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Lung cystic fibrosis (CF) is a lethal inherited disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, leading to a dysfunctional CFTR protein. Gene therapy offers promise for the treatment of lung CF. However, the development and clinical application of CF gene therapy have long been hampered by the absence of safe and highly efficient delivery vectors. In this work, a novel polymer-based gene replacement treatment approach was developed. A series of poly (β-amino esters) (PAEs) with various topological structures and chemical compositions were screened to create non-viral therapeutic systems for CFTR restoration in lung CF disease. A nanoparticle, formed by the selected highly branched PAE (HPAE) with a CpG-depleted CFTR plasmid, demonstrated CFTR gene expression and biocompatibility in lung epithelial cells, outperforming leading commercial gene transfection reagents such as Lipofectamine 3000 and Xfect. The newly developed gene therapy system successfully restored functional CFTR protein production in lung CF epithelial monolayers. This therapeutic approach holds great potential for use as an efficient and safe non-viral treatment for CF patients.

Summary: Natural silks are renewable proteins with impressive mechanical properties and biocompatibility that are useful in various fields. However, the cellular and spatial organization of silk-secreting organs remains unclear. Here, we combined single-nucleus and spatially resolved transcriptomics to systematically map the cellular and spatial composition of the silk glands (SGs) of mulberry silkworms late in larval development. This approach allowed us to profile SG cell types and cell state dynamics and identify regulatory networks and cell-cell communication related to efficient silk protein synthesis; key markers were validated via transgenic approaches. Notably, we demonstrated the indispensable role of the ecdysone receptor (ultraspiracle) in regulating endoreplication in SG cells. Our atlas presents the results of spatiotemporal analysis of silk-secreting organ architecture late in larval development; this atlas provides a valuable reference for elucidating the mechanism of efficient silk protein synthesis and developing sustainable products made from natural silk.

Background: The efficacy of Kinesio tape (KT) in lateral elbow tendinopathy (LET) has been widely discussed, but controversy remains. Objectives: To perform a meta-analysis of randomized controlled trials (RCTs) in the literature to ascertain the efficacy of KT in LET. Design: Systematic review and meta-analysis. Method: Two independent reviewers carried out a literature search in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Any discrepancies were addressed by a third author. Included in the study were RCTs comparing KT to a control group in the context of LET. The quality of evidence was assessed with the 2.0 version of Cochrane Collaboration risk of bias tool. Evaluation centered on clinical outcomes, such as function scores and pain, with comparison made using the risk ratio for dichotomous variables and the mean difference for continuous variables. Statistical significance was considered for P values

In the present study, we demonstrated that the presence of cysteine could remarkably enhance the degradation of atrazine by Fe3O4/persulfate system. The results of electron paramagnetic resonance (EPR) spectra confirmed the combination of cysteine and Fe3O4 exhibited much higher activity on activation of persulfate to generate more SO4•- and •OH than Fe3O4 alone. At pH of 3.0, SO4•- and •OH contributed to about 58.2 % and 41.8 % of atrazine removal respectively, while •OH gradually dominated the oxidation of atrazine from neutral condition to alkaline condition. The co-existing Cl− and HCO3− could quench SO4•-, resulting in the inhibition of atrazine degradation. The presence of low natural organic matters (NOM) concentration (0–2 mg L−1) could enhance the atrazine removal, and high concentration (>5 mg L−1) of NOM restrained the atrazine degradation. During the Cysteine/Fe3O4/Persulfate process, cysteine served as a complexing reagent and reductant. Through acidolysis and complexation, Fe3O4 could release dissolved and surface bound Fe2+, both of which contributed to the activation of persulfate together. Meanwhile, cysteine was not rapidly consumed due to a regeneration process, which was beneficial for maintaining Fe2+/Fe3+ cycle and constantly accelerating the activation of persulfate for atrazine degradation. The reused Fe3O4 and cysteine in the Cysteine/Fe3O4/Persulfate process exhibited high stability for the atrazine degradation after three cycles. The degradation pathway of atrazine included alkylic-oxidation, dealkylation, dechlorination-hydroxylation processes. The present study indicates the novel Cysteine/Fe3O4/Persulfate process might be a high potential for treatment of organic polluted water.

