Next Directions in the Neuroscience of Cancers Arising outside the CNS.

SUMMARY: The field of cancer neuroscience has begun to define the contributions of nerves to cancer initiation and progression; here, we highlight the future directions of basic and translational cancer neuroscience for malignancies arising outside of the central nervous system.

Deciphering the Roles of Extracellular Polymeric Substances (EPS) in Shaping Disinfection Kinetics through Permanent Removal via Genetic Disruption.

Extracellular polymeric substances (EPS) ubiquitously encapsulate microbes and play crucial roles in various environmental processes. However, understanding their complex interactions with dynamic bacterial behaviors, especially during the disinfection process, remains very limited. In this work, we investigated the impact of EPS on bacterial disinfection kinetics by developing a permanent EPS removal strategy. We genetically disrupted the synthesis of exopolysaccharides, the structural components of EPS, in Pseudomonas aeruginosa, a well-known EPS-producing opportunistic pathogen found in diverse environments, creating an EPS-deficient strain. This method ensured a lasting absence of EPS while maintaining bacterial integrity and viability, allowing for real-time in situ investigations of the roles of EPS in disinfection. Our findings indicate that removing EPS from bacteria substantially lowered their susceptibility threshold to disinfectants such as ozone, chloramine B, and free chlorine. This removal also substantially accelerated disinfection kinetics, shortened the resistance time, and increased disinfection efficiency, thereby enhancing the overall bactericidal effect. The absence of EPS was found to enhance bacterial motility and increase bacterial cell vulnerability to disinfectants, resulting in greater membrane damage and intensified reactive oxygen species (ROS) production upon exposure to disinfectants. These insights highlight the central role of EPS in bacterial defenses and offer promising implications for developing more effective disinfection strategies.

Construction and application of a time-saving mode in China for the treatment of acute ischemic stroke.

Objective: To explore the construction and application in the practice of green channel in No. 971 Naval Hospital of PLA (No. 971 Hospital mode) for the treatment of acute ischemic stroke (AIS). Methods: This retrospective study involved a cohort of 694 suspected stroke patients from December 2022 to November 2023 undergoing emergency treatment for stroke at our institution. Among them, 483 patients were treated with standard green channel (the control group), and 211 patients adopted the No. 971 Hospital mode for treatment (the study group). The biggest difference between the two groups was that the treatment process started before admission. We compared the effectiveness of the emergency treatment between the two groups and the thrombolysis treatment. Results: Compared with control group, the accuracy rate of determining stroke and the rate of thrombolysis were significantly higher (p = 0.002, 0.039) and the door to doctor arrival time (DAT) and the door to CT scan time (DCT) of the study group was significantly shorter (all p < 0.001). There were 49 patients (10.1%) and 33 patients (15.6%) from the control group and study group receiving thrombolysis, respectively. The DAT, DCT, imaging to needle time (INT), and door to needle time (DNT) of patients receiving thrombolysis in the study group were significantly shorter than that in the control group (all p < 0.01). The NIHSS in the study group after the thrombolysis was lower than that in the control group (p = 0.042). Conclusion: No. 971 Hospital model can effectively shorten DAT, DCT, INT, and DNT, and improve the effectiveness of thrombolysis and prognoses of AIS patients.

Hormonal basis of brain fog in cancer treatment.

The cognitive side effects of cancer treatment are common, but no targeted therapy exists yet to treat or prevent such neurological sequelae. We explore the role of hormones as mediators between cancer therapy and cognitive impairment, discussing potential future directions.

Common proteins analysis of different mammals' mature milk by 4D-Label-Free.

