Cannabinoid Analgesia in Postoperative Pain Management: From Molecular Mechanisms to Clinical Reality.

Postoperative pain (POP) is a challenging clinical phenomenon that affects the majority of surgical patients and demands effective management to mitigate adverse outcomes such as persistent pain. The primary goal of POP management is to alleviate suffering and facilitate a seamless return to normal function for the patient. Despite compelling evidence of its drawbacks, opioid analgesia remains the basis of POP treatment. Novel therapeutic approaches rely on multimodal analgesia, integrating different pharmacological strategies to optimize efficacy while minimizing adverse effects. The recognition of the imperative role of the endocannabinoid system in pain regulation has prompted the investigation of cannabinoid compounds as a new therapeutic avenue. Cannabinoids may serve as adjuvants, enhancing the analgesic effects of other drugs and potentially replacing or at least reducing the dependence on other long-term analgesics in pain management. This narrative review succinctly summarizes pertinent information on the molecular mechanisms, clinical therapeutic benefits, and considerations associated with the plausible use of various cannabinoid compounds in treating POP. According to the available evidence, cannabinoid compounds modulate specific molecular mechanisms intimately involved in POP. However, only two of the eleven clinical trials that evaluated the efficacy of different cannabinoid interventions showed positive results.

Spatial connectivity of reef manta rays across the Raja Ampat archipelago, Indonesia.

The reef manta ray Mobula alfredi is present throughout most island groups that form the Raja Ampat archipelago, Indonesia. The species is protected regionally and nationally and is currently managed as a single homogeneous population within the 6.7 million ha archipelago. However, scientific evidence is currently lacking regarding the spatial connectivity and population structure of M. alfredi within this archipelago. Using network analysis and an array of 34 acoustic receivers deployed throughout Raja Ampat between February 2016 and September 2021, we examined the movements of 72 subadult and adult M. alfredi tagged in seven regions of Raja Ampat. A total of 1094 M. alfredi movements were recorded and were primarily concentrated between nearby receiver stations, highlighting frequent local movements within, and limited long-distance movements between regional acoustic receiver arrays. Network analysis revealed highly connected nodes acting as hubs important for M. alfredi movements. A community detection algorithm further indicated clusters within the network. Our results suggest the existence of a metapopulation comprising three demographically and geographically distinct subpopulations within the archipelago. They also reveal the importance of Eagle Rock as a critical node in the M. alfredi movement network, justifying the urgent inclusion of this site within the Raja Ampat marine protected area network.

Machine-Learning-Driven High-Throughput Screening of Transition-Metal Atom Intercalated g-C3N4/MX2 (M = Mo, W; X = S, Se, Te) Heterostructures for the Hydrogen Evolution Reaction.

Rising global energy demand, accompanied by environmental concerns linked to conventional fossil fuels, necessitates a shift toward cleaner and sustainable alternatives. This study focuses on the machine-learning (ML)-driven high-throughput screening of transition-metal (TM) atom intercalated g-C3N4/MX2 (M = Mo, W; X = S, Se, Te) heterostructures to unravel the rich landscape of possibilities for enhancing the hydrogen evolution reaction (HER) activity. The stability of the heterostructures and the intercalation within the substrates are verified through adhesion and binding energies, showcasing the significant impact of chalcogenide selection on the interaction properties. Based on hydrogen adsorption Gibbs free energy (ΔGH) computed via density functional theory (DFT) calculations, several ML models were evaluated, particularly random forest regression (RFR) emerges as a robust tool in predicting HER activity with a low mean absolute error (MAE) of 0.118 eV, thereby paving the way for accelerated catalyst screening. The Shapley Additive exPlanation (SHAP) analysis elucidates pivotal descriptors that influence the HER activity, including hydrogen adsorption on the C site (HC), MX layer (HMX), S site (HS), and intercalation of TM atoms at the N site (IN). Overall, our integrated approach utilizing DFT and ML effectively identifies hydrogen adsorption on the N site (site-3) of g-C3N4 as a pivotal active site, showcasing exceptional HER activity in heterostructures intercalated with Sc and Ti, underscoring their potential for advancing catalytic performance.

Understanding the Biological Relationship between Migraine and Depression.

