Repetitive traumatic brain injury-induced complement C1-related inflammation impairs long-term hippocampal neurogenesis.

JOURNAL/nrgr/04.03/01300535-202503000-00027/figure1/v/2024-06-17T092413Z/r/image-tiff Repetitive traumatic brain injury impacts adult neurogenesis in the hippocampal dentate gyrus, leading to long-term cognitive impairment. However, the mechanism underlying this neurogenesis impairment remains unknown. In this study, we established a male mouse model of repetitive traumatic brain injury and performed long-term evaluation of neurogenesis of the hippocampal dentate gyrus after repetitive traumatic brain injury. Our results showed that repetitive traumatic brain injury inhibited neural stem cell proliferation and development, delayed neuronal maturation, and reduced the complexity of neuronal dendrites and spines. Mice with repetitive traumatic brain injuryalso showed deficits in spatial memory retrieval. Moreover, following repetitive traumatic brain injury, neuroinflammation was enhanced in the neurogenesis microenvironment where C1q levels were increased, C1q binding protein levels were decreased, and canonical Wnt/ß-catenin signaling was downregulated. An inhibitor of C1 reversed the long-term impairment of neurogenesis induced by repetitive traumatic brain injury and improved neurological function. These findings suggest that repetitive traumatic brain injury-induced C1-related inflammation impairs long-term neurogenesis in the dentate gyrus and contributes to spatial memory retrieval dysfunction.

A preliminary study of T-2 toxin that cause liver injury in rats via the NF-kB and NLRP3-mediated pyroptosis pathway.

T-2 toxin is recognized as the most potent and prevalent secondary metabolite among monotrichous mycotoxins produced by Fusarium species. Multiple studies have substantiated the hepatotoxic effects of T-2 toxin. This study aimed to investigate whether NF-κB and NLRP3-mediated pyroptosis is involved in the underlying mechanism of T-2 toxin hepatotoxicity. We designed three groups of rat models, blank control; solvent control and T-2 toxin (0.2 mg/kg body weight/day), which were euthanized at week 8 after gavage staining of the toxin. Through HE staining and biochemical indicators associated with liver injury, we observed that T-2 toxin induced liver damage in rats. By Western blot analysis and qRT-PCR, we found that the expression levels of pyroptosis-related genes and proteins were significantly higher in the T-2 toxin group. In addition, we also found a significant increase in the expression of p-NF-κB protein, an upstream regulator of NLRP3. In conclusion, NF-κB and NLRP3-mediated pyroptosis may be involved in the mechanism of hepatotoxic action of T-2 toxin, which provides a new perspective.

Temporal variation characteristics in the association between climate and vegetation in Northwest China.

Northwest China has undergone notable alterations in climate and vegetation growth in recent decades. Nevertheless, uncertainties persist concerning the response of different vegetation types to climate change and the underlying mechanisms. This study utilized the Normalized Difference Vegetation Index (NDVI) and three sets of meteorological data to investigate the interannual variations in the association between vegetation and climate (specifically precipitation and temperature) from 1982 to 2015. Several conclusions were drawn. (1) RNDVI-GP (relationship between Growing Season NDVI and precipitation) decreased significantly across all vegetation, while RNDVI-GT (relationship between Growing Season NDVI and temperature) showed an insignificant increase. (2) Trends of RNDVI-GP and RNDVI-GT exhibited great variations across various types of vegetation, with forests displaying notable downward trends in both indices. The grassland exhibited a declining trend in RNDVI-GP but an insignificant increase in RNDVI-GT, while no significant temporal changes in RNDVI-GP or RNDVI-GT were observed in the barren land. (3) The fluctuations in RNDVI-GP and RNDVI-GT closely aligned with variations in drought conditions. Specifically, in regions characterized by VPD (vapor pressure deficit) trends less than 0.02 hpa/yr, which are predominantly grasslands, a rise in SWV (soil water volume) tended to cause a reduction in RNDVI-GP but an increase in RNDVI-GT. However, a more negative trend in SWV was associated with a more negative trend in both RNDVI-GP and RNDVI-GT when the VPD trend exceeded 0.02 hPa/yr, primarily in forests. Our results underscore the variability in the relationship between climate change and vegetation across different vegetation types, as well as the role of drought in modulating these associations.

