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Abstract Previous studies have shown that scutellarin inhibits the excessive activation of microglia, reduces neuronal apoptosis, and exerts neuroprotective effects. However, whether scutellarin regulates activated microglia-mediated neuronal apoptosis and its mechanisms remains unclear. This study aimed to investigate whether scutellarin can attenuate PC12 cell apoptosis induced by activated microglia via the JAK2/STAT3 signalling pathway. Microglia were cultured in oxygen–glucose deprivation (OGD) medium, which acted as a conditioning medium (CM) to activate PC12 cells, to investigate the expression of apoptosis and JAK2/STAT3 signalling-related proteins. We observed that PC12 cells apoptosis in CM was significantly increased, the expression and fluorescence intensity of the pro-apoptotic protein Bax and apoptosis-related protein cleaved caspase-3 were increased, and expression of the anti-apoptotic protein B-cell lymphoma-2 (Bcl-2) was decreased. Phosphorylation levels and fluorescence intensity of the JAK2/STAT3 signalling pathway-related proteins JAK2 and STAT3 decreased. After treatment with scutellarin, PC12 cells apoptosis as well as cleaved caspase-3 and Bax protein expression and fluorescence intensity decreased. The expression and fluorescence intensity of Bcl-2, phosphorylated JAK2, and STAT3 increased. AG490, a specific inhibitor of the JAK2/STAT3 signalling pathway, was used. Our findings suggest that AG490 attenuates the effects of scutellarin. Our study revealed that scutellarin inhibited OGD-activated microglia-mediated PC12 cells apoptosis which was regulated via the JAK2/STAT3 signalling pathway.

The Runchang‐Tongbian (RCTB) formula is a traditional Chinese medicine (TCM) formula consisting of four herbs, namely Cannabis Fructus (Huomaren), Rehmanniae Radix (Dihuang), Atractylodis Macrocephalae Rhizoma (Baizhu), and Aurantii Fructus (Zhiqiao). It is widely used clinically because of its beneficial effect on constipation. However, its strong bitter taste leads to poor patient compliance. The bitter components of TCM compounds are complex and numerous, and inhibiting the bitter taste of TCM has become a major clinical challenge. Here, we use ultra‐high‐performance liquid chromatography coupled with mass spectrometry (UPLC–MS) and high‐resolution mass spectrometry to identify 59 chemical components in the TCM compound RCTB formula. Next, four bitter taste receptors, TAS2R39, TAS2R14, TAS2R7, and TAS2R5, which are tightly bound to the compounds in RCTB, were screened as molecular docking receptors using the BitterX database. The top‐three‐scoring receptor‐small‐molecule complexes for each of the four receptors were selected for molecular dynamics simulation. Finally, seven bitter components were identified, namely six flavonoids (rhoifolin, naringin, poncirin, diosmin, didymin, and narirutin) and one phenylpropanoid (purpureaside C). Thus, we proposed a new method for identifying the bitter components in TCM compounds, which provides a theoretical reference for bitter taste inhibition in TCM compounds. [ABSTRACT FROM AUTHOR]

Two‐photon polymerization direct laser writing (TPP‐DLW) technology has gained much popularity due to its precision and flexibility in creating intricate 3D micro/nano‐scale devices and machines. While TPP‐DLW enables complex 3D micro/nano patterning, developing multifunctional materials tailored for this process remains a challenge, limiting sophisticated micro/nano device performance. This work addresses key barriers by introducing a novel multifunctional network polymer with specifically designed for TPP‐DLW. The material integrates tailored functional groups allowing submicron 3D spatial arrangement under laser control. Remarkably, it demonstrates tunable pH response, programmed fluorescence, and dynamic reconfiguration upon optical illumination. By leveraging TPP‐DLW's programmability, reconfigurable encrypted microstructures are achieved, representing a new precision multifunctional material printing paradigm beyond single property systems. The synthesized material with its responsive properties, combined with digital fabrication control, fills critical gaps in developing smart, adaptive micro/nano systems. Potential applications requiring exquisite 3D control and multi‐tasking, such as biomedical sensors, micromachines and optics could see transformative advancement. Fundamentally, this integrated materials‐processing approach broadens micro/nano manufacturing design space and functional versatility. [ABSTRACT FROM AUTHOR]

