Integrative analysis of transcriptome and metabolome reveal the differential tolerance mechanisms to low and high salinity in the roots of facultative halophyte Avicennia marina.

Mangroves perform a crucial ecological role along the tropical and subtropical coastal intertidal zone where salinity fluctuation is frequently happened. However, the differential responses of mangrove plant at transcriptome combined metabolome level to variable salinity are not well documented. In this study, we used Avicennia marina, a pioneer species of mangrove wetlands and one of the most salt-tolerant mangroves, to investigate the differential salt tolerance mechanisms under low and high salinity using ICP-MS, transcriptomic and metabolomic analysis. The results showed that HAK8 was up-regulated and transported K+ into the roots under low salinity. However, under high salinity, AKT1 and NHX2 were strongly induced, which indicated the transport of K+ and Na+ compartmentalization to maintain ion homeostasis. In addition, A. marina tolerates low salinity by up-regulating ABA signaling pathway and accumulating more mannitol, unsaturated fatty acids, amino acids, and L-ascorbic acid in the roots. Under high salinity, A. marina undergoes a more drastic metabolic network rearrangement in the roots, such as more L-ascorbic acid and oxiglutatione were up-regulated, while carbohydrates, lipids and amino acids were down-regulated in the roots, finally glycolysis and TCA cycle were promoted to provide more energy to improve salt tolerance. Our findings suggest that the major salt tolerance traits in A. marina can be attributed to complex regulatory and signaling mechanisms, and show significant differences between low and high salinity.

Riociguat as bridging therapy to pulmonary endarterectomy in patients with chronic thromboembolic pulmonary hypertension: a retrospective cohort study.

Background: In operable chronic thromboembolic pulmonary hypertension (CTEPH) patients, the utilization of bridging therapy with targeted medications prior to pulmonary endarterectomy (PEA) remains a topic of controversy, despite being common in cases of severe hemodynamic impairment. This study aims to assess the impact of riociguat as a bridging therapy on postoperative hemodynamics and outcomes. Methods: We conducted a retrospective study involving patients undergoing PEA from December 2016 to November 2023. Patients were categorized into two groups based on the use of riociguat before PEA. Pulmonary vascular resistance (PVR) following riociguat administration was assessed pre-PEA. Postoperative outcomes, including mortality, complications, and hemodynamics, were compared, employing propensity score matching analysis. Results: Among the patients, 41.8% (n=56) received riociguat as bridging therapy. In patients with PVR ≥800 dynes·sec·cm-5, riociguat resulted in a reduction in PVR {1,207 [974-1,698] vs. 1,125 [928-1,486] dynes·sec·cm-5, P<0.01}, while no significant difference was observed in patients with PVR <800 dynes·sec·cm-5 {641 [474-740] vs. 600 [480-768] dynes·sec·cm-5, P=0.46}. After propensity score matching, each group included 26 patients. The overall perioperative mortality rate was 2.6%. Postoperative PVR {326 [254-398] vs. 361 [290-445] dynes·sec·cm-5, P=0.35} was similar in the riociguat group compared to the control group. The incidence of residual pulmonary hypertension (PH) and other postoperative outcomes were also comparable. Conclusions: The use of riociguat as bridging therapy demonstrated hemodynamic improvement before PEA in patients with high preoperative PVR. However, no additional benefits in postoperative mortality or hemodynamics were observed.

Combined prevention and treatment measures are essential to control nosocomial infections during the COVID-19 pandemic.

Severe acute respiratory syndrome coronavirus-2 is a highly contagious positive-sense, single-stranded RNA virus that has rapidly spread worldwide. As of December 17, 2023, 772838745 confirmed cases including 6988679 deaths have been reported globally. This virus primarily spreads through droplets, airborne transmission, and direct contact. Hospitals harbor a substantial number of confirmed coronavirus disease 2019 (COVID-19) patients and asymptomatic carriers, accompanied by high population density and a larger susceptible population. These factors serve as potential triggers for nosocomial infections, posing a threat during the COVID-19 pandemic. Nosocomial infections occur to varying degrees across different countries worldwide, emphasizing the urgent need for a practical approach to prevent and control the intra-hospital spread of COVID-19. This study primarily concentrated on a novel strategy combining preventive measures with treatment for combating COVID-19 nosocomial infections. It suggests preventive methods, such as vaccination, disinfection, and training of heathcare personnel to curb viral infections. Additionally, it explored therapeutic strategies targeting cellular inflammatory factors and certain new medications for COVID-19 patients. These methods hold promise in rapidly and effectively preventing and controlling nosocomial infections during the COVID-19 pandemic and provide a reliable reference for adopting preventive measures in the future pandemic.