Migraine is a highly prevalent neurological disorder. Among the risk factors identified, psychiatric comorbidities, such as depression, seem to play an important role in its onset and clinical course. Patients with migraine are 2.5 times more likely to develop a depressive disorder; this risk becomes even higher in patients suffering from chronic migraine or migraine with aura. This relationship is bidirectional, since depression also predicts an earlier/worse onset of migraine, increasing the risk of migraine chronicity and, consequently, requiring a higher healthcare expenditure compared to migraine alone. All these data suggest that migraine and depression may share overlapping biological mechanisms. Herein, this review explores this topic in further detail: firstly, by introducing the common epidemiological and risk factors for this comorbidity; secondly, by focusing on providing the cumulative evidence of common biological aspects, with a particular emphasis on the serotoninergic system, neuropeptides such as calcitonin-gene-related peptide (CGRP), pituitary adenylate cyclase-activating polypeptide (PACAP), substance P, neuropeptide Y and orexins, sexual hormones, and the immune system; lastly, by remarking on the future challenges required to elucidate the etiopathological mechanisms of migraine and depression and providing updated information regarding new key targets for the pharmacological treatment of these clinical entities.

A Numerical Model Supports the Evolutionary Advantage of Recombination Plasticity in Shifting Environments.

AbstractNumerous empirical studies have witnessed an increase in meiotic recombination rate in response to physiological stress imposed by unfavorable environmental conditions. Thus, inherited plasticity in recombination rate is hypothesized to be evolutionarily advantageous in changing environments. Previous theoretical models proceeded from the assumption that organisms increase their recombination rate when the environment becomes more stressful and demonstrated the evolutionary advantage of such a form of plasticity. Here, we numerically explore a complementary scenario-when the plastic increase in recombination rate is triggered by the environmental shifts. Specifically, we assume increased recombination in individuals developing in a different environment than their parents and, optionally, also in offspring of such individuals. We show that such shift-inducible recombination is always superior when the optimal constant recombination implies an intermediate rate. Moreover, under certain conditions, plastic recombination may also appear beneficial when the optimal constant recombination is either zero or free. The advantage of plastic recombination was better predicted by the range of the population's mean fitness over the period of environmental fluctuations, compared with the geometric mean fitness. These results hold for both panmixia and partial selfing, with faster dynamics of recombination modifier alleles under selfing. We think that recombination plasticity can be acquired under the control of environmentally responsive mechanisms, such as chromatin epigenetics remodeling.

Adolescent intermittent ethanol exposure decreases perineuronal nets in the hippocampus in a sex dependent manner: Modulation through pharmacological inhibition of RPTPß/ζ.

Adolescence is a critical period for brain maturation in which this organ undergoes critical plasticity mechanisms that increase its vulnerability to the effects of alcohol. Significantly, ethanol-induced disruption of hippocampal neurogenesis has been related to cognitive decline in adulthood. During adolescence, the maturation of perineuronal nets (PNNs), extracellular matrix structures highly affected by ethanol consumption, plays a fundamental role in neurogenesis and plasticity in the hippocampus. Receptor Protein Tyrosine Phosphatase (RPTP) ß/ζ is a critical anchor point for PNNs on the cell surface. Using the adolescent intermittent access to ethanol (IAE) model, we previously showed that MY10, a small-molecule inhibitor of RPTPß/ζ, reduces chronic ethanol consumption in adolescent male mice but not in females and prevents IAE-induced neurogenic loss in the male hippocampus. We have now tested if these effects of MY10 are related to sex-dependent modulatory actions on ethanol-induced effects in PNNs. Our findings suggest a complex interplay between alcohol exposure, neural structures, and sex-related differences in the modulation of PNNs and parvalbumin (PV)-positive cells in the hippocampus. In general, IAE increased the number of PV + cells in the female hippocampus and reduced PNNs intensity in different hippocampal regions, particularly in male mice. Notably, we found that pharmacological inhibition of RPTPß/ζ with MY10 regulates ethanol-induced alterations of PNNs intensity, which correlates with the protection of hippocampal neurogenesis from ethanol neurotoxic effects and may be related to the capacity of MY10 to increase the gene expression of key components of PNNs.

Solar-Driven Ammonia Production through Engineering of the Electronic Structure of a Zr-Based MOF.

