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The cell-type-specific recording and manipulation is instrumental to disentangle causal neural mechanisms in physiology and behavior and increasingly requires intersectional control; however, current approaches are largely limited by the number of intersectional features, incompatibility of common effectors and insufficient gene expression. Here, we utilized the protein-splicing technique mediated by intervening sequences (intein) and devised an intein-based intersectional synthesis of transactivator (IBIST) to selectively control gene expression of common effectors in multiple-feature defined cell types in mice. We validated the specificity and sufficiency of IBIST to control fluorophores, optogenetic opsins and Ca2+ indicators in various intersectional conditions. The IBIST-based Ca2+ imaging showed that the IBIST can intersect five features and that hippocampal neurons tune differently to distinct emotional stimuli depending on the pattern of projection targets. Collectively, the IBIST multiplexes the capability to intersect cell-type features and controls common effectors to effectively regulate gene expression, monitor and manipulate neural activities.

Background: Clear cell renal cell carcinoma (ccRCC) is one of the most common histological subtypes of renal tumors. Purpose: To identify high‐risk subregions associated with synchronous distant metastasis. Methods: This study enrolled a total of 277 patients with ccRCC. Voxel intensity and local entropy values were compiled within the region of interest for all patients. Unsupervised k‐means clustering yielded three subregions per tumor. Radiomic features were extracted, and random forest‐based feature selection was conducted. The selected features were used in a multi‐instance support vector machine (mi‐SVM) model for training, and predictions were made on the validation cohort. Model performance was evaluated using five‐fold cross‐validation. The subregion with the highest score for patients with synchronous distant metastasis was identified across all cohorts. Results: The mi‐SVM model yielded an average area under the curve (AUC) of 0.812 in the training cohort and 0.805 in the validation cohort. In the entire cohort of patients with synchronous distant metastasis, subregion 2, characterized by tumor periphery and intratumoral transitional components, accounted for the highest proportion (48.57%, 30.6/63) among all subregions. It represents a high‐risk subregion for synchronous distant metastasis of clear cell renal cell carcinoma. Conclusion: The peripheral and intratumoral transition zones of clear cell renal cell carcinoma are high‐risk subregions associated with synchronous distant metastasis. [ABSTRACT FROM AUTHOR]

In acidic proton exchange membrane water electrolysis (PEMWE), the anode oxygen evolution reaction (OER) catalysts rely heavily on the expensive and scarce iridium‐based materials. Ruthenium dioxide (RuO2) with lower price and higher OER activity, has been explored for the similar task, but has been restricted by the poor stability. Herein, we developed an anion modification strategy to improve the OER performance of RuO2 in acidic media. The designed multicomponent catalyst based on sulfate anchored on RuO2/MoO3 displays a low overpotential of 190 mV at 10 mA cm−2 and stably operates for 500 hours with a very low degradation rate of 20 μV h−1 in acidic electrolyte. When assembled in a PEMWE cell, this catalyst as an anode shows an excellent stability at 500 mA cm−2 for 150 h. Experimental and theoretical results revealed that MoO3 could stabilize sulfate anion on RuO2 surface to suppress its leaching during OER. Such MoO3‐anchored sulfate not only reduces the formation energy of *OOH intermediate on RuO2, but also impedes both the surface Ru and lattice oxygen loss, thereby achieving the high OER activity and exceptional durability. [ABSTRACT FROM AUTHOR]

This study evaluated the safety, tolerability, pharmacodynamics, and pharmacokinetics of recombinant neorudin (EPR‐hirudin [EH]) in patients with acute coronary syndrome (ACS), providing a basis for further therapeutic research. This open‐label, single‐center, nonrandomized, nonblinded, and noncontrolled trial categorized 24 patients with nonprogressive ACS who met the screening criteria into 3 groups. They received an intravenous injection of neorudin (0.4 mg/kg), followed by an intravenous drip at doses of 0.15, 0.30, and 0.45 mg/kg/h for 3 days in the low‐, medium‐, and high‐dose groups, respectively. The safety, tolerability, pharmacodynamics, and pharmacokinetics of EH were assessed after treatment, indicating that neorudin was safe and well tolerated in nonprogressive ACS. No serious adverse events or clinical composite end points were observed. The activated partial thromboplastin time and thrombin time increased significantly and dose dependently following EH administration across all groups compared to pretreatment values. Conversely, thrombin activity significantly decreased after drug administration but returned to baseline levels shortly after drug withdrawal. Within the administered dose range, neorudin exposure increased with the dose, and its half‐life was approximately 2 hours. Neorudin was found to be safe and tolerable for treating patients with nonprogressive ACS, demonstrating therapeutic efficacy at doses up to 0.45 mg/kg/h over a 3‐day period. [ABSTRACT FROM AUTHOR]

