Antigen self-presenting dendrosomes swallowing nanovaccines boost antigens and STING agonists codelivery for cancer immunotherapy.

Cancer vaccines show promise by eliciting tumor-specific cytotoxic T lymphocytes (CTL) responses. Efficient cytosolic co-delivery of antigens and adjuvants to dendritic cells (DCs) is crucial for vaccines to induce anti-tumor immunity. However, peptide- or nucleic acid-based biomolecules like tumor antigens and STING agonist cyclic-di-GMP (cdGMP) are prone to endosomal degradation, resulting in low cytosolic delivery and CTL response rates.

Analysis and actuation design of a novel at-scale 3-DOF biomimetic flapping-wing mechanism inspired by flying insects.

Insects' flight is imbued with endless mysteries, offering valuable inspiration to the flapping-wing robots. Particularly, the multi-mode wingbeat motion such as flapping, sweeping and twisting in coordination presents advantages in promoting unsteady aerodynamics and enhancing lift force. To achieve the flapping-twisting-sweeping motion capability, this paper proposes an at-scale three-degree-of-freedom (3-DOF) mechanism driven by three piezoelectric actuators, which consists of three four-bar mechanisms and a parallel spherical mechanism.

Cadmium uptake and transport in vegetables near a zinc-lead mine: Novel insights from Cd isotope fractionation.

In this study, Cd isotope analysis was conducted on drought-tolerant (cowpea and sesame) and less drought-tolerant vegetables (water spinach, green pepper, and mung bean) to elucidate the mechanisms underlying Cd uptake and transport. Cd isotopes in plants were identical to or lighter than those in the available pool and exhibited negative fractionation from roots to straws (ΔCd = -0.22 ‰ to -0.

Liquid Crystal Promoted Self-Assembly of Statistical Copolymers into Diverse Nanostructures with Precise Dimensions.

In both natural and synthetic systems, the segregation of multicomponent entities is vital for regulating functions and the ultimate usage of materials. To accomplish the desired properties via nanosegregation or microphase separation, great effort is usually demanded in the synthesis. For example, microphase-separated block copolymers rely on the delicate controlled/living polymerization of different monomers in sequence.

LN-439A, a novel BAP1 inhibitor, suppresses the growth of basal-like breast cancer by degrading KLF5.

Basal-like breast cancer (BLBC) is the most malignant subtype of breast cancer because of its aggressive clinical behaviour and lack of effective targeted agents. Krüppel-like factor 5 (KLF5) is an oncogenic transcription factor that is highly expressed in BLBC. The deubiquitinase (DUB) BRCA1-associated protein 1 (BAP1) stabilizes KLF5 and promotes BLBC growth and metastasis.

Loss of , an Arthrogryposis Multiplex Congenita Associated Gene, Promotes Osteoclastogenesis in Mice.

encodes a -type zinc finger protein, mutations of which lead to a spectrum of diseases known as associated rare disorders (ZARD). In addition to neurological phenotypes, the most typical symptoms of ZARD are multiple joint contractures of varying degrees, accompanied by abnormal development of muscles and bones, and osteoporosis in some cases. The pathogenic mechanisms of such bone related phenotypes, however, remain unclear.

Chloride-mediated enhancement in Cu(II)-catalyzed Fenton-like reaction: The overlooked reactive chlorine species.

The practical application of Cu(II)-catalyzed Fenton-like reaction (Cu(II)/HO) exhibits a low efficiency in the degradation of refractory compounds of wastewater. The impact of chloride ions (Cl) on Fenton-like reactions have been investigated, but the influence mechanism is still unclear. Herein, the presence of Cl (5 mM) significantly accelerated the degradation of benzoic acid (BA) under neutral conditions.

PI3K PROTAC overcomes the lapatinib resistance in PIK3CA-mutant HER2 positive breast cancer.

Although anti-HER2 therapy has made significant strides in reducing metastasis and relapse in HER2-positive breast cancer, resistance to agents like trastuzumab, pertuzumab, and lapatinib frequently develops in patients undergoing treatment. Previous studies suggest that the hyperactivation of the PI3K-AKT signaling pathway by PIK3CA/PTEN gene mutations is implicated in HER2 resistance. In this study, we introduce a novel PI3K-p110α Proteolysis TAargeting Chimera (PROTAC) that effectively inhibits the proliferation of breast cancer cells by degrading PI3K-p110α.

The Application of Multi-Parameter Multi-Modal Technology Integrating Biological Sensors and Artificial Intelligence in the Rapid Detection of Food Contaminants.

Against the backdrop of continuous socio-economic development, there is a growing concern among people about food quality and safety. Individuals are increasingly realizing the critical importance of healthy eating for bodily health; hence the continuous rise in demand for detecting food pollution. Simultaneously, the rapid expansion of global food trade has made people's pursuit of high-quality food more urgent.

Bilateral gene therapy in children with autosomal recessive deafness 9: single-arm trial results.

Gene therapy is a promising approach for hereditary deafness. We recently showed that unilateral AAV1-hOTOF gene therapy with dual adeno-associated virus (AAV) serotype 1 carrying human OTOF transgene is safe and associated with functional improvements in patients with autosomal recessive deafness 9 (DFNB9). The protocol was subsequently amended and approved to allow bilateral gene therapy administration.

