Nerve guide conduits promote nerve regeneration under a combination of electrical stimulation and RSCs combined with stem cell differentiation.

Nerve guide conduits (NGCs) offer a promising alternative to traditional tools for regenerating peripheral nerves. The efficacy of nerve regeneration and functional recovery is heavily dependent on the electrical, chemical, and physical properties of NGCs. A bionic melt electrowriting (MEW) NGC loaded with placental derived mesenchymal stem cells (PDMSCs) has been developed. Our study introduces a novel approach by utilizing Schwann cells induced from placental mesenchymal stem cells (PDMSCs), showcasing their potential in enhancing nerve regeneration when integrated with conductive nerve guidance conduits. Schwann cells (SCs) are crucial for nerve regeneration, and while various stem cells, including bone marrow stromal cells (BMSCs), have been investigated as sources of SCs for NGC loading, they are often limited by ethical concerns and restricted availability. PDMSCs, however, offer the advantages of widespread sourcing and unique ability to differentiate into SCs, making them an attractive alternative for NGC applications. This NGC utilizes an electrostatic direct writing technique employing polycaprolactone (PCL) for the sheath and a crimped fiber scaffold made of polypyrrole (PPY) incorporated with PDMSCs for its internal structure. The bionic PC-NGC loaded with PDMSCs exhibits favorable characteristics including permeability, mechanical stability, and electrical conductivity. The PPY component effectively transmits physiological nerve signals, thereby promoting nerve regeneration, while the PDMSCs differentiate into Schwann cells, creating a conducive environment for nerve regeneration. This research innovatively combines PDMSCs, known for their wide availability and SC differentiation potential, with a bionic NGC to enhance the treatment of peripheral nerve injuries (PNIs). In vitro evaluations have confirmed the excellent biocompatibility of the materials used. Animal experiments using a rat model with sciatic nerve injury demonstrated that the PC-NGC significently facilitated peripheral nerve regeneration. This was evidenced by improvements in axonal myelination, increased muscle mass, enhanced sciatic nerve function index, and positive electrophysiological findings. These outcomes are comparable to those achieved through autologous transplantation. Characterized by its layered oriented fibers, the bionic PC-NGC integrates multi-scale and multifunctional biomaterials with PDMSCs to effectively address peripheral nerve injuries (PNIs). The use of this printed NGC stimulates neuronal cell growth, thereby accelerating nerve regeneration. This innovative approach in tissue engineering presents a promising clinical treatment strategy for PNIs.

NSUN5 promotes tumorigenic phenotypes through the WNT signaling pathway and immunosuppression of CD8+ T cells in gastric cancer.

NSUN5, a key member of the M5C methylation family, plays a significant role in fundamental biological processes like cell proliferation and differentiation. However, its specific function and mechanisms in gastric cancer remain insufficiently understood. Initially, we examined NSUN5's differential expression in gastric cancer versus normal tissues, along with survival trends, associated signaling pathways, and immune infiltration using the TCGA database. Subsequently, we conducted immunohistochemistry experiments to assess NSUN5 expression in gastric cancer tissues. Gain-and loss-of-function experiments were carried out to investigate NSUN5's impact on the proliferation, stemness, and migratory capabilities of gastric cancer cells, as well as the expression of vital proteins in pertinent signaling pathways. Our findings demonstrate that NSUN5 is not only overexpressed in gastric cancer tissues, but also positively associated with tumor stage and inversely linked with patient prognosis. NSUN5 promotes the in vitro proliferation, stemness, and migration of gastric cancer cells, and the in vivo growth of these cells, chiefly through the activation of the WNT/ß-catenin signaling pathway. Additionally, NSUN5 appears to diminish the infiltration of CD8+ T cells in gastric cancer, contributing to immune evasion. In conclusion, NSUN5 functions as a proto-oncogene in the progression of gastric cancer and may serve as a potential therapeutic target.

Climate change drives fish communities: Changing multiple facets of fish biodiversity in the Northwest Pacific Ocean.

