Why are graminoid species more dominant? Trait-mediated plant-soil feedbacks shape community composition.

Species traits may determine plant interactions along with soil microbiome, further shaping plant-soil feedbacks (PSFs). However, how plant traits modulate PSFs and, consequently, the dominance of plant functional groups remains unclear. We used a combination of field surveys and a two-phase PSF experiment to investigate whether forbs and graminoids differed in PSFs and in their trait-PSF associations. When grown in forb-conditioned soils, forbs experienced stronger negative feedbacks, while graminoids experienced positive feedbacks. Graminoid-conditioned soil resulted in neutral PSFs for both functional types. Forbs with thin roots and small seeds showed more-negative PSFs than those with thick roots and large seeds. Conversely, graminoids with acquisitive root and leaf traits (i.e., thin roots and thin leaves) demonstrated greater positive PSFs than graminoids with thick roots and tough leaves. By distinguishing overall and soil biota-mediated PSFs, we found that the associations between plant traits and PSFs within both functional groups were mainly mediated by soil biota. A simulation model demonstrated that such differences in PSFs could lead to a dominance of graminoids over forbs in natural plant communities, which might explain why graminoids dominate in grasslands. Our study provides new insights into the differentiation and adaptation of plant life-history strategies under selection pressures imposed by soil biota.

Effect of Chinese quince proanthocyanidins on the inhibition of heterocyclic amines and quality of fried chicken meatballs and tofu.

Heterocyclic amines (HCAs) have potential carcinogenic and mutagenic activity and are generated in cooked protein-rich foods. Adding proanthocyanidins (PAs) to these foods before frying is an effective way to reduce HCAs. In this study, polymeric PAs (PPA) and ultrasound-assisted acid-catalyzed/catechin nucleophilic depolymerized PAs (UAPA, a type of oligomeric PA) were prepared from Chinese quince fruits (CQF). Different levels of PPA and UAPA (0.05%, 0.1%, and 0.15%) were added to chicken meatballs and tofu; then these foods were fried, and the content of HCAs in them after frying was investigated. The results showed that PPA and, particularly, UAPA significantly inhibited the formation of HCAs in fried meatballs and tofu, and this inhibition was dose-dependent. The inhibition of HCAs by both PPA and UAPA was stronger in the chicken meatballs than in fried tofu. The level of total HCAs was significantly reduced by 57.84% (from 11.93 to 5.03 ng/g) after treatment of meatballs with 0.15% UAPA, with inhibition rates of 78.94%, 50.37%, and 17.81% for norharman, harman, and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), respectively. Of note, there was a negative correlation between water, lipid, protein, creatine, and glucose content and HCA content in the crust, interior, and whole (crust-plus-interior) measurements of all fried samples. Interestingly, PPA and UAPA were found more effective in inhibiting HCAs in the exterior crust than in the interior of the fried chicken meatballs. These results provide evidence that further studies on the reduction of the formation of harmful HCAs in fried foods by adding CQF PAs could be valuable to the fried food industry. PRACTICAL APPLICATION: Chinese quince proanthocyanidins treatments significantly inhibited the generation of heterocyclic amines (HCAs) in chicken meatballs and tofu when deep-fried. These results suggest that Chinese quince proanthocyanidins can be used as natural food additive for reducing HCAs in fried foods, laying the foundation for using Chinese quince fruit proanthocyanidins for HCA inhibition in the food industry.

Bottom-up Growth of Convex Sphere with Adjustable Cu(0)/Cu(I) Interfaces for Effective C2 Production from CO2 Electroreduction.

One challenge confronting the Cu2O catalysts in the electrocatalysis of carbon dioxide reduction reaction (CO2RR) is the reduction of active Cu(I) species, resulting in low selectivity and quick deactivation. In this study, we for the first time introduce a bottom-up growth of convex sphere with adjustable Cu(0)/Cu(I) interfaces (Cux@Cu2O convex spheres). Interestingly, the interfaces are dynamically modulated by varying hydrothermal time, thus regulating the conversion of C1 and C2 products. In particular, the 4 h hydrothermal treatment applied to Cu0.25@Cu2O convex sphere with the favorable Cu(0)/Cu(I) interface results in the highest selectivity for C2 products (90.5%). In situ Fourier-transform infrared spectroscopy measurements and density functional theory calculations reveal that the Cu(0)/Cu(I) interface lowers the energy barrier for the production of ethylene and ethanol while increasing the coverage of localized *CO adsorbate for increased dimerization. This work establishes a novel approach for transforming the state of valence-sensitive electrocatalysts into high-value energy-related engineering products.

