Molecular structure of ß-amyloid fibrils in Alzheimer's disease brain tissue.

In vitro, ß-amyloid (Aß) peptides form polymorphic fibrils, with molecular structures that depend on growth conditions, plus various oligomeric and protofibrillar aggregates. Here, we investigate structures of human brain-derived Aß fibrils, using seeded fibril growth from brain extract and data from solid-state nuclear magnetic resonance and electron microscopy. Experiments on tissue from two Alzheimer's disease (AD) patients with distinct clinical histories showed a single predominant 40 residue Aß (Aß40) fibril structure in each patient; however, the structures were different from one another. A molecular structural model developed for Aß40 fibrils from one patient reveals features that distinguish in-vivo- from in-vitro-produced fibrils. The data suggest that fibrils in the brain may spread from a single nucleation site, that structural variations may correlate with variations in AD, and that structure-specific amyloid imaging agents may be an important future goal.

Modulation of aggregation and structural polymorphisms of ß-amyloid fibrils in cellular environments by pyroglutamate-3 variant cross-seeding.

Amyloidogenic deposition of ß-amyloid (Aß) peptides in human brain involves not only the wild-type Aß (wt-Aß) sequences, but also posttranslationally modified Aß (PTM-Aß) variants. Recent studies hypothesizes that the PTM-Aß variants may trigger the deposition of wt-Aß, which underlies the pathology of Sporadic Alzheimer's disease. Among PTM-Aß variants, the pyroglutamate-3-Aß (pyroE3-Aß) has attracted much attention because of their significant abundances and broad distributions in senile plaques and dispersible and soluble oligomers. pyroE3-specific antibodies are being tested as potential anti-Aß drugs in clinical trials. However, evidence that support the triggering effect of pyroE3-Aß on wt-Aß in cells remain lacking, which diminishes its pathological relevance. We show here that cross-seeding with pyroE3-Aß40 leads to accelerated extracellular and intracellular aggregation of wt-Aß40 in different neuronal cells. Cytotoxicity levels are elevated through the cross-seeded aggregation, comparing with the self-seeded aggregation of wt-Aß40 or the static presence of pyroE3-Aß40 seeds. For the extracellular deposition in mouse neuroblastoma Neuro2a (N2a) cells, the cytotoxicity elevation correlates positively with the seeding efficiency. Besides aggregation rates, cross-seeding with pyroE3-Aß40 also modulates the molecular level structural polymorphisms of the resultant wt-Aß40 fibrils. Using solid-state nuclear magnetic resonance (ssNMR) spectroscopy, we identified key structural differences between the parent pyroE3/ΔE3 and wt-Aß40 fibrils within their fibrillar cores. Structural propagation from seeds to daughter fibrils is demonstrated to be more pronounced in the extracellular seeding in N2a cells by comparing the ssNMR spectra from different seeded wt-Aß40 fibrils, but less significant in the intracellular seeding process in human neuroblastoma SH-SY5Y cells.

All-fiber multifunction differential absorption CO2 lidar integrating single-photon and coherent detection.

This study demonstrates a differential absorption lidar (DIAL) for CO2 that integrates both single-photon direct detection and coherent detection. Based on all-fiber 1572 nm wavelength devices, this compact lidar achieves detection of CO2 concentration, wind field, and single photon aerosol backscattering signal. First, by comparing DIAL with VAISALA-GMP343, the concentration deviation between the two devices is less than 5 ppm, proving the accuracy of the DIAL. Second, through the scanning detection experiment in Chaohu Lake, Hefei, not only the CO2 concentration between single-photon detection and coherent detection but also the wind field was obtained, proving the multifunctionality and stability of the DIAL. Benefiting from the advantages of combined the two detection methods, single photon detection offers 3-km CO2 and aerosol backscattering signals; coherent detection offers a 360-m shorter blind zone and wind field. This DIAL can achieve monitoring of CO2 flux and sudden emissions, which can effectively compensate for the shortages of in-situ sensors and spaceborne systems.

Palladium-Catalyzed Carbonylation Reaction of Indole/Pyrrole Involving HCFO-1233zd (E).