Global marine biodiversity is experiencing significant alterations due to climate change. Incorporating phylogenetic and functional diversity may provide novel insights into these impacts. This study used an ensemble model approach (random forest and boosted regression tree), to predict the habitat distribution of 47 fish species in the Northwestern Pacific under contemporary (2000-2014) and future scenarios (2040-2050, 2090-2100). We first examined the relationship between eleven functional traits and habitat changes, predicting the spatial distribution of functional traits within fish communities. A significant correlation was observed between temperature preference and habitat changes, highlighting the vulnerability of cold-water species and potential advantages for warm-water species in the future. Moreover, fish communities exhibited a spatial gradient distribution with southern regions characterized by shorter-lived and earlier maturity, contrasting with longer-lived and later maturity species in the north. Secondly, to assess the impact of climate change on marine biodiversity, we explored the taxonomic, phylogenetic, and functional diversity under contemporary and future scenarios, revealing higher indices in the East China Sea (ECS) and the coastal sea of Japan, with the Taiwan Strait emerging as a contemporary biodiversity hotspot. In future scenarios, the three biodiversity indices would decline in the Yellow Sea and ECS, but increase in the sea beyond the continental shelf, coastal sea of Hokkaido, and Sea of Okhotsk. Lastly, we explored processes and mechanisms in the change of community composition. By quantifying ß-diversity, we identified species loss (nestedness) as the primary driver of fish community change by 2040-2050, with species replacement (turnover) predicted to become dominant in the far future. Our results explore the potential changes in multiple facets of fish biodiversity, providing crucial insights for policymakers aiming to protect fish resources and biodiversity.

Seasonal Analysis of Spatial Distribution Patterns and Characteristics of Sepiella maindroni and Sepia kobiensis in the East China Sea Region.

Climate change is having important effects on the migration routes and seasonal-spatial distribution patterns of aquatic animals, including the cephalopods Sepiella maindroni de Rochebrune (Hoyle, 1886) and Sepia kobiensis (Hoyle, 1885) in the East China Sea region. We conducted bottom trawling surveys from 2018 to 2019 in the East China Sea region to identify the seasonal-spatial distribution patterns, including the locations of spawning and nursery grounds of both species, and to determine how they are related to environmental variables. We used random forests and boosted regression trees to identify the distribution patterns of both species from spring to winter to estimate the annual mean situations. We also predicted the habitat distribution variations in 2050 and 2100 under the SSP1-2.6 and SSP5-8.5 climate change scenarios. From our survey data, we detected increasing biomass densities of S. maindroni from 29.50° N to 28.50° N, where the largest value of 213.92 g·ind-1 occurred. In spring, juvenile groups were present in coastal areas and larger individuals were found in offshore areas. We identified potential spawning grounds at 29.50°-33.00° N 122.50°-123.00° E adjacent to the Zhejiang coastline, and larger individuals and higher biomass densities in south of the 29.50° N line in summer. In autumn, the average individual weight increased in the 28.00° N 122.00° E→124.00° E area. We located potential S. kobiensis spawning grounds at 27.00° N 122.00°-123.50° E in spring. Growing overwintering juveniles migrated to the area of 29.50°-30.50° N 125.00°-127.00° E in winter. The sea surface temperature of the areas inhabited by both species showed obvious seasonal variation. The SSP1-2.6 and SSP5-8.5 scenarios indicated that the habitat of S. maindroni would shift to the south first and then to the north of the study area with the intensification of CO2 emissions, and it would first expand and then greatly decrease. However, the habitat area of S. kobiensis would increase. Our results will contribute to a better understanding of the life history traits of both species and the changes in their distribution patterns under different climate scenarios to ensure sustainable exploitation and fisheries management.

Tree Frogs Alter Their Behavioral Strategies While Landing On Vertical Perches.

As an arboreal animal, tree frogs face diverse challenges when landing on perches, including variations in substrate shape, diameter, flexibility, and angular distribution, with potentially significant consequences for failed landings. Research on tree frog landing behavior on perches, especially concerning landing on vertical substrates, remains limited. This study investigated the landing strategies (forelimb, abdomen, and hindlimb) of tree frogs on vertical perches, considering perch diameter. Although all three strategies were observed across perches of different diameters, their frequencies differed. Forelimb landing was most common across all perch diameters, with its frequency increasing with perch diameter, while abdomen and hindlimb landing strategies were more prevalent on smaller diameter perches. During the process from take-off to landing, the body axis underwent some deviation owing to the asymmetric movement of the left and right limbs; however, these deviations did not significantly differ among landing strategies. Additionally, different landing strategies led to variations in the landing forces, with abdominal landings generating significantly higher impact forces than the other two strategies. These findings provide insights into the biomechanics and biological adaptations of tree frogs when landing on challenging substrates, such as leaves or branches.

