Author Correction: Reversing a model of Parkinson's disease with in situ converted nigral neurons.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Reversing a model of Parkinson's disease with in situ converted nigral neurons.

Parkinson's disease is characterized by loss of dopamine neurons in the substantia nigra1. Similar to other major neurodegenerative disorders, there are no disease-modifying treatments for Parkinson's disease. While most treatment strategies aim to prevent neuronal loss or protect vulnerable neuronal circuits, a potential alternative is to replace lost neurons to reconstruct disrupted circuits2. Here we report an efficient one-step conversion of isolated mouse and human astrocytes to functional neurons by depleting the RNA-binding protein PTB (also known as PTBP1). Applying this approach to the mouse brain, we demonstrate progressive conversion of astrocytes to new neurons that innervate into and repopulate endogenous neural circuits. Astrocytes from different brain regions are converted to different neuronal subtypes. Using a chemically induced model of Parkinson's disease in mouse, we show conversion of midbrain astrocytes to dopaminergic neurons, which provide axons to reconstruct the nigrostriatal circuit. Notably, re-innervation of striatum is accompanied by restoration of dopamine levels and rescue of motor deficits. A similar reversal of disease phenotype is also accomplished by converting astrocytes to neurons using antisense oligonucleotides to transiently suppress PTB. These findings identify a potentially powerful and clinically feasible approach to treating neurodegeneration by replacing lost neurons.

SnO2/SnS heterojunction anchoring on CMK-3 mesoporous network improves the reversibility of conversion reaction for lithium/sodium ions storage.

Tin oxide-based (SnO2) materials show high theoretical capacity for lithium and sodium storage benefiting from a double-reaction mechanism of conversion and alloying reactions. However, due to the limitation of the reaction thermodynamics and kinetics, the conversion reaction process of SnO2usually shows irreversibility, resulting in serious capacity decay and hindering the further application of the SnO2anode. Herein, SnO2/SnS heterojunction was anchored on the surface and inside of CMK-3 byinsitusynthesis method, forming a stable 3D structural material (SnO2/SnS@CMK-3). The electrochemical properties of SnO2/SnS@CMK-3 composite show high capacity and reversible conversion reaction, which was attributed to the synergistic effect of CMK-3 and SnO2/SnS heterojunction. To further investigate the influence of the heterojunction on the reversibility of the conversion reaction, the Gibbs free energy (ΔG) was calculated using density functional theory. The results show that SnO2/SnS heterojunction has a closer to zero ΔGfor lithium/sodium ion batteries compared to SnO2, indicating that the heterojunction enhances the reversibility of the conversion reaction in chemical reaction thermodynamics. Our work provides insights into the reversibility of the conversion reaction of SnO2-based materials, which is essential for improving their electrochemical performance.

Association of exposure to multiple heavy metals during pregnancy with the risk of gestational diabetes mellitus and insulin secretion phase after glucose stimulation.

