Development and clinical evaluation of a real-time multiple cross displacement amplification assay for rapid and sensitive detection of Mycobacterium tuberculosis.

Molecular techniques of nucleic acid testing recommended by the World Health Organization (WHO) for the Mycobacterium tuberculosis (MTB) detection were considered to have the potential access to the accurate tuberculosis (TB) notifications. In this study, a new method, which coupled real-time (rt) fluorescence technique with multiple cross displacement amplification (MCDA), was developed for the rapid, sensitive and specific detection of MTB (termed MTB-rt-MCDA). According to the principle of the rt-MCDA test, a set of ten primers were designed for the MCDA reaction, of which one was engineered with a restrictive endonuclease recognition site, a fluorophore and a quencher for achieving the real-time fluorescence detection. MTB-rt-MCDA test was conducted under the optimized conditions (67 °C, 40 min) on the real-time fluorescence platform. The MTB-rt-MCDA assay accurately identified the MTB strains with no cross reaction with other bacteria. The lowest detectable genomic DNA concentration of the MTB-rt-MCDA assay was 25 fg/µl. We employed the genomic DNA templates extracted from sputum of clinical cases for validating the practical applicability of this assay, and the detection power of the MTB-rt-MCDA assay was comparable to that of the Xpert method and MCDA-based biosensor detection and superior to smear microscope method. The complete process of the MTB-rt-MCDA assay, including rapid extraction of DNA and rt-MCDA test, takes less than 1 h. In conclusion, the presented MTB-rt-MCDA assay provided an effective and simple option for the rapid screening of MTB infection.

Bacterial Symbiont Mediates Aphid Antiviral Systems to Inhibit the Propagation of a New Pathogenic Densovirus in Chinese Wheat Aphid, Sitobion miscanthi.

Sitobion miscanthi L-type symbiont (SMLS) is a bacterial symbiont commonly found in the wheat aphid S. miscanthi. A new aphid densovirus, S. miscanthi densovirus (SmDV), was recently identified in S. miscanthi. In this study, the similar cellular tropism of SmDV and SMLS in aphid embryos was uncovered using in situ hybridization. SmDV infection significantly decreased the longevity and number of S. miscanthi offspring. However, the SmDV titers were significantly suppressed after SMLS transmission, thus reducing the negative effects of SmDV infection on S. miscanthi fitness. Moreover, an integrative analysis of RNA-seq datasets showed that SMLS inhibited the expression of genes related to the phosphatidylinositol 3-kinase (Pl3K)/Akt pathways and further induced the expression of antiviral factors associated with the apoptosis and FoxO signaling pathways. These results indicate that SMLS mediates host antiviral defenses to inhibit the propagation of SmDV, which was further verified by an RNA interference assay.

Visual and colorimetric detection of microRNA in clinical samples based on strand displacement amplification and nanozyme-mediated CRISPR-Cas12a system.

The sensitive and accurate detection of target microRNA is especially important for the diagnosis, staging, and treatment of hepatocellular carcinoma (HCC). Herein, we report a simple strand displacement and CRISPR-Cas12a amplification strategy with nanozymes as a signal reporter for the binary visual and colorimetric detection of the HCC related microRNA. Pt@Au nanozymes with excellent peroxidase enzyme activity were prepared and linked to magnetic beads via a single-stranded DNA (ssDNA) linker. The target microRNA was designed to trigger strand displacement amplification and release a DNA promoter to activate the CRISPR-Cas12a system. The activated CRISPR-Cas12a system efficiently cleaved the linker ssDNA and released Pt@Au nanozymes from magnetic beads to induce the colorimetric reaction of 3,3',5,5'-tetramethylbenzidine. The strand displacement amplification converted the single microRNA input into abundant DNA promoter output, which improved the detection sensitivity by over two orders of magnitude. Through integration of strand displacement amplification and the nanozyme-mediated CRISPR-Cas12a system, limits of detection of 0.5 pM and 10 pM for miRNA-21 were achieved with colorimetric and visual readouts, respectively. The proposed strategy can achieve accurate quantitative detection of miRNA-21 in the range from 1 pM to 500 pM. The detection results for miRNA-21 using both colorimetric and visual readouts were validated in 40 clinical serum samples. Significantly, the proposed strategy achieved visual HCC diagnosis with the naked eye and could distinguish distinct Barcelona clinical HCC stages by colorimetric detection, showing good application prospects for sensitive and facile point-of-care testing for HCC.