Phosphorus and sulfur co-doped nickel molybdate with rich-oxygen vacancies for efficient water splitting.

The rational design of high-performance electrocatalysts is essential for promoting the industrialization of electrocatalytic water-splitting technology. Herein, phosphorus and sulfur co-doped nickel molybdate with rich-oxygen vacancies (P, S-NiMoO4) was prepared as an efficient bifunctional self-supporting water-splitting catalyst from the perspective of enhancing the conductivity and optimizing the electronic configurations. The incorporation of P, S and oxygen vacancies greatly enhances the conductivity and charge-transfer efficiency of NiMoO4. Additionally, P and S can serve as proton carriers and electron acceptors to enhance the catalytic activity by accelerating proton activation and high-valent metal generation in the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER). As expected, P, S-NiMoO4 demonstrates efficient bifunctional catalytic activity with an overpotential of only 31/206 mV at 10 mA cm-2 for HER/OER in 1 M KOH. Meantime, the electrolyzer assembled with P, S-NiMoO4 as electrodes requires a voltage of only 1.55 V to achieve a water-splitting current density of 50 mA cm-2 along with good stability over 110 h. This work puts forward a novel approach based on elemental doping and vacancy engineering for the design of effective and enduring catalysts for water splitting.

A comprehensive review on potential role of selenium, selenoproteins and selenium nanoparticles in male fertility.

Selenium (Se), a component of selenoproteins and selenocompounds in the human body, is crucial for the development of male reproductive organs, DNA synthesis, thyroid hormone, metabolism, and defence against infections and oxidative damage. In the testis, it must exceed a desirable level since either a shortage or an overabundance causes aberrant growth. The antioxidant properties of selenium are essential for preserving human reproductive health. Selenoproteins, which have important structural and enzymatic properties, control the biological activities of Se primarily. These proteins specifically have a role in metabolism and a variety of cellular processes, such as the control of selenium transport, thyroid hormone metabolism, immunity, and redox balance. Selenium nanoparticles (SeNPs) are less hazardous than selenium-based inorganic and organic materials. Upon being functionalized with active targeting ligands, they are both biocompatible and capable of efficiently delivering combinations of payloads to particular cells. In this review, we discuss briefly the chemistry, structure and functions of selenium and milestones of selenium and selenoproteins. Next we discuss the various factors influences male infertility, biological functions of selenium and selenoproteins, and role of selenium and selenoproteins in spermatogenesis and male fertility. Furthermore, we discuss the molecular mechanism of selenium transport and protective effects of selenium on oxidative stress, apoptosis and inflammation. We also highlight critical contribution of selenium nanoparticles on male fertility and spermatogenesis. Finally ends with conclusion and future perspectives.

The hypoglycemic effect of enzymatic modified dietary fiber from bamboo shoot on type 2 diabetes rats.

Bamboo shoot is a healthy food rich in dietary fiber (DF). However, its highly insoluble DF and fibrous texture limit its application in industrially processed foods. To achieve industrial processing of bamboo shoot, cellulase was used to improve the physical characteristics of bamboo shoot DF in this study. After enzymatic hydrolysis, the content of soluble DF (SDF) of bamboo shoot increased by 99.28% (from 5.53% to 11.02%) significantly (p < 0.01). At the same time, the effect of enzymatic-modified bamboo SDF (EMBSDF) on streptozotocin-induced type 2 diabetes rats was explored. Results demonstrated that the high dose of EMBSDF (312.8 mg/kg) treated rats showed significant improvements in terms of glucose tolerance and insulin sensitivity (p < 0.01) compared with the diabetes rats. Meantime, it was observed that the levels of glucagon-like peptide-1, adiponectin and interleukin-4 of high dose of EMBSDF compared with diabetes rats were increased (p < 0.01) by 57.79%, 159.13%, and 6.17%, respectively. The tumor necrosis factor-α, C-reactive protein, and leptin levels were decreased (p < 0.01) by 62.89%, 31.53%, and 7.84%, respectively. Furthermore, apparent kidney and pancreas histology improvements were found in high-dose and mid-dose EMBSDF-treated diabetes rats. These results indicated that the modified DF significantly improved diabetes.