The relationship between integrons, antibiotic resistance genes and SXT resistance in Shigella flexneri strains.

OBJECTIVE: To investigate the correlation between sulfamethoxazole-trimethoprim (SXT) resistance in Shigella flexneri (S.flexneri) and the presence of integrons and relevant antibiotic resistance genes. METHODS: We collected 115 strains of Shigella flexneri isolated from feces of children with diarrhea in Jinan from 2012 to 2020 and determined the minimum inhibitory concentration (MIC) of SXT by Etest method. The presence of class 1, class 2, and class 3 integron genes, variable region antibiotic resistance gene cassettes, and sul1, sul2, sul3, and SXT elements were detected using polymerase chain reaction (PCR). Positive results were further analyzed by DNA sequencing and BLAST comparison. RESULTS: In total, the resistance rate to SXT was 60.9% among the 115 S.flexneri strains. The prevalence of class 1 and class 2 integrons were 88.7% and 87.0%, respectively, with no class 3 integrons detected. Among the strains, 13.0% carried typical class 1 integrons with variable region antibiotic resistance gene cassettes dfrA17-aadA5 and dfrV, while 85.2% carried atypical class 1 integrons with variable region antibiotic resistance gene cassette blaoxa-30-aadA1. The variable region antibiotic resistance gene cassettes of class 2 integrons were all dfrA1+sat1+aadA1. There was a statistical difference between the presence of class 1 integrons and class 2 integrons between the SXT-sensitive and resistant S.flexneri strains (χ2=22.800, χ2=16.365, P<0.01, P<0.01). Integrons carrying dfrV and dfrA1 by integrons also showed a statistical difference in SXT resistance (χ2=9.422, χ2=16.365, P<0.01, P<0.01). PCR revealed the presence of sul1 and sul2 in 13.0% and 47.0% of strains, respectively, with neither sul3 nor SXT elements detected. There was a significant difference between the presence of sul1, sul2 between the SXT-sensitive and resistant S.flexneri strains (χ2=9.588, χ2=65.445, P<0.01, P<0.01). CONCLUSION: In summary, integrons are involved in SXT resistance of S.flexneri, and dfrV, dfrA1, sul1, sul2 are closely related to SXT resistance of S.flexneri.

Construction of ultrathin solid electrolyte interface on Zn anode within 1 min for high current operating condition.

Organic acid treatment can facilitate the in-situ formation of a solid electrolyte interface (SEI) on Zn foil protecting the anode from corrosion. However, the generation of hydrogen (H2) during this process is inevitable, which is often considered detrimental to getting compact SEI. Herein, a H2 film-assisted method is proposed under concentrated Amino-Trimethylene-Phosphonic-Acid to construct ultrathin and dense SEI within 1 min. Specifically, the (002) crystal planes survive from the etching process of 1 min due to the adhered H2, inducing uniform deposition and enhanced corrosion-resistance. Moreover, the H2 can effectively regulate the reaction rate, leading to ultrathin SEI and initiating a morphology preservation behavior, which has been neglected by the previous reports. The quick-formed SEI has excellent compatibility, low resistance and effective isolation of electrolyte/anode, whose advantages work together with exposed (002) planes to get accustomed to high-current surge, leading to the ZAC1@Zn//ZAC1@Zn consistently cycling over 800 h at 15 mA cm-2 and 15 mAh cm-2, the ZAC1@Zn//Cu preserves high reversibility (CE 99.7 %), and the ZAC1@Zn//MVO exhibits notable capacity retention at 191.7 mAh/g after 1000 cycles.