To realize nanoscale manufacturing based on laser direct writing technology, objective lenses with high numerical apertures immersed in water or oil are necessary. The use of liquid medium restricts its application in semiconductors. Achieving nanoscale features on silicon by laser direct writing in a low refractive index medium has been a challenge. In this work, a microsphere assisted femtosecond laser far-field induced dewetting approach is proposed. A reduction in the full-width at half-maximum of the focused light spot is realized by modulating tightly focused light through microspheres and achieving a minimum feature size of 9 nm on silicon in ambient air with energy smaller than the ablation threshold. Theoretical analysis and numerical simulation of laser processing are performed based on a two-temperature model. Furthermore, we explored the potential of femtosecond laser-induced dewetting in nanolithography and demonstrated its ability to achieve an arbitrary structure on silicon. Our work enables laser-based far-field sub-10-nm feature etching on a large-scale, providing a novel avenue for nanoscale silicon manufacturing. [ABSTRACT FROM AUTHOR]

Coronaviruses (CoVs), the largest positive-sense RNA viruses, have caused infections in both humans and animals. The cross-species transmission of CoVs poses a serious threat to public health. Rodents and bats, the two largest orders of mammals, serve as significant natural reservoirs for CoVs. It is important to monitor the CoVs carried by bats and rodents. In this study, we collected 410 fecal samples from bats and 74 intestinal samples from rats in Yunnan Province, China. Using RT-PCR, we identified one positive sample for alphacoronavirus (TC-14) from Rhinolophus sinicus (Chinese rufous horseshoe bat) and two positive samples for betacoronavirus (GS-53, GS-56) from Apodemus ilex (Rodentia: Muridae). We successfully characterized the complete genomes of TC-14 and GS-56. Phylogenetic analysis revealed that TC-14 clustered with bat CoV HKU2 and SADS-CoV, while GS-56 was closely related to rat CoV HKU24. The identification of positive selection sites and estimation of divergence dates further helped characterize the genetic evolution of TC-14 and GS-56. In summary, this research reveals the genetic evolution characteristics of TC-14 and GS-56, providing valuable references for the study of CoVs carried by bats and rodents in Yunnan Province. [ABSTRACT FROM AUTHOR]

Merchants need not fear platform entry because that can raise merchants' profits by resolving quality uncertainty for consumers. Merchants are wary of a platform's competitive entry reducing sales and margins. Profit-maximizing platforms seek to provide credible quality information to gain consumer trust and confidence. Can a platform enter so that resulting multisender prices alleviate consumers' uncertainty by signaling quality? Can merchants also benefit from platform entry? We provide answers by analyzing strategic platform and merchant pricing under quality uncertainty. A modeling innovation is a leader-follower framework for platform-merchant competition. Consumers resolve uncertainty using both platform and merchant prices. Using what we label perfect Bayes-consistent beliefs, we identify perfect Bayesian equilibrium that satisfies the intuitive criterion, and also out-of-equilibrium beliefs that are unprejudiced. A substantive finding is that platform entry can raise merchant profits when the quality is high by moving the equilibrium from pooling to separating, and supporting higher prices. Another strategic consequence of platform entry could be a separating equilibrium with incomplete market coverage due to price distortion moving to one of complete market coverage due to seller competition. Indeed, conditions exist in our model for an equilibrium outcome identical to complete information. Finally, facing entry cost, a platform may choose to enter only with high quality but quality revelation remains price dependent and not based on mere entry. History: Yuxin Chen served as the senior editor for this article. Funding: Y. Qiu was supported by the Natural Science Foundation of China [Grant 71902142] toward completion of this paper. Supplemental Material: The online appendix is available at https://doi.org/10.1287/mksc.2021.0227. [ABSTRACT FROM AUTHOR]

