Spiral time-of-flight magnetic resonance angiography for intracranial vascular imaging: performance compared to conventional Cartesian angiogram.

Background: Computed tomography angiography (CTA) and digital subtraction angiography (DSA) usually raise the risk of potential malignancies with cumulative radiation doses. Current time-of-flight magnetic resonance angiography (TOF-MRA) (dubbed as cTOF), which is based on Cartesian sampling mode, may show limited diagnostic conspicuity at sinuous or branching regions. It is also prone to relatively high false positive diagnoses and undesirable display of distal intracranial vessels. This study aimed to use spiral TOF-MRA (sTOF) as a noninvasive alternative to explore possible improvement, such that the application of magnetic resonance angiography (MRA) can be extended to facilitate clinical examination or cerebrovascular disease diagnosis and follow-up studies. Methods: Initially, 37 patients with symptoms of dizziness or transient ischemic attack were consecutively recruited for suspected intracranial vascular disease examination from Zhongshan Hospital of Xiamen University between July 2020 and April 2021 in this cross-sectional prospective study. After excluding 1 patient with severe scanning artifacts, 1 patient whose scanning scope did not meet the requirement, and 1 patient with confounding tumor lesions, a total of 34 participants were included according to the inclusion and exclusion criteria. Each participant underwent intracranial vascular imaging with both sTOF and cTOF sequences on a 3.0 T MR scanner with a conventional head-neck coil of 16 channels. Contrast CTA or DSA was also performed for 15 patients showing pathology. Qualitative comparisons in terms of image quality and diagnostic efficacy ratings, quantitative comparisons in terms of signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), vessel length, and sharpness were evaluated. Pair-wise Wilcoxon test was performed to evaluate the imaging quality derived from cTOF and sTOF acquisitions and weighted Cohen's Kappa was conducted to assess the rating consistency between different physicians. Results: Compared to cTOF, sTOF showed better performance with fewer artifacts. It can effectively alleviate false positives of normal vessels being misdiagnosed as aneurysm or stenosis. Improved conspicuity was observed in cerebral distal regions with more clearly identifiable vasculature at finer scales. Quantitative comparisons in selected regions revealed significant improvement of sTOF in SNR (P<0.01 or P<0.001), CNR (P<0.001), vessel length (P<0.001), and sharpness (P<0.001) as compared to cTOF. Besides, sTOF can depict details of M1 and M2 segments of middle cerebral artery (MCA) at metallic implant region, showing its resistance to magnetic susceptibility. Conclusions: The sTOF shows higher imaging quality and lesion detectability with reduced artifacts and false positives, representing a potentially feasible surrogate in intracranial vascular imaging for future clinic routines.

Impact of Indacaterol/Glycopyrrolate on Pulmonary Function and St. George's Respiratory Questionnaire Score in Individuals with Stable Chronic Obstructive Pulmonary Disease.

Objective: This study aims to investigate the impact of indacaterol/glycopyrrolate on pulmonary function and St. George's Respiratory Questionnaire (SGRQ) scores in patients with stable chronic obstructive pulmonary disease (COPD). Methods: A prospective randomized controlled trial (RCT) was conducted. A total of 100 stable COPD patients admitted to our hospital between September 2020 and October 2022 were selected as study participants. They divided into a conventional group (n=50) and a combined compound preparation (CCP) group (n=50) using a random number table. The conventional group received oral carbocisteine tablets, while the combined compound preparation group received indacaterol/glycopyrrolate inhalation powder spray in addition to the conventional treatment. Clinical efficacy, pulmonary function indices, serum inflammatory factors, psychological resilience, and quality of life were compared between the two groups. Results: The CCP group exhibited a significantly higher total effective rate (92.00%) compared to the conventional group (76.00%) (P < .05). Post-treatment, both groups showed increased values in forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, and FEV1% with a more substantial improvement in the CCP group (P < .05). Additionally, the CCP group demonstrated decreased post-treatment levels of serum inflammatory factors (TNF-α, IL-6, CRP, and PCT), elevated scores on the Connor Davidson Resilience Scale (CD-RISC), and reduced SGRQ scores compared to the conventional group (P < .05). Conclusions: In treatment of stable COPD patients, the combination of indacaterol/glycopyrrolate with carbocisteine tablets enhances pulmonary function, alleviates airway inflammatory reactions, improves clinical efficacy, enhances psychological resilience, and elevates the quality of life compared to carbocisteine tablets alone. These findings underscore the potential therapeutic benefits of the combined compound preparation in managing stable COPD.