Anti-BCMA CAR-T therapy for multiple myeloma with extramedullary disease: A case report and review of the literature.

INTRODUCTION: Multiple myeloma (MM) with extramedullary disease (EMD) is rare in clinical practice, and B cell maturation antigen (BCMA) CAR-T cell therapy is a novel therapy for hematologic malignancies. Very few reports have been published on the effect of CAR-T-cell therapy in MM with EMD. Here, we report a case of MM with extramedullary lesions treated with BCMA CAR-T therapy. CASE PRESENTATION: A 66-year-old female patient presented to our hospital with an enlarged left maxillary gingiva. DIAGNOSIS: Diagnosis of indolent MM stage III (DS staging) and stage III (ISS and R ISS) with extramedullary lesions. INTERVENTION: The patient underwent a clinical trial of humanized anti-BCMA CAR T cell therapy. RESULTS: Symptoms improved; left gingival hyperplasia and swelling resolved; left buccal mass resolved; and neck and submandibular masses resolved. Pathological examination of the exfoliated masses showed necrotic tissue. CONCLUSION: MM with extramedullary lesions often has limited treatment options, and traditional chemotherapy methods are ineffective; however, BCMA CAR-T cell therapy can significantly improve the symptoms of extramedullary lesions in MM.

Homotherapy for heteropathy: therapeutic effect of Butein in NLRP3-driven diseases.

BACKGROUND: Aberrant inflammatory responses drive the initiation and progression of various diseases, and hyperactivation of NLRP3 inflammasome is a key pathogenetic mechanism. Pharmacological inhibitors of NLRP3 represent a potential therapy for treating these diseases but are not yet clinically available. The natural product butein has excellent anti-inflammatory activity, but its potential mechanisms remain to be investigated. In this study, we aimed to evaluate the ability of butein to block NLRP3 inflammasome activation and the ameliorative effects of butein on NLRP3-driven diseases. METHODS: Lipopolysaccharide (LPS)-primed bone-marrow-derived macrophages were pretreated with butein and various inflammasome stimuli. Intracellular potassium levels, ASC oligomerization and reactive oxygen species production were also detected to evaluate the regulatory mechanisms of butein. Moreover, mouse models of LPS-induced peritonitis, dextran sodium sulfate-induced colitis, and high-fat diet-induced non-alcoholic steatohepatitis were used to test whether butein has protective effects on these NLRP3-driven diseases. RESULTS: Butein blocks NLRP3 inflammasome activation in mouse macrophages by inhibiting ASC oligomerization, suppressing reactive oxygen species production, and upregulating the expression of the antioxidant pathway nuclear factor erythroid 2-related factor 2 (Nrf2). Importantly, in vivo experiments demonstrated that butein administration has a significant protective effect on the mouse models of LPS-induced peritonitis, dextran sodium sulfate-induced colitis, and high-fat diet-induced non-alcoholic steatohepatitis. CONCLUSION: Our study illustrates the connotation of homotherapy for heteropathy, i.e., the application of butein to broaden therapeutic approaches and treat multiple inflammatory diseases driven by NLRP3.

Anti-inflammatory and uric acid lowering effects of Euodiae fructus on hyperuricemia and gout mice.

