The nutritional profile of chia seeds and sprouts: tailoring germination practices for enhancing health benefits-a comprehensive review.

Chia seeds have gained significant attention due to their unique composition and potential health benefits, including high dietary fibers, omega-3 fatty acids, proteins, and phenolic compounds. These components contribute to their antioxidant, anti-inflammatory effects, as well as their ability to improve glucose metabolism and dyslipidemia. Germination is recognized as a promising strategy to enhance the nutritional value and bioavailability of chia seeds. Chia seed sprouts have been found to exhibit increased essential amino acid content, elevated levels of dietary fiber and total phenols, and enhanced antioxidant capability. However, there is limited information available concerning the dynamic changes of bioactive compounds during the germination process and the key factors influencing these alterations in biosynthetic pathways. Additionally, the influence of various processing conditions, such as temperature, light exposure, and duration, on the nutritional value of chia seed sprouts requires further investigation. This review aims to provide a comprehensive analysis of the nutritional profile of chia seeds and the dynamic changes that occur during germination. Furthermore, the potential for tailored germination practices to produce chia sprouts with personalized nutrition, targeting specific health needs, is also discussed.

RNF20 Reduces Cell Proliferation and Warburg Effect by Promoting NLRP3 Ubiquitination in Liver Cancer.

The present study explored that the effects and its possible mechanisms of ring finger protein 20 (RNF20) in Postoperative survival rate of liver cancer in clinical. All the serum samples were collected from our hospital. Quantitative polymerase chain reaction (PCR) and microarray analysis, and RNA pull down assay were used in this study. We found that the serum RNF20 mRNA expression level in patients with liver cancer were down-regulated. Postoperative survival rate of RNF20 high expression was higher than that of RNF20 low expression. Then, over-expression of RNF20 diminished liver cancer cell proliferation and metastasis. RNF20 reduced Warburg effect of liver cancer. RNF20 expression regulated NOD-like receptor protein 3 (NLRP3) expression and increased NLRP3 Ubiquitination. NLRP3 participated in the effects of RNF20 on cell proliferation, and not affected on Warburg effect of liver cancer. Our study demonstrated that the serum RNF20 expression level was down-regulated in liver cancer, and promoted postoperative survival rate. RNF20 can reduce cancer progression of liver cancer by NLRP3 signal pathway, suggesting that it may prove to be a potential therapeutic target for postoperative survival rate of liver cancer.

[Mechanism of Fushen Granules treat peritoneal dialysis-related peritonitis by regulating TLR4/NF-κB pathway:based on network pharmacology and animal experiments].