Small piezoelectric wind-induced vibration energy harvesting systems have been widely studied to provide long-term sustainable green energy for a large number of wireless sensor network nodes. Piezoelectric materials are commonly utilized as transducers because of their ability to produce high output power density and their simple structure, but they are prone to material fracture under large deformation conditions. This paper proposes a magnetic boundary modulated stepped beam wind energy harvesting system. On the one hand, the design incorporates a composite stepped beam with both high- and low-stiffness components, allowing for efficient vibration and electrical energy output at low wind speeds. On the other hand, a magnetic boundary constraint mechanism is constructed to prevent the piezoelectric sheet from breaking due to excessive deformation. Experiments have confirmed that the effective operational wind speed range of the harvester with magnetic boundary constraints is doubled compared to that of the harvester without magnetic boundary constraints. Furthermore, by adjusting the magnetic pole spacing of the boundary, the harvesting system can generate sufficiently high output power under high-wind-speed conditions without damaging the piezoelectric sheet. [ABSTRACT FROM AUTHOR]

Simultaneously improving the activity and stability of catalysts for anodic oxygen evolution reaction (OER) in proton exchange membrane water electrolysis (PEMWE) remains a notable challenge. Here, we report a chromium-doped ruthenium dioxide with oxygen vacancies, termed Cr0.2Ru0.8O2-x, that drives OER with an overpotential of 170 mV at 10 mA cm−2 and operates stably over 2000 h in acidic media. Experimental and theoretical studies show that the synergy of Cr dopant and oxygen vacancy induces an unconventional dopant-mediated hydroxyl spillover mechanism. Such dynamic hydroxyl spillover from Cr dopant to Ru active site changes the rate-determining step from OOH* formation to O2 formation and thus greatly improves the OER performance. Moreover, the Cr dopant and oxygen vacancy also play a crucial role in stabilizing surface Ru and lattice oxygen in the Ru-O-Cr structural motif. When assembled into the anode of a practical PEMWE device, Cr0.2Ru0.8O2-x enables long-term durability of over 200 h at an ampere-level current density and 60 degrees centigrade. Developing highly active and stable anode catalysts for green hydrogen production is crucial but challenging. Here, the authors report a Cr0.2Ru0.8O2-x catalyst with an unconventional dopant-mediated hydroxyl spillover mechanism for high-efficiency proton exchange membrane water electrolysis. [ABSTRACT FROM AUTHOR]

Tunnelling in complex geological strata is a challenging task that can affect the performance of shield machines and result in unexpected hazards. Therefore, extensive knowledge of unfavourable environments and shield operational parameters is essential for ensuring successful and safe tunnelling. This study aims to analyse the geological and hydrological conditions of the Chunfeng Tunnel and present the key construction technologies of a large slurry shield machine when crossing complex strata. To this end, attempts were made to (i) discuss the geological and environmental challenges encountered during the tunnelling process and present some early interpretations based on the database information, (ii) analyse the factors affecting tunnel performance and simulate the ground surface settlement along the tunnel alignment and (iii) discuss the countermeasures under adverse ground conditions and propose future directions. The results revealed that tunnelling in fault zones with soft upper and hard lower strata led to severe wear of disc cutters and controlling the tunnelling parameters could provide a suitable method for adjusting the construction process. This study leveraged extensive experience gained during tunnelling using a large slurry shield machine, with special emphasis on mixed ground strata, by providing valuable insights and suggested responses for effective tunnelling strategies. [ABSTRACT FROM AUTHOR]