Pd(II)-Catalyzed C4-Selective Alkynylation of Indoles by a Transient Directing Group.

With alanine as a transient directing group, Pd-catalyzed regioselective alkynylation at the indole C4-position was successfully established in a good yield. The total synthesis of the PAF antagonist demonstrated the synthetic utility of this protocol. The regioselectivity was explicitly proven by the prepared C4-selective palladacycle intermediate in the catalytic process and the DFT calculation of the energy barriers of C4- and C2-site-selective C-H activation of indole.

A nebular origin for the persistent radio emission of fast radio bursts.

Fast radio bursts (FRBs) are millisecond-duration, bright (approximately Jy) extragalactic bursts, whose production mechanism is still unclear1. Recently, two repeating FRBs were found to have a physically associated persistent radio source of non-thermal origin2,3. These two FRBs have unusually large Faraday rotation measure values2,3, probably tracing a dense magneto-ionic medium, consistent with synchrotron radiation originating from a nebula surrounding the FRB source4-8. Recent theoretical arguments predict that, if the observed Faraday rotation measure mostly arises from the persistent radio source region, there should be a simple relation between the persistent radio source luminosity and the rotation measure itself7,9. Here we report the detection of a third, less luminous persistent radio source associated with the repeating FRB source FRB 20201124A at a distance of 413 Mpc, substantially expanding the predicted relation into the low luminosity-low Faraday rotation measure regime (<1,000 rad m-2). At lower values of the Faraday rotation measure, the expected radio luminosity falls below the limit-of-detection threshold for present-day radio telescopes. These findings support the idea that the persistent radio sources observed so far are generated by a nebula in the FRB environment and that FRBs with low Faraday rotation measure may not show a persistent radio source because of a weaker magneto-ionic medium. This is generally consistent with models invoking a young magnetar as the central engine of the FRB, in which the surrounding ionized nebula-or the interacting shock in a binary system-powers the persistent radio source.

Mental health and meaning in life in Chinese military personnel: a cross-lagged analysis.

BACKGROUND: The burgeoning field of research on the dual-factor model of mental health (DFM) has highlighted its significance, yet the applicability of the DFM in military personnel and its longitudinal relationships with different dimensions of meaning in life remains unclear. This study aimed to clarify the applicability of the DFM for military personnel and to investigate longitudinal relationships between the dual factors of mental health (negative factor, positive factor) and the two dimensions of meaning in life (presence of meaning, search for meaning) in military personnel. METHODS: In this study, data were collected in two waves (April and August 2023) from 227 Chinese military personnel. We constructed a dual-factor model with depression as the negative factor and subjective well-being as the positive factor, and we compared it with a single-factor model to determine if DFM could be applied to military personnel. We also constructed a cross-lagged model to investigate longitudinal relationships between depression, subjective well-being, presence of meaning, and search for meaning. RESULTS: According to the findings, military personnel fit better with the DFM than with the single-factor model. Cross-lagged analysis results revealed that both the presence of meaning and the search for meaning negatively predicted depression and positively predicted subjective well-being. CONCLUSIONS: The DFM had good applicability among military personnel. Both the presence of meaning and the search for meaning could improve military mental health, suggesting that both dimensions of meaning in life may be potential targets for improving military mental health.

Sustained mucosal colonization and fecal metabolic dysfunction by Bacteroides associates with fecal microbial transplant failure in ulcerative colitis patients.