3-Indole-3-one is a key intermediate in the synthesis of many drugs and plays an important role in synthetic chemistry and biochemistry. A new method for synthesizing trifluoromethylated 3-indoleketones by Pd(0)-catalyzed carbonylation was introduced. In the absence of additives, 1-chloro-3,3,3-trifluoropropyl (an inexpensive and environmentally friendly synthetic block of trifluoromethyl) reacts with indole and carbon monoxide to generate trifluoromethylindole ketones with good yields, regioselectivity, and chemical selectivity; furthermore, the products exhibit strong resistance to basic functional groups, such as alkynes, aldehydes, and esters. In addition to the conversion of indole compounds into corresponding products, pyrrole and heteroindole may be suitable for corresponding chemical transformations. This study provides a synthetic method for the further construction of trifluoromethylated 3-indole ketones.

Rigidifying of the internal dynamics of amyloid-beta fibrils generated in the presence of synaptic plasma vesicles.

We investigated the changes in internal flexibility of amyloid-ß1-40 (Aß) fibrils grown in the presence of rat synaptic plasma vesicles. The fibrils are produced using a modified seeded growth protocol, in which the Aß concentration is progressively increased at the expense of the decreased lipid to protein ratio. The morphologies of each generation are carefully assessed at several fibrils' growth time points using transmission electron microscopy. The side-chain dynamics in the fibrils is investigated using deuterium solid-state NMR measurements, with techniques spanning line shapes analysis and several NMR relaxation rates measurements. The dynamics is probed in the site-specific fashion in the hydrophobic C-terminal domain and the disordered N-terminal domain. An overall strong rigidifying effect is observed in comparison with the wild-type fibrils generated in the absence of the membranes. In particular, the overall large-scale fluctuations of the N-terminal domain are significantly reduced, and the activation energies of rotameric inter-conversion in methyl-bearing side-chains of the core (L17, L34, M35, V36), as well as the ring-flipping motions of F19 are increased, indicating a restricted core environment. Membrane-induced flexibility changes in Aß aggregates can be important for the re-alignment of protein aggregates within the membrane, which in turn would act as a disruption pathway of the bilayers' integrity.

Decoupled response of microbial taxa and functions to nutrients: The role of stoichiometry in plantations.

The resource quantity and elemental stoichiometry play pivotal roles in shaping belowground biodiversity. However, a significant knowledge gap remains regarding the influence of different plant communities established through monoculture plantations on soil fungi and bacteria's taxonomic and functional dynamics. This study aimed to elucidate the mechanisms underlying the regulation and adaptation of microbial communities at the taxonomic and functional levels in response to communities formed over 34 years through monoculture plantations of coniferous species (Japanese larch, Armand pine, and Chinese pine), deciduous forest species (Katsura), and natural shrubland species (Asian hazel and Liaotung oak) in the temperate climate. The taxonomic and functional classifications of fungi and bacteria were examined for the mineral topsoil (0-10 cm) using MiSeq-sequencing and annotation tools of microorganisms (FAPROTAX and Funguild). Soil bacterial (6.52 ± 0.15) and fungal (4.46 ± 0.12) OTUs' diversity and richness (5.83*103±100 and 1.12*103±46.4, respectively) were higher in the Katsura plantation compared to Armand pine and Chinese pine. This difference was attributed to low soil DOC/OP (24) and DON/OP (11) ratios in the Katsura, indicating that phosphorus availability increased microbial community diversity. The Chinese pine plantation exhibited low functional diversity (3.34 ± 0.04) and richness (45.2 ± 0.41) in bacterial and fungal communities (diversity 3.16 ± 0.15 and richness 56.8 ± 3.13), which could be attributed to the high C/N ratio (25) of litter. These findings suggested that ecological stoichiometry, such as of enzyme, litter C/N, soil DOC/DOP, and DON/DOP ratios, was a sign of the decoupling of soil microorganisms at the genetic and functional levels to land restoration by plantations. It was found that the stoichiometric ratios of plant biomass served as indicators of microbial functions, whereas the stoichiometric ratios of available nutrients in soil regulated microbial genetic diversity. Therefore, nutrient stoichiometry could serve as a strong predictor of microbial diversity and composition during forest restoration.

Early stage ß-amyloid-membrane interactions modulate lipid dynamics and influence structural interfaces and fibrillation.