The milk proteins from samples of 13 different animals were identified utilizing 4D-Label-Free proteomics technology, leading to the identification of a substantial number of proteins. Among the various samples, Chinese people (CHP) milk proteins exhibited the highest count, with 1149 distinct proteins. Simultaneously, we identified common proteins present in these animal milk. It's notable presence in goat milk contributes to enhancing infant infection resistance, showcasing the beneficial role of lactoperoxidase. Galectin-3 binding protein (Gal-3BP) and tetraspanin in human milk are significantly higher than those in other animals, which determine the prominent antiviral effect of human milk and the important processes related to cell transduction. Furthermore, human milk, camel milk, goat milk and sheep milk proved to be rich sources of milk fat globule membrane (MFGM) proteins. The insights obtained from this study can serve as a foundational framework for exploring the role of different animal milk proteins in disease treatment and the composition of infant formula.

Inter-site structural heterogeneity induction of single atom Fe catalysts for robust oxygen reduction.

Metal-nitrogen-carbon catalysts with hierarchically dispersed porosity are deemed as efficient geometry for oxygen reduction reaction (ORR). However, catalytic performance determined by individual and interacting sites originating from structural heterogeneity is particularly elusive and yet remains to be understood. Here, an efficient hierarchically porous Fe single atom catalyst (Fe SAs-HP) is prepared with Fe atoms densely resided at micropores and mesopores. Fe SAs-HP exhibits robust ORR performance with half-wave potential of 0.94 V and turnover frequency of 5.99 e-1s-1site-1 at 0.80 V. Theoretical simulations unravel a structural heterogeneity induced optimization, where mesoporous Fe-N4 acts as real active centers as a result of long-range electron regulation by adjacent microporous sites, facilitating O2 activation and desorption of key intermediate *OH. Multilevel operando characterization results identify active Fe sites undergo a dynamic evolution from basic Fe-N4 to active Fe-N3 under working conditions. Our findings reveal the structural origin of enhanced intrinsic activity for hierarchically porous Fe-N4 sites.

Metagenomic analysis of individual mosquito viromes reveals the geographical patterns and drivers of viral diversity.

Mosquito transmitted viruses are responsible for an increasing burden of human disease. Despite this, little is known about the diversity and ecology of viruses within individual mosquito hosts. Here, using a meta-transcriptomic approach, we determined the viromes of 2,438 individual mosquitoes (81 species), spanning ~4,000 km along latitudes and longitudes in China. From these data we identified 393 viral species associated with mosquitoes, including 7 (putative) species of arthropod-borne viruses (that is, arboviruses). We identified potential mosquito species and geographic hotspots of viral diversity and arbovirus occurrence, and demonstrated that the composition of individual mosquito viromes was strongly associated with host phylogeny. Our data revealed a large number of viruses shared among mosquito species or genera, enhancing our understanding of the host specificity of insect-associated viruses. We also detected multiple virus species that were widespread throughout the country, perhaps reflecting long-distance mosquito dispersal. Together, these results greatly expand the known mosquito virome, linked viral diversity at the scale of individual insects to that at a country-wide scale, and offered unique insights into the biogeography and diversity of viruses in insect vectors.

Structural Design of Single-Atom Catalysts for Enhancing Petrochemical Catalytic Reaction Process.

Petroleum, as the "lifeblood" of industrial development, is the important energy source and raw material. The selective transformation of petroleum into high-end chemicals is of great significance, but still exists enormous challenges. Single-atom catalysts (SACs) with 100% atom utilization and homogeneous active sites, promise a broad application in petrochemical processes. Herein, the research systematically summarizes the recent research progress of SACs in petrochemical catalytic reaction, proposes the role of structural design of SACs in enhancing catalytic performance, elucidates the catalytic reaction mechanisms of SACs in the conversion of petrochemical processes, and reveals the high activity origins of SACs at the atomic scale. Finally, the key challenges are summarized and an outlook on the design, identification of active sites, and the appropriate application of artificial intelligence technology is provided for achieving scale-up application of SACs in petrochemical process.

High-Performance Photoinduced Tunneling Self-Driven Photodetector for Polarized Imaging and Polarization-Coded Optical Communication based on Broken-Gap ReSe2 /SnSe2 van der Waals Heterojunction.