The metabolic disease hyperuricemia (HUA) is caused by presence of excessive serum uric acid (UA), which leads to an increased risk of chronic kidney disease and gout. As a widely used traditional Chinese medicine, Euodiae fructus (ER) has strong anti-inflammatory and analgesic effects, however, its therapeutic effects on HUA and gout have not been investigated. To investigate the potential effects and underlying mechanisms, the effect of ER on proinflammatory cytokines and NLRP3 inflammasome activation was studied in mouse bone marrow macrophages. Moreover, a mouse model of HUA and gouty arthritis was established by coadministration of potassium oxonate (PO) and monosodium urate crystals to mice fed a high-fat diet (HFD) for 37 consecutive days. Oral administration of ER aqueous extract was given 1 hour later after the injection of PO for 10 days. Our study showed that ER is a powerful NLRP3 inhibitor in mouse macrophages. Most importantly, ER (0.75 g/kg) treatment substantially decreased the ankle joint thickness ratio, serum UA, creatinine and blood urea nitrogen levels (p < 0.05). Additionally, ER (0.75 g/kg) dramatically reversed the increases in renal urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9) as well as the decreases in organic anion transporter 1 (OAT1) and ATP binding cassette subfamily G member 2 (ABCG2) levels (p < 0.05). Moreover, ER (0.75 g/kg) markedly ameliorated the production of the serum inflammatory cytokines IL-1ß and TNF-α (p < 0.01), and improved the activation of NLRP3 inflammasome signaling in the kidneys. Taken together, these data indicate that ER, a powerful and specific NLRP3 inhibitor, has multiple anti-HUA, anti-gout and anti-inflammatory effects. Our investigation is designed to experimentally support the conventional use of ER-containing classical herbal formulas in the treatment of HUA-related disorders and may add a new dimension to the clinical application of ER.

Landscape of extrachromosomal circular DNAs, transcriptome, and proteome analysis reveals insights into alcoholic liver cirrhosis.

Alcoholic liver cirrhosis (ALC) is a result of excessive and chronic alcohol consumption. Because alchol can cause DNA damage, extrachromosomal circular DNA (eccDNA) was investigated in ALC liver due to it can be a result of DNA damage. Considering eccDNA has ability to lead to genomic instability as an enhancer of gene transcription, we utilized Circle-Seq to identify differences in eccDNA profiles and gene expression patterns in liver samples obtained from ALC patients (n = 3) and healthy controls (n = 3) to investigate the role of eccDNA in the development of ALC. The abundance of eccDNA in ALC (mean = 13,349) were higher than the healthy control (mean = 11,557) without significant difference (pvalue = 0.6530). We observed 1,032 eccDNA containing genes showed higher expression in ALC patients compared to healthy controls (p < 0.05, log2FC > 1). Notably, we discovered seven genes that exhibited a significant positive correlation between eccDNA abundance and gene expression levels. These genes include A disintegrin and metalloproteinase with thrombospondin motifs 2 (ADAMTS2), Voltage-dependent L-type calcium channel subunit alpha-1C (CACNA1C), Protein TANC1 (TANC1), Integrin alpha-2 (ITGA2), EH domain-containing protein 4 (EHD4), Phosphofurin acidic cluster sorting protein 1 (PACS1), and Neuron navigator 2 (NAV2). Through mass spectrometry proteomics, ITGA2 were found to have significantly higher abbudance in ALC. Integrins are a family of proteins plays key roles in the fibrosis development of liver. Thus, our study opens a new perspective for liver fibrosis development.

Genetic liability to inflammatory bowel disease is causally associated with increased risk of erectile dysfunction: Evidence from a bidirectional Mendelian randomization study.

Background: Several observational cohort studies suggested a close correlation between inflammatory bowel disease and erectile dysfunction. Nevertheless, whether there was a causal effect between them remained debatable. In this study, we aimed to detect the underlying causal links between genetically predicted inflammatory bowel disease and the risk of erectile dysfunction. Methods: A bidirectional Mendelian randomization (MR) study was performed to assess the causal link between inflammatory bowel disease and erectile dysfunction. Inverse variance weighted (IVW), MR-Egger, weighted median, weighted mode, and simple mode were utilized to estimate the causality. The top single nucleotide polymorphisms (SNPs) associated with inflammatory bowel disease cases (n = 25,800) and erectile dysfunction cases (n = 1,154) were extracted from the summary genome-wide association study (GWAS) data obtained from a publicly attainable database. MR-PRESSO global outlier test and MR-Egger regression were utilized to explore the horizontal pleiotropy and outlier instrumental variables. Cochran's Q statistic was utilized to detect the heterogeneity. Results: In the forward MR study, the IVW approach demonstrated that genetically determined inflammatory bowel disease exhibited a suggestively causal association with an increased risk of erectile dysfunction (OR: 1.11, 95% CI: 1.02-1.21, p = 0.019), and also the genetically determined Crohn's disease was found to be causally associated with an increased risk of erectile dysfunction (OR: 1.09, 95% CI: 1.02-1.17, p = 0.014). However, the MR analysis results showed no significant evidence supporting a causal effect of ulcerative colitis with erectile dysfunction (OR: 1.02, 95% CI: 0.92-1.14, p = 0.679). Furthermore, the reverse MR analysis showed no causal effects of genetically determined erectile dysfunction on inflammatory bowel disease. Additionally, sensitivity analysis demonstrated no pleiotropy and heterogeneity. Conclusion: Our MR analysis substantiated causal links of inflammatory bowel disease and Crohn's disease on erectile dysfunction, which may further elucidate how inflammatory bowel disease impacted the initiation and development of erectile dysfunction, and facilitated the prevention and clinical management of inflammatory bowel disease in individuals with erectile dysfunction.