Correction: Incorporating mesopelagic fish into the evaluation of marine protected areas under climate change scenarios.

[This corrects the article DOI: 10.1007/s42995-023-00188-9.].

In situ calibration of shear ratio for quadriwave lateral shearing interferometry using double-slit interference.

A new method, to the best of our knowledge, based on double-slit (DS) interference is proposed to accurately estimate the shear ratio of the system, with plane wave or spherical wave incidence. Existing shear ratio calibration methods, designed primarily for lateral shearing interferometry (LSI) with plane wave incidence, are not applicable to LSIs directly testing divergent or convergent spherical waves. Equations for calculating the shear ratio using the fringe spacing of the DS interferogram and the NA of the incident spherical wave are derived in this paper. The simulation result shows that the relative error of the shear ratio value is about 0.3%, when the shear ratio is 0.1. In the experiment, the quadriwave LSI is designed with a plug-in feature. The shear ratio at integer multiples of 1/6 Talbot distance from the modified Hartmann mask was calibrated using a DS, and the results were in good agreement with theoretical values, confirming the accuracy of the method. Subsequently, with the assistance of an inductance micrometer, the shear ratio was calibrated at intervals of 0.5 mm, and the results closely matched the theoretical variation of the shear ratio caused by displacement, confirming the high precision of the method.

Asymmetric Carbene-Alkyne Metathesis-Mediated Cascade: Synthesis of Benzoxazine Polychiral Polyheterocycles and Discovery of a Novel Pain Blocker.

This study introduces a novel approach for synthesizing Benzoxazine-centered Polychiral Polyheterocycles (BPCPHCs) via an innovative asymmetric carbene-alkyne metathesis-triggered cascade. Overcoming challenges associated with intricate stereochemistry and multiple chiral centers, the catalytic asymmetric Carbene Alkyne Metathesis-mediated Cascade (CAMC) is employed using dirhodium catalyst/Brønsted acid co-catalysis, ensuring precise stereo control as validated by X-ray crystallography. Systematic substrate scope evaluation establishes exceptional diastereo- and enantioselectivities, creating a unique library of BPCPHCs. Pharmacological exploration identifies twelve BPCPHCs as potent Nav ion channel blockers, notably compound 8 g. In vivo studies demonstrate that intrathecal injection of 8 g effectively reverses mechanical hyperalgesia associated with chemotherapy-induced peripheral neuropathy (CIPN), suggesting a promising therapeutic avenue. Electrophysiological investigations unveil the inhibitory effects of 8 g on Nav1.7 currents. Molecular docking, dynamics simulations and surface plasmon resonance (SPR) assay provide insights into the stable complex formation and favorable binding free energy of 8 g with C5aR1. This research represents a significant advancement in asymmetric CAMC for BPCPHCs and unveils BPCPHC 8 g as a promising, uniquely acting pain blocker, establishing a C5aR1-Nav1.7 connection in the context of CIPN.

Incorporating mesopelagic fish into the evaluation of conservation areas for marine living resources under climate change scenarios.

Mesopelagic fish (meso-fish) are central species within the Southern Ocean (SO). However, their ecosystem role and adaptive capacity to climate change are rarely integrated into protected areas assessments. This is a pity given their importance as crucial prey and predators in food webs, coupled with the impacts of climate change. Here, we estimate the habitat distribution of nine meso-fish using an ensemble model approach (MAXENT, random forest, and boosted regression tree). Four climate model simulations were used to project their distribution under two representative concentration pathways (RCP4.5 and RCP8.5) for short-term (2006-2055) and long-term (2050-2099) periods. In addition, we assess the ecological representativeness of protected areas under climate change scenarios using meso-fish as indicator species. Our models show that all species shift poleward in the future. Lanternfishes (family Myctophidae) are predicted to migrate poleward more than other families (Paralepididae, Nototheniidae, Bathylagidae, and Gonostomatidae). In comparison, lanternfishes were projected to increase habitat area in the eastern SO but lose area in the western SO; the opposite was projected for species in other families. Important areas (IAs) of meso-fish are mainly distributed near the Antarctic Peninsula and East Antarctica. Negotiated protected area cover 23% of IAs at present and 38% of IAs in the future (RCP8.5, long-term future). Many IAs of meso-fish still need to be included in protected areas, such as the Prydz Bay and the seas around the Antarctic Peninsula. Our results provide a framework for evaluating protected areas incorporating climate change adaptation strategies for protected areas management. Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-023-00188-9.