Molecular interactions between ß-amyloid (Aß) peptide and membranes contribute to the neuronal toxicity of Aß and the pathology of Alzheimer's disease. Neuronal plasma membranes serve as biologically relevant environments for the Aß aggregation process as well as affect the structural polymorphisms of Aß aggregates. However, the nature of these interactions is unknown. Here, we utilized solid-state NMR spectroscopy to explore the site-specific interactions between Aß peptides and lipids in synaptic plasma membranes at the membrane-associated nucleation stage. The key results show that different segments in the hydrophobic sequence of Aß initiate membrane binding and interstrand assembling. We demonstrate early stage Aß-lipid interactions modulate lipid dynamics, leading to more rapid lipid headgroup motion and reduced lateral diffusive motion. These early events influence the structural polymorphisms of yielded membrane-associated Aß fibrils with distinct C-terminal quaternary interface structure compared to fibrils grown in aqueous solutions. Based on our results, we propose a schematic mechanism by which Aß-lipid interactions drive membrane-associated nucleation processes, providing molecular insights into the early events of fibrillation in biological environments.

Structural variation in amyloid-ß fibrils from Alzheimer's disease clinical subtypes.

Aggregation of amyloid-ß peptides into fibrils or other self-assembled states is central to the pathogenesis of Alzheimer's disease. Fibrils formed in vitro by 40- and 42-residue amyloid-ß peptides (Aß40 and Aß42) are polymorphic, with variations in molecular structure that depend on fibril growth conditions. Recent experiments suggest that variations in amyloid-ß fibril structure in vivo may correlate with variations in Alzheimer's disease phenotype, in analogy to distinct prion strains that are associated with different clinical and pathological phenotypes. Here we investigate correlations between structural variation and Alzheimer's disease phenotype using solid-state nuclear magnetic resonance (ssNMR) measurements on Aß40 and Aß42 fibrils prepared by seeded growth from extracts of Alzheimer's disease brain cortex. We compared two atypical Alzheimer's disease clinical subtypes-the rapidly progressive form (r-AD) and the posterior cortical atrophy variant (PCA-AD)-with a typical prolonged-duration form (t-AD). On the basis of ssNMR data from 37 cortical tissue samples from 18 individuals, we find that a single Aß40 fibril structure is most abundant in samples from patients with t-AD and PCA-AD, whereas Aß40 fibrils from r-AD samples exhibit a significantly greater proportion of additional structures. Data for Aß42 fibrils indicate structural heterogeneity in most samples from all patient categories, with at least two prevalent structures. These results demonstrate the existence of a specific predominant Aß40 fibril structure in t-AD and PCA-AD, suggest that r-AD may relate to additional fibril structures and indicate that there is a qualitative difference between Aß40 and Aß42 aggregates in the brain tissue of patients with Alzheimer's disease.

Deep Learning-Assisted Gait Parameter Assessment for Neurodegenerative Diseases: Model Development and Validation.

BACKGROUND: Neurodegenerative diseases (NDDs) are prevalent among older adults worldwide. Early diagnosis of NDD is challenging yet crucial. Gait status has been identified as an indicator of early-stage NDD changes and can play a significant role in diagnosis, treatment, and rehabilitation. Historically, gait assessment has relied on intricate but imprecise scales by trained professionals or required patients to wear additional equipment, causing discomfort. Advancements in artificial intelligence may completely transform this and offer a novel approach to gait evaluation. OBJECTIVE: This study aimed to use cutting-edge machine learning techniques to offer patients a noninvasive, entirely contactless gait assessment and provide health care professionals with precise gait assessment results covering all common gait-related parameters to assist in diagnosis and rehabilitation planning. METHODS: Data collection involved motion data from 41 different participants aged 25 to 85 (mean 57.51, SD 12.93) years captured in motion sequences using the Azure Kinect (Microsoft Corp; a 3D camera with a 30-Hz sampling frequency). Support vector machine (SVM) and bidirectional long short-term memory (Bi-LSTM) classifiers trained using spatiotemporal features extracted from raw data were used to identify gait types in each walking frame. Gait semantics could then be obtained from the frame labels, and all the gait parameters could be calculated accordingly. For optimal generalization performance of the model, the classifiers were trained using a 10-fold cross-validation strategy. The proposed algorithm was also compared with the previous best heuristic method. Qualitative and quantitative feedback from medical staff and patients in actual medical scenarios was extensively collected for usability analysis. RESULTS: The evaluations comprised 3 aspects. Regarding the classification results from the 2 classifiers, Bi-LSTM achieved an average precision, recall, and F1-score of 90.54%, 90.41%, and 90.38%, respectively, whereas these metrics were 86.99%, 86.62%, and 86.67%, respectively, for SVM. Moreover, the Bi-LSTM-based method attained 93.2% accuracy in gait segmentation evaluation (tolerance set to 2), whereas that of the SVM-based method achieved only 77.5% accuracy. For the final gait parameter calculation result, the average error rate of the heuristic method, SVM, and Bi-LSTM was 20.91% (SD 24.69%), 5.85% (SD 5.45%), and 3.17% (SD 2.75%), respectively. CONCLUSIONS: This study demonstrated that the Bi-LSTM-based approach can effectively support accurate gait parameter assessment, assisting medical professionals in making early diagnoses and reasonable rehabilitation plans for patients with NDD.