LINC00313 suppresses autophagy and promotes stemness of nasopharyngeal carcinoma cells through PTBP1/STIM1 axis.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a kind of malignant head and neck tumor with high mortality. lncRNAs are valuable diagnostic biomarkers and therapeutic targets for various tumors. This study investigated the effects and mechanism of LINC00313 in nasopharyngeal carcinoma. METHODS: Cell Counting Kit-8 (CCK-8) and immunohistochemistry were used for assessing cell proliferation. The levels of autophagy-related proteins, and stem cell markers were detected. Immunofluorescence assay was used for LC3 detection. Methylated RNA Immunoprecipitation (meRIP) of LINC00313 in NPC cells was assessed. The localization of LINC00313 was verified by luorescence in situ hybridization (FIHS). The interaction between LINC00313 and the downstream targets were analyzed and confirmed by immunoprecipitation (RIP). Besides, the tumorigenesis roles of LINC00313 were confirmed in tumor growth mice model. RESULTS: LINC00313 was increased in NPC tissues and cells. LINC00313 knockdown enhanced autophagy, and decreased stemness and cell viability of NPC cells through regulating STIM1. METTL3/IGF2BP1-mediated m6A modification promoted the stabilization and up-regulation of LINC00313. LINC00313 activated AKT/mTOR pathway in NPC cells through PTBP1/STIM1 axis. Moreover, LINC00313 promoted tumor growth and metastasis in xenograft model. CONCLUSION: Upregulation of LINC00313 suppressed autophagy and promoted stemness of NPC cells through PTBP1/STIM1 axis.

Protective effect of esculentoside A against myocardial infarction via targeting C-X-C motif chemokine receptor 2.

Myocardial infarction (MI) is the primary cause of cardiac mortality. Esculentoside A (EsA), a triterpenoid saponin, has anti-inflammatory and antioxidant activities. However, its effect on MI remains unknown. In this study, the protective effect and mechanisms of EsA against MI were investigated. EsA significantly alleviated hypoxia-induced HL-1 cell injury, including increasing cell viability, inhibiting reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP) and lactate dehydrogenase (LDH) leakage. In mouse MI model by left coronary artery (LAD) ligating, EsA obviously restored serum levels of creatine kinase isoenzymes (CK-MB), cardiac troponin I (cTnI), superoxide dismutase (SOD) and malondialdehyde (MDA). In addition, the cardioprotective effect of EsA was further confirmed by infarct size, electrocardiogram and echocardiography. Mechanistically, the targeted binding relationship between EsA and C-X-C motif chemokine receptor 2 (CXCR2) was predicted by molecular docking and dynamics, and validated by small molecule pull-down and surface plasmon resonance tests. EsA inhibited CXCR2 level both in vitro and in vivo, correspondingly alleviated oxidative stress by suppressing NOX1 and NOX2 and relieved inflammation through inhibiting p65 and p-p65. It demonstrated that EsA could play a cardioprotective role by targeting CXCR2. However, the effect of EsA against MI was abolished in combination with CXCR2 overexpression both in vitro and in vivo. This study revealed that EsA showed excellent cardioprotective activities by targeting CXCR2 to alleviate oxidative stress and inflammation in MI. EsA may function as a novel CXCR2 inhibitor and a potent candidate for the prevention and intervention of MI in the future.