Design and optimization of an octuple-electrode array for micro-particle chain rotation via electrorotation integrated with machine vision technology.

Microparticle rotation is an important process in biomedical engineering, such as biosensors, cell injection or cell morphology. Single particle rotation has been widely investigated, while rotation of particle chains has gained rare attention. In this paper, we utilize a noncontact manipulation method to rotate microparticle chains via electrorotation by designing an octuple-electrode array (OEA). Finite element simulations were conducted for analyzing the desired electrode field and optimizing the structure of microelectrode pairs. The direction of the electric field in the workspace is investigated with different voltage signal inputs through specially designed circuits. In the experiment, microparticles are driven to form several chains in the proposed electrode fields. With the rotation of the electric field, particle chains could be rotated synchronously. Automated rotation and detection of polystyrene microspheres and yeast cell chains are achieved using machine vision technology. Results show that the proposed method could be utilized to rotate ordered microparticles with an appropriate input signal.

Prioritization of organic contaminants in China's groundwater based on national-scale monitoring data and their persistence, bioaccumulation, and toxicity.

There has been increasing concern regarding the adverse environmental and health effects of organic pollutants. A list of priority control organic pollutants (PCOPs) can provide regulatory frameworks for the use and monitoring of organic compounds in the environment. In this study, 20,010 groundwater samples were collected from 15 "first level" groundwater resource zones in China. Fifty (50) organic compounds were analyzed based on their prevalence, occurrence, and physicochemical properties (persistence, bioaccumulation, and toxicity). Results showed that 16 PCOPs, including 12 pesticides, 3 aromatic hydrocarbons (AHs), and 1 phthalate ester, were recognized. Pesticides and AHs accounted for 75 % and 18.75 % of the high-priority pollutants, respectively. There were significant differences in PCOPs between confined and phreatic groundwater. Higher concentrations of pesticides were mainly detected in phreatic groundwater. PCOPs detected in samples from the 15 groundwater resource zones were mainly pesticides and AHs. The groundwater data indicate that the organic compounds detected in the Yellow River Basin (YRB), Yangtze River Basin (YZB), Liaohe River Basin (LRB), and Songhua River Basin (SRB) are mainly categorized as Q1 (high priority) and Q2 (medium priority) pollutants based on the contaminants ranking system in China. The findings from this study offer a snapshot of the wide distribution of PCOPs in the surveyed regions, and are expected to establishing treatment and prevention measures at both the regional and national levels in China.

Alternative splicing of CARM1 regulated by LincGET-guided paraspeckles biases the first cell fate in mammalian early embryos.

The heterogeneity of CARM1 controls first cell fate bias during early mouse development. However, how this heterogeneity is established is unknown. Here, we show that Carm1 mRNA is of a variety of specific exon-skipping splicing (ESS) isoforms in mouse two-cell to four-cell embryos that contribute to CARM1 heterogeneity. Disruption of paraspeckles promotes the ESS of Carm1 precursor mRNAs (pre-mRNAs). LincGET, but not Neat1, is required for paraspeckle assembly and inhibits the ESS of Carm1 pre-mRNAs in mouse two-cell to four-cell embryos. We further find that LincGET recruits paraspeckles to the Carm1 gene locus through HNRNPU. Interestingly, PCBP1 binds the Carm1 pre-mRNAs and promotes its ESS in the absence of LincGET. Finally, we find that the ESS seen in mouse two-cell to four-cell embryos decreases CARM1 protein levels and leads to trophectoderm fate bias. Our findings demonstrate that alternative splicing of CARM1 has an important role in first cell fate determination.

Integrative chemoproteomics reveals anticancer mechanisms of silver(i) targeting the proteasome regulatory complex.