In addition to the common blood and urine, fresh sweat contains a diverse range of physiological indicators that can effectively reflect changes in the body's state. Wearable sweat sensors are crucial for understanding human physiological health; however, real-time in situ measurement of multiple biomarkers in sweat remains a significant challenge. Here, we propose a wearable microfluidic patch featuring an integrated microfluidic channel and evaporation pump for accelerated and continuous sweat collection, eliminating the need for additional sweat storage cavities that typically impede real-time detection. Capillary forces are harnessed to facilitate the rapid flow of sweat through the detection area, while an evaporation pump based on porous laser-induced graphene enhances sweat evaporation. The synergistic integration of these two components enables an uninterrupted flow of fresh sweat within the patch, ensuring real-time monitoring. The influence of channel size parameters on sweat flow velocity is analyzed, and the optimal width-to-height ratio for achieving the desired flow velocity is determined. By implementing a multi-channel parallel design with chamfering, liquid flow resistance is effectively reduced. Furthermore, the patch integrates sensor modules for sodium ion, chloride ion, glucose, and pH value measurements, ensuring excellent sealing and stability of the assembled system. This work presents a simplified approach to developing wearable sweat sensors that hold the potential for health monitoring and disease diagnosis. [ABSTRACT FROM AUTHOR]

Proteins capable of switching between distinct active states in response to biochemical cues are ideal for sensing and controlling biological processes. Activatable CRISPR‐Cas systems are significant in precise genetic manipulation and sensitive molecular diagnostics, yet directly controlling Cas protein function remains challenging. Herein, we explore anti‐CRISPR (Acr) proteins as modules to create synthetic Cas protein switches (CasPSs) based on computational chemistry‐directed rational protein interface engineering. Guided by molecular fingerprint analysis, electrostatic potential mapping, and binding free energy calculations, we rationally engineer the molecular interaction interface between Cas12a and its cognate Acr proteins (AcrVA4 and AcrVA5) to generate a series of orthogonal protease‐responsive CasPSs. These CasPSs enable the conversion of specific proteolytic events into activation of Cas12a function with high switching ratios (up to 34.3‐fold). These advancements enable specific proteolysis‐inducible genome editing in mammalian cells and sensitive detection of viral protease activities during virus infection. This work provides a promising strategy for developing CRISPR‐Cas tools for controllable gene manipulation and regulation and clinical diagnostics. [ABSTRACT FROM AUTHOR]

Identification of viruses and further assembly of viral genomes from the next-generation-sequencing data are essential steps in virome studies. This study presented a one-stop tool named VIGA (available at https://github.com/viralInformatics/VIGA) for eukaryotic virus identification and genome assembly from NGS data. It was composed of four modules, namely, identification, taxonomic annotation, assembly and novel virus discovery, which integrated several third-party tools such as BLAST, Trinity, MetaCompass and RagTag. Evaluation on multiple simulated and real virome datasets showed that VIGA assembled more complete virus genomes than its competitors on both the metatranscriptomic and metagenomic data and performed well in assembling virus genomes at the strain level. Finally, VIGA was used to investigate the virome in metatranscriptomic data from the Human Microbiome Project and revealed different composition and positive rate of viromes in diseases of prediabetes, Crohn's disease and ulcerative colitis. Overall, VIGA would help much in identification and characterization of viromes, especially the known viruses, in future studies. [ABSTRACT FROM AUTHOR]

Background: The development and progression of hepatocellular carcinoma (HCC) have been reported to be associated with immune-related genes and the tumor microenvironment. Nevertheless, there are not enough prognostic biomarkers and models available for clinical use. Based on seven prognostic genes, this study calculated overall survival in patients with HCC using a prognostic survival model and revealed the immune status of the tumor microenvironment (TME)., Aim: To develop a novel immune cell-related prognostic model of HCC and depict the basic profile of the immune response in HCC., Methods: We obtained clinical information and gene expression data of HCC from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) datasets. TCGA and ICGC datasets were used for screening prognostic genes along with developing and validating a seven-gene prognostic survival model by weighted gene coexpression network analysis and least absolute shrinkage and selection operator regression with Cox regression. The relative analysis of tumor mutation burden (TMB), TME cell infiltration, immune checkpoints, immune therapy, and functional pathways was also performed based on prognostic genes., Results: Seven prognostic genes were identified for signature construction. Survival receiver operating characteristic curve analysis showed the good performance of survival prediction. TMB could be regarded as an independent factor in HCC survival prediction. There was a significant difference in stromal score, immune score, and estimate score between the high-risk and low-risk groups stratified based on the risk score derived from the seven-gene prognostic model. Several immune checkpoints, including VTCN1 and TNFSF9, were found to be associated with the seven prognostic genes and risk score. Different combinations of checkpoint blockade targeting inhibitory CTLA4 and PD1 receptors and potential chemotherapy drugs hold great promise for specific HCC therapies. Potential pathways, such as cell cycle regulation and metabolism of some amino acids, were also identified and analyzed., Conclusion: The novel seven-gene ( CYTH3, ENG, HTRA3, PDZD4, SAMD14, PGF , and PLN ) prognostic model showed high predictive efficiency. The TMB analysis based on the seven genes could depict the basic profile of the immune response in HCC, which might be worthy of clinical application., Competing Interests: Conflict-of-interest statement: All the authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