Novel 2D materials with low-symmetry structures exhibit great potential applications in developing monolithic polarization-sensitive photodetectors with small volume. However, owing to the fact that at least half of them presented a small anisotropic factor of ≈2, comprehensive performance of present polarization-sensitive photodetectors based on 2D materials is still lower than the practical application requirements. Herein, a self-driven photodetector with high polarization sensitivity using a broken-gap ReSe2 /SnSe2 van der Waals heterojunction (vdWH) is demonstrated. Anisotropic ratio of the photocurrent (Imax /Imin ) could reach 12.26 (635 nm, 179 mW cm-2 ). Furthermore, after a facile combination of the ReSe2 /SnSe2 device with multilayer graphene (MLG), Imax /Imin of the MLG/ReSe2 /SnSe2 can be further increased up to13.27, which is 4 times more than that of pristine ReSe2 photodetector (3.1) and other 2D material photodetectors even at a bias voltage. Additionally, benefitting from the synergistic effect of unilateral depletion and photoinduced tunneling mechanism, the MLG/ReSe2 /SnSe2 device exhibits a fast response speed (752/928 µs) and an ultrahigh light on/off ratio (105 ). More importantly, MLG/ReSe2 /SnSe2 device exhibits excellent potential applications in polarized imaging and polarization-coded optical communication with quaternary logic state without any power supply. This work provides a novel feasible avenue for constructing next-generation smart polarization-sensitive photodetector with low energy consumption.

UHPLC-QTOF-MS-based untargeted metabolomic authentication of Chinese red wines according to their grape varieties.

Wine is a very popular alcoholic drink owing to its health benefits of antioxidant effects. However, profits-driven frauds of wine especially false declarations of variety frequently occurred in markets. In this work, an UHPLC-QTOF-MS-based untargeted metabolomics method was developed for metabolite profiling of 119 bottles of Chinese red wines from four varieties (Cabernet Sauvignon, Merlot, Cabernet Gernischt, and Pinot Noir). The metabolites of red wines from different varieties were assessed using orthogonal partial least-squares discriminant analysis (OPLS-DA) and analyzed using KEGG metabolic pathway analysis. Results showed that the differential compounds among different varieties of red wines are mainly flavonoids, phenols, indoles and amino acids. The KEGG metabolic pathway analysis showed that indoles metabolism and flavonoids metabolism are closely related to wine varieties. Based on the differential compounds, OPLS-DA models could identify external validation wine samples with a total correct rate of 90.9 % in positive ionization mode and 100 % in negative ionization mode. This study indicated that the developed untargeted metabolomics method based on UHPLC-QTOF-MS is a potential tool to identify the varieties of Chinese red wines.

[Ubiquitin-specific protease 42 regulates osteogenic differentiation of human adipose-derived stem cells].