BACKGROUND: Epidemiological evidence for the association between heavy metals exposure during pregnancy and gestational diabetes mellitus (GDM) is still inconsistent. Additionally, that is poorly understood about the potential cause behind the association, for instance, whether heavy metal exposure is related to the change of insulin secretion phase is unknown. OBJECTIVES: We aimed to explore the relationships of blood levels of arsenic (As), lead (Pb), thallium (Tl), nickel (Ni), cadmium (Cd), cobalt (Co), barium (Ba), chromium (Cr), mercury (Hg) and copper (Cu) during early pregnancy with the odds of GDM, either as an individual or a mixture, as well as the association of the metals with insulin secretion phase after glucose stimulation. METHODS: We performed a nested case-control study consisting of 302 pregnant women with GDM and 302 controls at the First Affiliated Hospital of Anhui Medical University in Hefei, China. Around the 12th week of pregnancy, blood samples of pregnant women were collected and levels of As, Pb, Tl, Ni, Cd, Co, Ba, Cr, Hg and Cu in blood were measured. An oral glucose tolerance test (OGTT) was done in each pregnant woman during the 24-28th week of pregnancy to diagnose GDM and C-peptide (CP) levels during OGTT were measured simultaneously. The four metals (As, Pb, Tl and Ni) with the highest effect on odds of GDM were selected for the subsequent analyses via the random forest model. Conditional logistic regression models were performed to analyze the relationships of blood As, Pb, Tl and Ni levels with the odds of GDM. The weighted quantile sum (WQS) regression and bayesian kernel machine regression (BKMR) were used to assess the joint effects of levels of As, Pb, Tl and Ni on the odds of GDM as well as to evaluate which metal level contributed most to the association. Latent profile analysis (LPA) was conducted to identify profiles of glycemic and C-peptide levels at different time points. Multiple linear regression models were employed to explore the relationships of metals with glycaemia-related indices (fasting blood glucose (FBG), 1-hour blood glucose (1h BG), 2-hour blood glucose (2h BG), fasting C-peptide (FCP), 1-hour C-peptide (1h CP), 2-hour C-peptide (2h CP), FCP/FBG, 1h CP/1h BG, 2h CP/2h BG, area under the curve of C-peptide (AUCP), area under the curve of glucose (AUCG), AUCP/AUCG and profiles of BGs and CPs, respectively. Mixed-effects models with repeated measures data were used to explore the relationship between As (the ultimately selected metal) level and glucose-stimulated insulin secretion phase. The mediation effects of AUCP and AUCG on the association of As exposure with odds of GDM were investigated using mediation models. RESULTS: The odds of GDM in pregnant women increased with every ln unit increase in blood As concentration (odds ratio (OR) = 1.46, 95% confidence interval (CI) = 1.04-2.05). The joint effects of As, Pb, Tl and Ni levels on the odds of GDM was statistically significant when blood levels of four metals were exceeded their 50th percentile, with As level being a major contributor. Blood As level was positively associated with AUCG and the category of glucose latent profile, the values of AUCG were much higher in GDM group than those in non-GDM group, which suggested that As exposure associated with the odds of GDM may be due to that As exposure was related to the impairment of glucose tolerance among pregnant women. The significant and positive relationships of As level with AUCP, CP latent profile category, 2h CP and 2h CP/2h BG were observed, respectively; and the values of 1h CP/1h BG and AUCP/AUCG were much lower in GDM group than those in non-GDM group, which suggested that As exposure may not relate to the impairment of insulin secretion (pancreatic ß-cell function) among pregnant women. The relationships between As level and 2h CP as well as 2h CP/2h BG were positive and significant; additionally, the values of 2h CP/2h BG in GDM group were comparable with those in non-GDM group; the peak value of CP occurred at 2h in GDM group, as well as the values of 2h CP/2h BG in high As exposure group were much higher than those in low As exposure group, which suggested that As exposure associated with the increased odds of GDM may be due to that As exposure was related to the change of insulin secretion phase (delayment of the peak of insulin secretion) among pregnant women. In addition, AUCP mediated 11% (p < 0.05) and AUCG mediated 43% (p < 0.05) of the association between As exposure and the odds of GDM. CONCLUSION: Our results suggested that joint exposure to As, Pb, Tl and Ni during early pregnancy was positively associated with the odds of GDM, As was a major contributor; and the association of environmental As exposure with the increased odds of GDM may be due to that As exposure was related to the impairment of glucose tolerance and change of insulin secretion phase after glucose stimulation (delayment of the peak of insulin secretion) among pregnant women.

Whether weekend warriors (WWs) achieve equivalent benefits in lipid accumulation products (LAP) reduction as other leisure-time physical activity patterns? -Results from a population-based analysis of NHANES 2007-2018.

BACKGROUND: Obesity is characterized by excessive fat accumulation in the body. Physical activity (PA) is an effective intervention to combat obesity, but the effectiveness of different PA patterns on controlling obesity is unclear. Lipid accumulation product (LAP), derived from waist circumference and triglycerides, is a novel indicator for obesity evaluation. However, the association between PA patterns (i.e., weekend warriors and regularly active) and LAP remains unexplored. This study aims to elucidate the relationship between PA patterns and LAP in US adult population. METHODS: Adult individuals with complete data on LAP, PA patterns, and other covariates from the National Health and Nutrition Examination Survey (NHANES) database (2007-2018) were included in this study. Multivariate linear regression models were utilized to explore the association between PA patterns and LAP. Subgroup analyses, interaction tests, restricted cubic spline (RCS) regression analyses, and threshold and saturation effect analyses were also performed to investigate the stability and nonlinearity of PA-LAP association, respectively. RESULTS: A total of 11,212 participants were included in this study. After adjusting for all potential covariates, being regularly active (RA) (ß=-8.85, P < 0.05) obtained significantly higher LAP reduction as opposed to being weekend warriors (WWs) (ß=-4.70, P = 0.3841). Furthermore, subgroup analyses and interaction tests indicated that the PA-LAP association was more pronounced in individuals with higher education levels (P interaction = 0.0084) and diabetes (P interaction = 0.0062). Additionally, a significant, non-linear, and negative correlation between weekly total PA and LAP in non-inactive individuals was identified by RCS analysis (P for overall < 0.001, P for nonlinearity = 0.009). A threshold of 440 min in weekly total PA was found to arouse favorable LAP reduction. CONCLUSIONS: Being regularly active obtained better LAP reduction as opposed to being WWs. For non-inactive adults, engaging in more than 440 min of PA per week helps to reduce LAP effectively.