TMF suppresses chondrocyte hypertrophy in osteoarthritic cartilage by mediating the FOXO3a/BMPER pathway.

Osteoarthritis (OA) is a disease of the joints, characterized by chronic inflammation, cartilage destruction and extracellular matrix (ECM) remodeling. Aberrant chondrocyte hypertrophy promotes cartilage destruction and OA development. Collagen X, the biomarker of chondrocyte hypertrophy, is upregulated by runt-related transcription factor 2 (Runx2), which is mediated by the bone morphogenetic protein 4 (BMP4)/Smad1 signaling pathway. BMP binding endothelial regulator (BMPER), a secreted glycoprotein, acts as an agonist of BMP4. 5,7,3',4'-tetramethoxyflavone (TMF) is a natural flavonoid derived from Murraya exotica L. Results of our previous study demonstrated that TMF exhibits chondroprotective effects against OA development through the activation of Forkhead box protein O3a (FOXO3a) expression. However, whether TMF suppresses chondrocyte hypertrophy through activation of FOXO3a expression and inhibition of BMPER/BMP4/Smad1 signaling remains unknown. Results of the present study revealed that TMF inhibited collagen X and Runx2 expression, inhibited BMPER/BMP4/Smad1 signaling, and activated FOXO3a expression; thus, protecting against chondrocyte hypertrophy and OA development. However, BMPER overexpression and FOXO3a knockdown impacted the protective effects of TMF. Thus, TMF inhibited chondrocyte hypertrophy in OA cartilage through mediating the FOXO3a/BMPER signaling pathway.

Bifunctional Protein TC1 Mediated One-Pot Strategy for Robust Immobilization of DNA with High Accessibility.

Immobilizing DNA with high accessibility at the interface is attractive but challenging. Current methods often involve multiple chemical reactions and derivatives. In this study, an endonuclease, TC1, is introduced to develop a robust strategy for immobilizing DNA with enhanced accessibility. TC1 enables direct immobilization of DNA onto a solid support through self-catalytic DNA covalent coupling and robust solid adsorption capabilities. This method demonstrates high accessibility to target molecules, supported by the improved sensitivity of DNA hybridization and aptamer-target recognition assays. TC1-mediated DNA immobilization is a one-pot reaction that does not require chemical derivatives, making it promising for the development of high-performance DNA materials and technologies.

Research on Deformation Prediction of VMD-GRU Deep Foundation Pit Based on PSO Optimization Parameters.

As a key guarantee and cornerstone of building quality, the importance of deformation prediction for deep foundation pits cannot be ignored. However, the deformation data of deep foundation pits have the characteristics of nonlinearity and instability, which will increase the difficulty of deformation prediction. In response to this characteristic and the difficulty of traditional deformation prediction methods to excavate the correlation between data of different time spans, the advantages of variational mode decomposition (VMD) in processing non-stationary series and a gated cycle unit (GRU) in processing complex time series data are considered. A predictive model combining particle swarm optimization (PSO), variational mode decomposition, and a gated cyclic unit is proposed. Firstly, the VMD optimized by the PSO algorithm was used to decompose the original data and obtain the Internet Message Format (IMF). Secondly, the GRU model optimized by PSO was used to predict each IMF. Finally, the predicted value of each component was summed with equal weight to obtain the final predicted value. The case study results show that the average absolute errors of the PSO-GRU prediction model on the original sequence, EMD decomposition, and VMD decomposition data are 0.502 mm, 0.462 mm, and 0.127 mm, respectively. Compared with the prediction mean square errors of the LSTM, GRU, and PSO-LSTM prediction models, the PSO-GRU on the PTB0 data of VMD decomposition decreased by 62.76%, 75.99%, and 53.14%, respectively. The PTB04 data decreased by 70%, 85.17%, and 69.36%, respectively. In addition, compared to the PSO-LSTM model, it decreased by 8.57% in terms of the model time. When the prediction step size increased from three stages to five stages, the mean errors of the four prediction models on the original data, EMD decomposed data, and VMD decomposed data increased by 28.17%, 3.44%, and 14.24%, respectively. The data decomposed by VMD are more conducive to model prediction and can effectively improve the accuracy of model prediction. An increase in the prediction step size will reduce the accuracy of the deformation prediction. The PSO-VMD-GRU model constructed has the advantages of reliable accuracy and a wide application range, and can effectively guide the construction of foundation pit engineering.