The Zr–2.5Nb alloy is a typical pressure tube material in heavy water nuclear reactors, and an increase of hydrogen isotope content in the alloy during service can pose major safety risks; hot vacuum extraction-mass spectrometry is an efficient method for evaluating hydrogen isotope concentrations in the Zr–2.5Nb alloy. This work investigates the kinetics and thermodynamic properties of deuterium (D) absorption and desorption of the Zr–2.5Nb alloy using the constant volume adsorption method and the hot vacuum extraction method. In addition to the previously reported volume contraction model, it was observed that at 600 °C and above, the reaction between D2 and Zr–2.5Nb is dominated by diffusion, while the reaction is predominantly influenced by surface adsorption and dissociation below 600 °C. Phase transition sequence of Zr–2.5Nb deuterides during non-isothermal desorption was established using quantitatively calibrated thermal desorption spectra combined with the phase transition process of deuteride decomposition. These results can provide important references for optimizing the process parameters of the hot vacuum extraction-mass spectrometry method. [ABSTRACT FROM AUTHOR]

Alongside the proceeding of rural land system reform in China, it becomes more and more critical to conduct policy performance evaluations on collective-owned construction land for profitable use to reflect the achievements and deficiencies of the reform. Traditionally, land policy performance evaluation is based on the theory of "policy-performance", which fails to explain the mechanism of transaction costs. From the perspective of spatial planning, land use and the spatial form shaped by land development management and control are a representation of land property rights, as well as an expression of land policy performance. Thus, a correct understanding of the role of spatial form in the relationship between land policy and land performance is of great significance in accurately evaluating land policy performance and further improving land policies. Focusing on the interrelation among the three factors, this article highlights and elaborates on the intermediary role of spatial form between land property rights and land policy performance and puts forward the analytical framework of "land property right–spatial form–land policy performance". It then takes the case of Wujiang District of Suzhou in southern Jiangsu Province to prove the effectiveness of this analytical framework. The outcome of this study can serve as a supplement to "policy-performance" theory, which refines and deepens the analysis of transaction costs from the perspective of spatial planning. It may also help deepen the recognition of land policy performance through visualized presentations, providing a new perspective for performance evaluation in quantitative and qualitative ways. [ABSTRACT FROM AUTHOR]

Ground reaction curves (GRCs) are increasingly used to simulate the progressive development of soil arching resulting from differential movement in soil. In this study, 20 single, double, and multiple trapdoor tests were conducted under a simultaneous displacement mode (i.e., trapdoors settle simultaneously), while 8 double trapdoor tests were carried out under a successive displacement mode (i.e., trapdoors settle successively) to examine the evolution of soil arching including the parameters related to the GRCs. This study identified and analyzed the key parameters of the GRCs. For the trapdoor tests conducted under the simultaneous displacement mode, an increase of the fill height led to a decrease in the minimum pressure and its corresponding trapdoor displacement. Furthermore, the ultimate normalized pressure and recovery rate exhibited a decreasing trend with an increase of the fill height. As compared to the single and double trapdoor tests, the multiple trapdoor tests had similar initial soil arching, minimum normalized pressure, and its corresponding trapdoor displacement but a relatively lower stress recovery rate. In the trapdoor tests conducted with the successive displacement mode, the pressure on the first settled trapdoor decreased while it increased on the later settled trapdoor during the settlement of the first settled trapdoor. Conversely, during the settlement of the later settled trapdoor, the pressure on the first settled trapdoor increased, while it decreased on the later settled trapdoor. Analyzing the GRCs on the later settled trapdoor under the successive displacement mode revealed that the initial slope and ultimate pressure of the GRC decreased as the fill height increased. [ABSTRACT FROM AUTHOR]