Fecal microbial transplantation (FMT) offers promise for treating ulcerative colitis (UC), though the mechanisms underlying treatment failure are unknown. This study harnessed longitudinally collected colonic biopsies (n = 38) and fecal samples (n = 179) from 19 adults with mild-to-moderate UC undergoing serial FMT in which antimicrobial pre-treatment and delivery mode (capsules versus enema) were assessed for clinical response (≥ 3 points decrease from the pre-treatment Mayo score). Colonic biopsies underwent dual RNA-Seq; fecal samples underwent parallel 16S rRNA and shotgun metagenomic sequencing as well as untargeted metabolomic analyses. Pre-FMT, the colonic mucosa of non-responsive (NR) patients harbored an increased burden of bacteria, including Bacteroides, that expressed more antimicrobial resistance genes compared to responsive (R) patients. NR patients also exhibited muted mucosal expression of innate immune antimicrobial response genes. Post-FMT, NR and R fecal microbiomes and metabolomes exhibited significant divergence. NR metabolomes had elevated concentrations of immunostimulatory compounds including sphingomyelins, lysophospholipids and taurine. NR fecal microbiomes were enriched for Bacteroides fragilis and Bacteroides salyersiae strains that encoded genes capable of taurine production. These findings suggest that both effective mucosal microbial clearance and reintroduction of bacteria that reshape luminal metabolism associate with FMT success and that persistent mucosal and fecal colonization by antimicrobial-resistant Bacteroides species may contribute to FMT failure.

Intercalating Architecture for the Design of Charge Density Wave in Metallic MA2Z4 Materials.

We present a novel approach to induce charge density waves (CDWs) in metallic MA2Z4 materials, resembling the behavior observed in transition metal dichalcogenides (TMDCs). This method leverages the intercalating architecture to maintain the same crystal field and Fermi surface topologies. Our investigation reveals that CDW instability in these materials arises from electron-phonon coupling (EPC) between the d band and longitudinal acoustic (LA) phonons, mirroring TMDC's behavior. By combining α-MA2Z4 with 1H-MX2 materials in a predictive CDW phase diagram using critical EPC constants, we demonstrate the feasibility of extending CDW across material families with comparable crystal fields and reveal the crucial role in CDW instability of the competition between ionic charge transfer and electron correlation. We further uncover a strain-induced Mott transition in ß2-NbGe2N4 monolayer featuring star-of-David patterns. This work highlights the potential of intercalating architecture to engineer CDW materials, expanding our understanding of CDW instability and correlation physics.

Mechanisms underlying the detrimental impact of micro(nano)plastics on the stability of aerobic granular sludge: Interactions between micro(nano)plastics and extracellular polymeric substances.

Microplastics (MPs) and nanoplastics (NPs) present in wastewater can pose a negative impact to aerobic granular sludge (AGS). Herein, this study found that MPs and NPs (20 mg/L) deteriorated the sludge settleability and granule integrity, resulting in a 15.7 % and 21.9 % decrease in the total nitrogen removal efficiency of the AGS system, respectively. This was possibly due to the reduction of the extracellular polymeric substances (EPS) content. The subsequent analysis revealed that tyrosine, tryptophan, and humic acid-like substances in EPS exhibited a higher propensity for chemisorption and inhomogeneous multilayer adsorption onto NPs compared to MPs. The binding of EPS onto the surface of plastic particles increased the electronegativity of the MPs, but facilitated the aggregation of NPs through reducing the electrostatic repulsion, thereby mitigating the adverse effects of MPs/NPs on the AGS stability. Additionally, comprehensive analysis of the extended Derjaguin-Landau-Verwey-Overbeek theory indicated that the suppressed aggregation of microorganisms was the internal mechanisms contributing to the inadequate stability of AGS induced by MPs/NPs. This study provides novel insights into the detrimental mechanisms of MPs/NPs on the AGS stability, highlighting the key role of EPS in maintaining the structural stability of AGS when exposed to MPs/NPs.