The associations of the concentrations of toxic metals (including metalloid) in blood and follicular fluid with the risk of diminished ovarian reserve.

BACKGROUND: Diminished ovarian reserve (DOR), a triggering factor for female infertility, affects 10% ∼ 35% of women of reproductive age. It is still unclear whether exposure to toxic metals (including metalloid) is associated with DOR risk, especially with respect to their relationships with the clinical phenotypes of DOR. METHODS: A case-control study including 439 patients was conducted, and Ba, Ni, As, Tl, Cd, Pb, Hg, Al and Cr levels in BL and FF were measured. Subsequent analyses were focused on Ba, Ni, As and Tl, which had the highest weights in the associations of the nine toxic metals (including metalloid) with DOR risk, by integrating weighted quantile sum (WQS) regression and bayesian kernel machine regression (BKMR) models. Conditional logistic regression models and BKMR models were used to assess the individual and combined effects of Ba, Ni, As and Tl exposures on DOR risk. Multiple linear regression models were used to investigate the relationships between toxic metal (including metalloid) levels in BL and FF and the clinical characteristics of DOR. RESULTS: The levels of Ba [second vs. lowest tertile: adjusted odds ratio (aOR) and 95 % confidence interval (CI) = 1.97 (1.13, 3.44); highest vs. lowest tertile: aOR (95 % CI) = 2.38 (1.32, 4.26)], Ni [highest vs. lowest tertile: aOR (95 % CI) = 2.59 (1.45, 4.65)] and As [highest vs. lowest tertile: aOR (95 % CI) = 1.96 (1.18, 3.25)] in BL, and Ba [highest vs. lowest tertile: aOR (95 % CI) = 4.60 (1.68, 12.61)] in FF were significantly associated with a higher risk of DOR, respectively. The significantly positive combined effect of the four toxic metals (including metalloid) on DOR risk was exhibited when their BL levels exceeded the 25th percentile compared with their median levels. Among these, As (0.9822) and Ba (0.9704) were the primary contributors to this relationship. Similarly, this finding was confirmed by the statistical results from FF samples, with a linear positive correlation between combined exposure and DOR risk, where Ba (0.9440) was the primary contributor. Finally, elevated levels of Ba, Ni, and As in BL and Ba in FF were significantly linked to the higher follicle-stimulating hormone (FSH) levels. The levels of Ba in BL and FF, as well as As in BL, were significantly associated with the lower luteinizing hormone (LH)/FSH ratio values. CONCLUSION: Overall, the results of this study indicate that elevated levels of Ba, Ni, As and Tl are associated with a higher risk of DOR, whether individually or in combination, and that Ba levels in BL and FF are stable contributors. In addition, exposure to Ba, Ni, As and Tl is linked to various clinical phenotype parameters of DOR. Further research is needed to confirm these associations and to identify potential mechanisms involved.

Genome-Wide Analysis of Nuclear factor-YC Genes in the Tea Plant (Camellia sinensis) and Functional Identification of CsNF-YC6.