Gut microbiome-based thiamine metabolism contributes to the protective effect of one acidic polysaccharide from Selaginella uncinata (Desv.) Spring against inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a serious disorder, and exploration of active compounds to treat it is necessary. An acidic polysaccharide named SUSP-4 was purified from Selaginella uncinata (Desv.) Spring, which contained galacturonic acid, galactose, xylose, arabinose, and rhamnose with the main chain structure of →4)-α-d-GalAp-(1→ and →6)-ß-d-Galp-(1→ and the branched structure of →5)-α-l-Araf-(1→ . Animal experiments showed that compared with Model group, SUSP-4 significantly improved body weight status, disease activity index (DAI), colonic shortening, and histopathological damage, and elevated occludin and zonula occludens protein 1 (ZO-1) expression in mice induced by dextran sulfate sodium salt (DSS). 16S ribosomal RNA (rRNA) sequencing indicated that SUSP-4 markedly downregulated the level of Akkermansia and Alistipes. Metabolomics results confirmed that SUSP-4 obviously elevated thiamine levels compared with Model mice by adjusting thiamine metabolism, which was further confirmed by a targeted metabolism study. Fecal transplantation experiments showed that SUSP-4 exerted an anti-IBD effect by altering the intestinal flora in mice. A mechanistic study showed that SUSP-4 markedly inhibited macrophage activation by decreasing the levels of phospho-nuclear factor kappa-B (p-NF-κB) and cyclooxygenase-2 (COX-2) and elevating NF-E2-related factor 2 (Nrf2) levels compared with Model group. In conclusion, SUSP-4 affected thiamine metabolism by regulating Akkermania and inhibited macrophage activation to adjust NF-κB/Nrf2/COX-2-mediated inflammation and oxidative stress against IBD. This is the first time that plant polysaccharides have been shown to affect thiamine metabolism against IBD, showing great potential for in-depth research and development applications.

Responses in Plant Growth and Root Exudates of Pistia stratiotes under Zn and Cu Stress.

At present, the situation regarding heavy metal pollution in aquatic environments is becoming more and more serious. The bioaccumulation of heavy metals in aquatic plants causes obvious phytotoxicity, which can also induce secondary pollution in the aquatic environment. Zinc and copper, as indispensable elements for plant growth, are also prominent heavy metals in water pollution in China, and their concentrations play a crucial role in plant growth. In this study, we investigated the response of Pistia stratiotes (P. stratiotes) to different concentrations of Zn and Cu, and the results showed that plant growth and photosynthesis were inhibited under both Zn (1, 2, 4, and 8 mg/L) and Cu (0.2, 0.4, 0.8, and 1 mg/L) stresses. The relative growth rates of P. stratiotes under 8 mg/L Zn or 1 mg/L Cu stress were 6.33% and 6.90%, which were much lower than those in the control group (10.86%). Meanwhile, Zn and Cu stress caused insignificant change in the relative water contents of plants. The decrease in phlorophyll fluorescence parameters and chlorophyll contents suggested the significant photoinhibition of Zn and Cu stress. Chemical analysis of plant root exudates showed that the root secretion species obtained by gas chromatography-mass spectrometry (GC-MS) mainly included amino acids, alkanes, aldehydes, ketones, phenols, and more. Compared with the control group, the influence of Zn or Cu on the reduction in relative amounts of exudates was greater than that on the increase. The results of this study provide important data for the utilization of P. stratiotes in heavy metal-polluted water environments.

High serum uric acid is a risk factor for arterial stiffness in a Chinese hypertensive population: a cohort study.