Impact of Mechanical and Manual Peeling on the Volatile Profile of White Pepper (Piper nigrum L.).

Mechanical peeling is more efficient and environmentally friendly compared to manual peeling. However, comparative studies on the quality of mechanically peeled pepper and manually peeled pepper are limited. This study utilized GC-MS to investigate the effects of immersion, steaming, and peeling machinery speed on the volatile composition of white pepper. A total of thirteen monoterpenes and seven sesquiterpenes were detected, with 3-carene, D-limonene, and sabinene being the most abundant monoterpenoids and ß-caryophyllene, δ-elemene, and α-copaene being the most abundant sesquiterpenes. The total volatiles increased with longer steaming times and higher peeling machinery speeds. Compared to manual peeling or steaming followed by mechanical peeling, the volatile content of pepper was higher when using mechanical peeling alone. Additionally, relative odor activity values showed that 3-carene and D-limonene were the main contributors to flavor, with 3-carene, ß-caryophyllene, and α-copaene being key volatiles responsible for flavor distinctions. This research aims to provide theoretical support for developing a superior and environmentally friendly mechanical method to replace manual labor.

Behavior and Activity Patterns of the Critically Endangered Mangshan Pit Viper (Protobothrops mangshanensis) Determined Using Remote Monitoring.

This study focuses on understanding the behavior and activity patterns of the critically endangered Protobothrops mangshanensis in China in order to better provide scientific data for upcoming artificial breeding and propagation efforts. We conducted a long-term observation of 15 Mangshan pit vipers at different sites in Hunan Province during the summer and autumn of 2021. Our methods involved analyzing the influence of environmental factors such as temperature, relative humidity, and light condition on the snakes' day and night activity and behaviors. The results revealed that the wild behaviors of Protobothrops mangshanensis include resting, sunbathing, crawling, and exploring, with distinct rhythms in their diel behavior. The snakes' diel activity exhibits three peak periods which may be related to food activity and sunbathing. This study also highlights the complex interplay of environmental factors on the activity of Protobothrops mangshanensis. Relative humidity was identified as a critical factor accounting for the difference in activity between observation groups. There was little inter-individual variation among the 15 Protobothrops mangshanensis, even though these snakes used terrestrial and arboreal habitats under different environmental conditions. These findings enhance our understanding of Protobothrops mangshanensis behavior and provide a basis for effective conservation measures for this rare and critically endangered species.

Primary intraspinal neuroendocrine tumor: A case report and literature review.

RATIONALE: Neuroendocrine tumors (NET) refer to a group of uncommon tumors arising in the neuroendocrine system. Most NETs occur in the digestive tract and bronchi but are rare in the central nervous system, especially in the spinal canal. NET in the central nervous system mainly metastasize from other systems, with non-specific clinical symptoms. In this study, we report the diagnosis and treatment of intraspinal NET to provide clinical guidance as well as to avoid misdiagnosis and missed diagnosis. PATIENT CONCERNS: A 59-year-old male patient, presented with recurrent right lower limb pain for half a year, accompanied by numbness and weakness for 4 months and aggravation for 2 months. Lumbar spine magnetic resonance imaging (MRI) revealed a space-occupying lesion in the spinal canal. The diagnosis of primary intraspinal NET was confirmed by topathological examination. DIAGNOSIS: Primary intraspinal NET tumor. INTERVENTIONS: Surgical resection. OUTCOMES: Significant improvements in right lower limb pain, numbness, and weakness were observed, and lumbar spine MRI was performed again to dynamically observe the changes in intraspinal NET. CONCLUSIONS: Surgical resection may be an effective treatment for intraspinal NETs. LESSONS: Intraspinal NETs are relatively rare and mostly manifest as limb numbness, weakness, and pain. Due to its nonspecific clinical symptoms, intraspinal NETs are easily misdiagnosed as lumbar disc herniation with radiculopathy and lumbar spondylolisthesis. Therefore, in patients with long-term symptoms, in addition to common lumbar neuromuscular diseases, lumbar MRI should be performed promptly to exclude the possibility of lumbar NETs.