Network pharmacology was employed to probe into the mechanism of Fushen Granules in treating peritoneal dialysis-rela-ted peritonitis(PDRP) in rats. The main active components of Fushen Granules were searched against the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, and their targets were predicted. PDRP-related targets were retrieved from DisGeNET and other databases. The common targets shared by the drug and the disease were identified by the online tool, and protein-protein interaction(PPI) network of the common targets. The obtained 276 common targets were imported into DAVID for GO function enrichment and KEGG pathway enrichment. The main signaling pathway of Fushen Granules in the treatment of PDRP was predicted as Toll-like receptor 4(TLR4)/nuclear factor(NF)-κB. The rat model of uremia was induced by 5/6 nephrectomy. From two weeks after operation, the rat model of peritoneal dialysis(PD) was established by intraperitoneal injection of 20 mL dialysate with 1.25% glucose every day. The sham operation group and model group received 2 mL normal saline by gavage every day. The rats in Fushen Gra-nules groups were administrated with 2 mL solutions of low-(0.54 g·kg~(-1)), medium-(1.08 g·kg~(-1)) and high-dose(2.16 g·kg~(-1)) Fushen Granules every day. The bifico group received 2 mL(113.4 mg·kg~(-1)) of bifico solution every day. At the end of the 8th week, the levels of serum creatinine(Scr) and blood urea nitrogen(BUN) in each group were measured. The serum levels of hypersensitive C reactive protein(hs-CRP), tumor necrosis factor(TNF)-α, and interleukin(IL)-6 were measured, and the pathological changes in the colon tissue were observed by hematoxylin-eosin(HE) staining. The serum levels of lipopolysaccharide(LPS) and lipopolysaccharide-binding protein(LBP) of rats were measured, and the expression levels of LBP, TLR4, NF-κB p65, inhibitor of κB kinase α(IκBα), TNF-α, and IL-1ß in the colon tissue were determined. Compared with sham operation group, the model group had abnormal structure of all layers of colon tissue, sparse and shorter intestinal villi, visible edema in mucosal layer, wider gap, obvious local inflammatory cell infiltration, significantly decreased body weight(P<0.01), and significantly increased kidney function index(Scr, BUN) content(P<0.01). Serum levels of inflammatory cytokines(hs-CRP, TNF-α, IL-6), LPS and LBP were significantly increased(P<0.01), protein expressions of LBP, TLR4, NF-κB p65, TNF-α and IL-1ß were significantly increased(P<0.01), and protein expressions of IκBα were significantly decreased(P<0.01). Compared with model group, intestinal villi damage in colonic tissue of rats in low-, medium-and high-dose Fushen Granules groups and bifico group were alleviated to different degrees, edema in submucosa was alleviated, space was narrowed, and inflammatory cell infiltration in lamina propria was reduced. The contents of renal function index(Scr, BUN) and serum inflammatory factors(hs-CRP, TNF-α, IL-6) were significantly decreased(P<0.05 or P<0.01) in medium-and high-dose Fushen Granules groups and bifico group(P<0.05 or P<0.01). Serum LPS and LBP contents in Fushen Granules group and bifico group were significantly decreased(P<0.01), protein expressions of LBP, TLR4, NF-κB p65, TNF-α and IL-1ß in Fushen Granules group were significantly decreased(P<0.05 or P<0.01), and protein expressions of IκBα were significantly increased(P<0.01). The expression of LBP protein in bifico group was significantly decreased(P<0.01). The results suggest that Fushen Granules can protect the residual renal function of PD rats, reduce the inflammatory response, and protect the colon tissue. Based on network pharmacology, TLR4/NF-κB pathway may be the main signaling pathway of Fushen granule in the treatment of PDRP. The results showed that Fushen Granules could improve intestinal inflammation and protect intestinal barrier to prevent PDRP by regulating the expression of key factors in TLR4/NF-κB pathway in colon of PD rats.

Long lifetimes white afterglow in slightly crosslinked polymer systems.

Intrinsic polymer room-temperature phosphorescence (IPRTP) materials have attracted considerable attention for application in flexible electronics, information encryption, lighting displays, and other fields due to their excellent processabilities and luminescence properties. However, achieving multicolor long-lived luminescence, particularly white afterglow, in undoped polymers is challenging. Herein, we propose a strategy of covalently coupling different conjugated chromophores with poly(acrylic acid (AA)-AA-N-succinimide ester) (PAA-NHS) by a simple and rapid one-pot reaction to obtain pure polymers with long-lived RTPs of various colors. Among these polymers, the highest phosphorescence quantum yield of PAPHE reaches 14.7%. Furthermore, the afterglow colors of polymers can be modulated from blue to red by introducing three chromophores into them. Importantly, the acquired polymer TPAP-514 exhibits a white afterglow at room temperature with the chromaticity coordinates (0.33, 0.33) when the ratio of chromophores reaches a suitable value owing to the three-primary-color mechanism. Systematic studies prove that the emission comes from the superposition of different triplet excited states of the three components. Moreover, the potential applications of the obtained polymers in light-emitting diodes and dynamic anti-counterfeiting are explored. The proposed strategy provides a new idea for constructing intrinsic polymers with diverse white-light emission RTPs.

KSNP: a fast de Bruijn graph-based haplotyping tool approaching data-in time cost.

Long reads that cover more variants per read raise opportunities for accurate haplotype construction, whereas the genotype errors of single nucleotide polymorphisms pose great computational challenges for haplotyping tools. Here we introduce KSNP, an efficient haplotype construction tool based on the de Bruijn graph (DBG). KSNP leverages the ability of DBG in handling high-throughput erroneous reads to tackle the challenges. Compared to other notable tools in this field, KSNP achieves at least 5-fold speedup while producing comparable haplotype results. The time required for assembling human haplotypes is reduced to nearly the data-in time.

Review of biomimetic ordered microstructures in advancing synergistic integration of adhesion and microfluidics.