The prospective cohort study was to explore the association between serum uric acid (SUA) and arterial stiffness in a Chinese hypertensive population. A total of 7444 participants with hypertension who completed two or more measurements of brachial-ankle pulse wave velocity (baPWV) and baseline SUA detection were followed-up in the Kailuan Study from 2010 to 2020. A restricted cubic spline curve was used to verify whether there was a linear association between baseline SUA and arterial stiffness. A Cox proportional hazard regression model was used to explore the association of between baseline SUA and the incidence of arterial stiffness. Our results showed that the restricted cubic spline curve revealed a linear relationship between baseline SUA and arterial stiffness in total participants (p < 0.001). After follow-up 4.6 ± 2.8 years, Kaplan-Meier survival curves indicated that the risk of arterial stiffness was increased in the high level of baseline SUA (Log-rank p = 0.0002). After adjusting for potential confounding factors, the HR (95% CI) for risk of stiffness was 1.33 (1.17-1.52, p < 0.001) in the highest SUA group. Hierarchical analysis showed that the HRs (95% CI) for risk of arterial stiffness were 1.45 (1.25-1.69), 1.38 (1.19-1.60), 1.41 (1.21-1.64), and 1.35 (1.15-1.58) in the highest SUA group of males, <65 years old, not taking antihypertensive drugs, and failure to achieve the control targets of blood pressure respectively (p < 0.001). These results reveal that high SUA is a risk factor for arterial stiffness in the Chinese hypertensive population.

Relationship between resting heart rate and long-term outcomes in stabilized patients with myocardial infarction: A prospective community-based cohort study.

BACKGROUND: Resting heart rate (RHR) during hospitalization has been shown to be associated with adverse outcomes in patients with myocardial infarction (MI). This study aimed to evaluate the long-term prognostic effect of RHR during the stable phase after MI in post-MI patients. METHODS: Patients who had prior or new-onset MI and RHR measurements during the stable period after MI between 2006 and 2018 in the community-based Kailuan Study were enrolled. RHR was divided into four groups based on quartiles. Cox regression analysis was used to analyze the association of RHR with primary composite outcome of all-cause death, hospitalization for heart failure (HF), stroke, and recurrent MI and its components. RESULTS: A total of 4447 post-MI patients were included. During a median follow-up of 7.5 years, 1813 patients (40.8%) developed primary outcomes. Compared to RHR ≤67 bpm, patients with 72 < RHR ≤80 bpm and RHR >80 bpm had increased risks of primary outcome, with adjusted hazard ratios (95% confidence intervals) of 1.23 (1.08-1.40) and 1.35 (1.18-1.55), respectively. The risk of primary outcome increased by 12% (1.07-1.17) for each 10-bpm increase in RHR. Similar results were observed in all-cause death and hospitalization for HF. Restricted cubic splines revealed a linear relationship between RHR and primary outcome, all-cause death, and hospitalization for HF (P for nonlinearity >0.05). CONCLUSIONS: RHR during the stable phase after MI was an independent predictor for primary outcome and all-cause death in post-MI patients, and RHR >72 bpm was associated with increased risk for primary outcome and all-cause death.

Transparent multifunctional cellulose-based conductive hydrogel for wearable strain sensors and arrays.

Conductive hydrogels as promising candidate materials for flexible strain sensors have gained considerable attentions. However, it is still a great challenge to construct hydrogel with multifunctional performance via natural polymer. Herein, a novel multifunctional conductive hydrogel based on methylcellulose and cellulose nanocrystal was prepared via a facile and low-cost strategy. Methylcellulose (MC) was introduced to not only guarantee the stability of tannic acid coated cellulose nanocrystal (TA@CNCs) in LiCl solution, but also improve anti-freezing ability. The obtained hydrogel exhibited high transparency (98 % at 800 nm), good stretchability (663.1 %), low temperature tolerance (-23.9 °C), superior conductivity (2.89 S/m) and excellent UV shielding behavior. Flexible strain sensor assembled by the prepared hydrogels can be used to detect human body motions include subtle and large motions, and exhibited good sensitivity and stability over a wide temperature range. Multiple flexible hydrogels can also be assembled into a 3D sensor array to detect the distribution and magnitude of spatial pressure. Therefore, the hydrogels prepared via natural polymers will have broad application prospects in wearable devices, electronic skin and multifunctional sensor components.