Nerve Guide Conduits Integrated with Fisetin-Loaded Chitosan Hydrogels for Reducing Oxidative Stress, Inflammation, and Nerve Regeneration.

Peripheral nerve injuries (PNI) represent a prevalent and severe category of damage resulting from traumatic incidents. Predominantly, the deficiency in nerve regeneration can be ascribed to enduring inflammatory reactions, hence imposing substantial clinical implications for patients. Fisetin, a flavonoid derived from plants, is naturally present in an array of vegetables and fruits, including strawberries, apples, onions, and cucumbers. It exhibits immunomodulatory properties through the reduction of inflammation and oxidative stress. In the present research, a nerve defect is addressed for the first time utilizing a scaffold primed for controlled fisetin release. In this regard, fisetin-loaded chitosan hydrogels are incorporated into the lumen of polycaprolactone (PCL) nerve guide conduits (NGCs). The hydrogel maintained a steady release of an appropriate fisetin dosage. The study outcomes indicated that the fisetin/chitosan/polycaprolactone (FIS/CS/PCL) NGCs amplified Schwann cell proliferation and neural expression, curtailed oxidative stress, alleviated inflammation, and improved functions, electrophysiological properties, and morphology. This pioneering scaffold has the potential to contribute significantly to the field of neuroengineering.

Chlorogenic acid releasing microspheres enhanced electrospun conduits to promote peripheral nerve regeneration.

Chlorogenic acid (CGA) has been confirmed as a polyphenol, and existing research has suggested the high bioactivity of CGA for therapeutic effects on a wide variety of diseases. Despite the existing reports of anti-inflammatory, antioxidant, and neuroprotective effects of CGA, the role and mechanism of CGA in facilitating the regeneration of peripheral nerve defects have been rarely investigated. Herein, a biodegradable polycaprolactone (PCL) conduit with embedded CGA-releasing GelMA microspheres (CGM/PCL) was successfully prepared and used for repairing a rate model with sciatic nerve defects. CGM and CGM/PCL conduits displayed high in vitro biocompatibility and can support the growth of cells for nerve regeneration. Furthermore, CGM/PCL conduits displayed high performance which is close to that of autologous nerve grafts in promoting in vivo PNI regeneration, compared with PCL conduits. The sciatic nerve functional index analysis, electrophysiological examination, and immunological analysis performed to evaluate the functional recovery of the injurious sciatic nerve of rats have indeed proved the favorable effects of CGM/PCL conduits. The result of this study not only aimed to explore CGA's contribution to nerve regeneration but also provided a new strategy for designing and preparing functional NGCs for PNI treatment.

Durable superhydrophobic coatings for stainless-steel: An effective defense against Escherichia coli and Listeria fouling in the post-harvest environment.

Increasing concerns revolve around bacterial cross-contamination of leafy green vegetables via food-contact surfaces. Given that stainless-steel is among the commonly used food-contact surfaces, this study reports a coating strategy enhancing its hygiene and microbiological safety through an antifouling approach via superhydrophobicity. The developed method involves growing a nickel-nanodiamond nanocomposite film on 304 stainless-steel via electroplating and sequential functionalization of the outer surface layer with nonpolar organosilane molecules via polydopamine moieties. The resultant superhydrophobic stainless-steel surfaces had a static water contact angle of 156.3 ± 1.9° with only 2.3 ± 0.5° contact angle hysteresis. Application of the coating to stainless-steel was demonstrated to yield 2.3 ± 0.6 log10 and 2.0 ± 0.9 log10 reductions in the number of adherent gram-negative Escherichia coli O157:H7 and gram-positive Listeria innocua cells, respectively. These population reductions were shown to be statistically significant (α = 0.05). Coated stainless-steel also resisted fouling when contacted with contaminated romaine lettuce leaves and maintained significant non-wetting character when abraded with sand or contacted with high concentration surfactant solutions. The incorporation of superhydrophobic stainless-steel surfaces into food processing equipment used for washing and packaging leafy green vegetables has the potential to mitigate the transmission of pathogenic bacteria within food production facilities.