Many ordered arrangements are observable in the natural world, serving not only as pleasing aesthetics but also as functional improvements. These structured arrangements streamline cohesion while also facilitating the spontaneous drainage of liquids in microfluidics, resulting in effective separation and signal enhancement. Nevertheless, there is a substantial challenge when handling microstructured chips with microfluidic detection and adhesion. The arrangement of the adhesive interface's microstructure affects the liquid flow in the microfluidic chip, impacting the detection's sensitivity and accuracy. Additionally, the liquid in the microfluidic chip corrodes the adhesive material and structure, reducing the adhesion strength due to the hydration layer between the material and the contact interface. Therefore, this review explores the application of ordered structures in the integration of adhesion and microfluidics. We discussed the standard preparation method, appropriate materials, and the application of ordered structures in biomimetic adhesion and microfluidics. Furthermore, the paper discusses the major challenges in this field and provides opinions on its future developments.

Effects of proprioceptive neuromuscular facilitation combined with threshold inspiratory muscle training on respiratory function in neurocritical patients with weaning failure: a randomized controlled trial.

The purpose of this study was to determine the effects of combining proprioceptive neuromuscular facilitation (PNF) with threshold inspiratory muscle training (TIMT), compared with TIMT alone, on respiratory function in neurocritical patients who experienced a weaning failure. Forty-seven participants (mostly after a stroke), were randomly divided into the experimental group (n = 24) and the control group (n = 23). The control group received usual care and TIMT, whereas the experimental group, in addition, underwent four 90-s periods of manual PNF. Both groups performed training in the ICU twice a day for 5 consecutive days. The main outcome measures included maximum inspiratory pressure, diaphragmatic excursions, diaphragm thickening fraction, oxygenation index, and forced expiratory volume in 1 s/forced vital capacity. The results showed a significant group-by-time interaction effect for maximum inspiratory pressure [F (1, 45) = 17.84, η2 = 0.328, P < 0.001] and oxygenation index [F [1, 45) = 5.58, η2 = 0.11, P = 0.023]. When compared with the control group, the experimental group showed overall significantly higher maximum inspiratory pressure [mean difference = 4.37 cm H2O, 95% confidence interval (CI) 0.25-8.50, P = 0.038]. No other significant group differences were found. Combining PNF with TIMT may improve respiratory function in neurocritical patients with weaning failure. This combination approach may increase the likelihood of survival of neurocritical patients in the ICU.

Exenatide reduces atrial fibrillation susceptibility by inhibiting hKv1.5 and hNav1.5 channels.

Exenatide, a promising cardioprotective agent, protects against cardiac structural remodeling and diastolic dysfunction. Combined blockade of sodium and potassium channels is valuable for managing atrial fibrillation (AF). Here, we explored whether exenatide displayed anti-AF effects by inhibiting human Kv1.5 and Nav1.5 channels. We used the whole-cell patch-clamp technique to investigate the effects of exenatide on hKv1.5 and hNav1.5 channels expressed in human embryonic kidney 293 cells and studied the effects of exenatide on action potential (AP) and other cardiac ionic currents in rat atrial myocytes. Additionally, an electrical mapping system was used to explore the effects of exenatide on electrical properties and AF activity in isolated rat hearts. Finally, a rat AF model, established using acetylcholine and calcium chloride, was employed to evaluate the anti-AF potential of exenatide in rats. Exenatide reversibly suppressed IKv1.5 with IC50 of 3.08 µM, preferentially blocked hKv1.5 channel in its closed state, and positively shifted the voltage-dependent activation curve. Exenatide also reversibly inhibited INav1.5 with IC50 of 3.30 µM, negatively shifted the voltage-dependent inactivation curve, and slowed its recovery from inactivation with significant use-dependency at 5 and 10 Hz. Furthermore, exenatide prolonged AP duration and suppressed the sustained K+ current (Iss) and transient outward K+ current (Ito), but without inhibition of L-type Ca2+ current (ICa,L) in rat atrial myocytes. Exenatide prevented AF incidence and duration in rat hearts and rats. These findings demonstrate that exenatide inhibits IKv1.5 and INav1.5in vitro and reduces AF susceptibility in isolated rat hearts and rats.

BcABF1 Plays a Role in the Feedback Regulation of Abscisic Acid Signaling via the Direct Activation of BcPYL4 Expression in Pakchoi.