Waste-green infrastructure nexus: Green roof promotion by digestate and digestate biochar from food waste.

Waste-Green Infrastructure Nexus is crucial to mitigate carbon emissions in waste disposal and promote eco-functions of green infrastructure in a circular bio-economy. Our purpose is to verify the feasibility of the nexus via "food waste anaerobic digestion - digestate/digestate biochar - green roof promotion". The results found that food waste digestate and digestate biochar significantly promoted green roof plant growth, evapotranspiration, rainwater retention, runoff reduction, and prevention of nutrient leaching. Digestate treatments were better than digestate biochar for the green roof promotion. The promotion ranked consistently with 20 % digestate > 10 % digestate > 20 % digestate biochar > 10 % digestate biochar > control in stolon growth, leaf emergence, branching of Paspalum vaginatum, green roof establishment, rainwater retention, runoff reduction, and the leaching of nitrogen, phosphorus, potassium. This study demonstrated that food waste could be regenerated to promote urban green infrastructure to form a circular bio-economy by the Waste-Green Infrastructure Nexus.

Amelioration of Dextran Sodium Sulfate-Induced Colitis in Mice through Oral Administration of Palmitoylethanolamide.

Inflammatory bowel disease (IBD) is a group of chronic disorders characterized by pain, ulceration, and the inflammation of the gastrointestinal tract (GIT) and categorized into two major subtypes: ulcerative colitis (UC) and Crohn's disease. The inflammation in UC is typically restricted to the mucosal surface, beginning in the rectum and extending through the entire colon. UC patients typically show increased levels of pro-inflammatory cytokines, leading to intestinal epithelial apoptosis and mucosal inflammation, which impair barrier integrity. Chronic inflammation is associated with the rapid recruitment and inappropriate retention of leukocytes at the site of inflammation, further amplifying the inflammation. While UC can be managed using a number of treatments, these drugs are expensive and cause unwanted side effects. Therefore, a safe and effective treatment for UC patients is needed. Palmitoylethanolamide (PEA) is an endogenous fatty acid amide and an analog of the endocannabinoid anandamine. PEA administration has been found to normalize intestinal GIT motility and reduce injury in rodents and humans. In the current study, we examined the efficacy of PEA encapsulated in phytosomes following oral administration in experimental ulcerative colitis. Here, we showed that PEA at a human-equivalent dose of 123 mg/kg (OD or BID) attenuated DSS-induced experimental colitis as represented by the reduction in clinical signs of colitis, reduction in gross mucosal injury, and suppression of leukocyte recruitment at inflamed venules. These findings add to the growing body of data demonstrating the beneficial effects of PEA to control the acute phase of intestinal inflammation occurring during UC.

Development of multi-epitope mRNA vaccine against Clostridioides difficile using reverse vaccinology and immunoinformatics approaches.