Bioinspired Rigid-Flexible Coupled Adaptive Compliant Motion Control of Robot Gecko for Space Stations.

This paper presents a study on bioinspired rigid-flexible coupling adaptive compliant motion control of a robot gecko with hybrid actuation for space stations. The biomimetic robot gecko is made of a rigid trunk, four motor-driven active legs with dual-degree-of-freedom shoulder joints, and four pneumatic flexible pleated active attachment-detachment feet. The adaptive impedance model consists of four input parameters: the inertia coefficient, stiffness coefficient, damping coefficient, and segmented expected plantar force. The robot gecko is equipped with four force sensors mounted on its four feet, from which the normal force of each foot can be sensed in real-time. Based on the sensor signal, the variable stiffness characteristics of the feet in different states are analyzed. Furthermore, an adaptive active compliance control strategy with whole-body rigidity-flexibility-force feedback coupling is proposed for the robot gecko. Four sets of experiments are presented, including open-loop motion control, static anti-interference experiment, segmented variable stiffness experiment, and adaptative compliant motion control, both in a microgravity environment. The experiment results indicated that the presented control strategy worked well and the robot gecko demonstrates the capability of stable attachment and compliant detachment, thereby normal impact and microgravity instability are avoided. It achieves position tracking and force tracking while exhibiting strong robustness for external disturbances.

Exosomes derived from schwann cells alleviate mitochondrial dysfunction and necroptosis after spinal cord injury via AMPK signaling pathway-mediated mitophagy.

Although spinal cord injury (SCI) represents a primary etiology of disability, currently, there are exist limited viable therapies modalities. Acquiring comprehension of the diverse pathways that drive mitochondrial aberration may facilitate the identification of noteworthy targets for ameliorating the deleterious consequences precipitated by SCI. Our objective was to determine the efficiency of exosomes produced from Schwann cells (SCDEs) in protecting against mitochondrial dysfunction. This evaluation was conducted using a rat model of compressed SCI and in vitro experiments involving rat pheochromocytoma cells (PC12) exposed to oxygen-glucose deprivation (OGD). The conducted experiments yielded evidence that SCDEs effectively mitigated oxidative stress (OS) and inflammation subsequent to SCI, while concurrently diminishing necroptosis. Subsequent in vitro inquiry assessed the impact of SCDEs on PC12, with a specific emphasis on mitochondrial functionality, necrotic cell prevalence, and mitophagy. The study findings revealed that SCDEs enhanced mitophagy in PC12 cells, leading to a decrease in the generation of reactive oxygen species (ROS) and inflammatory cytokines (CK) provoked by OGD-induced injury. This, in turn, mitigated mitochondrial dysfunction and necroptosis. Mechanistically, SCDEs facilitated cellular mitophagy through activation of the AMPK signaling pathway. In conclusion, our data strongly support the notion that SCDEs hold considerable promise as a therapeutic approach for managing SCI. Furthermore, our investigation serves to elucidate the pivotal role of AMPK-mediated mitophagy in reducing cell damage, thereby unveiling novel prospects for enhancing neuro-pathological outcomes following SCI.

pH- and temperature-responsive supramolecular assemblies with highly adjustable viscoelasticity: a multi-stimuli binary system.

Stimuli-responsive materials are increasingly needed for the development of smart electronic, mechanical, and biological devices and systems relying on switchable, tunable, and adaptable properties. Herein, we report a novel pH- and temperature-responsive binary supramolecular assembly involving a long-chain hydroxyamino amide (HAA) and an inorganic hydrotrope, boric acid, with highly tunable viscous and viscoelastic properties. The system under investigation demonstrates a high degree of control over its viscosity, with the capacity to achieve over four orders of magnitude of control through the concomitant manipulation of pH and temperature. In addition, the transformation from non-Maxwellian to Maxwellian fluid behavior could also be induced by changing the pH and temperature. Switchable rheological properties were ascribed to the morphological transformation between spherical vesicles, aggregated/fused spherical vesicles, and bicontinuous gyroid structures revealed by cryo-TEM studies. The observed transitions are attributed to the modulation of the head group spacing between HAA molecules under different pH conditions. Specifically, acidic conditions induce electrostatic repulsion between the protonated amino head groups, leading to an increased spacing. Conversely, under basic conditions, the HAA head group spacing is reduced due to the intercalation of tetrahydroxyborate, facilitated by hydrogen bonding.