Abscisic acid-responsive element-binding factor 1 (ABF1), a key transcription factor in the ABA signal transduction process, regulates the expression of downstream ABA-responsive genes and is involved in modulating plant responses to abiotic stress and developmental processes. However, there is currently limited research on the feedback regulation of ABF1 in ABA signaling. This study delves into the function of BcABF1 in Pakchoi. We observed a marked increase in BcABF1 expression in leaves upon ABA induction. The overexpression of BcABF1 not only spurred Arabidopsis growth but also augmented the levels of endogenous IAA. Furthermore, BcABF1 overexpression in Arabidopsis significantly decreased leaf water loss and enhanced the expression of genes associated with drought tolerance in the ABA pathway. Intriguingly, we found that BcABF1 can directly activate BcPYL4 expression, a critical receptor in the ABA pathway. Similar to BcABF1, the overexpression of BcPYL4 in Arabidopsis also reduces leaf water loss and promotes the expression of drought and other ABA-responsive genes. Finally, our findings suggested a novel feedback regulation mechanism within the ABA signaling pathway, wherein BcABF1 positively amplifies the ABA signal by directly binding to and activating the BcPYL4 promoter.

Comparison of Alternative Protein Hydrogels for Delivering Myricetin: Interaction Mechanism and Stability Evaluation.

Food protein carriers from different sources might have distinct stabilizing and enhancing effects on the same small molecule. To elucidate the molecular mechanism, five different sourced proteins including soy protein isolates (SPIs), whey protein isolates (WPIs), edible dock protein (EDP), Tenebrio molitor protein (TMP), and yeast protein (YP) were used to prepare protein hydrogels for delivering myricetin (Myr). The results suggested that the loading capacity order of Myr in different protein hydrogels was EDP (11.5%) > WPI (9.3%) > TMP (8.9%) > YP (8.0%) > SPI (7.6%), which was consistent with the sequence of binding affinity between Myr and different proteins. Among five protein hydrogels, EDP had an optimum loading ability since it possessed the highest hydrophobic amino acid content (45.52%) and thus provided a broad hydrophobic cavity for loading Myr. In addition, these protein-Myr composite hydrogels displayed the core-shell structure, wherein hydrogen bonding and hydrophobic interaction were the primary binding forces between proteins and Myr. Moreover, the thermal stability, storage stability, and sustained-release properties of Myr were significantly enhanced via these protein delivery systems. These findings can provide scientific guidance for deeper utilization of food alternative protein sources.

The long-term efficacy of imatinib with hepatic resection or other local treatment for gastrointestinal stromal tumours liver metastases：a retrospective cohort study.

BACKGROUND: The liver is the most common site of metastasis from gastrointestinal stromal tumours (GISTs). We aimed to evaluate imatinib (IM) combined with hepatic resection (HR) or other local treatments such as radiofrequency ablation (RFA) and transarterial chemoembolization (TACE), compared to IM monotherapy in long-term survival benefits in patients suffering from GIST liver metastases. METHODS: Our research encompassed 238 patients diagnosed with liver metastases of GISTs from January 2002 to April 2022 at the XXX Hospital of XXX University. The oncological outcomes of concern included overall survival (OS), progression-free survival (PFS) and liver-specific PFS. RESULTS: Of all 238 patients, 126 were treated with IM alone (IM group), 81 with IM combined with HR (IM+HR group), and 31 with IM combined with RFA/TACE (IM+RFA/TACE group). The median follow-up time was 44.83 months. The median OS in the IM group was 132.60 months and was not reached in either the IM+HR group or the IM+RFA/TACE group. The 10-year OS rate in the IM+HR group was significantly superior to the IM group and the IM+RFA/TACE group (91.9% vs. 61.1% vs. 55.2%, respectively, P=0.015), and the liver-specific PFS (P=0.642) and PFS (P=0.369) in the three groups showed a beneficial trend in the combined treatment group. Multivariate analyses showed that age ≤60 years (HR 0.280, P<0.001) and IM+HR (HR 0.361, P=0.047) were independently associated with better OS. Achieving no evidence of disease (NED) through surgical intervention was independently correlated with enhanced OS (HR 0.099, P=0.034), liver-specific PFS (HR 0.388, P=0.014), and PFS (HR 0.402, P=0.004). CONCLUSIONS: In patients with GIST liver metastases, IM combined with HR might improve OS in selected patients compared with IM alone and IM combined with RFA/TACE. Achieving NED status with surgical treatment of patients results in significant prolonging of OS, liver-specific PFS and PFS.

Purple rice starch in wheat: Effect on retrogradation dependent on addition amount.