Silver compounds have favorable properties as promising anticancer drug candidates, such as low side effects, anti-inflammatory properties, and high potential to overcome drug resistance. However, the exact mechanism by which Ag(i) confers anticancer activity remains unclear, which hinders further development of anticancer applications of silver compounds. Here, we combine thermal proteome profiling, cysteine profiling, and ubiquitome profiling to study the molecular mechanisms of silver(i) complexes supported by non-toxic thiourea (TU) ligands. Through the formation of AgTU complexes, TU ligands deliver Ag+ ions to cancer cells and tumour xenografts to elicit inhibitory potency. Our chemical proteomics studies show that AgTU acts on the ubiquitin-proteasome system (UPS) and disrupts protein homeostasis, which has been identified as a main anticancer mechanism. Specifically, Ag+ ions are released from AgTU in the cellular environment, directly target the 19S proteasome regulatory complex, and may oxidize its cysteine residues, thereby inhibiting proteasomal activity and accumulating ubiquitinated proteins. After AgTU treatment, proteasome subunits are massively ubiquitinated and aberrantly aggregated, leading to impaired protein homeostasis and paraptotic death of cancer cells. This work reveals the unique anticancer mechanism of Ag(i) targeting the 19S proteasome regulatory complex and opens up new avenues for optimizing silver-based anticancer efficacy.

Influence of Strong Shear Field on Structure and Performance of HDPE/PA6 In Situ Microfibril Composites.

As one of the most widely applied general-purpose plastics, high-density polyethylene (HDPE) exhibits good comprehensive performance. However, mechanical strength limits its wider application. In this work, we introduced the engineering plastic PA6 as a dispersed phase to modify the HDPE matrix and applied multiple shears generated by vibration to the polymer melt during the packing stage of injection molding. SEM, 2D-WXRD and 2D-SAXS were used to characterize the morphology and structure of the samples. The results show that under the effect of a strong shear field, the dispersed phase in the composites can form in situ microfibers and numerous high-strength shish-kebab and hybrid shish-kebab structures are formed. Additionally, the distribution of fibers and high-strength oriented structures in the composites expands to the core region with the increase in vibration times. As a result, the tensile strength, tensile modulus and surface hardness of VIM-6 can reach a high level of 66.5 MPa, 981.4 MPa and 72, respectively. Therefore, a high-performance HDPE product is successfully prepared in this study, which is of great importance for expanding the application range of HDPE products.

Accurate Finite Element Simulations of Dynamic Behaviour: Constitutive Models and Analysis with Deep Learning.

Owing to the challenge of capturing the dynamic behaviour of metal experimentally, high-precision numerical simulations have become essential for analysing dynamic characteristics. In this study, calculation accuracy was improved by analysing the impact of constitutive models using the finite element (FE) model, and the deep learning (DL) model was employed for result analysis. The results showed that FE simulations with these models effectively capture the elastic-plastic response, and the ZA model exhibits the highest accuracy, with a 26.0% accuracy improvement compared with other models at 502 m/s for Hugoniot elastic limit (HEL) stress. The different constitutive models offer diverse descriptions of stress during the elastic-plastic response because of temperature effects. Concurrently, the parameters related to the yield strength at quasi-static influence the propagation speed of elastic waves. Calculation show that the yield strength at quasi-static of 6061 Al adheres to y = ax + b for HEL stress. The R-squared (R2) and mean absolute error (MAE) values of the DL model for HEL stress predictions are 0.998 and 0.0062, respectively. This research provides a reference for selecting constitutive models for simulation under the same conditions.

Feasibility and prognostic value of tissue motion annular displacement in patients with heart transplantation.

BACKGROUND: Tissue motion of mitral annular displacement (TMAD) assessment has proved to be an effective method for several cardiovascular diseases including hypertrophic cardiomyopathy, heart failure, non-ST-elevation myocardial infarction, etc. However, there are no studies exploring the feasibility of TMAD in heart transplantation (HT) recipients, and the predictive value of this parameter for adverse outcomes in these patients remains unknown. Consequently, this study aimed to evaluate the feasibility of TMAD in the evaluation of left ventricular (LV) systolic function in clinically well adult HT patients, and further investigate the prognostic value of TMAD. METHODS: Echocardiography was performed in 155 adult HT patients and 49 healthy subjects. All the subjects were examined by conventional transthoracic two-dimensional echocardiography and two-dimensional speckle tracking echocardiography (2D-STE) with evaluation of the LV end-diastolic diameter, LV end-diastolic volume index, LV end-systolic volume index, interventricular septal thickness, left atrial diameter, mitral annular plane systolic excursion (MAPSE), LV ejection fraction (LVEF), TMAD and LV global longitudinal strain (LVGLS). The end point was defined as all-causes mortality or posttransplant related hospitalization during follow up. Cox proportional hazards regression was performed to evaluate the prognostic value of the parameters for predicting poor outcomes in HT patients. RESULTS: A significant positive correlation was found between the measurements of TMAD and LVGLS (r = .714, p < .001). TMAD obtained by 2D-STE had good reproducibility. The LVGLS and TMAD were significantly lower in HT group than in control group (both p < .001). In HT patients, compared with event free group, adverse outcome group displayed reduced TMAD and LVGLS, and elevated age (p < .001, < .001, = .017, respectively). Patients with higher TMAD (> 9.1 mm) had comparatively better survival when stratified by cutoff value (log-rank p < .001). LVGLS and TMAD were independently associated with adverse outcomes in multivariable analysis (both p < .001). CONCLUSION: Assessment of TMAD is effective for evaluating LV longitudinal systolic function and predicting adverse outcomes in clinically well adult HT patients.