OBJECTIVE: To explore the effect of ubiquitin-specific protease 42 (USP42) on osteogenic differentiation of human adipose-derived stem cells (hASCs) in vivo and in vitro. METHODS: A combination of experiments was carried out with genetic depletion of USP42 using a lentiviral strategy. Alkaline phosphatase (ALP) staining and quantification, alizarin red S (ARS) staining and quantification were used to determine the osteogenic differentiation ability of hASCs under osteogenic induction between the experimental group (knockdown group and overexpression group) and the control group. Quantitative reverse transcription PCR (qRT-PCR) was used to detect the expression levels of osteogenesis related genes in the experimental group and control group, and Western blotting was used to detect the expression levels of osteogenesis related proteins in the experimental group and control group. Nude mice ectopic implantation experiment was used to evaluate the effect of USP42 on the osteogenic differentiation of hASCs in vivo. RESULTS: The mRNA and protein expressions of USP42 in knockdown group were significantly lower than those in control group, and those in overexpression group were significantly higher than those in control group. After 7 days of osteogenic induction, the ALP activity in the knockdown group was significantly higher than that in the control group, and ALP activity in overexpression group was significantly lower than that in control group. After 14 days of osteogenic induction, ARS staining was significantly deeper in the knockdown group than in the control group, and significantly lighter in overexpression group than in the control group. The results of qRT-PCR showed that the mRNA expression levels of ALP, osterix (OSX) and collagen type Ⅰ (COLⅠ) in the knockdown group were significantly higher than those in the control group after 14 days of osteogenic induction, and those in overexpression group were significantly lower than those in control group. The results of Western blotting showed that the expression levels of runt-related transcription factor 2 (RUNX2), OSX and COLⅠ in the knockout group were significantly higher than those in the control group at 14 days after osteogenic induction, while the expression levels of RUNX2, OSX and COLⅠ in the overexpression group were significantly lower than those in the control group. Hematoxylin-eosin staining of subcutaneous grafts in nude mice showed that the percentage of osteoid area in the knockdown group was significantly higher than that in the control group. CONCLUSION: Knockdown of USP42 can significantly promote the osteogenic differentiation of hASCs in vitro and in vivo, and overexpression of USP42 significantly inhibits in vivo osteogenic differentiation of hASCs, and USP42 can provide a potential therapeutic target for bone tissue engineering.

Advanced Fog Harvesting Method by Coupling Plasma and Micro/Nano Materials.

Harvesting fog is a potential and effective way to alleviate the crisis of water resource shortage. A highly efficient and economical fog harvesting method has always been a global and common goal. Here, a promising fog harvesting method by coupling plasma and micro/nano materials is proposed, which can achieve 93% fog collection efficiency with consuming power of only 0.76 W/0.04 m2. The basic method is to utilize nanoparticles to decorate both the discharge electrode and the collecting electrode of the micro/nano electrostatic fog collector. For the discharge electrode, the nanoparticles can achieve an order of magnitude higher electric field strength and a 28.6% decrease in the operating voltage (14 kV decreases to 10 kV). For the collecting electrode, a novel composite structure of hydrophobic/hydrophilic (HB/HL) is proposed. The core advantage is the directional droplet transport at the junction of HB and HL caused by surface tension can adjust the accumulated droplets on the two sides, which avoids the droplet residue and mesh blockage in the general structure. This technology provides an innovative approach for the collection of microdroplets and a new design idea for the fog collector to deal with the water crisis.

Schottky Junction and D-A1 -A2 System Dual Regulation of Covalent Triazine Frameworks for Highly Efficient CO2 Photoreduction.

Covalent triazine frameworks (CTFs) are emerging as a promising molecular platform for photocatalysis. Nevertheless, the construction of highly effective charge transfer pathways in CTFs for oriented delivery of photoexcited electrons to enhance photocatalytic performance remains highly challenging. Herein, a molecular engineering strategy is presented to achieve highly efficient charge separation and transport in both the lateral and vertical directions for solar-to-formate conversion. Specifically, a large π-delocalized and π-stacked Schottky junction (Ru-Th-CTF/RGO) that synergistically knits a rebuilt extended π-delocalized network of the D-A1 -A2 system (multiple donor or acceptor units, Ru-Th-CTF) with reduced graphene oxide (RGO) is developed. It is verified that the single-site Ru units in Ru-Th-CTF/RGO act as effective secondary electron acceptors in the lateral direction for multistage charge separation/transport. Simultaneously, the π-stacked and covalently bonded graphene is regarded as a hole extraction layer, accelerating the separation/transport of the photogenerated charges in the vertical direction over the Ru-Th-CTF/RGO Schottky junction with full use of photogenerated electrons for the reduction reaction. Thus, the obtained photocatalyst has an excellent CO2 -to-formate conversion rate (≈11050 µmol g-1 h-1 ) and selectivity (≈99%), producing a state-of-the-art catalyst for the heterogeneous conversion of CO2 to formate without an extra photosensitizer.

