype and brain pathology. This study-for the first time-shows that a non-invasive functional MRI measure detects therapeutic efficacy in the premanifest stage and demonstrates long-term benefits of a non-allele-selective HTT silencing treatment introduced in the premanifest Huntington's disease.