Clostridioides difficile (C. difficile), as the major pathogen of diarrhea in healthcare settings, has become increasingly prevalent within community populations, resulting in significant morbidity and mortality. However, the therapeutic options for Clostridioides difficile infection (CDI) remain limited, and as of now, no authorized vaccine is available to combat this disease. Therefore, the development of a novel vaccine against C. difficile is of paramount importance. In our study, the complete proteome sequences of 118 strains of C. difficile were downloaded and analyzed. We found four antigenic proteins that were highly conserved and can be used for epitope identification. We designed two vaccines, WLcd1 and WLcd2, that contain the ideal T-cell and B-cell epitopes, adjuvants, and the pan HLA DR-binding epitope (PADRE) sequences. The biophysical and chemical assessments of these vaccine candidates indicated that they were suitable for immunogenic applications. Molecular docking analyses revealed that WLcd1 bonded with higher affinity to Toll-like receptors (TLRs) than WLcd2. Furthermore, molecular dynamics (MD) simulations, performed using Gmx_MMPBSA v1.56, confirmed the binding stability of WLcd1 with TLR2 and TLR4. The preliminary findings suggested that this multi-epitope vaccine could be a promising candidate for protection against CDI; however, experimental studies are necessary to confirm these predictions.

Plasma Neurofilament Light Relates to Divergent Default and Salience Network Connectivity in Alzheimer's Disease and Behavioral Variant Frontotemporal Dementia.

Background: Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) show differential vulnerability to large-scale brain functional networks. Plasma neurofilament light (NfL), a promising biomarker of neurodegeneration, has been linked in AD patients to glucose metabolism changes in AD-related regions. However, it is unknown whether plasma NfL would be similarly associated with disease-specific functional connectivity changes in AD and bvFTD. Objective: Our study examined the associations between plasma NfL and functional connectivity of the default mode and salience networks in patients with AD and bvFTD. Methods: Plasma NfL and neuroimaging data from patients with bvFTD (n = 16) and AD or mild cognitive impairment (n = 38; AD + MCI) were analyzed. Seed-based functional connectivity maps of key regions within the default mode and salience networks were obtained and associated with plasma NfL in these patients. RESULTS: We demonstrated divergent associations between NfL and functional connectivity in AD + MCI and bvFTD patients. Specifically, AD + MCI patients showed lower default mode network functional connectivity with higher plasma NfL, while bvFTD patients showed lower salience network functional connectivity with higher plasma NfL. Further, lower NfL-related default mode network connectivity in AD + MCI patients was associated with lower Montreal Cognitive Assessment scores and higher Clinical Dementia Rating sum-of-boxes scores, although NfL-related salience network connectivity in bvFTD patients was not associated with Neuropsychiatric Inventory Questionnaire scores. CONCLUSIONS: Our findings indicate that plasma NfL is differentially associated with brain functional connectivity changes in AD and bvFTD.

Correction: Promoter-regulated in vivo asymmetric self-assembly strategy to synthesize heterogeneous nanoparticles for signal amplification.

Correction for 'Promoter-regulated in vivo asymmetric self-assembly strategy to synthesize heterogeneous nanoparticles for signal amplification' by Chen Chen et al., Nanoscale, 2022, 14, 16180-16184, https://doi.org/10.1039/D2NR04661J.

In vivo whole-cortex marker of excitation-inhibition ratio indexes cortical maturation and cognitive ability in youth.

A balanced excitation-inhibition ratio (E/I ratio) is critical for healthy brain function. Normative development of cortex-wide E/I ratio remains unknown. Here, we noninvasively estimate a putative marker of whole-cortex E/I ratio by fitting a large-scale biophysically plausible circuit model to resting-state functional MRI (fMRI) data. We first confirm that our model generates realistic brain dynamics in the Human Connectome Project. Next, we show that the estimated E/I ratio marker is sensitive to the gamma-aminobutyric acid (GABA) agonist benzodiazepine alprazolam during fMRI. Alprazolam-induced E/I changes are spatially consistent with positron emission tomography measurement of benzodiazepine receptor density. We then investigate the relationship between the E/I ratio marker and neurodevelopment. We find that the E/I ratio marker declines heterogeneously across the cerebral cortex during youth, with the greatest reduction occurring in sensorimotor systems relative to association systems. Importantly, among children with the same chronological age, a lower E/I ratio marker (especially in the association cortex) is linked to better cognitive performance. This result is replicated across North American (8.2 to 23.0 y old) and Asian (7.2 to 7.9 y old) cohorts, suggesting that a more mature E/I ratio indexes improved cognition during normative development. Overall, our findings open the door to studying how disrupted E/I trajectories may lead to cognitive dysfunction in psychopathology that emerges during youth.

mRNA Delivery Systems Based on Protein Nanocages: How Far Can We Go?