Inhibition of autophagy and RIP1/RIP3/MLKL-mediated necroptosis by edaravone attenuates blood spinal cord barrier disruption following spinal cord injury.

The disruption of the blood spinal cord barrier (BSCB) after spinal cord injury (SCI) can trigger secondary tissue damage. Edaravone is likely to protect the BSCB as a free radical scavenger, whereas it has been rarely reported thus far. In this study, the protective effect of edaravone was investigated with the use of compression spinal cord injured rats and human brain microvascular endothelial cells (HBMECs) injury. As indicated by the result of this study, edaravone treatment facilitated functional recovery after rats were subjected to SCI, ameliorated the vascular damage, and up-regulated the expression of BSCB-associated proteins. In vitro results, edaravone improved HBMECs viability, restored intercellular junctions, and promoted cellular angiogenic activities. It is noteworthy that autophagy was activated and RIP1/RIP3/MLKL phosphorylation was notably up-regulated. However, edaravone treatment exhibited the capability of mitigating above-mentioned tendency in vivo and in vitro. Moreover, rapamycin (Rapa) treatment deteriorated the protective effect of edaravone while aggravating the phosphorylation of RIP1/RIP3/MLKL expression. In the model of necrotic activator-induced HBMECs, autophagic expression was increased, whereas edaravone prevented autophagy and phosphorylation of RIP1/RIP3/MLKL. In general, our results suggested that edaravone is capable of reducing the destruction of BSCB and promoting functional recovery after SCI. The possible underlying mechanism is that edaravone is capable of protecting angiogenic activity and improving autophagy and the phosphorylation of RIP1/RIP3/MLKL, as well as their mutual deterioration. Accordingly, edaravone can be a favorable option for the treatment of SCI.

Anomalous High-Temperature Magnetoresistance in a Dilute 2D Hole System.

We report an unusual magnetoresistance that strengthens with the temperature in a dilute two-dimensional (2D) hole system in GaAs/AlGaAs quantum wells with densities p=1.98-0.99×10^{10}/cm^{2} where r_{s}, the ratio between Coulomb energy and Fermi energy, is as large as 20-30. We show that, while the system exhibits a negative parabolic magnetoresistance at low temperatures (≲0.4 K) characteristic of an interacting Fermi liquid, a positive magnetoresistance emerges unexpectedly at higher temperatures, and grows with increasing temperature even in the regime T∼E_{F}, close to the Fermi energy. This unusual positive magnetoresistance at high temperatures can be attributed to the viscous transport of 2D hole fluid in the hydrodynamic regime where holes scatter frequently with each other. These findings give insight into the collective transport of strongly interacting carriers in the r_{s}≫1 regime and new routes toward magnetoresistance at high temperatures.

Influence of Surface Roughness, Nanostructure, and Wetting on Bacterial Adhesion.

Bacterial fouling is a persistent problem causing the deterioration and failure of functional surfaces for industrial equipment/components; numerous human, animal, and plant infections/diseases; and energy waste due to the inefficiencies at internal and external geometries of transport systems. This work gains new insights into the effect of surface roughness on bacterial fouling by systematically studying bacterial adhesion on model hydrophobic (methyl-terminated) surfaces with roughness scales spanning from ∼2 nm to ∼390 nm. Additionally, a surface energy integration framework is developed to elucidate the role of surface roughness on the energetics of bacteria and substrate interactions. For a given bacteria type and surface chemistry; the extent of bacterial fouling was found to demonstrate up to a 75-fold variation with surface roughness. For the cases showing hydrophobic wetting behavior, both increased effective surface area with increasing roughness and decreased activation energy with increased surface roughness was concluded to enhance the extent of bacterial adhesion. For the cases of superhydrophobic surfaces, the combination of factors including (i) the surpassing of Laplace pressure force of interstitial air over bacterial adhesive force, (ii) the reduced effective substrate area for bacteria wall due to air gaps to have direct/solid contact, and (iii) the reduction of attractive van der Waals force that holds adhering bacteria on the substrate were summarized to weaken the bacterial adhesion. Overall, this study is significant in the context of designing antifouling coatings and systems as well as explaining variations in bacterial contamination and biofilm formation processes on functional surfaces.