Selective Delivery of Tofacitinib Citrate to Hair Follicles Using Lipid-Coated Calcium Carbonate Nanocarrier Controls Chemotherapy-Induced Alopecia Areata.

Chemotherapy-induced alopecia (CIA) is one of the common side effects in cancer treatment. The psychological distress caused by hair loss may cause patients to discontinue chemotherapy, affecting the efficacy of the treatment. The JAK inhibitor, Tofacitinib citrate (TFC), showed huge potential in therapeutic applications for treating baldness, but the systemic adverse effects of oral administration and low absorption rate at the target site limited its widespread application in alopecia. To overcome these problems, we designed phospholipid-calcium carbonate hybrid nanoparticles (PL/ACC NPs) for a topical application to target deliver TFC. The results proved that PL/ACC-TFC NPs showed excellent pH sensitivity and transdermal penetration in vitro. PL/ACC NPs offered an efficient follicular targeting approach to deliver TFC in a Cyclophosphamide (CYP)-induced alopecia areata mouse model. Compared to the topical application of TFC solution, PL/ACC-TFC NPs significantly inhibited apoptosis of mouse hair follicles and accelerated hair growth. These findings support that PL/ACC-TFC NPs has the potential for topical application in preventing and mitigating CYP-induced Alopecia areata.

Does the low-carbon city pilot policy work in China? A company-level analysis based on the PSM-DID model.

To reduce carbon emissions and pursue sustainable economic development, China's central government formulated the low-carbon city pilot (LCCP) policy. Current studies focus primarily on the impact of the policy at the macro level (provinces and cities). So far, no study has looked at the impact of the LCCP policy on companies' environmental expenditures. Besides, as the LCCP policy is a weak-constraining central policy, it is interesting to see how it works at the company level. We employ company-level empirical data and the Propensity Score Matching - Difference in Differences (PSM-DID) method, which outperforms the traditional DID model in avoiding sample selection bias, to address the above issues. We concentrate on the second phase of the LCCP policy from 2010 to 2016, encompassing 197 listed companies in China's secondary and transportation industries. Our statistical results show that if the listed company's host city has piloted the LCCP policy, the company's environmental expenditures are reduced by 0.91 points at the 1% significance level. The above finding calls attention to the policy-implementation gap between the central and the local governments in China, which may make those weak-constraining central policies like the LCCP policy have purpose-defeating outcomes at the company level.

Shifts of understory vegetation induced by thinning drive the expansion of soil rare fungi.

The gap formation due to forest thinning regulates the understorey microclimate, ground vegetation, and soil biodiversity. However, little is known about abundant and rare taxa's various patterns and assemblage mechanisms under thinning gaps. Thinning gaps with increasing sizes (0, 74, 109, and 196 m2) were established 12 years ago in a 36-year-old spruce plantation in a temperate mountain climate. Soil fungal and bacterial communities were analyzed by MiSeq sequencing and related to soil physicochemical properties and aboveground vegetation. The functional microbial taxa were sorted by FAPROTAX and Fungi Functional Guild database. The bacterial community stabilized under varied thinning intensities and was not different from the control plots, whereas the richness of the rare fungal taxa was at least 1.5-fold higher in the large gaps than in the small ones. Total phosphorus and dissolved organic carbon were the main factors influencing microbial communities in soil under various thinning gaps. The diversity and richness of the entire fungal community and rare fungal taxa increased with the understorey vegetation coverage and shrub biomass after thinning. Gap formation by thinning stimulated the understorey vegetation, the rare saprotroph (Undefined Saprotroph), and mycorrhizal fungi (Ectomycorrhizal-Endophyte-Ericoid Mycorrhizal-Litter Saprotroph-Orchid Mycorrhizal and Bryophyte Parasite-Lichen Parasite-Ectomycorrhizal-Ericoid Mycorrhizal-Undefined Saprotroph), which may accelerate nutrient cycling in forest ecosystems. However, the abundance of Endophyte-Plant Pathogens increased by eight times, which showed the potential risk for the artificial spruce forests. Thus, fungi may be the driving force of forest restoration and nutrient cycling under the increasing intensity of thinning and may induce plant diseases. Therefore, vegetation coverage and microbial functional diversity should be considered to evaluate the sustainability of the artificial forest ecosystem and forest restoration.