High Performance Nacre Fibers by Engineering Interfacial Entanglement.

Biological materials exhibit fascinating mechanical properties for intricate interactions at multiple interfaces to combine superb toughness with wondrous strength and stiffness. Recently, strong interlayer entanglement has emerged to replicate the powerful dissipation of natural proteins and alleviate the conflict between strength and toughness. However, designing intricate interactions in a strong entanglement network needs to be further explored. Here, we modulate interlayer entanglement by introducing multiple interactions, including hydrogen and ionic bonding, and achieve ultrahigh mechanical performance of graphene-based nacre fibers. Two essential modulating trends are directed. One is modulating dynamic hydrogen bonding to improve the strength and toughness up to 1.58 GPa and 52 MJ/m3, simultaneously. The other is tailoring ionic coordinating bonding to raise the strength and stiffness, reaching 2.3 and 253 GPa. Modulating various interactions within robust entanglement provides an effective approach to extend performance limits of bioinspired nacre and optimize multiscale interfaces in diverse composites.

Network pharmacology combined with affinity ultrafiltration to elucidate the potential compounds of Shaoyao Gancao Fuzi Decoction for the treatment of rheumatoid arthritis.

ETHNOPHARMACOLOGICAL RELEVANCE: Shaoyao Gancao Fuzi Decoction (SGFD), has been employed for thousands of years in the treatment of rheumatoid arthritis (RA) with remarkable clinical efficacy. However, the material basis underlying the effectiveness of SGFD still remains unclear. AIM OF THE REVIEW: This study aims to elucidate the material basis of SGFD through the application of network pharmacology and biological affinity ultrafiltration. RESULTS: UPLC-Q-TOF-MS/MS was employed to characterize the components in SGFD, the identified 145 chemical components were mainly categorized into alkaloids, flavonoids, triterpenoids, and monoterpenoids according to the structures. Network pharmacology method was utilized to identify potential targets and signaling pathways of SGFD in the RA treatment, and the anti-inflammatory and anti-RA effects of SGFD were validated through in vivo and in vitro experiments. Moreover, as the significant node in the pharmacology network, TNF-α, a classical therapeutic target in RA, was subsequent employed to screen the interacting compounds in SGFD via affinity ultrafiltration screening method, 6 active molecules (i.e.,glycyrrhizic acid, paeoniflorin, formononetin, isoliquiritigenin, benzoyl mesaconitine, and glycyrrhetinic acid) were exhibited significant interactions. Finally, the significant anti-inflammatory and anti-TNF-α effects of these compounds were validated at the cellular level. CONCLUSIONS: In conclusion, this study comprehensively elucidates the pharmacodynamic material basis of SGFD, offering a practical reference model for the systematic investigation of traditional Chinese medicine formulas.

High-throughput and proteome-wide discovery of endogenous biomolecular condensates.

Phase separation inside mammalian cells regulates the formation of the biomolecular condensates that are related to gene expression, signalling, development and disease. However, a large population of endogenous condensates and their candidate phase-separating proteins have yet to be discovered in a quantitative and high-throughput manner. Here we demonstrate that endogenously expressed biomolecular condensates can be identified across a cell's proteome by sorting proteins across varying oligomeric states. We employ volumetric compression to modulate the concentrations of intracellular proteins and the degree of crowdedness, which are physical regulators of cellular biomolecular condensates. The changes in degree of the partition of proteins into condensates or phase separation led to varying oligomeric states of the proteins, which can be detected by coupling density gradient ultracentrifugation and quantitative mass spectrometry. In total, we identified 1,518 endogenous condensate proteins, of which 538 have not been reported before. Furthermore, we demonstrate that our strategy can identify condensate proteins that respond to specific biological processes.