Engineering of the AAV-Compatible Hair Cell-Specific Small-Size Myo15 Promoter for Gene Therapy in the Inner Ear.

Adeno-associated virus (AAV)-mediated gene therapy is widely applied to treat numerous hereditary diseases in animal models and humans. The specific expression of AAV-delivered transgenes driven by cell type-specific promoters should further increase the safety of gene therapy. However, current methods for screening cell type-specific promoters are labor-intensive and time-consuming.

Using UV/peracetic acid as pretreatment for subsequent bio-treatment of antibiotic-containing wastewater treatment: Mitigating microbial inhibition and antibiotic resistance genes proliferation.

UV/peracetic acid (PAA) treatment presents a promising approach for antibiotic removal, but its effects on microbial community and proliferation of antibiotic resistance genes (ARGs) during the subsequent bio-treatment remain unclear. Thus, we evaluated the effects of the UV/PAA on tetracycline (TTC) degradation, followed by introduction of the treated wastewater into the bio-treatment system to monitor changes in ARG expression and biodegradability. Results demonstrated effective TTC elimination by the UV/PAA system, with carbon-centered radicals playing a significant role.

Predicting the Posture of High-Rise Building Machines Based on Multivariate Time Series Neural Network Models.

High-rise building machines (HBMs) play a critical role in the successful construction of super-high skyscrapers, providing essential support and ensuring safety. The HBM's climbing system relies on a jacking mechanism consisting of several independent jacking cylinders. A reliable control system is imperative to maintain the smooth posture of the construction steel platform (SP) under the action of the jacking mechanism.

Hair cell-specific Myo15 promoter-mediated gene therapy rescues hearing in DFNB9 mouse model.

Adeno-associated viral (AAV) vectors are increasingly used as vehicles for gene delivery to treat hearing loss. However, lack of specificity of the transgene expression may lead to overexpression of the transgene in nontarget tissues. In this study, we evaluated the expression efficiency and specificity of transgene delivered by AAV-PHP.

Toxoflavin analog D43 exerts antiproliferative effects on breast cancer by inducing ROS-mediated apoptosis and DNA damage.

Triple-negative breast cancer (TNBC) is regarded as the deadliest subtype of breast cancer because of its high heterogeneity, aggressiveness, and limited treatment options. Toxoflavin has been reported to possess antitumor activity. In this study, a series of toxoflavin analogs were synthesized, among which D43 displayed a significant dose-dependent inhibitory effect on the proliferation of TNBC cells (MDA-MB-231 and HCC1806).

Electrochemically Exfoliated Graphene Additive-Free Inks for 3D Printing Customizable Monolithic Integrated Micro-Supercapacitors on a Large Scale.

Three-dimensional (3D) printing technology with enhanced fidelity can achieve multiple functionalities and boost electrochemical performance of customizable planar micro-supercapacitors (MSCs), however, precise structural control of additive-free graphene-based macro-assembly electrode for monolithic integrated MSCs (MIMSCs) remains challenging. Here, the large-scale 3D printing fabrication of customizable planar MIMSCs is reported utilizing additive-free, high-quality electrochemically exfoliated graphene inks, which is not required the conventional cryogenic assistance during the printing process and any post-processing reduction. The resulting MSCs reveal an extremely small engineering footprint of 0.

AAV1-hOTOF gene therapy for autosomal recessive deafness 9: a single-arm trial.

Background: Autosomal recessive deafness 9, caused by mutations of the OTOF gene, is characterised by congenital or prelingual, severe-to-complete, bilateral hearing loss. However, no pharmacological treatment is currently available for congenital deafness. In this Article, we report the safety and efficacy of gene therapy with an adeno-associated virus (AAV) serotype 1 carrying a human OTOF transgene (AAV1-hOTOF) as a treatment for children with autosomal recessive deafness 9.

Computer Vision Interaction Design in Sustainable Urban Development: A Case Study of Roof Garden Landscape Plants in Marine Cities.

The rapid urbanization and the increasing need for sustainable development have led to the emergence of green roof landscapes in ocean cities. These rooftop gardens provide numerous environmental benefits and contribute to the overall well-being of urban dwellers. However, optimizing the design and interaction experience of green roof landscapes requires the integration of intelligent technologies.

Phosphorus recovery from sewage sludge ash (SSA): An integrated technical, environmental and economic assessment of wet-chemical and thermochemical methods.

Incineration is a promising disposal method for sewage sludge (SS), enriching more than 90% of phosphorus (P) in the influent into the powdered product, sewage sludge ash (SSA), which is convenient for further P recovery. Due to insufficient bioavailable P and enriched heavy metals (HMs) in SSA, it is limited to be used directly as fertilizer. Hence, this paper provides an overview of P transformation in SS incineration, characterization of SSA components, and wet-chemical and thermochemical processes for P recovery with a comprehensive technical, economic, and environmental assessment.

Peracetic acid disinfection induces antibiotic-resistant E. coli into VBNC state but ineffectively eliminates the transmission potential of ARGs.

The occurrence of a viable but nonculturable (VBNC) state in antibiotic-resistant E. coli (AR E. coli) and inefficient degradation of their antibiotic resistance genes (ARGs) may cause potential health risks during disinfection.