Design Principles of Single-Atom Catalysts for Oxygen Evolution Reaction: From Targeted Structures to Active Sites.

Hydrogen production from electrolytic water electrolysis is considered a viable method for hydrogen production with significant social value due to its clean and pollution-free nature, high hydrogen production efficiency, and purity, but the anode oxygen evolution reaction (OER) process is complex and kinetically slow. Single-atom catalysts (SACs) with 100% atom utilization and homogeneous active sites often exhibit high catalytic activity and are expected to be extensively applied. The catalytic performance of OER can be further improved by precise regulation of the structure through electronic effects, coordination environment, heteroatomic doping, and so on. In this review, the mechanisms of OER under different conditions are introduced, the latest research progress of SACs in the field of OER is systematically summarized, and then the effects of various structural regulation strategies on catalytic performance are discussed, and principles and ideas for the design of SACs for OER are proposed. In the end, the outstanding issues and current challenges in this field are summarized.

Atomic-Level Regulation of Cu-Based Electrocatalyst for Enhancing Oxygen Reduction Reaction: From Single Atoms to Polymetallic Active Sites.

The slow kinetics of cathodic oxygen reduction reactions (ORR) in fuel cells and the high cost of commercial Pt-based catalysts limit their large-scale application. Cu-based single-atom catalysts (SACs) have received increasing attention as a promising ORR catalyst due to their high atom utilization, high thermodynamic activity, adjustable electronic structure, and low cost. Herein, the recent research progress of Cu-based catalysts is reviewed from single atom to polymetallic active sites for ORR. First, the design and synthesis method of Cu-based SACs are summarized. Then the atomic-level structure regulation strategy of Cu-based catalyst is proposed to improve the ORR performance. The different ORR catalytic mechanism based on the different Cu active sites is further revealed. Finally, the design principle of high-performance Cu-based SACs is proposed for ORR and the opportunities and challenges are further prospected.

Vacancy Defects Inductive Effect of Asymmetrically Coordinated Single-Atom Fe─N3 S1 Active Sites for Robust Electrocatalytic Oxygen Reduction with High Turnover Frequency and Mass Activity.

The development of facile, efficient synthesis method to construct low-cost and high-performance single-atom catalysts (SACs) for oxygen reduction reaction (ORR) is extremely important, yet still challenging. Herein, an atomically dispersed N, S co-doped carbon with abundant vacancy defects (NSC-vd) anchored Fe single atoms (SAs) is reported and a vacancy defects inductive effect is proposed for promoting electrocatalytic ORR. The optimized catalyst featured of stable Fe─N3 S1 active sites exhibits excellent ORR activity with high turnover frequency and mass activity. In situ Raman, attenuated total reflectance surface enhanced infrared absorption spectroscopy reveal the Fe─N3 S1 active sites exhibit different kinetic mechanisms in acidic and alkaline solutions. Operando X-ray absorption spectra reveal the ORR activity of Fe SAs/NSC-vd catalyst in different electrolyte is closely related to the coordination structure. Theoretical calculation reveals the upshifted d band center of Fe─N3 S1 active sites facilitates the adsorption of O2 and accelerates the kinetics process of *OH reduction. The abundant vacancy defects around the Fe─N3 S1 active sites balance the OOH* formation and *OH reduction, thus synergetically promoting the electrocatalytic ORR process.

Analysis for lipid nutrient differences in the milk of 13 species from a quantitative non-targeted lipidomics perspective.

Lipids are essential organic components in milk and have been associated with various health benefits for newborns. However, a comprehensive analysis of lipid profiles across multiple species and levels has been lacking. In this study, we employed liquid chromatography-tandem mass spectrometry (LC-MS/MS) to accurately determine the absolute content of lipid molecules. It revealed that ruminants exhibit a higher concentration of short-chain fatty acids compared to non-ruminants. Additionally, we identified ALC (camel), MGH (horse), and DZD (donkey) as species that display similarities to components found in human milk fat. Remarkably, it reveals that porcine milk fat is characterized by long chain lengths, low saturation, and a high proportion of essential fatty acids. PS (22:5_18:2) could potentially serve as a biomarker in porcine milk. These unique characteristics present potential opportunities for the utilization of porcine milk. Overall, our findings provide valuable insights into the lipidomics profiles of milk from different species.