As a hydrogen carrier and a vital component in fertilizer production, ammonia (NH3) is set to play a crucial role in the planet's future. While its industrial production feeds half of the global population, it uses fossil fuels and emits greenhouse gases. To tackle this issue, photocatalytic nitrogen fixation using visible light is emerging as an effective alternative method. This strategy avoids carbon dioxide (CO2) emissions and harnesses the largest share of sunlight. In this work, we successfully incorporated a 5-nitro isophthalic acid linker into MOF-808 to introduce structural defects and open metal sites. This has allowed modulation of the electronic structure of the MOF and effectively reduced the band gap energy from 3.8 to 2.6 eV. Combination with g-C3N4 enhanced further NH3 production, as these two materials possess similar band gap energies, and g-C3N4 has shown excellent performance for this reaction. The nitro groups serve as acceptors, and their integration into the MOF structure allowed effective interaction with the free electron pairs on N-(C)3 in the g-C3N4 network nodes. Based on DFT calculations, it was concluded that the adsorption of N2 molecules on open metal sites caused a decrease in their triple bond energy. The modified MOF-808 showed superior performance compared with the other MOFs studied in terms of N2 photoreduction under visible light. This design concept offers valuable information about how to engineer band gap energy in MOF structures and their combination with appropriate semiconductors for solar-powered photocatalytic reactions, such as N2 or CO2 photoreduction.

Single-Atom Ru Catalyst-Decorated CNF(ZnO) Nanocages for Efficient H2 Evolution and CH3OH Production.

The presence of transition-metal single-atom catalysts effectively enhances the interaction between the substrate and reactant molecules, thus exhibiting extraordinary catalytic performance. In this work, we for the first time report a facile synthetic procedure for placing highly dispersed Ru single atoms on stable CNF(ZnO) nanocages. We unravel the atomistic nature of the Ru single atoms in CNF(ZnO)/Ru systems using advanced HAADF-STEM, HRTEM, and XANES analytical methods. Density functional theory calculations further support the presence of ruthenium single-atom sites in the CNF(ZnO)/Ru system. Our work further demonstrates the excellent photocatalytic ability of the CNF(ZnO)/Ru system with respect to H2 production (5.8 mmol g-1 h-1) and reduction of CO2 to CH3OH [249 µmol (g of catalyst)-1] with apparent quantum efficiencies of 3.8% and 1.4% for H2 and CH3OH generation, respectively. Our studies unambiguously demonstrate the presence of atomically dispersed ruthenium sites in CNF(ZnO)/Ru catalysts, which greatly enhance charge transfer, thus facilitating the aforementioned photocatalytic redox reactions.

Computer controlled expansion of equine cord blood mesenchymal stromal cells on microcarriers in 3 L vertical-wheel® bioreactors.

Mesenchymal stromal cells (MSCs) are an ideal cell source for allogenic cell therapy due to their immunomodulatory and differentiation properties. Equine MSCs (eMSCs) have been found to be a promising treatment for equine joint injuries including meniscal injuries, cartilage degradation, and osteoarthritis. Although the use of eMSCs has shown efficacy in preliminary studies, challenges associated with biomanufacturing remain. To achieve the required cell numbers for clinical application, bioreactor-based processes are required. Initial studies have shown that eMSCs can be cultivated in microcarrier-based, stirred suspension bioreactor culture at the laboratory 0.1 L scale using a Vertical-Wheel® (VW) bioreactor. However, investigations regarding scale up of these processes to the required biomanufacturing scales are required. This study investigated the scale-up of a equine cord blood MSC (eCB-MSC) bioprocess in VW bioreactors at three scales. This included scale-up from the 0.1-0.5 L bioreactor, scale-up from static culture to the 3 L computer-controlled bioreactor, and scale-up into the 3 L computer-controlled bioreactor using a mock clinical trial process. Results from the various scale-up experiments demonstrated similar cell expansion at the various tested scales. The 3 L computer-controlled system resulted in a final cell densities of 1.5 × 105 cells/cm2 on average, achieving 1.5 × 109 harvested cells. Biological testing of the cells showed that cell phenotype and functionality were maintained after scale-up. These findings demonstrate the scalability of an eCB-MSC bioprocess using microcarriers in VW bioreactors to achieve clinically relevant cell numbers, a critical step to translate MSC treatments from research to clinical applications. This study also represents the first known published study expanding any cell type in the 3 L VW bioreactor.

Influence of Fluorinated Substituents on the Near-Infrared Phosphorescence of 5d Metallocorroles.