Recessive dystrophic epidermolysis bullosa (RDEB) is an autosomal monogenic skin disease caused by mutations in COL7A1 gene and lack of functional type VII collagen (C7). Currently, there is no cure for RDEB, and most of the gene therapies under development have been designed as ex vivo strategies because of the shortage of efficient and safe carriers for gene delivery. Herein, we designed, synthesized, and screened a new group of highly branched poly(β amino ester)s (HPAEs) as non-viral carriers for the delivery of plasmids encoding dual single-guide RNA (sgRNA)-guided CRISPR-Cas9 machinery to delete COL7A1 exon 80 containing the c.6527dupC mutation. The selected HPAEs (named PTTA-DATOD) showed robust transfection efficiency, comparable with or surpassing that of leading commercial gene transfection reagents such as Lipofectamine 3000, Xfect, and jetPEI, while maintaining negligible cytotoxicity. Furthermore, CRISPR-Cas9 plasmids delivered by PTTA-DATOD achieved efficient targeted deletion and restored bulk C7 production in RDEB patient keratinocyte polyclones. The non-viral CRISPR-Cas9-based COL7A1 exon deletion approach developed here has great potential to be used as a topical treatment for RDEB patients with mutations in COL7A1 exon 80. Besides, this therapeutic strategy can easily be adapted for mutations in other COL7A1 exons, other epidermolysis bullosa subtypes, and other genetic diseases.

Laser shock peening (LSP) is a novel metal surface modifying technology, which can enhance the mechanical properties of materials and extend fatigue performance of components evidently. The outstanding mechanical properties induced by LSP occurs through severe plastic deformation, which will cause the surface topography evolution. With the rapid development of artificial intelligence (AI), which provide an effective solution to solve complex problems when with limited experimental data. In this work, FGH4095 superalloy was selected as the experimental material. LSP experiments were conducted with a Q-switched Nd: YAG laser. Laser energy of 4 J, 6 J and 8 J were used with overlap rate of 30 % and 50 %. The residual stress, microhardness and surface topography of experimental samples treated by LSP was investigated. What is more, the AI method based on XGBoost was applied to predict the mechanical properties and surface roughness of FGH4095 treated by LSP. The laser energy, overlap rate, depth were set as input parameters, while the residual stress, microhardness and surface roughness were set as output parameters. The predicted results showed a great agreement with the experimental data. It can be indicated that XGBoost is a suitable method for accurately performing prediction of mechanical properties and surface roughness of materials treated by LSP.

Summary: The widespread use of biological tissue adhesives for tissue repair is limited by their weak adhesion in a wet environment. Herein, we report the wet adhesion mechanism of a dry granular natural bioadhesive from Andrias davidianus skin secretion (ADS). Once contacting water, ADS granules self-assemble to form a hydrophobic hydrogel strongly bonding to wet substrates in seconds. ADS showed higher shear adhesion than current commercial tissue adhesives and an impressive 72-h underwater adhesion strength of ∼47kPa on porcine skin tissue. The assembled hydrogel in water maintained a dissipation energy of ∼8 kJ/m3, comparable to the work density of muscle, exhibiting its robustness. Unlike catechol adhesion mechanism, ADS wet adhesion mechanism is attributed to water absorption by granules, and the unique equilibrium of protein hydrophobicity, hydrogen bonding, and ionic complexation. The in vivo adhesion study demonstrated its excellent wet adhesion and hemostasis performance in a rat hepatic and cardiac hemorrhage model.