Improved emulsifying properties of water-soluble myofibrillar proteins at acidic pH conditions: Emphasizing pH-regulated electrostatic interactions with chitosan.

Water-soluble muscle protein with enhanced functionalities has attracted great interest for low-salt food design. Electrostatic interactions of chitosan (CS) with myofibrillar proteins (MP) in water-aqueous solution at acidic pHs (4.0-6.5) were investigated, and how pH regulated complex formation, microstructures, conformation changes, and emulsifying capacity was systematically explored. At pH 4.0-4.5, MP and CS were positively charged and displayed a co-soluble system, exhibiting small particles and high solubility. When the pH increased to near the isoelectric point (pI) of MP (pH 5.0-6.0), electrostatic interactions largely inhibited the aggregation of MP by forming smaller particle complexes. The flexible structures and improved amphiphilic properties promoted protein absorption at the oil-water interface, further improving the emulsion stability. When the pH increased to 6.5, large aggregates were formed causing poor functionalities. This study could provide great insights to further exploit meat-protein-based low-salt functional foods in novel food design.

Apigenin-7-glucoside-loaded nanoparticle alleviates intestinal ischemia-reperfusion by ATF3/SLC7A11-mediated ferroptosis.

Intestinal ischemia reperfusion injury (II/R injury) is a common and intractable pathophysiological process in critical patients, for which exploring new treatments and mechanisms is of great importance to improve treatment outcomes. Apigenin-7-O-Glucoside (AGL) is a sugar derivative of apigenin natural product with various pharmacological activities to protect against intestinal diseases. In this study, we synthesized two amphiphilic molecules, namely DTPA-N10-10 and mPEG-TK-DA, which can scavenge free radicals and reactive oxygen species (ROS). They were successfully encapsulated AGL through self-assembly, resulting in the formation of multi-site ROS scavenging nanoparticles called PDN@AGL. In vitro and in vivo experiments demonstrated that PDN@AGL could protect intestinal tissues by reducing lipid peroxidation, lowering ROS levels and inhibiting ferroptosis during II/R injury. Furthermore, our study revealed, for the first time, that the regulation of the ATF3/SLC7A11 pathway by PDN@AGL may play a crucial role in mitigating II/R injury. In conclusion, our study confirmed the beneficial effects of PDN@AGL in combating II/R injury through the ATF3/SLC7A11-mediated regulation of ferroptosis and oxidative stress. These findings lay the groundwork for the potential application of PDN@AGL in the treatment of II/R injury.

LncRNA Gm28382 promotes lipogenesis by interacting with miR-326-3p to regulate ChREBP signaling pathway in NAFLD.

Long non-coding RNAs (lncRNAs) have been demonstrated to play vital roles in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). However, their biological roles and function mechanisms in NAFLD remain largely unknown. In this study, we found that Gm28382 may be a potential pathogenic lncRNA of NAFLD and highly expressed in NAFLD through RNA-seq. Overexpression of Gm28382 significantly enhanced the lipid accumulation in AML12 cells, whereas Gm28382 silencing reduced lipogenesis both in palmitic acid (PA)-induced AML12 cells and high fat diet (HFD)-induced mice. Then, bioinformatics were employed to speculate the potential interacting genes of Gm28382, and found that Gm28382 may regulate ChREBP expression through binding with miR-326-3p. Fluorescence in situ hybridization (FISH), dual luciferase reporter assay, immunofluorescence RNA pull-down and RNA immunoprecipitation (RIP) assays were used to validate the binding and targeting relationship of these genes, and we confirmed that Gm28382 competitively binds to miR-326-3p to increase ChREBP expression as a ceRNA. Mechanistically, overexpression of Gm28382 upregulated the ChREBP-mediated lipid synthesis signaling pathway, but the function was sabotaged by miR-326-3p deletion or ChREBP overexpression. Furthermore, in PA-challenged AML12 cells or HFD-induced mice, silencing of Gm28382 reversed the aberrant ChREBP signaling pathway and lipid accumulation, whereas ChREBP overexpression or liver-specific silencing of miR-326-3p blocked this function of Gm28382. Collectively, these findings reveal a critical role of Gm28382 in the promotion of lipogenesis in NAFLD by regulating the ChREBP signaling pathway through interaction with miR-326-3p, which could serve as a potential therapeutic target for NAFLD treatment.

