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BACKGROUND: Few studies have estimated the associations of systemic inflammation markers and high blood pressure (HBP) in the pediatric population. METHODS: Basing on data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018, we assessed the associations between four inflammation-related factors based on blood cell counts: systemic immune inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and risk for pediatric HBP by estimating odds ratios (ORs) using multivariable logistic regression models. RESULTS: A total of 17,936 children aged 8-19 years were included in the analysis, representing about 36.7 million American children. The prevalence rates of elevated blood pressure (EBP) and hypertension (HTN) were 15.79% and 6.77%, respectively. The results showed that the ORs for EBP per standard deviation (SD) increment in SII and NLR were estimated at 1.11 [95% confidence interval (95%CI): 1.04, 1.17] and 1.08 (95%CI: 1.02, 1.15), respectively; and the OR for EBP per SD increment in LMP were estimated at 0.90 (95%CI: 0.83, 0.96). These associations were stronger in boys and younger children. CONCLUSIONS: The study suggested that inflammation-related factors could serve as easily accessible early biomarkers for HBP risk prediction and prevention in children and adolescents. IMPACT: The study suggested that inflammation-related factors could serve as easily accessible early biomarkers for HBP risk prediction and prevention in children and adolescents. This is the first study that demonstrates the close association between systemic inflammation markers and HBP in children and adolescents using nationally representative population data. The findings have more public health implications and support that systemic inflammation markers based on blood cell counts could serve as easily accessible biomarkers of HBP risk and prevention in earlier identification of the diseases.
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Immunotherapy with immune checkpoint inhibitors (ICIs) is increasingly used to treat various tumor types. Determining patient responses to ICIs presents a significant clinical challenge. Although components of the tumor microenvironment (TME) are used to predict patient outcomes, comprehensive assessments of the TME are frequently overlooked. Using a top-down approach, the TME was divided into five layers-outcome, immune role, cell, cellular component, and gene. Using this structure, a neural network called TME-NET was developed to predict responses to ICIs. Model parameter weights and cell ablation studies were used to investigate the influence of TME components. The model was developed and evaluated using a pan-cancer cohort of 948 patients across four cancer types, with Area Under the Curve (AUC) and accuracy as performance metrics. Results show that TME-NET surpasses established models such as support vector machine and k-nearest neighbors in AUC and accuracy. Visualization of model parameter weights showed that at the cellular layer, Th1 cells enhance immune responses, whereas myeloid-derived suppressor cells and M2 macrophages show strong immunosuppressive effects. Cell ablation studies further confirmed the impact of these cells. At the gene layer, the transcription factors STAT4 in Th1 cells and IRF4 in M2 macrophages significantly affect TME dynamics. Additionally, the cytokine-encoding genes IFNG from Th1 cells and ARG1 from M2 macrophages are crucial for modulating immune responses within the TME. Survival data from immunotherapy cohorts confirmed the prognostic ability of these markers, with p-values <0.01. In summary, TME-NET performs well in predicting immunotherapy responses and offers interpretable insights into the immunotherapy process. It can be customized at https://immbal.shinyapps.io/TME-NET.
Subject(s)
Immune Checkpoint Inhibitors , Neoplasms , Tumor Microenvironment , Humans , Immune Checkpoint Inhibitors/therapeutic use , Immune Checkpoint Inhibitors/pharmacology , Tumor Microenvironment/immunology , Neoplasms/immunology , Neural Networks, Computer , ImmunotherapyABSTRACT
PURPOSE: To evaluate the therapeutic efficacy of intravenous amoxicillin clavulanate potassium combined with nebulized budesonide and ambroxol hydrochloride in pediatric community-acquired pneumonia (CAP) and its impact across various microbial strains and clinical symptoms. The primary objective of this study is to evaluate the efficacy of intravenous amoxicillin-clavulanate combined with nebulized budesonide and ambroxol hydrochloride in the treatment of pediatric community-acquired pneumonia (CAP), and to analyze their impact on different microbial strains and clinical symptoms. Secondary objectives include assessing the treatment's effect on the improvement of clinical symptoms, hospital stay duration, and the levels of inflammatory markers. DESIGN: Prospective, single-center study. METHODS: Fifty-six children with CAP, aged under 6 years, from Affiliated Maternity and Child Health Care Hospital of Nantong University were included. Patients were treated with conventional therapy and the study medication. Clinical characteristics, microbiological data, symptom improvement, and hospitalization times were analyzed. FINDINGS: Young children, particularly under 1 year, exhibited a higher incidence of multiple microbial infections and severe clinical manifestations. Treatment with budesonide and ambroxol hydrochloride led to significant clinical improvement across all age groups, with notable efficacy against various pathogens. CONCLUSIONS: Nebulized budesonide and ambroxol hydrochloride are effective in treating pediatric CAP, offering a promising therapeutic option, particularly for young children with severe presentations.