Performance assessment of an artificial intelligence-based coronary artery calcium scoring algorithm in non-gated chest CT scans of different slice thickness.

Background: The coronary artery calcium score (CACS) has been shown to be an independent predictor of cardiovascular events. The traditional coronary artery calcium scoring algorithm has been optimized for electrocardiogram (ECG)-gated images, which are acquired with specific settings and timing. Therefore, if the artificial intelligence-based coronary artery calcium score (AI-CACS) could be calculated from a chest low-dose computed tomography (LDCT) examination, it could be valuable in assessing the risk of coronary artery disease (CAD) in advance, and it could potentially reduce the occurrence of cardiovascular events in patients. This study aimed to assess the performance of an AI-CACS algorithm in non-gated chest scans with three different slice thicknesses (1, 3, and 5 mm). Methods: A total of 135 patients who underwent both LDCT of the chest and ECG-gated non-contrast enhanced cardiac CT were prospectively included in this study. The Agatston scores were automatically derived from chest CT images reconstructed at slice thicknesses of 1, 3, and 5 mm using the AI-CACS software. These scores were then compared to those obtained from the ECG-gated cardiac CT data using a conventional semi-automatic method that served as the reference. The correlations between the AI-CACS and electrocardiogram-gated coronary artery calcium score (ECG-CACS) were analyzed, and Bland-Altman plots were used to assess agreement. Risk stratification was based on the calculated CACS, and the concordance rate was determined. Results: A total of 112 patients were included in the final analysis. The correlations between the AI-CACS at three different thicknesses (1, 3, and 5 mm) and the ECG-CACS were 0.973, 0.941, and 0.834 (all P<0.01), respectively. The Bland-Altman plots showed mean differences in the AI-CACS for the three thicknesses of -6.5, 15.4, and 53.1, respectively. The risk category agreement for the three AI-CACS groups was 0.868, 0.772, and 0.412 (all P<0.01), respectively. While the concordance rates were 91%, 84.8%, and 62.5%, respectively. Conclusions: The AI-based algorithm successfully calculated the CACS from LDCT scans of the chest, demonstrating its utility in risk categorization. Furthermore, the CACS derived from images with a slice thickness of 1 mm was more accurate than those obtained from images with slice thicknesses of 3 and 5 mm.

Scaffold Hopping of Pristimerin Provides Derivatives Containing a Privileged Quinoxaline Substructure as Potent Autophagy Inducers in Breast Cancer Cells.

Pristimerin is a natural triterpenoid that has received much attention from medicinal chemists for its multiple biological activities. However, structural modifications of pristimerin, especially those aimed at discovering antitumor agents, are relatively limited. In this study, two series of pristimerin derivatives containing phenyloxazole and quinoxaline moieties, respectively, were designed via the scaffold hopping strategy. The target compounds were synthesized and analyzed for their cytotoxic activities in vitro using the MTT assay. The most potent cytotoxic compound (21o) significantly inhibited the proliferation of MCF-7 cells with an IC50 value of 2.0 µM, 1.5-fold more potent than pristimerin (IC50 = 3.0 µM). Compared with pristimerin, compound 21o displayed the greatest improvement in selectivity (25.7-fold) against the MCF-7 and MCF-10A cell lines. Transmission electron microscopy, monodansylcadaverine and DCFH-DA staining, Western blotting, and different inhibitor assays were performed to elucidate the mechanism of action of compound 21o. Compound 21o induced autophagy-mediated cell death in MCF-7 cells by activating the ROS/JNK signaling pathway. Therefore, incorporating a quinoxaline substructure into pristimerin could be advantageous for enhancing its cytotoxic activity. Compound 21o may serve as a lead compound for developing new therapies to treat breast cancer.