The evaluation of mixed-layer emulsions stabilized by myofibrillar protein-chitosan complex for delivering astaxanthin: Fabrication, characterization, stability and in vitro digestibility.

Muscle protein based functional foods have been attracted great interests in novel food designing. Herein, myofibrillar protein (MP)-chitosan (CH) electrostatic complexes were employed to fabricate mixed-layer emulsions to protect and deliver astaxanthin. The MP/CH complex fabricated mixed-layer emulsions displayed higher stability against pH and temperature changes, exhibiting smaller droplet and homogenous distributions. After UV-light irradiation for 8 h, the mixed-layer emulsions had higher astaxanthin retention (69.11 %, 1:1 group). During storage, a lower degree of lipid oxidation, protein oxidation and higher astaxanthin retention were obtained, indicating desirable protections of mixed-layer emulsions. The vitro digestion reveled the mixed-layer emulsions could decrease the release of free fatty acids. Meanwhile, the bioaccessibility of astaxanthin was higher (30.43 %, 2:1 group) than monolayer emulsion. In all, the MP/CH prepared mixed-layer emulsions could protect and deliver fat-soluble bioactive compounds, and contributed to develop muscle protein based functional foods to meet the needs of slow and controlled release.

Protective effects of dioscin against Parkinson's disease via regulating bile acid metabolism through remodeling gut microbiome/GLP-1 signaling.

It is necessary to explore potent therapeutic agents via regulating gut microbiota and metabolism to combat Parkinson's disease (PD). Dioscin, a bioactive steroidal saponin, shows various activities. However, its effects and mechanisms against PD are limited. In this study, dioscin dramatically alleviated neuroinflammation and oxidative stress, and restored the disorders of mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). 16 S rDNA sequencing assay demonstrated that dioscin reversed MPTP-induced gut dysbiosis to decrease Firmicutes-to-Bacteroidetes ratio and the abundances of Enterococcus, Streptococcus, Bacteroides and Lactobacillus genera, which further inhibited bile salt hydrolase (BSH) activity and blocked bile acid (BA) deconjugation. Fecal microbiome transplantation test showed that the anti-PD effect of dioscin was gut microbiota-dependent. In addition, non-targeted fecal metabolomics assays revealed many differential metabolites in adjusting steroid biosynthesis and primary bile acid biosynthesis. Moreover, targeted bile acid metabolomics assay indicated that dioscin increased the levels of ursodeoxycholic acid, tauroursodeoxycholic acid, taurodeoxycholic acid and ß-muricholic acid in feces and serum. In addition, ursodeoxycholic acid administration markedly improved the protective effects of dioscin against PD in mice. Mechanistic test indicated that dioscin significantly up-regulated the levels of takeda G protein-coupled receptor 5 (TGR5), glucagon-like peptide-1 receptor (GLP-1R), GLP-1, superoxide dismutase (SOD), and down-regulated NADPH oxidases 2 (NOX2) and nuclear factor-kappaB (NF-κB) levels. Our data indicated that dioscin ameliorated PD phenotype by restoring gut dysbiosis and regulating bile acid-mediated oxidative stress and neuroinflammation via targeting GLP-1 signal in MPTP-induced PD mice, suggesting that the compound should be considered as a prebiotic agent to treat PD in the future.

Construction of Graphene@Ag-MLF composite structure SERS platform and its differentiating performance for different foodborne bacterial spores.