Nuclear factor Y (NF-Y) is a class of transcription factors consisting of NF-YA, NF-YB and NF-YC subunits, which are widely distributed in eukaryotes. The NF-YC subunit regulates plant growth and development and plays an important role in the response to stresses. However, there are few reports on this gene subfamily in tea plants. In this study, nine CsNF-YC genes were identified in the genome of 'Longjing 43'. Their phylogeny, gene structure, promoter cis-acting elements, motifs and chromosomal localization of these gene were analyzed. Tissue expression characterization revealed that most of the CsNF-YCs were expressed at low levels in the terminal buds and at relatively high levels in the flowers and roots. CsNF-YC genes responded significantly to gibberellic acid (GA) and abscisic acid (ABA) treatments. We further focused on CsNF-YC6 because it may be involved in the growth and development of tea plants and the regulation of response to abiotic stresses. The CsNF-YC6 protein is localized in the nucleus. Arabidopsis that overexpressed CsNF-YC6 (CsNF-YC6-OE) showed increased seed germination and increased root length under ABA and GA treatments. In addition, the number of cauline leaves, stem lengths and silique numbers were significantly higher in overexpressing Arabidopsis lines than wild type under long-day growth conditions, and CsNF-YC6 promoted primary root growth and increased flowering in Arabidopsis. qPCR analysis showed that in CsNF-YC6-OE lines, flowering pathway-related genes were transcribed at higher levels than wild type. The investigation of the CsNF-YC gene has unveiled that CsNF-YC6 plays a pivotal role in plant growth, root and flower development, as well as responses to abiotic stress.

Multiple Stabilization Effects of Benzylhydrazine on Scalable Perovskite Precursor Inks for Improved Perovskite Solar Cell Production.

Perovskite precursor inks suffer various forms of degradation, such as iodide anion oxidation and organic cation breakdown, hindering reliable perovskite solar cell manufacturing. Here we report that benzylhydrazine hydrochloride (BHC) not only retards the buildup of iodine as previously reported but also prevents the breakdown of organic cations. Through investigating BHC and iodine chemical reactions, we elucidate protonation and dehydration mechanisms, converting BHC to harmless volatile compounds, thus preserving perovskite film crystallization and solar cell performance. This inhibition effect lasts nearly a month with minimal BHC, contrasting control inks without BHC where organic cations fully react in less than a week. This enhanced understanding, from additive stabilization to end products, promises improved perovskite solar cell production reliability.

Elastic Relaxor Ferroelectric by Thiol-ene Click Reaction.

As ferroelectrics hold significance and application prospects in wearable devices, the elastification of ferroelectrics becomes more and more important. Nevertheless, achieving elastic ferroelectrics requires stringent synthesis conditions, while the elastification of relaxor ferroelectric materials remains unexplored, presenting an untapped potential for utilization in energy storage and actuation for wearable electronics. The thiol-ene click reaction offers a mild and rapid reaction platform to prepare functional polymers. Therefore, we employed this approach to obtain an elastic relaxor ferroelectric by crosslinking an intramolecular carbon-carbon double bonds (CF=CH) polymer matrix with multiple thiol groups via a thiol-ene click reaction. The resulting elastic relaxor ferroelectric demonstrates pronounced relaxor-type ferroelectric behaviour. This material exhibits low modulus, excellent resilience, and fatigue resistance, maintaining a stable ferroelectric response even under strains up to 70 %. This study introduces a straightforward and efficient approach for the construction of elastic relaxor ferroelectrics, thereby expanding the application possibilities in wearable electronics.

High-Throughput Exploration of Triple-Cation Perovskites via All-in-One Compositionally-Graded Films.

Many devices heavily rely on combinatorial material optimization. However, new material alloys are classically developed by studying only a fraction of giant chemical space, while many intermediate compositions remain unmade in light of the lack of methods to synthesize gapless material libraries. Here report a high-throughput all-in-one material platform to obtain and study compositionally-tunable alloys from solution is reported. This strategy is applied to make all Csx MAy FAz PbI3 perovskite alloys (MA and FA stand for methylammonium and formamidinium, respectively), in less than 10 min, on a single film, on which 520 unique alloys are then studied. Through stability mapping of all these alloys in air supersaturated with moisture, a range of targeted perovskites are found, which are then chosen to make efficient and stable solar cells in relaxed fabrication conditions, in ambient air. This all-in-one platform provides access to an unprecedented library of compositional space with no unmade alloys, and hence aids in a comprehensive accelerated discovery of efficient energy materials.

The EPFL-ERf-SERK signaling controls integument development in Arabidopsis.