Tumor microenvironment is associated with clinical and genetic properties of diffuse gliomas and predicts overall survival.

Tumor microenvironment (TME) is a complex and dynamic evolving environment which facilitates tumor proliferation and progression. We aimed at investigating the characteristics of tumor microenvironment and its prognostic value in gliomas. Transcriptome data of 702 glioma samples from The Cancer Genome Atlas were included as training dataset, while 325 samples from Chinese Glioma Genome Atlas database and 268 samples from GSE16011 database were used to validate. We found that the infiltration of stromal and immune cell varied in gliomas of different grades and pathological types, and was associated with poor prognosis. Based on the gene expression profile, we constructed a TME-related signature (TMERS), which was closely related to clinical features and genomic variation of gliomas. In TMERS-high group, specific gene mutations and increased copy number alternations were observed. Kaplan-Meier survival and Cox regression analysis showed that TMERS was an independent prognostic indicator. Then we developed a nomogram prognostic model to predict 1-year, 3-year and 5-year survival of patients. Functional analysis confirmed that TMERS could reflect the status of glioma microenvironment, and immunological analysis showed that macrophages were significantly enriched in the TMERS-high group. We established a novel TME-related signature for predicting prognosis and provided new insights into immunotherapy.

Engineering tropane alkaloid production and glyphosate resistance by overexpressing AbCaM1 and G2-EPSPS in Atropa belladonna.

Atropa belladonna is an important industrial crop for producing anticholinergic tropane alkaloids (TAs). Using glyphosate as selection pressure, transgenic homozygous plants of A. belladonna are generated, in which a novel calmodulin gene (AbCaM1) and a reported EPSPS gene (G2-EPSPS) are co-overexpressed. AbCaM1 is highly expressed in secondary roots of A. belladonna and has calcium-binding activity. Three transgenic homozygous lines were generated and their glyphosate tolerance and TAs' production were evaluated in the field. Transgenic homozygous lines produced TAs at much higher levels than wild-type plants. In the leaves of T2GC02, T2GC05, and T2GC06, the hyoscyamine content was 8.95-, 10.61-, and 9.96 mg/g DW, the scopolamine content was 1.34-, 1.50- and 0.86 mg/g DW, respectively. Wild-type plants of A. belladonna produced hyoscyamine and scopolamine respectively at the levels of 2.45 mg/g DW and 0.30 mg/g DW in leaves. Gene expression analysis indicated that AbCaM1 significantly up-regulated seven key TA biosynthesis genes. Transgenic homozygous lines could tolerate a commercial recommended dose of glyphosate in the field. In summary, new varieties of A. belladonna not only produce pharmaceutical TAs at high levels but tolerate glyphosate, facilitating industrial production of TAs and weed management at a much lower cost.

Mitigation of amplified spontaneous emission noise for an all-fiber coaxial aerosol lidar with different single-photon detectors.

For a coaxial single-photon lidar system, amplified spontaneous emission (ASE) noise from the fiber amplifier is inevitable. The ASE backscattering from specular reflection annihilates the far-field weak signal, resulting in low signal-to-noise ratio, short measurement distance, and even misidentification. We propose a method for calibrating and mitigating ASE noise in all-fiber coaxial aerosol lidar and demonstrate the method for a lidar system with different single-photon detectors (SPDs). The accuracy of the coaxial aerosol lidar is comparable to that of the biaxial one. We conducted an experiment using three different detectors, namely, InGaAs/InP SPD, up-conversion SPD, and superconducting nanowire SPD in the same coaxial lidar system. Compared with the biaxial system, the three different detectors we used have achieved more than 90% ASE noise suppression, the measured visibility percent errors of InGaAs/InP SPD data, up-conversion SPD data, and superconducting nanowire SPD data all within 20%, and the percent error within 10% are 99.47%, 100%, and 95.12%, respectively. Moreover, time-sharing optical switching allowed to obtain background noise with high accuracy.