Messenger RNA (mRNA) therapeutics hold great potential in the prevention and treatment of many diseases owing to several unique advantages. Delivery of mRNA into target cells is a critical step in mRNA therapy. Efficient and safe delivery systems remain an urgent need. Here, we provide an overview of the current applications of protein nanocages (PNCs), which include different types of PNCs, such as viral capsids, nonviral PNCs, and artificial PNCs, in mRNA delivery. PNCs have the features of uniform size, controllable assembly, modifiable inner and outer surfaces, good biocompatibility, and biodegradability, making them ideal candidates for mRNA delivery. In this review, the properties, loading strategies, and delivery outcomes of each tested PNC are introduced. The challenges faced by PNC-based mRNA carriers are discussed. We also share our perspectives on possible strategies to address these challenges, emphasizing the opportunities brought by emerging technologies and disciplinary convergence.

Validation of a Simplified Model for Subarachnoid Hemorrhage in Mice.

BACKGROUND: Subarachnoid hemorrhage (SAH) represents a severe injury to the brain and is associated with a high mortality (40%). Several experimental SAH models are described in the literature requiring specialized equipment and a high degree of surgical expertise. Our goal was to validate a simplified, cost-effective model to permit future studies of SAH. METHODS: SAH was induced by injection of homologous blood into the cisterna magna. Perfusion-fixation then perfusion of gelatinous India ink was performed. Brains and brainstems were collected and imaged for analysis of cerebral vasospasm. Triphenyl tetrazolium chloride (TTC) staining was used to analyze brain tissue cell death 24 hours following stroke. A composite neuroscore was utilized to assess SAH-related neurologic deficits. RESULTS: Anterior cerebral artery and basilary artery diameters were significantly reduced at 24 hours post SAH induction. Middle cerebral artery diameter was also reduced; however, the results were not significant. TTC staining showed no infarcted tissue. Neuroscores were significantly lower in the SAH mice, indicating the presence of functional deficits. CONCLUSIONS: This simplified model of SAH elicits pathological changes consistent with those described for more complex models in the literature. Therefore, it can be used in future preclinical studies examining the pathophysiology of SAH and novel treatment options.

Examining the associations between microglia genetic capacity, early life exposures and white matter development at the level of the individual.

There are inter-individual differences in susceptibility to the influence of early life experiences for which the underlying neurobiological mechanisms are poorly understood. Microglia play a role in environmental surveillance and may influence individual susceptibility to environmental factors. As an index of neurodevelopment, we estimated individual slopes of mean white matter fractional anisotropy (WM-FA) across three time-points (age 4.5, 6.0, and 7.5 years) for 351 participants. Individual variation in microglia reactivity was derived from an expression-based polygenic score(ePGS) comprised of Single Nucleotide Polymorphisms (SNPs) functionally related to the expression of microglia-enriched genes.A higher ePGS denotes an increased genetic capacity for the expression of microglia-related genes, and thus may confer a greater capacity to respond to the early environment and to influence brain development. We hypothesized that this ePGS would associate with the WM-FA index of neurodevelopment and moderate the influence of early environmental factors.Our findings show sex dependency, where a significant association between WM-FA and microglia ePGS was only obtained for females.We then examined associations with perinatal factors known to decrease (optimal birth outcomes and familial conditions) or increase (systemic inflammation) the risk for later mental health problems.In females, individuals with high microglia ePGS showed a negative association between systemic inflammation and WM-FA and a positive association between more advantageous environmental conditions and WM-FA. The microglia ePGS in females thus accounted for variations in the influence of the quality of the early environment on WM-FA.Finally, WM-FA slopes mediated the association of microglia ePGS with interpersonal problems and social hostility in females. Our findings suggest the genetic capacity for microglia function as a potential factor underlying differential susceptibility to early life exposuresthrough influences on neurodevelopment.