As the seed precursor, the ovule produces the female gametophyte (or embryo sac), and the subsequent double fertilization occurs in it. The integuments emerge sequentially from the integument primordia at the early stages of ovule development and finally enwrap the embryo sac gradually during gametogenesis, protecting and nursing the embryo sac. However, the mechanisms regulating integument development are still obscure. In this study, we show that SOMATIC EMBRYOGENESIS RECEPTOR-LIKE KINASES (SERKs) play essential roles during integument development in Arabidopsis thaliana. The serk1/2/3 triple mutant shows arrested integuments and abnormal embryo sacs, similar defects also found in the triple loss-of-function mutants of ERECTA family (ERf) genes. Ovules of serk1/2/3 er erl1/2 show defects similar to er erl1/2 and serk1/2/3. Results of yeast two-hybrid analyses, bimolecular fluorescence complementation (BiFC) analyses, and co-immunoprecipitation assays demonstrated that SERKs interact with ERf, which depends on EPIDERMAL PATTERNING FACTOR-LIKE (EPFL) family small peptides. The sextuple mutant epfl1/2/3/4/5/6 shows integument defects similar to both of er erl1/2 and serk1/2/3. Our results demonstrate that ERf-SERK-mediated EPFL signaling orchestrates the development of the female gametophyte and the surrounding sporophytic integuments.

Fluorescent cellulose nanocrystals/waterborne polyurethane nanocomposites for anti-counterfeiting applications.

The development of eco-friendly anti-counterfeiting materials with high optical transparency and bright luminescence in the aggregate state is tremendously challenging. Herein, waterborne polyurethane/tetraphenylethylene-cellulose nanocrystal (WPU/TPE-CNC) nanocomposite aqueous solutions and films were prepared via direct blending aggregation-induced emission (AIE) active fluorescent CNCs (TPE-CNCs) with WPU and then applied in the anti-counterfeiting field. TPE-CNCs are compatible with WPU and dispersed homogeneously in the nanocomposite aqueous solutions and films. The thermal stability and mechanical properties of these films significantly improved with the increase in the content of TPE-CNCs. WPU/TPE-CNC nanocomposite films display high transparency (above 80%), excellent fluorescence properties, high mechanical strength, and good flexibility and then successfully applied to anti-counterfeit marking. Moreover, the dispersions of the aqueous WPU/TPE-CNC nanocomposite were nearly colorless and demonstrated promise as fluorescent anti-counterfeiting inks. This novel eco-friendly nanocomposite exhibited the potential for applications in anti-counterfeiting, fluorescent transparent paper and coating, fluorescent 3D printing, and optical/sensing devices.

Polymorphisms of mtDNA in the D-loop region moderate the associations of BMI with HOMA-IR and HOMA-ß among women with polycystic ovary syndrome: a cross-sectional study.

PURPOSE: Polycystic ovary syndrome (PCOS) is one of the leading causes of infertility in women of childbearing age, and many patients with PCOS have obesity and insulin resistance (IR). Although obesity is related to an increased risk of IR, in clinical practice, PCOS patients exhibit different effects on improving insulin sensitivity after weight loss. Therefore, in the present study, we aimed to examine the moderating effect of polymorphisms of mtDNA in the D-loop region on the associations of body mass index (BMI) with the homeostasis model assessment of insulin resistance index (HOMA-IR) and pancreatic ß cell function index (HOMA-ß) among women with PCOS. METHODS: Based on a cross-sectional study, women with PCOS were recruited from the Reproductive Center of the First Affiliated Hospital of Anhui Medical University from 2015 to 2018. A total of 520 women who were diagnosed with PCOS based on the revised 2003 Rotterdam criteria were included in the study. Peripheral blood was collected from these patients, followed by DNA extraction, PCR amplification, and sequencing at baseline. HOMA-IR and HOMA-ß were calculated according to blood glucose-related indices. Moderating effect models were performed with BMI as an independent variable, polymorphisms of mtDNA in the D-loop region as moderators, and ln (HOMA-IR) and ln (HOMA-ß) as dependent variables. To verify the stability of moderating effect, sensitivity analysis was performed with the quantitative insulin sensitivity check index (QUICKI), fasting plasma glucose/fasting insulin (G/I), and fasting insulin as dependent variables. RESULTS: BMI was positively associated with ln (HOMA-IR) and ln (HOMA-ß) (ß = 0.090, p < 0.001; ß = 0.059, p < 0.001, respectively), and the relationship between BMI and ln (HOMA-IR) or ln (HOMA-ß) was moderated by the polymorphisms of mtDNA in the D-loop region. Compared with the respective wild-type, the variant -type of m.16217 T > C enhanced the association between BMI and HOMA-IR, while the variant-type of m.16316 A > G weakened the association. On the other hand, the variant-type of m.16316 A > G and m.16203 A > G weakened the association between BMI and HOMA-ß, respectively. The results of QUICKI and fasting insulin as dependent variables were generally consistent with HOMA-IR, and the results of G/I as dependent variables were generally consistent with HOMA-ß. CONCLUSION: Polymorphisms of mtDNA in the D-loop region moderate the associations of BMI with HOMA-IR and HOMA-ß among women with PCOS.