Depression heightened the association of the systemic immune-inflammation index with all-cause mortality among osteoarthritis patient.

BACKGROUND: Systemic immune-inflammatory index (SII) has been recognized as a novel inflammatory indicator in numerous diseases. It remains unknown how SII affects all-cause mortality among patients with osteoarthritis (OA). In this prospective cohort study, we intended to examine the relationship of SII with all-cause mortality among OA populations and assess the interaction between depression and SII. METHODS: Data was collected from National Health and Nutrition Examination Survey (NHANES) in 2005-2018. The National Death Index (NDI) provided vital status records. Multivariable Cox regression analyses with cubic spines were applied to estimate the association between SII and all-cause and CVD mortality. Stratified analysis and interaction tests assessed the interaction of SII and depression on all-cause mortality. RESULTS: In total 3174 OA adults were included. The lowest quartile Q1 (HR:1.44, 95%CI:1.02-2.04) and highest quartile Q4 (HR:1.44, 95%CI:1.02-2.04) of SII presented a higher risk of death compared with those in second quartile Q2 (Ref.) and third quartile Q3 (HR:1.23, 95%CI:0.89-1.68. Restricted cubic splines analysis revealed a U-shaped association of SII with all-cause mortality, the inflection points were 412.93 × 109/L. The interaction test observed a more significant relationship of SII with all-cause mortality in depression patients than in non-depression patients, indicating that depression can modify this association. LIMITATIONS: First, the observational study design failed to make causal inferences. Second, the baseline SII cannot reflect the long-term level of inflammation. Finally, there may be potential bias. CONCLUSION: SII was U-shaped associated with all-cause mortality in OA patients, and this association was significantly heightened by depression.

Feasibility Value of Right Ventricular Longitudinal Shortening Fraction and the Prognostic Implications in Patients With Heart Transplantation.

BACKGROUND: Right ventricular longitudinal shortening fraction (RVLSF) is a 2-dimensional speckle tracking echocardiography parameter based on tricuspid annular displacement analysis that could be used to assess right ventricular (RV) systolic function. The value of RVLSF in the assessment of RV systolic function in recipients of heart transplantation (HT) and whether RVLSF can replace strain parameters remains unknown. METHODS AND RESULTS: A total of 153 adult patients who underwent HT were consecutively enrolled in this prospective longitudinal study. All subjects were examined by conventional transthoracic 2-dimensional echocardiography and 2-dimensional speckle tracking echocardiography to evaluate the RV end-diastolic basal diameter, RV end-diastolic area, fractional area change, peak systolic velocity of tricuspid annulus, tricuspid annular plane systolic excursion, RV free wall strain, and RVLSF. Cox proportional hazards regression was used to test if the parameters of interest had independent prognostic value for adverse outcome prediction in patients who underwent HT. A significant positive correlation was found between the measurements of RVLSF and RV free wall strain (r=0.927, P<0.001). Compared with the event-free group, the adverse outcome group displayed reduced RVLSF and RV free wall strain and higher age (P<0.001, <0.001, =0.016, respectively) in patients who underwent HT. RVLSF and RV free wall strain were independently associated with poor prognosis in multivariable analysis (both P<0.001). CONCLUSIONS: RVLSF assessment provides an effective evaluation of RV longitudinal systolic function in the transplanted hearts and has prognostic value for adverse outcomes in patients undergoing HT.

Plasmodium falciparum selectively degrades α-spectrin of infected erythrocytes after invasion.

