A one-two punch targeting reactive oxygen species and fibril for rescuing Alzheimer's disease.

Toxic amyloid-beta (Aß) plaque and harmful inflammation are two leading symptoms of Alzheimer's disease (AD). However, precise AD therapy is unrealizable due to the lack of dual-targeting therapy function, poor BBB penetration, and low imaging sensitivity. Here, we design a near-infrared-II aggregation-induced emission (AIE) nanotheranostic for precise AD therapy. The anti-quenching emission at 1350 nm accurately monitors the in vivo BBB penetration and specifically binding of nanotheranostic with plaques. Triggered by reactive oxygen species (ROS), two encapsulated therapeutic-type AIE molecules are controllably released to activate a self-enhanced therapy program. One specifically inhibits the Aß fibrils formation, degrades Aß fibrils, and prevents the reaggregation via multi-competitive interactions that are verified by computational analysis, which further alleviates the inflammation. Another effectively scavenges ROS and inflammation to remodel the cerebral redox balance and enhances the therapy effect, together reversing the neurotoxicity and achieving effective behavioral and cognitive improvements in the female AD mice model.

Durable response to afatinib in advanced lung adenocarcinoma harboring a novel NPTN-NRG1 fusion: a case report.

BACKGROUND: NRG1 fusions are rare oncogenic drivers in solid tumors, and the incidence of NRG1 fusions in non-small cell lung cancer (NSCLC) was 0.26%. It is essential to explore potential therapeutic strategies and efficacy predictors for NRG1 fusion-positive cancers. CASE PRESENTATION: We report an advanced lung adenocarcinoma patient harboring a novel NPTN-NRG1 fusion identified by RNA-based next-generation sequencing (NGS), which was not detected by DNA-based NGS at initial diagnosis. Transcriptomics data of the tissue biopsy showed NRG1α isoform accounted for 30% of total NRG1 reads, and NRG1ß isoform was undetectable. The patient received afatinib as fourth-line treatment and received a progression-free survival (PFS) of 14 months. CONCLUSIONS: This report supports afatinib can provide potential benefit for NRG1 fusion patients, and RNA-based NGS is an accurate and cost-effective strategy for fusion detection and isoform identification.

A Brain-Targeting NIR-II Ferroptosis System: Effective Visualization and Oncotherapy for Orthotopic Glioblastoma.

Near-infrared-II (NIR-II) ferroptosis activators offer promising potentials in in vivo theranostics of deep tumors, such as glioma. However, most cases are nonvisual iron-based systems that are blind for in vivo precise theranostic study. Additionally, the iron species and their associated nonspecific activations might trigger undesired detrimental effects on normal cells. Considering gold (Au) is an essential cofactor for life and it can specifically bind to tumor cells, Au(I)-based NIR-II ferroptosis nanoparticles (TBTP-Au NPs) for brain-targeted orthotopic glioblastoma theranostics are innovatively constructed. It achieves the real-time visual monitoring of both the BBB penetration and the glioblastoma targeting processes. Moreover, it is first validated that the released TBTP-Au specifically activates the effective heme oxygenase-1-regulated ferroptosis of glioma cells to greatly extend the survival time of glioma-bearing mice. This new ferroptosis mechanism based on Au(I) may open a new way for the fabrication of advanced and high-specificity visual anticancer drugs for clinical trials.

Chloroplast genome structure and phylogenetic analysis of Juniperus chinensis.

The chloroplast genome of Juniperus chinensis L. was assembled and annotated in this research. The size of the chloroplast genome is 127,811 bp. It contains a 91,322 bp large single-copy region and a 35,960 bp small single-copy region; it does not contain inverted repeats. The genome encodes 82 protein-encoding genes, 33 tRNAs, and four rRNAs. Phylogenetic analysis showed that J. chinensis was closer to congeneric species than those of Cupressaceae. These results provide a genomic basis for further evolutionary research on conifers.