Starch and Sucrose Metabolism and Plant Hormone Signaling Pathways Play Crucial Roles in Aquilegia Salt Stress Adaption.

Salt stress is one of the main abiotic stresses that strongly affects plant growth. Clarifying the molecular regulatory mechanism in ornamental plants under salt stress is of great significance for the ecological development of saline soil areas. Aquilegia vulgaris is a perennial with a high ornamental and commercial value. To narrow down the key responsive pathways and regulatory genes, we analyzed the transcriptome of A. vulgaris under a 200 mM NaCl treatment. A total of 5600 differentially expressed genes were identified. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis pointed out that starch and sucrose metabolism and plant hormone signal transduction were significantly improved. The above pathways played crucial roles when A. vulgaris was coping with salt stress, and their protein-protein interactions (PPIs) were predicted. This research provides new insights into the molecular regulatory mechanism, which could be the theoretical basis for screening candidate genes in Aquilegia.

Time-Course Transcriptome Analysis of Aquilegia vulgaris Root Reveals the Cell Wall's Roles in Salinity Tolerance.

Salt stress has a considerable impact on the development and growth of plants. The soil is currently affected by salinisation, a problem that is becoming worse every year. This means that a significant amount of salt-tolerant plant material needs to be added. Aquilegia vulgaris has aesthetically pleasing leaves, unique flowers, and a remarkable tolerance to salt. In this study, RNA-seq technology was used to sequence and analyse the transcriptome of the root of Aquilegia vulgaris seedlings subjected to 200 mM NaCl treatment for 12, 24, and 48 h. In total, 12 Aquilegia vulgaris seedling root transcriptome libraries were constructed. At the three time points of salt treatment compared with the control, 3888, 1907, and 1479 differentially expressed genes (DEGs) were identified, respectively. Various families of transcription factors (TFs), mainly AP2, MYB, and bHLH, were identified and might be linked to salt tolerance. Gene Ontology (GO) analysis of DEGs revealed that the structure and composition of the cell wall and cytoskeleton may be crucial in the response to salt stress. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of the DEGs showed a significant enrichment of the pentose and glucuronate interconversion pathway, which is associated with cell wall metabolism after 24 and 48 h of salt treatment. Based on GO and KEGG analyses of DEGs, the pentose and glucuronate interconversion pathway was selected for further investigation. AP2, MYB, and bHLH were found to be correlated with the functional genes in this pathway based on a correlation network. This study provides the groundwork for understanding the key pathways and gene networks in response to salt stress, thereby providing a theoretical basis for improving salt tolerance in Aquilegia vulgaris.

Site-Specific and Enzymatic Cross-Linking of sgRNA Enables Wavelength-Selectable Photoactivated Control of CRISPR Gene Editing.

Chemical cross-linking enables rapid identification of RNA-protein and RNA-nucleic acid inter- and intramolecular interactions. However, no method exists to site-specifically and covalently cross-link two user-defined sites within an RNA. Here, we develop RNA-CLAMP, which enables site-specific and enzymatic cross-linking (clamping) of two selected guanine residues within an RNA. Intramolecular clamping can disrupt normal RNA function, whereas subsequent photocleavage of the cross-linker restores activity. We used RNA-CLAMP to clamp two stem loops within the single-guide RNA (sgRNA) of the CRISPR-Cas9 gene editing system via a photocleavable cross-linker, completely inhibiting gene editing. Visible light irradiation cleaved the cross-linker and restored gene editing with high spatiotemporal resolution. Design of two photocleavable linkers responsive to different wavelengths of light allowed multiplexed photoactivation of gene editing in mammalian cells. This photoactivated CRISPR-Cas9 gene editing platform benefits from undetectable background activity, provides a choice of activation wavelengths, and has multiplexing capabilities.

Photoelastic Organogel with Multiple Stimuli Responses.