The influence of fluorinated substituents on the luminescent properties of rhenium-oxo, osmium-nitrido, and gold triarylcorroles was studied via a comparison of four ligands: triphenylcorrole (TPC), tris(p-trifluoromethylphenyl)corrole (TpCF3PC), tris{3,5-bis(trifluoromethyl)phenyl}corrole (T3,5-CF3PC), and tris(pentafluorophenyl)corrole (TPFPC). For each metal series examined, fluorinated substituents were found to enhance the luminescent properties, with the phosphorescence quantum yields and triplet decay times increasing in the order TPC < TpCF3PC < T3,5-CF3PC < TPFPC. Among the 11 complexes examined, the highest phosphorescence quantum yield, 2.2%, was recorded for Re[TPFPC](O).

ß-Galactosidase-activated nitroxyl (HNO) donors provide insights into redox cross-talk in senescent cells.

The cross-talk among reductive and oxidative species (redox cross-talk), especially those derived from sulfur, nitrogen and oxygen, influence several physiological processes including aging. One major hallmark of aging is cellular senescence, which is associated with chronic systemic inflammation. Here, we report a chemical tool that generates nitoxyl (HNO) upon activation by ß-galactosidase, an enzyme that is over-expressed in senescent cells. In a radiation-induced senescence model, the HNO donor suppressed reactive oxygen species (ROS) in a hydrogen sulfide (H2S)-dependent manner. Hence, the newly developed tool provides insights into redox cross-talk and establishes the foundation for new interventions that modulate levels of these species to mitigate oxidative stress and inflammation.

Comparing the efficacy of data-driven denoising methods for a multi-echo fMRI acquisition at 7T.

In functional magnetic resonance imaging (fMRI) of the brain the measured signal is corrupted by several (e.g. physiological, motion, and thermal) noise sources and depends on the image acquisition. Imaging at ultrahigh field strength is becoming increasingly popular as it offers increased spatial accuracy. The latter is of particular benefit in brainstem neuroimaging given the small cross-sectional area of most nuclei. However, physiological noise scales with field strength in fMRI acquisitions. Although this problem is in part solved by decreasing voxel size, it is clear that adequate physiological denoising is of utmost importance in brainstem-focused fMRI experiments. Multi-echo sequences have been reported to facilitate highly effective denoising through TE-dependence of Blood Oxygen Level Dependent (BOLD) signals, in a denoising method referred to as multi-echo independent component analysis (ME-ICA). It has not been explored previously how ME-ICA compares to other data-driven denoising approaches at ultrahigh field strength. In the current study, we compared the efficacy of several denoising methods, including anatomical component based correction (aCompCor), Automatic Removal of Motion Artifacts (ICA-AROMA) aggressive and non-aggressive options, ME-ICA, and a combination of ME-ICA and aCompCor. We assessed several data quality metrics, including temporal signal-to-noise ratio (tSNR), delta variation signal (DVARS), spectral density of the global signal, functional connectivity and Shannon spectral entropy. Moreover, we looked at the ability of each method to uncouple the global signal and respiration. In line with previous reports at lower field strengths, we demonstrate that after applying ME-ICA, the data is best post-processed in order to remove spatially diffuse noise with a method such as aCompCor. Our findings indicate that ME-ICA combined with aCompCor and the aggressive option of ICA-AROMA are highly effective denoising approaches for multi-echo data acquired at 7T. ME-ICA combined with aCompCor potentially preserves more signal-of-interest as compared to the aggressive option of ICA-AROMA.

S-Scheme ZIF-67/CuFe-LDH Heterojunction for High-Performance Photocatalytic H2 Evolution and CO2 to MeOH Production.

The S-scheme heterojunction photocatalyst holds potential for better photocatalysis owing to its capacity to broaden the light absorption range, ease electron-hole separation, extend the charge carrier lifespan, and maximize the redox ability. In this study, we integrate zeolitic imidazolate frameworks (ZIFs-67) with the CuFe-LDH composite, offering a straightforward approach towards creating a novel hybrid nanostructure, enabling remarkable performance in both photocatalytic hydrogen (H2) evolution and carbon dioxide (CO2) to methanol (MeOH) conversion. The ZIF-67/CuFe-LDH photocatalyst exhibits an enhanced photocatalytic hydrogen evolution rate of 7.4 mmol g-1 h-1 and an AQY of 4.8%. The superior activity of CO2 reduction to MeOH generation was 227 µmol g-1 h-1 and an AQY of 5.1%, and it still exhibited superior activity after continuously working for 4 runs with nearly negligible decay in activity. The combined spectroscopic analysis, electrochemical study, and computational data strongly demonstrate that this hybrid material integrates the advantageous properties of the individual ZIF-67 and CuFe-LDH exhibiting distinguished photon harvesting, suppression of the photoinduced electron-hole recombination kinetics, extended lifetime, and efficient charge transfer, subsequently boosting higher photocatalytic activities.