While individual starch types may not possess the ideal gelatinization and retrogradation properties for specific applications, the amalgamation of multiple starch varieties might bestow desirable physicochemical properties upon resulting starch-based products. This study explored the impact of incorporating purple rice starch (PRS), as a novel starch variant (up to 15 % PRS), on the gelatinization and retrogradation (within 14 days) of regular wheat starch (WS). Rheological and texture assessments demonstrated that the introduction of PRS diminished the viscoelasticity and hardness of fresh WS paste. Additionally, in the case of retrograded WS pastes stored at 4 °C for 1-14 days, the incorporation of 10 % or 15 % PRS effectively retarded the reduction in transparency and significantly reduced hardness, retrogradation degree, the ratio of absorbance at 1047/1017 cm-1, and relative crystallinity. Notably, 10 % PRS results in a more pronounced effect. Conversely, 5 % PRS induced an opposing impact on retrograded WS post-storage. Moreover, scanning electron microscopy revealed that as the proportion of PRS increased, the microstructure of gelatinized WS-PRS closely resembled that of pure PRS. In conclusion, the diverse effects of varying PRS proportions on WS alter the texture and characteristics of starch-based foods, underscoring the potential of starch blending for improved applications.

Targeted delivery of HSP90 inhibitors for efficient therapy of CD44-positive acute myeloid leukemia and solid tumor-colon cancer.

Heat shock protein 90 (HSP90) is overexpressed in numerous cancers, promotes the maturation of numerous oncoproteins and facilitates cancer cell growth. Certain HSP90 inhibitors have entered clinical trials. Although less than satisfactory clinical effects or insurmountable toxicity have compelled these trials to be terminated or postponed, these results of preclinical and clinical studies demonstrated that the prospects of targeting therapeutic strategies involving HSP90 inhibitors deserve enough attention. Nanoparticulate-based drug delivery systems have been generally supposed as one of the most promising formulations especially for targeting strategies. However, so far, no active targeting nano-formulations have succeeded in clinical translation, mainly due to complicated preparation, complex formulations leading to difficult industrialization, incomplete biocompatibility or nontoxicity. In this study, HSP90 and CD44-targeted A6 peptide functionalized biomimetic nanoparticles (A6-NP) was designed and various degrees of A6-modification on nanoparticles were fabricated to evaluate targeting ability and anticancer efficiency. With no excipients, the hydrophobic HSP90 inhibitor G2111 and A6-conjugated human serum albumin could self-assemble into nanoparticles with a uniform particle size of approximately 200 nm, easy fabrication, well biocompatibility and avoidance of hepatotoxicity. Besides, G2111 encapsulated in A6-NP was only released less than 5% in 12 h, which may avoid off-target cell toxicity before entering into cancer cells. A6 peptide modification could significantly enhance uptake within a short time. Moreover, A6-NP continues to exert the broad anticancer spectrum of Hsp90 inhibitors and displays remarkable targeting ability and anticancer efficacy both in hematological malignancies and solid tumors (with colon tumors as the model cancer) both in vitro and in vivo. Overall, A6-NP, as a simple, biomimetic and active dual-targeting (CD44 and HSP90) nanomedicine, displays high potential for clinical translation.

Microscopic Mechanism for Further NO Heterogeneous Reduction by Potassium-Doped Biochar: A DFT Study.

Biomass reburning is an efficient and low-cost way to control nitric oxide (NO), and the abundant potassium (K) element in biomass affects the heterogeneous reaction between NO and biochar. Due to the incomplete simulation of the NO heterogeneous reduction reaction pathway at the molecular level and the unclear catalytic effect of K element in biochar, further research is needed on the possible next reaction and the influencing mechanism of the element. After the products of the existing reaction pathways are referenced, two reasonably simplified biochar structural models are selected as the basic reactants to study the microscopic mechanism for further NO heterogeneous reduction on the biochar surface before and after doping with the K atom based on density functional theory. In studying the two further NO heterogeneous reduction reaction pathways, we find that the carbon monoxide (CO) molecule fragment protrudes from the surface of biochar models with the desorption of N2 at the TS4 transition state, and the two edge types of biochar product models obtained by simulation calculation are Klein edge and ac56 edge observed in the experiment. In studying the catalytic effect of potassium in biochar, we find that the presence of K increases the heat release of adsorption of NO molecules, reduces the energy barrier of the rate-determining step in the nitrogen (N2) generation and desorption process (by 50.88 and 69.97%), and hinders the CO molecule from desorbing from the biochar model surface. Thermodynamic and kinetic analyses also confirm its influence. The study proves that the heterogeneous reduction reaction of four NO molecules on the surface of biochar completes the whole reaction process and provides a basic theoretical basis for the emission of nitrogen oxides (NOx) during biomass reburning.