A new surface-enhanced Raman spectroscopy (SERS) biosensor of Graphene@Ag-MLF composite structure has been fabricated by loading AgNPs on graphene films. The response of the biosensor is  based on plasmonic sensing. The results showed that the enhancement factor of three different spores reached 107 based on the Graphene@Ag-MLF substrate. In addition, the SERS performance was stable, with good reproducibility (RSD<3%). Multivariate statistical analysis and chemometrics were used to distinguish different spores. The accumulated variance contribution rate was up to 96.35% for the top three PCs, while HCA results revealed that the spectra were differentiated completely. Based on optimal principal components, chemometrics of KNN and LS-SVM were applied to construct a model for rapid qualitative identification of different spores, of which the prediction set and training set of LS-SVM achieved 100%. Finally, based on the Graphene@Ag-MLF substrate, the LOD of three different spores was lower than 102 CFU/mL. Hence, this novel Graphene@Ag-MLF SERS substrate sensor was rapid, sensitive, and stable in detecting spores, providing strong technical support for the application of SERS technology in food safety.

Structural basis for recruitment of TASL by SLC15A4 in human endolysosomal TLR signaling.

Toll-like receptors (TLRs) are a class of proteins that play critical roles in recognizing pathogens and initiating innate immune responses. TASL, a recently identified innate immune adaptor protein for endolysosomal TLR7/8/9 signaling, is recruited by the lysosomal proton-coupled amino-acid transporter SLC15A4, and then activates IRF5, which in turn triggers the transcription of type I interferons and cytokines. Here, we report three cryo-electron microscopy (cryo-EM) structures of human SLC15A4 in the apo monomeric and dimeric state and as a TASL-bound complex. The apo forms are in an outward-facing conformation, with the dimeric form showing an extensive interface involving four cholesterol molecules. The structure of the TASL-bound complex reveals an unprecedented interaction mode with solute carriers. During the recruitment of TASL, SLC15A4 undergoes a conformational change from an outward-facing, lysosomal lumen-exposed state to an inward-facing state to form a binding pocket, allowing the N-terminal helix of TASL to be inserted into. Our findings provide insights into the molecular basis of regulatory switch involving a human solute carrier and offers an important framework for structure-guided drug discovery targeting SLC15A4-TASL-related human autoimmune diseases.

Silicon Combined with Melatonin Reduces Cd Absorption and Translocation in Maize.

Cadmium (Cd) is one of the most toxic and widely distributed heavy metal pollutants, posing a huge threat to crop production, food security, and human health. Corn is an important food source and feed crop. Corn growth is subject to Cd stress; thus, reducing cadmium stress, absorption, and transportation is of great significance for achieving high yields, a high efficiency, and sustainable and safe corn production. The use of silicon or melatonin alone can reduce cadmium accumulation and toxicity in plants, but it is unclear whether the combination of silicon and melatonin can further reduce the damage caused by cadmium. Therefore, pot experiments were conducted to study the effects of melatonin and silicon on maize growth and cadmium accumulation. The results showed that cadmium stress significantly inhibited the growth of maize, disrupted its physiological processes, and led to cadmium accumulation in plants. Compared to the single treatment of silicon or melatonin, the combined application of melatonin and silicon significantly alleviated the inhibition of the growth of maize seedlings caused by cadmium stress. This was demonstrated by the increased plant heights, stem diameters, and characteristic root parameters and the bioaccumulation in maize seedlings. Under cadmium stress, the combined application of silicon and melatonin increased the plant height and stem diameter by 17.03% and 59.33%, respectively, and increased the total leaf area by 43.98%. The promotion of corn growth is related to the reduced oxidative damage under cadmium stress, manifested in decreases in the malondialdehyde content and relative conductivity and increases in antioxidant enzyme superoxide dismutase and guaiacol peroxidase activities, as well as in soluble protein and chlorophyll contents. In addition, cadmium accumulation in different parts of maize seedlings and the health risk index of cadmium were significantly reduced, reaching 48.44% (leaves), 19.15% (roots), and 20.86% (health risk index), respectively. Therefore, melatonin and silicon have a significant synergistic effect in inhibiting cadmium absorption and reducing the adverse effects of cadmium toxicity.