The Neuroimmune Regulation and Potential Therapeutic Strategies of Optic Pathway Glioma.

Optic pathway glioma (OPG) is one of the causes of pediatric visual impairment. Unfortunately, there is as yet no cure for such a disease. Understanding the underlying mechanisms and the potential therapeutic strategies may help to delay the progression of OPG and rescue the visual morbidities. Here, we provide an overview of preclinical OPG studies and the regulatory pathways controlling OPG pathophysiology. We next discuss the role of microenvironmental cells (neurons, T cells, and tumor-associated microglia and macrophages) in OPG development. Last, we provide insight into potential therapeutic strategies for treating OPG and promoting axon regeneration.

Single-Cell RNA Sequencing (scRNA-seq) Identifies L1CAM as a Key Mediator between Epithelial Tuft Cell and Innate Lymphoid Cell in the Colon of Hnrnp I Knockout Mice.

(1) Background: Knockout (KO) of heterogeneous nuclear ribonucleoprotein I (Hnrnp I) in mouse intestinal epithelial cells (IECs) induced a severe inflammatory response in the colon, followed by hyperproliferation. This study aimed to investigate the epithelial lineage dynamics and cell-cell communications that underlie inflammation and colitis. (2) Methods: Single cells were isolated from the colons of wildtype (WT) and KO mice and used in scRNA-seq. Whole colons were collected for immunofluorescence staining and cytokine assays. (3) Results: from scRNA-seq, the number of DCLK1 + colonic tuft cells was significantly higher in the Hnrnp I KO mice compared to the WT mice. This was confirmed by immunofluorescent staining of DCLK1. The DCLK1 + colonic tuft cells in KO mice developed unique communications with lymphocytes via interactions between surface L1 cell adhesion molecule (L1CAM) and integrins. In the KO mice colons, a significantly elevated level of inflammatory cytokines IL4, IL6, and IL13 were observed, which marks type-2 immune responses directed by group 2 innate lymphoid cells (ILC2s). (4) Conclusions: This study demonstrates one critical cellular function of colonic tuft cells, which facilitates type-2 immune responses by communicating with ILC2s via the L1CAM-integrins interaction. This communication promotes pro-inflammatory signaling pathways in ILC2, leading to the increased secretion of inflammatory cytokines.

Hydroxamic acid hybrids: Histone deacetylase inhibitors with anticancer therapeutic potency.

Histone deacetylases (HDACs), a class of enzymes responsible for the removal of acetyl functional groups from the lysine residues in the amino-terminal tails of core histones, play a critical role in the modulation of chromatin architecture and the regulation of gene expression. Dysregulation of HDAC expression has been closely associated with the development of various cancers. Histone deacetylase inhibitors (HDACis) could regulate diverse cellular pathways, cause cell cycle arrest, and promote programmed cell death, making them promising avenues for cancer therapy with potent efficacy and favorable toxicity profiles. Hybrid molecules incorporating two or more pharmacophores in one single molecule, have the potential to simultaneously inhibit two distinct cancer targets, potentially overcome drug resistance and minimize drug-drug interactions. Notably, hydroxamic acid hybrids, exemplified by fimepinostat and tinostamustine as potential HDACis, could exert the anticancer effects through induction of apoptosis, differentiation, and growth arrest in cancer cells, representing useful scaffolds for the discovery of novel HDACis. The purpose of this review is to summarize the current scenario of hydroxamic acid hybrids as HDACis with anticancer therapeutic potential developed since 2020 to facilitate further rational exploitation of more effective candidates.