[Risk factors for the failure of ibuprofen treatment in preterm infants with hemodynamically significant patent ductus arteriosus]. / æœ‰è¡€æµåŠ¨åŠ›å­¦æ„ä¹‰çš„åŠ¨è„‰å¯¼ç®¡æœªé—­æ—©äº§å„¿å¸ƒæ´›èŠ¬æ²»ç–—å¤±è´¥çš„å±é™©å› ç´ åˆ†æž.

OBJECTIVES: To investigate the risk factors for the failure of ibuprofen treatment in preterm infants with hemodynamically significant patent ductus arteriosus (hsPDA). METHODS: A retrospective collection of clinical data was conducted on preterm infants with a gestational age of <34 weeks who were diagnosed with hsPDA and treated at the Department of Neonatology, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, from January 2018 to June 2023. The subjects were divided into two groups based on the treatment approach: the ibuprofen group (95 cases) and the ibuprofen plus surgery group (44 cases). The risk factors for the failure of ibuprofen treatment in preterm infants with hsPDA were identified by binary logistic regression analysis. RESULTS: The binary logistic regression analysis revealed that an increased diameter of the ductus arteriosus, a resistance index (RI) value of the middle cerebral artery ≥0.80, and prolonged total invasive mechanical ventilation time were risk factors for the failure of ibuprofen treatment in preterm infants with hsPDA (P<0.05). Receiver operating characteristic curve analysis showed that a ductus arteriosus diameter >2.85 mm, a middle cerebral artery RI value ≥0.80, and a total invasive mechanical ventilation time >16 days had significant predictive value for the failure of ibuprofen treatment in preterm infants with hsPDA (P<0.05). The combined predictive value of these three factors was the highest, with an area under the curve of 0.843, a sensitivity of 86.5%, and a specificity of 75.0% (P<0.05). CONCLUSIONS: A ductus arteriosus diameter >2.85 mm, a middle cerebral artery RI value ≥0.80, and a total invasive mechanical ventilation time >16 days are risk factors for the failure of ibuprofen treatment in preterm infants with hsPDA, and they are of significant predictive value for the necessity of surgical treatment following the failure of ibuprofen treatment.

Metabolic profiles outperform the microbiota in assessing the response of vaginal microenvironments to the changed state of HPV infection.

There is a deficiency in population-based studies investigating the impact of HPV infection on vaginal microenvironment, which influences the risk of persistent HPV infection. This prospective study aimed to unravel the dynamics of vaginal microbiota (VM) and vaginal metabolome in reaction to the changed state of HPV infection. Our results propose that the vaginal metabolome may be a superior indicator to VM when assessing the impact of altered HPV state on the vaginal microenvironment.

Engineered extracellular vesicles enable high-efficient delivery of intracellular therapeutic proteins.

Developing an intracellular delivery system is of key importance in the expansion of protein-based therapeutics acting on cytosolic or nuclear targets. Recently, extracellular vesicles (EVs) have been exploited as next-generation delivery modalities due to their natural role in intercellular communication and biocompatibility. However, fusion of protein of interest to a scaffold represents a widely-used strategy for cargo enrichment in EVs, which could compromise t the stability and functionality of cargo. Herein, we report intracellular delivery via EV-based approach (IDEA) that efficiently packages and delivers native proteins both in vitro and in vivo without the use of a scaffold. As a proof-of-concept, we applied the IDEA to deliver cyclic GMP-AMP synthase (cGAS), an innate immune sensor. The results showed that cGAS-carrying EVs activated interferon signaling and elicited enhanced antitumor immunity in multiple syngeneic tumor models. Combining cGAS EVs with immune checkpoint inhibition further synergistically boosted antitumor efficacy in vivo. Mechanistically, scRNA-seq demonstrated that cGAS EVs mediated significant remodelling of intratumoral microenvironment, revealing a pivotal role of infiltrating neutrophils in the antitumor immune milieu. Collectively, IDEA, as a universal and facile strategy, can be applied to expand and advance the development of protein-based therapeutics.