DC-SIGN of Largemouth Bass (Micropterus salmoides) Mediates Immune Functions against Aeromonas hydrophila through Collaboration with the TLR Signaling Pathway.

C-type lectins in organisms play an important role in the process of innate immunity. In this study, a C-type lectin belonging to the DC-SIGN class of Micropterus salmoides was identified. MsDC-SIGN is classified as a type II transmembrane protein. The extracellular segment of MsDC-SIGN possesses a coiled-coil region and a carbohydrate recognition domain (CRD). The key amino acid motifs of the extracellular CRD of MsDC-SIGN in Ca2+-binding site 2 were EPN (Glu-Pro-Asn) and WYD (Trp-Tyr-Asp). MsDC-SIGN-CRD can bind to four pathogen-associated molecular patterns (PAMPs), including lipopolysaccharide (LPS), glucan, peptidoglycan (PGN), and mannan. Moreover, it can also bind to Gram-positive, Gram-negative bacteria, and fungi. Its CRD can agglutinate microbes and displays D-mannose and D-galactose binding specificity. MsDC-SIGN was distributed in seven tissues of the largemouth bass, among which the highest expression was observed in the liver, followed by the spleen and intestine. Additionally, MsDC-SIGN was present on the membrane of M. salmoides leukocytes, thereby augmenting the phagocytic activity against bacteria. In a subsequent investigation, the expression patterns of the MsDC-SIGN gene and key genes associated with the TLR signaling pathway (TLR4, NF-κB, and IL10) exhibited an up-regulated expression response to the stimulation of Aeromonas hydrophila. Furthermore, through RNA interference of MsDC-SIGN, the expression level of the DC-SIGN signaling pathway-related gene (RAF1) and key genes associated with the TLR signaling pathway (TLR4, NF-κB, and IL10) was decreased. Therefore, MsDC-SIGN plays a pivotal role in the immune defense against A. hydrophila by modulating the TLR signaling pathway.

Building Flame-Retardant Polymer Electrolytes via Microcapsule Technology for Stable Lithium Batteries.

Flame retardants could improve the safety properties of lithium batteries (LBs) with the sacrifice of electrochemical performance due to parasitic reactions. To concur with this, we designed thermal-response clothes for hexachlorophosphazene (HCP) additives by the microcapsule technique with urea-formaldehyde (UF) resin as the shell. HCP@UF combines with polyacrylonitrile (PAN) by hydrogen bonds successfully to form PAN-HCP@UF as the flame-retardant solid polymer electrolyte. The hydrogen bonds ensure excellent mechanical properties of the polymer electrolyte. The multiscale free radical-annihilating agent HCP effectively eliminates hydrogen free radicals of electrolytes under high temperature, showing excellent flame retardation. During the operation of the battery, functional groups on the UF resin act as active sites to promote the migration of lithium ions, while the internal HCP is protected from electrochemical reaction. With 25% HCP@UF addition, the limiting oxygen index of the PAN-HCP@UF increases to 28% and the Li+ transfer number up to 0.80. By UF protection, the initial capacity retention rate of the Li||LFP battery that assembles with PAN-HCP@UF is 88.8% after 500 cycles at 0.5 C. Thus, the microcapsule-encapsulated approach is deemed to provide an innovative strategy to prepare high-safety solid-state LB with a stable long cycle life.

