Altered White-Matter Functional Network in Children with Idiopathic Generalized Epilepsy.

RATIONALE AND OBJECTIVES: The white matter (WM) functional network changes offers insights into the potential pathological mechanisms of certain diseases, the alterations of WM functional network in idiopathic generalized epilepsy (IGE) remain unclear. We aimed to explore the topological characteristics changes of WM functional network in childhood IGE using resting-state functional Magnetic resonance imaging (MRI) and T1-weighted images. METHODS: A total of 84 children (42 IGE and 42 matched healthy controls) were included in this study. Functional and structural MRI data were acquired to construct a WM functional network. Group differences in the global and regional topological characteristics were assessed by graph theory and the correlations with clinical and neuropsychological scores were analyzed. A support vector machine algorithm model was employed to classify individuals with IGE using WM functional connectivity as features, and the model's accuracy was evaluated using leave-one-out cross-validation. RESULTS: In IGE group, at the network level, the WM functional network exhibited increased assortativity; at the nodal level, 17 nodes presented nodal disturbances in WM functional network, and nodal disturbances of 11 nodes were correlated with cognitive performance scores, disease duration and age of onset. The classification model achieved the 72.6% accuracy, 0.746 area under the curve, 69.1% sensitivity, 76.2% specificity. CONCLUSION: Our study demonstrated that the WM functional network topological properties changes in childhood IGE, which were associated with cognitive function, and WM functional network may help clinical classification for childhood IGE. These findings provide novel information for understanding the pathogenesis of IGE and suggest that the WM function network might be qualified as potential biomarkers.

Stimuli-Responsive PROTACs for Controlled Protein Degradation.

Proteolysis Targeting Chimeras (PROTACs) represent a promising therapeutic modality to address undruggable and resistant issues in drug discovery. However, potential on-target toxicity remains clinically challenging. We developed a generalized caging strategy to synthesize a series of stimuli-responsive PROTACs (sr-PROTACs) with diverse molecular blocks bearing robust and cleavable linkers, presenting "turn on" features in manipulating protein degradation. By leveraging pathological cues, such as elevated ROS, phosphatase, H2 S, or hypoxia, and external triggers, such as ultraviolet light, X-Ray, or bioorthogonal reagents, we achieved site-specific activation and traceless release of original PROTACs through de-caging and subsequent self-immolative cleavage, realizing selective uptake and controlled protein degradation in vitro. An in vivo study revealed that two sr-PROTACs with phosphate- and fluorine-containing cages exhibited high solubility and long plasma exposure, which were specifically activated by tumor overexpressing phosphatase or low dosage of X-Ray irradiation in situ, leading to efficient protein degradation and potent tumor remission. With more reactive biomarkers to be screened from clinical practice, our caging library could provide a general tool to design activatable PROTACs, prodrugs, antibody-drug conjugates, and smart biomaterials for personalized treatment, tissue engineering or regenerative medicine.

Recent progress of aptamer‒drug conjugates in cancer therapy.

Aptamers are single-stranded DNA or RNA sequences that can specifically bind with the target protein or molecule via specific secondary structures. Compared to antibody-drug conjugates (ADC), aptamer‒drug conjugate (ApDC) is also an efficient, targeted drug for cancer therapy with a smaller size, higher chemical stability, lower immunogenicity, faster tissue penetration, and facile engineering. Despite all these advantages, several key factors have delayed the clinical translation of ApDC, such as in vivo off-target effects and potential safety issues. In this review, we highlight the most recent progress in the development of ApDC and discuss solutions to the problems noted above.

Aptamer-Based Targeted Protein Degradation.

The selective removal of misfolded, aggregated, or aberrantly overexpressed protein plays an essential role in maintaining protein-dominated biological processes. In parallel, the precise knockout of abnormal proteins is inseparable from the accurate identification of proteins within complex environments. Guided by these precepts, small molecules, or antibodies, are commonly used as protein recognition tools for developing targeted protein degradation (TPD) technology. Indeed, TPD has shown tremendous prospects in chronic diseases, rare diseases, cancer research, and other fields. Meanwhile, aptamers are short RNA or DNA oligonucleotides that can bind to target proteins with high specificity and strong affinity. Accordingly, aptamers are actively used in designing and constructing TPD technology. In this perspective, we provide a brief introduction to TPD technology in its current progress, and we summarize its application challenges. Recent advances in aptamer-based TPD technology are reviewed, together with corresponding challenges and outlooks.