Brain-Targeted Aggregation-Induced-Emission Nanoparticles with Near-Infrared Imaging at 1550 nm Boosts Orthotopic Glioblastoma Theranostics.

A remaining challenge in the treatment of glioblastoma multiforme (GBM) is surmounting the blood-brain barrier (BBB). Such a challenge prevents the development of efficient theranostic approaches that combine reliable diagnosis with targeted therapy. In this study, brain-targeted near-infrared IIb (NIR-IIb) aggregation-induced-emission (AIE) nanoparticles are developed via rational design, which involves twisting the planar molecular backbone with steric hindrance. The resulting nanoparticles can balance competing responsiveness demands for radiation-mediated NIR fluorescence imaging at 1550 nm and non-radiation NIR photothermal therapy (NIR-PTT). The brain-targeting peptide apolipoprotein E peptide (ApoE) is grafted onto these nanoparticles (termed as ApoE-Ph NPs) to target glioma and promote efficient BBB traversal. A long imaging wavelength 1550 nm band-pass filter is utilized to monitor the in vivo biodistribution and accumulation of the nanoparticles in a model of orthotopic glioma, which overcomes previous limitations in wavelength range and equipment. The results demonstrate that the ApoE-Ph NPs have a higher PTT efficiency and significantly enhanced survival of mice bearing orthotopic GBM with moderate irradiation (0.5 W cm-2 ). Collectively, the work highlights the smart design of a brain-targeted NIR-II AIE theranostic approach that opens new diagnosis and treatment options in the photonic therapy of GBM.

A Quasi-Solid-State Flexible Fiber-Shaped Li-CO2 Battery with Low Overpotential and High Energy Efficiency.

The rapid development of wearable electronics requires a revolution of power accessories regarding flexibility and energy density. The Li-CO2 battery was recently proposed as a novel and promising candidate for next-generation energy-storage systems. However, the current Li-CO2 batteries usually suffer from the difficulties of poor stability, low energy efficiency, and leakage of liquid electrolyte, and few flexible Li-CO2 batteries for wearable electronics have been reported so far. Herein, a quasi-solid-state flexible fiber-shaped Li-CO2 battery with low overpotential and high energy efficiency, by employing ultrafine Mo2 C nanoparticles anchored on a carbon nanotube (CNT) cloth freestanding hybrid film as the cathode, is demonstrated. Due to the synergistic effects of the CNT substrate and Mo2 C catalyst, it achieves a low charge potential below 3.4 V, a high energy efficiency of ≈80%, and can be reversibly discharged and charged for 40 cycles. Experimental results and theoretical simulation show that the intermediate discharge product Li2 C2 O4 stabilized by Mo2 C via coordinative electrons transfer should be responsible for the reduction of overpotential. The as-fabricated quasi-solid-state flexible fiber-shaped Li-CO2 battery can also keep working normally even under various deformation conditions, giving it great potential of becoming an advanced energy accessory for wearable electronics.

Acute and subchronic toxicity as well as evaluation of safety pharmacology of traditional Chinese medicine "Huhezi".

The study was conducted to evaluate the toxicity and safety pharmacology of the traditional Chinese medicine, "Huhezi" granules. The results of acute toxicity test showed that the granules' LD50 was more than 5000 mg/kg, which indicated that the "Huhezi" belonged to actually non-toxic drug. Subchronic toxicity study showed that non-toxic reaction were detected in high (1000 mg/kg), medium (500 mg/kg) and low dose (250 mg/kg) of "Huhezi" groups by measuring rat body weight, organ coefficient, blood physiological indexes and blood biochemical indexes. Pathological examination showed that no tissue lesions were observed in test organs except liver (mild granular degenerationand reversible vesicular degeneration), spleen (Langerhans cells infiltrating) and kidney (homogeneous red staining of renal tubule). Safety pharmacology study found that "Huhezi" had no effects on the central nervous system, respiratory system and cardiovascular system. These results suggested that the dose of "Huhezi" at or below 1000 mg/kg through oral administration is considered safe.