Endoplasmic reticulum-targeted NIR-II phototherapy combined with inflammatory vascular suppression elicits a synergistic effect against TNBC.

Recurrence and metastasis are the main reasons for failure in the treatment of triple-negative breast cancer (TNBC). Phototherapy, one of the most well-known potent cancer treatment models is highlighted by ablating primitive tumors with immunogenic cell death (ICD) and is associated with endoplasmic reticulum (ER) stress to elicit long-lasting anti-tumor immunity. However, the provoked inflammatory response after phototherapy will stimulate angiogenesis, which provides nutrition for tumor recurrence. Here, an ER-targeted nanoplatform was constructed based on hollow mesoporous Cu2-XS (HMCu2-XS) nanoparticles to suppress recurrence and metastasis of TNBC by combining photo-ablation and microenvironment remodeling. Profiting from the metal ion coordination and large hollow space, HMCu2-XS can be easily modified with p-toluenesulfonamide for ER-targeting and quantitatively loaded celecoxib (CXB) as a vascular inhibitor, thus obtaining ER-HMCu2-XS/CXB. ER-HMCu2-XS showed great photothermal and photodynamic efficiency for ablating 4T1 tumors and inducing ICD under NIR-II laser irradiation. Compared with non-ER-targeted nanosystems, the ER-targeted nanosystem elicited stronger ICDs and recruited more immune cells. Moreover, the thermal-responsively released CXB successfully inhibited angiogenesis after photothermal therapy. The data showed that the ER-HMCu2-XS/CXB mediated the triplicate therapeutic effect of photo-ablation, immune response activation, and vascular suppression effectively, preventing the recurrence and metastasis of TNBC. In conclusion, this work provides a synergistic strategy to enhance therapeutic outcomes in TNBC.

Targeting NAD metabolism regulates extracellular adenosine levels to improve the cytotoxicity of CD8+ effector T cells in the tumor microenvironment of gastric cancer.

PURPOSE: Nicotinamide adenine dinucleotide (NAD+) is closely related to the pathogenesis of tumors. However, the effect of NAD+ metabolism of gastric cancer (GC) cells on immune cells remains unexplained. We targeted nicotinamide phosphoribosyltransferase (NAMPT), a rate-limiting enzyme in the NAD+ synthesis salvage pathway, to observe its effect in the immune microenvironment. METHODS: NAMPT of GC cell lines was inhibited by using the small molecule inhibitor (FK866) and short hairpin RNA (shRNA). CCK-8 test and flow cytometry were performed to detect cell viability and apoptosis. Immunofluorescence was used to observe changes in mitochondrial membrane potential (MMP).The transfected GC cells (AGS) and patient-derived organoids (PDOs) were cocultured with activated PBMCs, followed by flow cytometric analysis (FCA) for cytokines and inhibitory marker. The level of NAD and ATP of GC cells (AGS & MKN45) was tested combined with NMN and CD39 inhibitor. RESULTS: Targeting NAD+ by FK866 obviously reduced MMP, which ultimately inhibited proliferation and increased the apoptosis of GC cells. NAMPT silencing reduced intracellular NAD and ATP，further decreased extracellular adenosine. Meawhile, the cytokines of CD8+T cells were significantly increased after cocultured with transfected AGS, and the expression of PD-1 was distinctly decreased. NMN reversed the effect of shNAMPT and enhanced the immunosuppression. Consistent results were obtained by coculturing PBMCs with PDOs. CONCLUSION: Restraining the function of NAMPT resulted in the functional improvement of effector CD8+ T cells by decreasing extracellular adenosine levels and inducing apoptosis of GC cells simultaneously. Therefore, this study demonstrates that NAMPT can be an effective target for gastric cancer immunotherapy.