[Soil respiration and carbon balance in wheat field under conservation tillage].

In order to study the characteristics of carbon sources and sinks in the winter wheat farmland ecosystem in southwest hilly region of China, the LI6400-09 respiratory chamber was adopted in the experiment conducted in the experimental field in Southwest University in Chongqing. The soil respiration and plant growth dynamics were analyzed during the growth period of wheat in the triple intercropping system of wheat-maize-soybean. Four treatments including T (traditional tillage), R (ridge tillage), TS (traditional tillage + straw mulching), and RS (ridge tillage + straw mulching) were designed. Root biomass regression (RR) and root exclusion (RE) were used to compare the contribution of root respiration to total soil respiration. The results showed that the average soil respiration rate was 1.71 micromol x (m2 x s)(-1) with a variation of 0.62-2.91 micromol x (m2 x s)(-1). Significant differences in soil respiration rate were detected among different treatments. The average soil respiration rate of T, R, TS and RS were 1.29, 1.59, 1.99 and 1.96 micromol x (m2 x s)(-1), respectively. R treatment did not increase the soil respiration rate significantly until the jointing stage. Straw mulching treatment significantly increased soil respiration, with a steadily high rate during the whole growth period. During the 169 days of growth, the total soil respiration was 2 266.82, 2799.52, 3 483.73 and 3 443.89 kg x hm(-2) while the cumulative aboveground biomasses were 51 800.84, 59 563.20, 66 015.37 and 7 1331.63 kg x hm(-2). Compared with the control, the yield of R, TS and RS increased by 14.99%, 27.44% and 37.70%, respectively. The contribution of root respiration to total soil respiration was 47.05% by RBR, while it was 53.97% by RE. In the early growth period, the carbon source was weak. The capacity of carbon sink started to increase at the jointing stage and reached the maximum during the filling stage. The carbon budget of wheat field was 5 924.512, 6743.807, 8350.741, 8 876.115 kg x hm(-2), respectively. The results indicated that ridge tillage and straw mulching conservation tillage significantly improved the carbon sink in the wheat farmland ecosystem.

Effects of concentrations of sodium chloride on photosynthesis, antioxidative enzymes, growth and fiber yield of hybrid ramie.

Ramie (Boehmeria nivea L.) is one of the oldest and most important fiber crops in China due to the comfortable textile of its fine fiber. Increased ramie fiber demand brings ramie cultivation to salt-affected regions. The aim of this research was to determine morphological, physiological and biochemical responses of ramie by subjecting plants to varying concentrations of NaCl (0, 2, 4, 6 and 8 g NaCl/kg dry soil) at vigorous growth stage for 10 and 20 days. Results indicated that salinity stress substantially inhibited the growth of hybrid ramie plants and led to remarkable decline in fiber yield. However, when grown at 2 g NaCl/kg growth and fiber yield were similar to non-saline control. In addition, chlorophyll fluorescence and gas exchange parameters were correlated with growth and yield response. Salt treatments promoted a subsequent decrease in maximum quantum efficiency of PSII photochemistry (Fv/Fm), quantum efficiency of open PSII reaction centers (Fv'/Fm') and quantum yield of PSII (φPSII) while non-photochemical quenching (NPQ) changed conversely. Photochemical quenching (qP) and electron transport rate of PSII (ETR) increased at 2 and 4 g NaCl/kg then decreased at 6 and 8 g NaCl/kg. Substantial decline in the PSII activity at high salinity was associated with the loss of chlorophyll contents. Moreover, marked decrease in net photosynthetic rate (A), transpiration rate (E), stomatal conductance (gs) was also recorded. Nonetheless, intercellular CO2 (Ci) decreased at low salt stress, subsequently increased at high salt stress while water use efficiency (WUE) and instantaneous water use efficiency (WUEi) altered in opposite direction. Substantial decrease of photosynthesis at high salinity was due to non-stomatal factors. Furthermore, salinity stress led to decrease of proteins and accumulation of proline and malondialdehyde (MDA), as well as enhanced activities of superoxide dismutase (SOD, EC 1.15.1.1) and peroxidase (POD, EC 1.11.1.6), whereas, catalase (CAT, EC 1.11.1.7) enhanced at low salinity, decreased at high salinity. Nonetheless, these changes were closely related with the severity and duration of the salinity stress and their interaction. The results suggested a certain tolerance to salinity stress for hybrid ramie. This meets the essential condition for utilization in salinity-prone environments.