Genome-wide association study identified five quantitative trait loci and two candidate genes for digestive traits in Suhuai pigs.

This work aimed to identify markers and candidate genes underlying porcine digestive traits. In total, 331 pigs were genotyped by 80 K Chip data or 50 K Chip data. For apparent neutral detergent fiber digestibility, a total of 19 and 21 candidate single nucleotide polymorphisms (SNP) were respectively identified using a genome-wide efficient mixed-model association algorithm and linkage-disequilibrium adjusted kinship. Among them, three quantitative trait locus (QTL) regions were identified. For apparent acid detergent fiber digestibility, a total of 16 and 17 SNPs were identified by these two methods, respectively. Of these, three QTL regions were also identified. Moreover, two candidate genes (MST1 and LATS1), which are functionally related to intestinal homeostasis and health, were detected near these significant SNPs. Taken together, our results could provide a basis for deeper research on digestive traits in pigs.

Rapid detection of monkeypox virus and differentiation of West African and Congo Basin strains using endonuclease restriction-mediated real-time PCR-based testing.

The ongoing multi-country outbreak of monkeypox virus (MPXV) has continuously attracted global attention, highlighting the critical need for timely and accurate methods to detect MPXV and differentiate its clades. Herein, we devised a novel multiplex ET-PCR (endonuclease restriction-mediated real-time PCR) assay that integrates PCR amplification, restriction endonuclease cleavage and real-time fluorescence detection to diagnose MPXV infection and distinguish the Congo Basin and West African MPXV strains. In the MPXV ET-PCR system, three sets of specific primers were designed for MPXV, Congo Basin and West African strains. A short sequence, which could be recognized by restriction endonuclease enzyme BstUI, was added to the 5'end of amplification primers. Then, the modified primers were assigned different reporter dyes and corresponding quenching dyes to each of the three targets, enabling real-time fluorescence reporting of the results and multiplex detection. The designed assay enabled the detection of single or three targets in a single tube, with excellent specificity and analytical sensitivity in terms of plasmid and pseudotyped virus. Moreover, the clinical feasibility of our assay was validated using artificially simulated plasma, nasopharyngeal swab and skin swab samples. In conclusion, the multiplex ET-PCR assay devised here had the advantages of simple primer design, cost-effectiveness, low contamination risk, excellent sensitivity, high specificity and multiplex detection, making it a valuable and dependable tool for curbing the extensive spread of MPXV.

Insight into Cu (II) adsorption on pyrochar and hydrochar resultant from Acacia Senegal waste for wastewater decontamination.

Acacia Senegal waste (ASW) is remaining biomass following gum Arabic harvesting and has no use mentioned in the literature as of yet. This study aims to convert ASW into valuable biochar via two comparative thermal and hydrothermal techniques, which include pyrochar ASW at 300 °C (PC ASW300) and hydrochar ASW at 180 °C (HC ASW180), respectively, for Cu (II) adsorption from aqueous solutions. SEM-EDS, FTIR, XRD, and XPS were used to characterize the biochar. Adsorption performance was studied as a function of pH, contact time, and adsorbent concentration. Adsorption kinetics were best fit for a pseudo-second-order model. And thermodynamics studies revealed that Cu (II) on biochar was endothermic, spontaneous, and best fitted to the Langmuir isotherm model. Pyrochar adsorption capacity (31.93 mg g-1) was seven times that of hydrochar (5.45 mg g-1). ASW treated with phosphorus (PC H3PO4 and HC H3PO4) prior to the carbonization altered the pore structure and surface functional groups as well (O-P-O, P-CH3, and P-OH) of biochar. It was found that treating with phosphorous acid increased adsorption capacity to 141.7 mg g-1 and 22.24 mg g-1 for PC H3PO4 and HC H3PO4, respectively. The surface functional groups of biochar resulted from lignin, alkaloids, and polysaccharides combined with Cu (II) during the adsorption process via surface complexation accompanied by π-electron interaction and Cu (II) reduction. These findings shed light on the ASW biochar potential as a new green cost-effective adsorbent and drew an insightful understanding of Cu (II) adsorption performance and mechanism. It is concluded that ASW-derived biochar is highly effective and a promising alternative for Cu (II) decontamination from wastewater.