Alterations of BDNF, mGluR5, Homer1a, p11 and excitatory/inhibitory balance in corticolimbic brain regions of suicide decedents.

BACKGROUND: Developing biological based approaches for preventing suicide has become a priority. In recent years, there has been a surge in studies investigating the role of the glutamatergic system in suicide, although it remains unclear. METHODS: We evaluated changes in the gene expression of the metabotropic glutamate receptor 5 (mGluR5) and its scaffolding proteins Homer1a and p11 in the dorsolateral prefrontal cortex (DLPFC), amygdala (AMY), and hippocampus (HIP) of 28 suicide decedents (S) (with no clinical psychiatric history or treatment with anxiolytics or antidepressants) and 26 controls (C) by real-time PCR (qPCR). Indeed, we measured BDNF gene expression and VGluT1 and VGAT immunoreactivities in the HIP by qPCR and immunohistochemistry, respectively. Cases and controls matched for age (C: 48.6 ± 11.6 years; S: 46.9 ± 14.5 years) and postmortem interval (PMI; C: 20.1 ± 13h; S: 16.9 ± 5h). RESULTS: In DLPFC, S had lower p11 gene expression levels, but no differences were found in mGluR5 or Homer1a. In the AMY and HIP, mGluR5 and Homer1a were increased, p11 and BDNF were reduced. In the HIP, there were less VGAT-ir and more VGluT1-ir. LIMITATIONS: Future studies are necessary to evaluate protein levels, and determine the cell types and potential compensatory mechanisms in a larger sample including S diagnosed with psychiatric disorders, females and different ethnicities. CONCLUSIONS: This study identified significant alterations in mGluR5, Homer1a, p11, BDNF and excitatory/inhibitory balance in corticolimbic brain areas of S. These results further characterize the biological basis of suicide, contributing to the identification of potential biomarkers for suicide prevention.

Machine Learning-Driven Discovery of Key Descriptors for CO2 Activation over Two-Dimensional Transition Metal Carbides and Nitrides.

Fusing high-throughput quantum mechanical screening techniques with modern artificial intelligence strategies is among the most fundamental ─yet revolutionary─ science activities, capable of opening new horizons in catalyst discovery. Here, we apply this strategy to the process of finding appropriate key descriptors for CO2 activation over two-dimensional transition metal (TM) carbides/nitrides (MXenes). Various machine learning (ML) models are developed to screen over 114 pure and defective MXenes, where the random forest regressor (RFR) ML scheme exhibits the best predictive performance for the CO2 adsorption energy, with a mean absolute error ± standard deviation of 0.16 ± 0.01 and 0.42 ± 0.06 eV for training and test data sets, respectively. Feature importance analysis revealed d-band center (εd), surface metal electronegativity (χM), and valence electron number of metal atoms (MV) as key descriptors for CO2 activation. These findings furnish a fundamental basis for designing novel MXene-based catalysts through the prediction of potential indicators for CO2 activation and their posterior usage.

Acetylcholine Structure-Based Small Activatable Fluorogenic Probe for Specific Detection of Acetylcholinesterase.

Early detection of Alzheimer's disease (AD) is important for taking proper measures against AD pathogenesis. Acetylcholinesterase (AChE) is widely reported to be associated with the pathogenicity of AD. Here, employing the "acetylcholine-mimic" approach, we designed and synthesized a new class of naphthalimide (Naph)-based fluorogenic probes for specific detection of AChE and avoiding interference of butyrylcholinesterase (BuChE), the pseudocholinesterase. We investigated the action of the probes on Electrophorus electricus AChE, and the native human brain AChE that we expressed in Escherichia coli and purified in the active form for the first time. The probe Naph-3 exhibited a substantial fluorescence enhancement with AChE and majorly avoided BuChE. Naph-3 successfully crossed the cell membrane of the Neuro-2a cells and fluoresced upon reaction with endogenous AChE. We further established that the probe could be effectively used for screening AChE inhibitors. Our study provides a new avenue for the specific detection of AChE, which can be extended to the diagnosis of AChE-related complications.