Remodeling the erythrocyte membrane and skeleton by the malarial parasite Plasmodium falciparum is closely associated with intraerythrocytic development. However, the mechanisms underlying this association remain unclear. In this study, we present evidence that erythrocytic α-spectrin, but not ß-spectrin, was dynamically ubiquitinated and progressively degraded during the intraerythrocytic development of P. falciparum, from the ring to the schizont stage. We further observed an upregulated expression of P. falciparum phosphatidylinositol 3-kinase (PfPI3K) in the infected red blood cells during the intraerythrocytic development of the parasite. The data indicated that PfPI3K phosphorylated and activated erythrocytic ubiquitin-protein ligase, leading to increased α-spectrin ubiquitination and degradation during P. falciparum development. We further revealed that inhibition of the activity of PfPI3K impaired P. falciparum development in vitro and Plasmodium berghei infectivity in mice. These findings collectively unveil an important mechanism of PfPI3K-ubiquitin-mediated degradation of α-spectrin during the intraerythrocytic development of Plasmodium species. Proteins in the PfPI3K regulatory pathway are novel targets for effective treatment of severe malaria. IMPORTANCE: Plasmodium falciparum is the causative agent of severe malaria that causes millions of deaths globally. The parasite invades human red blood cells and induces a cascade of alterations in erythrocytes for development and proliferation. Remodeling the host erythrocytic cytoskeleton is a necessary process during parasitization, but its regulatory mechanisms remain to be elucidated. In this study, we observed that erythrocytic α-spectrin is selectively degraded after P. falciparum invasion, while ß-spectrin remained intact. We found that the α-spectrin chain was profoundly ubiquitinated by E3 ubiquitin ligase and degraded by the 26S proteasome. E3 ubiquitin ligase activity was regulated by P. falciparum phosphatidylinositol 3-kinase (PfPI3K) signaling. Additionally, blocking the PfPI3K-ubiquitin-proteasome pathway in P. falciparum-infected red blood cells reduced parasite proliferation and infectivity. This study deepens our understanding of the regulatory mechanisms of host and malarial parasite interactions and paves the way for the exploration of novel antimalarial drugs.

Toxoplasma sortilin interacts with secretory proteins and it is critical for parasite proliferation.

BACKGROUND: The human sortilin protein is an important drug target and detection marker for cancer research. The sortilin from Toxoplasma gondii transports proteins associated with the apical organelles of the parasite. In this study, we aimed to determine the intracellular localization and structural domains of T. gondii sortilin, which may mediate protein transportation. Approaches to the functional inhibition of sortilin to establish novel treatments for T. gondii infections were explored. METHODS: A gene encoding the sortilin protein was identified in the T. gondii genome. Immunoprecipitation and mass spectrometry were performed to identify the protein species transported by T. gondii sortilin. The interaction of each structural domain of sortilin with the transported proteins was investigated using bio-layer interferometry. The binding regions of the transported proteins in sortilin were identified. The effect of the sortilin inhibitor AF38469 on the infectivity of T. gondii was investigated. The binding site of AF38469 on sortilin was determined. RESULTS: The subdomains Vps10, sortilin-C, and sortilin-M of the sortilin were identified as the binding regions for intracellular transportation of the target proteins. The sortilin inhibitor AF38469 bound to the Vps10 structural domain of T. gondii sortilin, which inhibited parasite invasion, replication, and intracellular growth in vitro and was therapeutic in mice infected with T. gondii. CONCLUSION: The Vps10, sortilin-C, and sortilin-M subdomains of T. gondii sortilin were identified as functional regions for intracellular protein transport. The binding region for the sortilin inhibitor AF38469 was also identified as the Vps10 subdomain. This study establishes sortilin as a promising drug target against T. gondii and provides a valuable reference for the development of anti-T. gondii drug-target studies.

Targeting the "tumor microenvironment": RNA-binding proteins in the spotlight in colorectal cancer therapy.

Colorectal cancer (CRC) is the third most common cancer and has the second highest mortality rate among cancers. The development of CRC involves both genetic and epigenetic abnormalities, and recent research has focused on exploring the ex-transcriptome, particularly post-transcriptional modifications. RNA-binding proteins (RBPs) are emerging epigenetic regulators that play crucial roles in post-transcriptional events. Dysregulation of RBPs can result in aberrant expression of downstream target genes, thereby affecting the progression of colorectal tumors and the prognosis of patients. Recent studies have shown that RBPs can influence CRC pathogenesis and progression by regulating various components of the tumor microenvironment (TME). Although previous research on RBPs has primarily focused on their direct regulation of colorectal tumor development, their involvement in the remodeling of the TME has not been systematically reported. This review aims to highlight the significant role of RBPs in the intricate interactions within the CRC tumor microenvironment, including tumor immune microenvironment, inflammatory microenvironment, extracellular matrix, tumor vasculature, and CRC cancer stem cells. We also highlight several compounds under investigation for RBP-TME-based treatment of CRC, including small molecule inhibitors such as antisense oligonucleotides (ASOs), siRNAs, agonists, gene manipulation, and tumor vaccines. The insights gained from this review may lead to the development of RBP-based targeted novel therapeutic strategies aimed at modulating the TME, potentially inhibiting the progression and metastasis of CRC.