The relationship between event-related potential components and suicide risk in major depressive disorder.

BACKGROUND: Suicide is a serious global issue, with major depressive disorder (MDD) being a significant risk factor for suicidal thoughts and behaviors. There is an urgent need to determine whether event-related potential components (ERPs) could be used as an indicator to assess suicidal risk. METHODS: From 2020 to 2023, 258 participants in total were recruited into the study. All participants were divided into four groups: MDD patients at high (n = 66), moderate (n = 66), and low risk (n = 56) of suicide, and healthy controls (HCs)(n = 70). Each participant provided socio-demographic information and underwent evaluations using clinical psychological scales such as 7-item Generalized Anxiety Disorder (GAD-7), Health Questionnaire-9 items (PHQ-9), and Nurses' Global Assessment of Suicide Risk (NGASR). The auditory brainstem response test and ERP examination were performed for all subjects. RESULTS: Our study found that the amplitude of P2-P3 and N2-P3 was significantly reduced in MDD patients at moderate and high risk of suicide, and these were negatively correlated with NGASR total score (all P < 0.05). Point B latency was positively correlated with NGASR total score (P < 0.05). Patients with MDD patients at low risk for suicide had a lower A-B amplitude compared to HCs (P < 0.05). No differences were found in MMN or P50 components between the four groups (all P > 0.05). CONCLUSIONS: MDD patients at higher risk of suicide exhibited severe impairment of cognitive function. ERP indices, such as the amplitude of P2-P3 and N2-P3, could be associated with the risk of suicide in MDD patients.

Blockade of the deubiquitinating enzyme USP48 degrades oncogenic HMGA2 and inhibits colorectal cancer invasion and metastasis.

HMGA2, a pivotal transcription factor, functions as a versatile regulator implicated in the progression of diverse aggressive malignancies. In this study, mass spectrometry was employed to identify ubiquitin-specific proteases that potentially interact with HMGA2, and USP48 was identified as a deubiquitinating enzyme of HMGA2. The enforced expression of USP48 significantly increased HMGA2 protein levels by inhibiting its degradation, while the deprivation of USP48 promoted HMGA2 degradation, thereby suppressing tumor invasion and metastasis. We discovered that USP48 undergoes SUMOylation at lysine 258, which enhances its binding affinity to HMGA2. Through subsequent phenotypic screening of small molecules, we identified DUB-IN-2 as a remarkably potent pharmacological inhibitor of USP48. Interestingly, the small-molecule inhibitor targeting USP48 induces destabilization of HMGA2. Clinically, upregulation of USP48 or HMGA2 in cancerous tissues is indicative of poor prognosis for patients with colorectal cancer (CRC). Collectively, our study not only elucidates the regulatory mechanism of DUBs involved in HMGA2 stability and validates USP48 as a potential therapeutic target for CRC, but also identifies DUB-IN-2 as a potent inhibitor of USP48 and a promising candidate for CRC treatment.

Transsynaptic degeneration of ventral horn motor neurons exists but plays a minor role in lower motor system dysfunction in acute ischemic rats.

BACKGROUND: As a leading cause of mortality and long-term disability, acute ischemic stroke can produce far-reaching pathophysiological consequences. Accumulating evidence has demonstrated abnormalities in the lower motor system following stroke, while the existence of Transsynaptic degeneration of contralateral spinal cord ventral horn (VH) neurons is still debated. METHODS: Using a rat model of acute ischemic stroke, we analyzed spinal cord VH neuron counts contralaterally and ipsilaterally after stroke with immunofluorescence staining. Furthermore, we estimated the overall lower motor unit abnormalities after stroke by simultaneously measuring the modified neurological severity score (mNSS), compound muscle action potential (CMAP) amplitude, repetitive nerve stimulation (RNS), spinal cord VH neuron counts, and the corresponding muscle fiber morphology. The activation status of microglia and extracellular signal-regulated kinase 1/2 (ERK 1/2) in the spinal cord VH was also assessed. RESULTS: At 7 days after stroke, the contralateral CMAP amplitudes declined to a nadir indicating lower motor function damage, and significant muscle disuse atrophy was observed on the same side; meanwhile, the VH neurons remained intact. At 14 days after focal stroke, lower motor function recovered with alleviated muscle disuse atrophy, while transsynaptic degeneration occurred on the contralateral side with elevated activation of ERK 1/2, along with the occurrence of neurogenic muscle atrophy. No apparent decrement of CMAP amplitude was observed with RNS during the whole experimental process. CONCLUSIONS: This study offered an overview of changes in the lower motor system in experimental ischemic rats. We demonstrated that transsynaptic degeneration of contralateral VH neurons occurred when lower motor function significantly recovered, which indicated the minor role of transsynaptic degeneration in lower motor dysfunction during the acute and subacute phases of focal ischemic stroke.