Transcriptomic analysis of salt-tolerant and sensitive high-yield japonica rice (Oryza sativa L.) reveals complicated salt-tolerant mechanisms.

Developing and cultivating rice varieties is a potent strategy for reclaiming salinity-affected soils for rice production. Nevertheless, the molecular mechanisms conferring salt tolerance, especially in conventional high-yield japonica rice varieties, remain obscure. In this study, Zhendao 23309 (ZD23309) exhibited significantly less grain yield reduction under a salt stress gradient than the control variety Wuyunjing 30 (WYJ30). High positive correlations between grain yield and dry matter accumulation at the jointing, heading and maturity stages indicated that early salt tolerance performance is a crucial hallmark for yield formation. After a mild salt stress (85 mM NaCl) of young seedlings, RNA sequencing (RNA-seq) of shoot and root separately identified a total of 1952 and 3647 differentially expressed genes (DEGs) in ZD23309, and 2114 and 2711 DEGs in WYJ30, respectively. Gene ontology (GO) analysis revealed numerous DEGs in ZD23309 that play pivotal roles in strengthening salt tolerance, encompassing the response to stimulus (GO:0050896) in shoots and nucleoside binding (GO:0001882) in roots. Additionally, distinct expression patterns were observed in a fraction of genes in the two rice varieties under salt stress, corroborating the efficacy of previously reported salt tolerance genes. Our research not only offers fresh insights into the differences in salt stress tolerance among conventional high-yield rice varieties but also unveils the intricate nature of salt tolerance mechanisms. These findings lay a solid groundwork for deciphering the mechanisms underlying salt tolerance.

Sea Cucumber and Blueberry Extracts Suppress Inflammation and Reduce Acute Lung Injury through the Regulation of NF-κB/MAPK/JNK Signaling Pathway in Lipopolysaccharide-Treated C57BL/6 Mice.

Acute lung injury (ALI) represents a life-threatening condition with high morbidity and mortality despite modern mechanical ventilators and multiple pharmacological strategies. Therefore, there is a need to develop efficacious interventions with minimal side effects. The anti-inflammatory activities of sea cucumber (Cucumaria frondosa) and wild blueberry (Vaccinium angustifolium) extracts have been reported recently. However, their anti-inflammatory activities and the mechanism of action against ALI are not fully elucidated. Thus, the present study aims to understand the mechanism of the anti-inflammatory activity of sea cucumber and wild blueberry extracts in the context of ALI. Experimental ALI was induced via intranasal lipopolysaccharide (LPS) instillation in C57BL/6 mice and the anti-inflammatory properties were determined by cytokine analysis, histological examination, western blot, and qRT-PCR. The results showed that oral supplementation of sea cucumber extracts repressed nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways, thereby downregulating the expression of interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF) in the lung tissue and in the plasma. Wild blueberry extracts also suppressed the expression of IL-4. Furthermore, the combination of sea cucumber and wild blueberry extracts restrained MAPK signaling pathways by prominent attenuation of phosphorylation of NF-κB, c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK) while the levels of pro-inflammatory cytokines were significantly suppressed. Moreover, there was a significant and synergistic reduction in varying degrees of ALI lesions such as distorted parenchyma, increased alveoli thickness, lymphocyte and neutrophil infiltrations, fibrin deposition, pulmonary emphysema, pneumonia, intra-alveolar hemorrhage, and edema. The anti-inflammatory effect of the combination of sea cucumber and wild blueberry extracts is associated with suppressing MAPK and NF-κB signaling pathways, thereby significantly reducing cytokine storm in LPS-induced experimental ALI.