Phosphorus addition decreases plant lignin but increases microbial necromass contribution to soil organic carbon in a subalpine forest.

Increasing phosphorus (P) inputs induced by anthropogenic activities have increased P availability in soils considerably, with dramatic effects on carbon (C) cycling and storage. However, the underlying mechanisms via which P drives plant and microbial regulation of soil organic C (SOC) formation and stabilization remain unclear, hampering the accurate projection of soil C sequestration under future global change scenarios. Taking the advantage of an 8-year field experiment with increasing P addition levels in a subalpine forest on the eastern Tibetan Plateau, we explored plant C inputs, soil microbial communities, plant and microbial biomarkers, as well as SOC physical and chemical fractions. We found that continuous P addition reduced fine root biomass, but did not affect total SOC content. P addition decreased plant lignin contribution to SOC, primarily from declined vanillyl-type phenols, which was coincided with a reduction in methoxyl/N-alkyl C by 2.1%-5.5%. Despite a decline in lignin decomposition due to suppressed oxidase activity by P addition, the content of lignin-derived compounds decreased because of low C input from fine roots. In contrast, P addition increased microbial (mainly fungal) necromass and its contribution to SOC due to the slower necromass decomposition under reduced N-acquisition enzyme activity. The larger microbial necromass contribution to SOC corresponded with a 9.1%-12.4% increase in carbonyl C abundance. Moreover, P addition had no influence on the slow-cycing mineral-associated organic C pool, and SOC chemical stability indicated by aliphaticity and recalcitrance indices. Overall, P addition in the subalpine forest over 8 years influenced SOC composition through divergent alterations of plant- and microbial-derived C contributions, but did not shape SOC physical and chemical stability. Such findings may aid in accurately forecasting SOC dynamics and their potential feedbacks to climate change with future scenarios of increasing soil P availability in Earth system models.

Comprehensive analysis of a TNF family based-signature in diffuse gliomas with regard to prognosis and immune significance.

BACKGROUND: Several studies have shown that members of the tumor necrosis factor (TNF) family play an important role in cancer immunoregulation, and trials targeting these molecules are already underway. Our study aimed to integrate and analyze the expression patterns and clinical significance of TNF family-related genes in gliomas. METHODS: A total of 1749 gliomas from 4 datasets were enrolled in our study, including the Cancer Genome Atlas (TCGA) dataset as the training cohort and the other three datasets (CGGA, GSE16011, and Rembrandt) as validation cohorts. Clinical information, RNA expression data, and genomic profile were collected for analysis. We screened the signature gene set by Cox proportional hazards modelling. We evaluated the prognostic value of the signature by Kaplan-Meier analysis and timeROC curve. Gene Ontology (GO) and Gene set enrichment analysis (GSEA) analysis were performed for functional annotation. CIBERSORT algorithm and inflammatory metagenes were used to reveal immune characteristics. RESULTS: In gliomas, the expression of most TNF family members was positively correlated. Univariate analysis showed that most TNF family members were related to the overall survival of patients. Then through the LASSO regression model, we developed a TNF family-based signature, which was related to clinical, molecular, and genetic characteristics of patients with glioma. Moreover, the signature was found to be an independent prognostic marker through survival curve analysis and Cox regression analysis. Furthermore, a nomogram prognostic model was constructed to predict individual survival rates at 1, 3 and 5 years. Functional annotation analysis revealed that the immune and inflammatory response pathways were enriched in the high-risk group. Immunological analysis showed the immunosuppressive status in the high-risk group. CONCLUSIONS: We developed a TNF family-based signature to predict the prognosis of patients with glioma. Video abstract.

The Critical Transition from Soluble Complexes to Colloidal Aggregates of Polyelectrolyte Complexes at Non-Stoichiometric Charge Ratios.

The transition from soluble to colloidal polyelectrolyte complex normally occurs at a critical non-stoichiometric charge ratio. Here, it is demonstrated that the conventional batch mixing produces heterogeneous binding and complexation, which can easily mask this soluble-colloidal complex transition (sol-col transition) even for weakly binding polyelectrolytes like polyacrylic acid (PAA) and poly(diallyldimethylammonium chloride) (PDADMAC). When mixed efficiently using multi-inlet vortex mixer (MIVM), the sol-col transition occurs beyond a critical charge ratio (n-/n+) and the large colloidal complexes are formed through the aggregation of small primary complexes (as revealed by atomic force microscopy). Moreover, the sol-col transition occurs at a constant charge ratio below the overlapping concentration (c*) of the long host polyelectrolyte, but at lower charge ratios above c* due to chain entanglement. When adding NaCl to the solution, the sol-col transition charge ratio first decreases, then remained stable for a period, and finally increased and vanished at high ionic strength. When replacing NaCl with chaotropic salts, the sol-col transition occurs at lower charge ratios, while kosmotropes has little impact. The solvent quality and polymer hydrophobicity effects are also discussed. With the assistance of rapid mixing, this study provides a more reliable way of studying the sol-col transition of polyelectrolyte complexes.