Comparative analysis of tropomyosin allergenicity in three different species of molluscs: insights into the role of amino acid composition in IgE epitopes.

Limited research has been conducted on the differences in allergenicity among Alectryonella plicatula tropomyosin (ATM), Haliotis discus hannai tropomyosin (HTM), and Mimachlamys nobilis tropomyosin (MTM) in molluscs. Our study aimed to comprehensively analyze and compare their immunoreactivity, sensitization, and allergenicity while simultaneously elucidating the underlying molecular mechanisms involved. We assessed the immune binding activity of TM utilizing 86 sera from allergic patients and evaluated sensitization and allergenicity through two different types of mouse models. The dot-blot and basophil activation test assays revealed strong immunoreactivity for HTM, ATM, and MTM, with HTM exhibiting significantly lower levels compared to ATM. In the BALB/c mouse sensitization model, all TM groups stimulated the production of specific antibodies, elicited IgE-mediated immediate hypersensitivity responses, and caused an imbalance in the IL-4/IFN-γ ratio. Similarly, in the BALB/c mouse model of food allergy, all TM variants induced IgE-mediated type I hypersensitivity responses, leading to the development of food allergies characterized by clinical symptoms and an imbalance in the IL-4/IFN-γ ratio. The stimulation ability of sensitization and the severity of food allergies consistently ranked as ATM > MTM > HTM. Through an in-depth analysis of non-polar amino acid frequency and polar hydrogen bonds, HTM exhibited higher frequencies of non-polar amino acids in its amino acid sequence and IgE epitopes, in comparison with ATM and MTM. Furthermore, HTM demonstrated a lower number of polar hydrogen bonds in IgE epitopes. Overall, HTM exhibited the lowest allergenic potential in both allergic patients and mouse models, likely due to its lower polarity in the amino acid sequence and IgE epitopes.

Curcuma wenyujin rhizomes extract ameliorates lipid accumulation.

Curcuma wenyujin (C. wenyujin) is a medicinal plant that is traditionally used to treat blood stagnation, liver fibrosis, pain, and jaundice. In this study, we examined the effect of C. wenyujin rhizome extract on hepatic lipid accumulation both in vivo and in vitro. We found that the petroleum ether fraction of C. wenyujin rhizome extract (CWP) considerably reduced the accumulation of lipids in HepG2 cells treated with oleic and palmitic acid. Ultra-high-performance liquid chromatography coupled with LTQ-Orbitrap mass spectrometry was used to analyze the main chemical constituents of CWP, and 21 sesquiterpenes were identified. In vivo experiments revealed that the administration of CWP significantly reduced the body weight and serum total cholesterol (TC) level of low-density-lipoprotein receptor knockout mice treated with a high-fat diet without affecting their food intake. CWP also significantly reduced the levels of liver TC, liver triglycerides, aspartate transaminase, and alanine transaminase. Histological examination revealed that CWP dose-dependently reduced steatosis in liver tissue, significantly downregulated the expression of lipogenesis genes, and increased the ß-oxidation of fatty acids. CWP also significantly increased autophagy-related proteins. In conclusion, CWP rich in sesquiterpenes reduces the accumulation of lipids in vivo and in vitro by improving lipid metabolism and activating autophagy.

A preliminary investigation of epigenome-wide DNA methylation and temperament during infancy.