The effectiveness of legal framework of Arctic vessel-source black carbon governance.

The Arctic is particularly vulnerable to the impacts of climate change, of which vessel-source black carbon aerosols serving as a prominent catalyst for these changes. This situation is poised to worsen as sea ice melts and shipping lanes change. Rapid action aimed at mitigating short-term climate forcing factors can yield almost immediate climate benefits in the Arctic. This article provides an overview of the legal framework governing black carbon in the Arctic, considering three distinct perspectives: the global, regional, and national dimensions. These perspectives encompass global forums represented by the International Maritime Organization (IMO) and the United Nations Framework Convention on Climate Change (UNFCCC), with a focus on recent developments concerning black carbon governance, notably the amendments to MARPOL Annex VI and Annex I. Regionally, forums represented by the Arctic Council and the European Union are examined. Black carbon emissions exhibit migratory characteristics, yet the primary legal responsibilities for emission reduction are concentrated within Arctic states. Therefore, this article also delves into the laws and practices of Arctic coastal states in their efforts to combat black carbon emissions, using Canada and Norway as examples. The analysis of institutional effectiveness in this article indicates that, at present, specialized legislation on black carbon is either vague or non-existent. The current Arctic ship-source black carbon governance system faces issues related to leadership ambiguity in its institutional structure, a limited scope of responsible entities, and a lack of diverse implementation measures. Simultaneously, the governance system is questioned for having weak or non-legally binding regulations at the level of legal enforcement. The article anticipates the introduction of more mandatory regulations while also encouraging the selection of non-coercive policy tools. Accordingly, this article argues that a coordinated governance system centered on IMO and the Arctic Council needs to be established. Such a framework should adopt a more inclusive approach to stimulate positive interactions between regulations, aiming to create a broader winning alliance based on the existing foundations.

Tetrahydropiperine, a natural alkaloid with neuroprotective effects in ischemic stroke.

BACKGROUND: Ischemic stroke (IS) is a life-threatening neurological disease with various pathological mechanisms. Tetrahydropiperine (THP) is a natural alkaloid with protective effects against multiple diseases, such as seizure, and pain. This study was to examine the impact of THP on IS and investigate its potential mechanism. MATERIAL AND METHODS: We employed network pharmacology and molecular docking techniques to identify the target proteins of THP for intervention in IS. Adult male Sprague-Dawley rats were used to create a permanent middle cerebral artery occlusion model. PC-12 cells were chosen to establish an oxygen-glucose deprivation (OGD) cell model. Disease modeling followed by nimodipine (NIMO); 3-methyladenine (3-MA) and rapamycin (RAP) interventions. Open field test, Longa score, balance beam test, and forelimb grip test were used to measure motor and neurological functions. The degree of neurological damage recovery was assessed through behavioral analysis, and cerebral infarction volume was determined using TTC staining. Morphological changes were examined through HE and Nissl staining, and ultrastructural changes in neurons were observed using transmission electron microscopy. The protein expression of autophagy and related pathways was analyzed through Western blot (WB). The appropriate hypoxia time and drug concentration were determined using CCK-8 assay, which also measured cell survival rate. RESULTS: The network pharmacology findings indicated that the impact of THP on IS was enhanced in the PI3K/Akt signaling pathway. THP demonstrated robust docking capability with proteins associated with the autophagy and PI3K/Akt/mTOR, as indicated by the molecular docking outcomes. THP significantly improved behavioral damage, reduced the area of cerebral infarction, ameliorated histopathological damage from ischemia, increase neuronal survival, and alleviated ultrastructural damage in neurons (P < 0.05). THP enhanced the survival of PC-12 cells induced by OGD and ameliorated the morphological harm to the cells (P < 0.05). THP was found to elevate the quantities of P62, LC3-Ⅰ, PI3K, P-AKt/Akt, and P-mTOR/mTOR proteins while reducing the levels of Atg7 and Beclin1 proteins. The results of transmission electron microscopy showed no autophagosomes in the THP, 3-MA, and 3-MA + THP groups. CONCLUSION: The activation of the PI3K/Akt/mTOR signaling pathway by THP inhibits autophagy and provides relief from neurological damage in IS.