Transcriptome revealing the dual regulatory mechanism of ethylene on the rhynchophylline and isorhynchophylline in Uncaria rhynchophylla.

Rhynchophylline (RIN) and isorhynchophylline (IRN) are extracted from Uncaria rhynchophylla, which are used to treat Alzheimer's disease. However, the massive accumulation of RIN and IRN in U. rhynchophylla requires exogenous stimulation. Ethylene is a potential stimulant for RIN and IRN biosynthesis, but there is no study on the role of ethylene in RIN or IRN synthesis. This study investigated the regulation of ethylene in RIN and IRN biosynthesis in U. rhynchophylla. An increase in the content of RIN and IRN was observed that could be attributed to the release of ethylene from 18 mM ethephon, while ethylene released from 36 mM ethephon reduced the content of RIN and IRN. The transcriptome and weighted gene co-expression network analysis indicated the up-regulation of seven key enzyme genes related to the RIN/IRN biosynthesis pathway and starch/sucrose metabolism pathway favored RIN/IRN synthesis. In comparison, the down-regulation of these seven key enzyme genes contributed to the reduction of RIN/IRN. Moreover, the inhibition of photosynthesis is associated with a reduction in RIN/IRN. Photosynthesis was restrained owing to the down-regulation of Lhcb1 and Lhcb6 after 36 mM ethephon treatment and further prevented supply of primary metabolites (such as α-D-glucose) for RIN/IRN synthesis. However, uninterrupted photosynthesis ensured a normal supply of primary metabolites at 18 mM ethephon treatment. AP2/ERF1, bHLH1, and bHLH2 may positively regulate the RIN/IRN accumulation, while NAC1 may play a negative regulatory role. Our results construct the potential bidirectional model for ethylene regulation on RIN/IRN synthesis and provide novel insight into the ethylene-mediated regulation of the metabolism of terpenoid indole alkaloids.

Low-intensity, long-wavelength red light slows the progression of myopia in children: an Eastern China-based cohort.

PURPOSE: To determine the effect of low-intensity, long-wavelength red light therapy (LLRT) on the inhibition of myopia progression in children. METHODS: A retrospective study was conducted. One hundred and five myopic children (spherical equivalent refractive error [SER] -3.09 ± 1.74 dioptres [D]; mean age, 9.19 ± 2.40 years) who underwent LLRT treatment (power 0.4 mW, wavelength 635 nm) twice per day for 3 min each session, with at least a 4-h interval between sessions, and a control group of 56 myopic children (SER -3.04 ± 1.66 D; mean age, 8.62 ± 2.45 years) were evaluated. Both groups wore single-vision distance spectacles. Each child returned for a follow-up examination every 3 months after the initial measurements for a total of 9 months. RESULTS: At 9 months, the mean SER in the LLRT group was -2.87 ± 1.89 D, significantly greater than that of the control group (-3.57 ± 1.49 D, p < 0.001). Axial length (AL) changes were -0.06 ± 0.19 mm and 0.26 ± 0.15 mm in the LLRT group and control group (p < 0.001), respectively. The subfoveal choroidal thickness changed by 45.32 ± 30.88 µm for children treated with LLRT at the 9-month examination (p < 0.001). Specifically, a substantial hyperopic shift (0.31 ± 0.24 D and 0.20 ± 0.14 D, respectively, p = 0.02) was found in the 8-14 year olds compared with 4-7 year old children. The decrease in AL in subjects with baseline AL >24 mm was -0.08 ± 0.19 mm, significantly greater than those with a baseline AL ≤24 mm (-0.04 ± 0.18 mm, p = 0.03). CONCLUSIONS: Repetitive exposure to LLRT therapy was associated with slower myopia progression and reduced axial growth after short durations of treatment. These results require further validation in randomised controlled trials.