The photoelastic effect has many uses in mechanics today, but it is usually disregarded in flexible materials. Using 2-phenoxyethyl acrylate as a monomer and 4-cyano-4'-pentylbiphenyl (5CB) as a solvent, a multiple responsive photoelastic organogel (PO) with strong birefringence but low modulus is created. 5CB is a liquid crystal molecule that does not participate in the polymerization process and is always present as tiny molecules in the polymer. It endows the PO low modulus and high birefringence, as well as the ability to drive the birefringence using an electric field. This PO not only has high sensitivity and fast response as a photoelastic strain sensor, but also has a very sensitive response to heat, especially in the range of human body temperature. It also has a high dielectric constant and a strong correlation between the interference color and the applied electric field, allowing for easy writing and erasure of encrypted data. This unique multisignal response feature and low modulus that mimics human skin bring up new opportunities in the potential applications such as multiple information encryption, anticounterfeiting, and multifunctional wearable sensors.

In-situ TiO2-x decoration of titanium carbide MXene for photo/sono-responsive antitumor theranostics.

BACKGROUND: Sonodynamic therapy (SDT) has emerged as a noninvasive therapeutic modality that involves sonosensitizers and low-intensity ultrasound. However, owing to the rapid recombination of charge carriers, most of the sonosensitizers triggered poor reactive oxygen species (ROS) generation, resulting in unsatisfactory sonodynamic therapeutic effects. RESULTS: Herein, a photo/sono-responsive nanoplatform was developed through the in-situ systhesis of TiO2-x on the surface of two-dimensional MXene (titanium carbide, Ti3C2) for photoacoustic/photothermal bimodal imaging-guided near-infrared II (NIR-II) photothermal enhanced SDT of tumor. Because of several oxygen vacancies and smaller size (~ 10 nm), the in-situ formed TiO2-x nanoparticles possessed narrow band gap (2.65 eV) and high surface area, and thus served as a charge trap to restrict charge recombination under ultrasound (US) activation, resulting in enhanced sonodynamic ROS generation. Moreover, Ti3C2 nanosheets induced extensive localized hyperthermia relieves tumor hypoxia by accelerating intratumoral blood flow and tumor oxygenation, and thus further strengthened the efficacy of SDT. Upon US/NIR-II laser dual-stimuli, Ti3C2@TiO2-x nanoplatform triggered substantial cellular killing in vitro and complete tumor eradication in vivo, without any tumor recurrence and systemic toxicity. CONCLUSION: Our work presents the promising design of photo/sono-responsive nanoplatform for cancer nanotheranostics.

Evaluation of the Chemical Composition and Antioxidant Activity of Mulberry (Morus alba L.) Fruits from Different Varieties in China.

Mulberry (Morus alba L.) fruit is a fruit with nutritional and medicinal value. It is widely cultivated in different regions of China, which may result in differences in its chemical composition. In this research, 25 mulberry fruit samples from six provinces in China were investigated. The contents of anthocyanins were evaluated by high-performance liquid chromatography (HPLC). The contents of two main anthocyanins, cyanidin-3-O-glucoside (C3G) and cyanidin-3-O-rutinoside (C3R), ranged from 0.656 ± 0.006 mg/g to 4.367 ± 0.243 mg/g and from 0.226 ± 0.007 mg/g to 1.649 ± 0.013 mg/g, respectively. Additionally, the contents of total phenolic, total flavonoid, vitamin C, titratable acids, reducing sugars and antioxidant capacity (FRAP, DPPH, scavenging and hydroxyl radical scavenging activity) were also assessed. The results and principal component analysis showed that the Zhongsang 5801 variety from Sichuan, Dechang had the greatest health value with the highest active compound contents. Based on our analysis, the variety from Sichuan, Dechang is a high-quality plant source for mulberry fruit cultivation. This research provides a basis for the rational development and utilization of mulberry fruit resources in China.

Increased anxiety was found in serpini1 knockout zebrafish larval.

Serpini1, which encodes neuroserpin, has been implicated in the development and normal function of the nervous system. Mutations in serpini1 cause familial encephalopathy, a rare neurodegenerative disorder characterized with neuroserpin inclusion bodies. However, function of neuroserpin in the nervous system is not fully understood. In this study, we generated a novel serpini1 mutant zebrafish model to investigate the loss of function of neuroserpin. Serpini1- deficient mutation was created with the CRISPR/Cas9 technique. No severe morphological characteristics were found in serpini1- deficient zebrafish. Serpini1-/- zebrafish larvae did not cause locomotor defects but displayed anxiety-like behavior. Extension of motoneurons axon defect was observed in serpini1-/- zebrafish. Furthermore, RNA-sequencing analysis revealed that loss of serpini1 resulted in affected expression of neurodegeneration-related genes.