Identification and quantification of N6-methyladenosine by chemical derivatization coupled with 19F NMR spectroscopy.

N 6-Methyladenosine (6mA) is a well-known prokaryotic DNA modification that has been shown to play epigenetic roles in eukaryotic DNA. Accurate detection and quantification of 6mA are prerequisites for molecular understanding of the impact of 6mA modification on DNA. However, the existing methods have several problems, such as high false-positive rate, time-consuming and complex operating procedures. Chemical sensors for the selective detection of 6mA modification are rarely reported in the literature. Fluorinated phenylboronic acid combined with 19F NMR analysis is an effective method for determining DNA or RNA modification. In this study, we presented a simple and fast chemical method for labelling the 6th imino group of 6mA using a boric-acid-derived probe. Besides, the trifluoromethyl group of trifluoromethyl phenylboronic acid (2a) could detect 6mA modification through 19F NMR. Combined with this sensor system, 6mA modification could be detected well and quickly in 6 types of deoxynucleoside mixtures and DNA samples. Taken together, the method developed in the current study has potential for specific detection of 6mA in biological samples.

Antimicrobial resistance and genomic investigation of Salmonella isolated from retail foods in Guizhou, China.

Introduction: Salmonella is a major foodborne pathogen worldwide that causes severe morbidity and mortality. It is mainly caused by consuming contaminated food, with retail food considered the primary source. Methods: In Guizhou, China, 102 Salmonella strains isolated from 2016 to 2021 underwent phenotypic antimicrobial resistance testing and whole-genome sequencing (WGS) to understand Salmonella diversity, including serotypes, sequencing types (STs), antimicrobial genes, virulence genes, plasmid types, multi-locus sequence types (MLST), and core genome MLST (cgMLST). Results and discussion: S.Typhimurium was the dominant serotype, and O:4(B) was the leading serogroup. The most prevalent genotype was ST40. Phenotypic antimicrobial resistance identified 66.7% of the sampled isolates as multi-drug resistant (MDR). S.Enteritidis (n = 7), S.Typhimurium (n = 1), S.Indiana (n = 1), S.Kentucky (n = 1), S.Uganda (n = 1), all of which were MDR, were resistant to Colistin. Resistance rates varied significantly across different strains and food types, particularly meat products exhibiting higher resistance. Notably, significant increases in resistance were observed from 2016 to 2021 for the following: ≥ 1 resistant (P = 0.001), MDR (P = 0.001), ampicillin (P = 0.001), tetracycline (P < 0.001), chloramphenicol (P = 0.030), and trimethoprim/sulfamethoxazole (P = 0.003). The marked escalation in drug resistance over the recent years, coupled with the varying resistance rates among food sources, underscores the growing public health concern. Our findings highlight the need for a coordinated approach to effectively monitor and respond to Salmonella infections in Guizhou, China.

Lactate dehydrogenase A is implicated in the pathogenesis of B-cell lymphoma through regulation of the FER signaling pathway.

Lactate dehydrogenase A (LDHA) is highly expressed in various tumors. However, the role of LDHA in the pathogenesis of B-cell lymphoma remains unclear. Analysis of data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases revealed an elevated LDHA expression in diffuse large B-cell lymphoma (DLBC) tissues compared with normal tissues. Similarly, our results demonstrated a significant increase in LDHA expression in tumor tissues from the patients with B-cell lymphoma compared with those with lymphadenitis. To further elucidate potential roles of LDHA in B-cell lymphoma pathogenesis, we silenced LDHA in the Raji cells (a B-cell lymphoma cell line) using shRNA techniques. Silencing LDHA led to reduced mitochondrial membrane integrity, adenosine triphosphate (ATP) production, glycolytic activity, cell viability and invasion. Notably, LDHA knockdown substantially suppressed in vivo growth of Raji cells and extended survival in mice bearing lymphoma (Raji cells). Moreover, proteomic analysis identified feline sarcoma-related protein (FER) as a differential protein positively associated with LDHA expression. Treatment with E260, a FER inhibitor, significantly reduced the metabolism, proliferation and invasion of Raji cells. In summary, our findings highlight that LDHA plays multiple roles in B-cell lymphoma pathogenesis via FER pathways, establishing LDHA/FER may as a potential therapeutic target.