Multiple omics integration analysis reveals the regulatory effect of chitosan oligosaccharide on testicular development.

Infertility is a global health problem affecting millions of people of reproductive age worldwide, with approximately half caused by males. Chitosan oligosaccharide (COS) has strong antioxidant capacity, but its impact on the male reproductive system has not been effectively evaluated. To address this, we integrated RNA-seq, serum metabolomics and intestinal 16 S rDNA analysis to conduct a comprehensive investigation on the male reproductive system. The results showed that COS has potential targets for the treatment of oligospermia, which can promote the expression of meiotic proteins DDX4, DAZL and SYCP1, benefit germ cell proliferation and testicular development, enhance antioxidant capacity, and increase the expression of testicular steroid proteins STAR and CYP11A1. At the same time, COS can activate PI3K-Akt signaling pathway in testis and TM3 cells. Microbiome and metabolomics analysis suggested that COS alters gut microbial community composition and cooperates with serum metabolites to regulate spermatogenesis. Therefore, COS promotes male reproduction by regulating intestinal microorganisms and serum metabolism, activating PI3K-Akt signaling pathway, improving testicular antioxidant capacity and steroid regulation.

High-entropy Sulfide Catalyst Boosts Energy-saving Electrochemical Sulfion Upgrading to Thiosulfate Coupled with Hydrogen Production.

Electrochemical sulfion oxidation reaction (SOR) offers a sustainable strategy for sulfion-rich wastewater treatment, which can couple with cathodic hydrogen evolution reaction (HER) for energy-saving hydrogen production. However, the corrosion and passivation of sulfur species render the inferior catalytic SOR performance, and the oxidation product, polysulfide, requires further acidification to recover cheap elementary sulfur. Here, we reported an amorphous high-entropy sulfide catalyst of CuCoNiMnCrSx nanosheets in-situ growth on the nickel foam (CuCoNiMnCrSx/NF) for SOR, which achieved an ultra-low potential of 0.25 V to afford 100 mA cm-2, and stable electrolysis at as high as 1 A cm-2 for 100 h. These were endowed by the manipulated chemical environments surrounding Cu+ sites and the constructed "soft-acid" to "hard-acid" adsorption/desorption sites, enabling synergistically boosted adsorption/desorption process of sulfur species during SOR. Moreover, we developed an electrochemical-chemical tandem process to convert sulfions to value-added thiosulfate, providing a good choice for simultaneous wastewater utilization and hydrogen production.

Triterpenoids-templated self-assembly nanosystem for biomimetic delivery of CRISPR/Cas9 based on the synergy of TLR-2 and ICB to enhance HCC immunotherapy.

Combination immunotherapy has shown promising potential for enhancing the objective response rate compared to immune checkpoint blockade (ICB) monotherapy. However, combination therapy with multi-drugs is limited by the different properties of the agents and inconsistent synergistic targeted delivery. Herein, based on a universal triterpene template and the anticancer active agent ursolic acid (UA), a cytomembrane-coated biomimetic delivery nanoplatform (UR@M) prepared by the self-assembly of a PD-L1 targeted CRISPR/Cas9 system and UA was designed for hepatocellular carcinoma (HCC) treatment. UR@M showed enhanced tumor accumulation in vivo with homologous tumor targeting, and CRISPR in the nanosystem exhibited potent gene-editing efficiency of 76.53% in vitro and 62.42% in vivo with no off-target effects. UA activated the natural immune system through the TLR-2-MyD88-TRAF6 pathway, which synergistically enhanced the proliferation of natural killer cells and dendritic cells and realized excellent immune cytotoxic T cell infiltration by combining with the ICB of PD-L1. The strategy of work along both lines based on innate immune and adaptive immunity displayed a significant effect in tumor regression. Overall, the UA-templated strategy "killed three birds with one stone" by establishing a self-assembly nanosystem, inducing tumor cell death, and promoting synergistic immunostimulation for HCC treatment.