Objective: To investigate the acute effects of blood flow restriction (BFR) with single-leg low load resistance exercise and high load resistance exercise on serum insulin-like growth factor-1 (IGF-1), growth hormone (GH), and testosterone in patients with unilateral knee osteoarthritis (OA). Methods: This study recruited 18 postmenopausal female patients with mild to moderate unilateral knee OA, which was then followed by randomly conducting three resistance exercise protocols by drawing lots: 1. A 30% 1-repetition maximum (1-RM) resistance exercise with BFR of 70% arterial occlusive pressure (AOP) (BFR group); 2. A 70% 1-RM resistance exercise without BFR (RES group); 3. A 30% 1-RM resistance exercise without BFR (CON group). Blood lactate (BLA) and muscle growth related hormone levels were tested at 4-time points: before exercise, immediately after exercise, 15 min after exercise, and 30 min after exercise. Results: There was no statistical difference between the indexes in each group before exercise, but the different exercise had different effects on each index and also an interactive effect (P < 0.05). The increase of rating of perceived exertion in the BFR and RES groups, which were of similar magnitude, was greater compared to the levels in the CON group (P < 0.05). Post-exercise BLA levels were lower in the CON group in comparison to the BFR and RES groups (P < 0.05). Rather than the RES group, GH levels of the BFR group were also significantly higher than the CON group (P < 0.05) at 15 min post-exercise. At post- and 15 min after exercise, the CON group recorded significantly lower IGF-1 levels compared to the BFR and RES groups (P < 0.05). At post- and 15 min after exercise, the CON group (P < 0.05) reflected the lowest testosterone levels, followed by the RES group (P < 0.05), and the highest in the BFR group (P < 0.05). Conclusions: Myogenesis-related hormones in women with unilateral knee OA could be increased by high load resistance exercise and low load resistance exercise with BFR on unaffected limb.

Apple replant disease (ARD) negatively affects plant growth and reduces yields in replanted orchards. In this study, biochar and humic acid were applied to apple replant soil. We aimed to investigate whether biochar and humic acid could promote plant growth and alleviate apple replant disease by reducing the growth of harmful soil microorganisms, changing soil microbial community structure, and improving the soil environment. This experiment included five treatments: apple replant soil (CK), apple replant soil with methyl bromide fumigation (FM), replant soil with biochar addition (2 %), replant soil with humic acid addition (1.5 ‰), and replant soil with biochar combined with humic acid. Seedling biomass, the activity of antioxidant enzymes in the leaves and roots, and soil environmental variables were measured. Microbial community composition and structure were analyzed using ITS gene sequencing. Biochar and humic acid significantly reduced the abundance of Fusarium and promoted the recovery of replant soil microbial communities. Biochar and humic acid also increased the soil enzymes activity (urease, invertase, neutral phosphatase, and catalase), the plant height, fresh weight, dry weight, the activity of antioxidant enzymes (superoxide dismutase, peroxidase, and catalase), and root indexes of apple seedlings increased in replant soil. In sum, We can use biochar combined with humic acid to alleviate apple replant disease.

Summary: The generation of neurons from quiescent radial-glia-like neural stem cells (RGLs) in adult brain goes hand in hand with the modulation of cellular metabolism. However, it is still unclear how the exact metabolic program governs the balance between quiescent and activated RGLs. Here, we find that loss of mitochondrial D-2-hydroxyglutarate dehydrogenase (D2HGDH) leads to aberrant accumulation of D-2-hydroxyglutarate (D-2-HG) and impaired RGL activation. Mechanistically, accumulated D-2-HG bonds directly to ATP-citrate lyase and competitively inhibits its enzymatic activity, thereby reducing acetyl-CoA production and diminishing histone acetylation. However, administration of acetate restores the acetyl-CoA levels via acetyl-CoA synthetase-mediated catabolism and rescues the deficiencies in histone acetylation and RGL activation caused by loss of D2HGDH. Therefore, our findings define the role of cross talk between mitochondria and the nucleus via a mitochondrial metabolite, D-2-HG, the aberrant accumulation of which hinders the regulation of histone acetylation in RGL activation and attenuates continuous neurogenesis in adult mammalian brain.

Subculture, includes animation, comics, games (ACG), and idol fan culture, is popular among young generations in Japan. Previous studies have shown different psychological outcomes within different subcultural groups; however, underlying mechanisms remain unclear. This study proposes that subcultural identity may play a crucial role in mental health outcomes by interweaving social support and reputation. We examined the interplay between subcultural identity, social support, reputation, and different psychological outcomes through structural equation modeling (N = 300). Furthermore, we trained neural networks (NN) by applying a deep learning algorithm to predict psychological outcomes of different subcultures. The results suggest identity related to anime, idol, and hip-hop was positively associated with anxiety, aggression, depressive symptoms, and suicidal tendencies. By contrast, fashion and sports identities associated with no adverse or positive psychological outcomes. Perceived reputation mediates adverse psychological outcomes in the ACG, idol, and hip-hop groups. The highest accuracy in our NN reached 71%, indicating that NN could be an effective tool for predicting mental problems. Our work points up an urgent need to improve the mental health of the young generation by de-stigmatizing discriminated cultural groups.