Rhenium Biscorrole Sandwich Compounds: XAS Evidence for a New Coordination Motif.

The interaction of three free-base meso-tris(p-X-phenyl)corroles H3[TpXPC] (X = H, CH3, OCH3) with Re2(CO)10 at 235 °C in the presence of K2CO3 in o-dichlorobenzene has led to putative rhenium biscorrole sandwich compounds with the formula ReH[TpXPC]2. Density functional theory calculations and Re L3-edge extended X-ray absorption fine structure measurements suggest a seven-coordinate metal center, with the "extra" hydrogen located on one of the corrole nitrogens. The complexes can be deprotonated by a base such as 1,8-diazabicyclo[5.4.0]undec-7-ene, resulting in a substantial sharpening of the UV-vis spectra and split Soret bands, consistent with the generation of C2-symmetric anions. Both the seven-coordinate neutral and eight-coordinate anionic forms of the complexes represent a new coordination motif in the field of rhenium-porphyrinoid interactions.

Modeling the evolution of recombination plasticity: A prospective review.

Meiotic recombination is one of the main sources of genetic variation, a fundamental factor in the evolutionary adaptation of sexual eukaryotes. Yet, the role of variation in recombination rate and other recombination features remains underexplored. In this review, we focus on the sensitivity of recombination rates to different extrinsic and intrinsic factors. We briefly present the empirical evidence for recombination plasticity in response to environmental perturbations and/or poor genetic background and discuss theoretical models developed to explain how such plasticity could have evolved and how it can affect important population characteristics. We highlight a gap between the evidence, which comes mostly from experiments with diploids, and theory, which typically assumes haploid selection. Finally, we formulate open questions whose solving would help to outline conditions favoring recombination plasticity. This will contribute to answering the long-standing question of why sexual recombination exists despite its costs, since plastic recombination may be evolutionary advantageous even in selection regimes rejecting any non-zero constant recombination.

Potassium Molten Salt-Mediated In Situ Structural Reconstruction of a Carbon Nitride Photocatalyst.

Metal-free polymeric carbon nitride (PCN) materials are at the forefront of photocatalytic applications. Nevertheless, the overall functionality and performance of bulk PCN are limited by rapid charge recombination, high chemical inertness, and inadequate surface-active sites. To address these, here, we employed potassium molten salts (K+X-, where X- is Cl-, Br-, and I-) as a template for the in situ generation of surface reactive sites in thermal pyrolyzed PCN. Theoretical calculations imply that addition of KX salts to PCN-forming monomers causes halogen ions to be doped into C or N sites of PCN with a relative trend of halogen ion doping being Cl < Br < I. The experimental results show that reconstructing C and N sites in PCN develops newer reactive sites that are beneficial for surface catalysis. Interestingly, the photocatalytic H2O2 generation rate of KBr-modified PCN was 199.0 µmol h-1, about three times that of bulk PCN. Owing to the simple and straightforward approach, we expect molten salt-assisted synthesis to have wide exploration in modifying PCN photocatalytic activity.

Accelerating NADH oxidation and hydrogen production with mid-gap states of nitrogen-rich carbon nitride photocatalyst.

Regeneration of electron carriers such as NAD+/NADH is highly desirable and essential for enzymatic conversions. Here, we demonstrate a sustainable strategy for the regeneration of NAD+ as an electron carrier via photon-assisted heterogeneous catalysis. For this, a mid-gap state induced nitrogen-rich polymeric carbon nitride (NPCN) catalyst was synthesized by an additive-assisted thermal copolymerization. Utilizing NPCN as a photocatalyst presented NADH photooxidation efficiency of over 98% and a high hydrogen production rate of 11.18 mmolg-1h-1 with an apparent quantum yield of 9.16% (λ = 420 nm), outperforming other state-of-art metal-free photocatalysts. The experimental and theoretical simulations suggest that mid-gap states in NPCN catalyst are main platform for charge-carrier separation that enhances the overall photocatalytic performance.