This study provides preliminary evidence for an epigenetic architecture of infant temperament. At 12 months of age, blood was collected and assayed for DNA methylation and maternally reported infant temperament was assessed using the Infant Behavior Questionnaire in 67 mother-infant dyads. Epigenome-wide analyses showed that the higher order temperament dimensions Surgency and Negative Affect were associated with DNA methylation. The epigenetic signatures of Surgency and Negative Affect were situated at genes involved in synaptic signaling and plasticity. Although replication is required, these results are consistent with a biologically based model of temperament, create new avenues for hypothesis-driven research into epigenetic pathways that underlie individual differences in temperament, and demonstrate that infant temperament has a widespread epigenetic signature in the methylome.

Intervention Efficacy of Slightly Processed Allergen/Meat in Oral Immunotherapy for Seafood Allergy: A Systematic Review, Meta-Analysis, and Meta-Regression Analysis in Mouse Models and Clinical Patients.

Background: Seafood allergy is a significant global health concern that greatly impacts a patient's quality of life. The intervention efficacy of oral immunotherapy (OIT), an emerging intervention strategy, for seafood allergy remains controversial. This study aimed to perform a systematic review and meta-analysis to evaluate the efficacy of slightly processed allergen/meat from fish and crustacea in OIT, both in mouse models and clinical patients. Methods: A comprehensive literature search was performed in four mainstream databases and the EBSCOhost database to identify all relevant case-control and cohort studies. The aim was to elucidate the intervention efficacy, encompassing various processing methods and assessing the efficacy of multiple major allergens in OIT. Results: The meta-analysis included five case-control studies on crustacean allergens in mouse models and 11 cohort studies on meat from fish and crustacea in clinical patients for final quantitative assessments. In mouse models, crustacean allergen substantially decreased the anaphylactic score after OIT treatment (mean difference (MD) = -1.30, p < 0.01). Subgroup analyses with low-level heterogeneities provided more reliable results for crab species (MD = -0.63, p < 0.01, I2 = 0), arginine kinase allergen (MD = -0.83, p < 0.01, I2 = 0), and Maillard reaction processing method (MD = -0.65, p < 0.01, I2 = 29%), respectively. In clinical patients, the main meta-analysis showed that the slightly processed meat significantly increased the incidence rate of oral tolerance (OT, incidence rate ratio (IRR) = 2.90, p < 0.01). Subgroup analyses for fish meat (IRR = 2.79, p < 0.01) and a simple cooking treatment (IRR = 2.36, p = 0.01) also demonstrated a substantial increase in the incidence rate of OT. Sensitivity and meta-regression analyses successfully identified specific studies contributing to heterogeneity in mouse models and clinical patients, although these studies did not impact the overall significant pooled effects. Conclusions: This meta-analysis provides preliminary evidence for the high intervention efficacy of slightly processed allergen/meat from fish and crustacea in OIT, both in mouse models and clinical patients. The Maillard reaction and cooking processing methods may emerge as potentially effective approaches to treating allergen/meat in OIT for clinical patients, offering a promising and specific treatment strategy for seafood allergy. However, these findings should be interpreted cautiously, and further supporting evidence is necessary.

Unidirectional gene delivery electrospun fibrous membrane via charge repulsion for tendon repair.

Gene therapy is capable of efficiently regulating the expression of abnormal genes in diseased tissues and expected to be a therapeutic option for refractory diseases. However, unidirectional targeting gene therapy is always desired at the tissue interface. In this study, inspired by the principle that like charges repulse each other, a positively charged micro-nano electrospun fibrous membrane with dual-layer structure was developed by electrospinning technology to achieve unidirectional delivery of siRNA-loaded cationic nanocarriers, thus realizing unidirectional gene therapy at the tendon-paratenon interface. Under the charge repulsion of positively charged layer, more cationic COX-2 siRNA nanocarriers were enriched in peritendinous tissue, which not only improved the bioavailability of the gene drug to prevent the peritendinous adhesion formation, but also avoided adverse effects on the fragile endogenous healing of tendon itself. In summary, this study provides an innovative strategy for unidirectional targeting gene therapy of tissue interface diseases by utilizing charge repulsion to facilitate unidirectional delivery of gene drugs.