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Ambroxol , Budesonide , Community-Acquired Infections , Nebulizers and Vaporizers , Humans , Ambroxol/administration & dosage , Ambroxol/therapeutic use , Budesonide/administration & dosage , Budesonide/therapeutic use , Female , Male , Child, Preschool , Infant , Prospective Studies , Community-Acquired Infections/drug therapy , Treatment Outcome , Administration, Inhalation , Amoxicillin-Potassium Clavulanate Combination/administration & dosage , Amoxicillin-Potassium Clavulanate Combination/therapeutic use , Child , Pneumonia/drug therapy , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/therapeutic use , Expectorants/administration & dosage , Expectorants/therapeutic use , Biomarkers/blood , Drug Therapy, Combination , Length of StayABSTRACT
As a representative item of chemical carcinogen, MNNG is closely associated with the onset of gastric cancer (GC), where N6-methyladonosine (m6A) RNA methylation is recognized as a critical epigenetic event. In our previous study, we found that the m6A modification by methyltransferase METTL3 was up-regulated in MNNG-exposed malignant GES-1 cells (MC cells) compared to control cells in vitro, and long non-coding RNA SNHG7 as a downstream target of the METTL3. However, the functional role of METTL3 in mediating the SNHG7 axis in MNNG-induced GC remains unclear. In the present study, we continuously investigate the functional role of METTL3 in mediating the SNHG7 axis in MNNG-induced GC. RIP-PCR and m6A-IP-qPCR were used to examine the molecular mechanism underlying the METTL3/m6A/SNHG7 axis in MNNG-induced GC. A METTL3 knockout mice model was constructed and exposed by MNNG. Western blot analysis, IHC analysis, and RT-qPCR were used to measure the expression of METTL3, SNHG7, and EMT markers. In this study, we demonstrated that in MNNG-induced GC tumorigenesis, the m6A modification regulator METTL3 facilitates cellular EMT and biological functions through the m6A/SNHG7 axis using in vitro and in vivo models. In conclusion, our study provides novel insights into critical epigenetic molecular events vital to MNNG-induced gastric carcinogenesis. These findings suggest the potential therapeutic targets of METTL3 for GC treatment.
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Automatic seizure detection from Electroencephalography (EEG) is of great importance in aiding the diagnosis and treatment of epilepsy due to the advantages of convenience and economy. Existing seizure detection methods are usually patient-specific, the training and testing are carried out on the same patient, limiting their scalability to other patients. To address this issue, we propose a cross-subject seizure detection method via unsupervised domain adaptation. The proposed method aims to obtain seizure specific information through shallow and deep feature alignments. For shallow feature alignment, we use convolutional neural network (CNN) to extract seizure-related features. The distribution gap of the shallow features between different patients is minimized by multi-kernel maximum mean discrepancies (MK-MMD). For deep feature alignment, adversarial learning is utilized. The feature extractor tries to learn feature representations that try to confuse the domain classifier, making the extracted deep features more generalizable to new patients. The performance of our method is evaluated on the CHB-MIT and Siena databases in epoch-based experiments. Additionally, event-based experiments are also conducted on the CHB-MIT dataset. The results validate the feasibility of our method in diminishing the domain disparities among different patients.
Subject(s)
Electroencephalography , Neural Networks, Computer , Seizures , Unsupervised Machine Learning , Humans , Electroencephalography/methods , Seizures/diagnosis , Seizures/physiopathology , Deep Learning , Signal Processing, Computer-AssistedABSTRACT
PURPOSE: To judge the injury mode and injury severity of the real human body through the measured values of anthropomorphic test devices (ATD) injury indices, the mapping relationship of lumbar injury between ATD and human body model (HBM) was explored. METHODS: Through the ATD model and HBM simulation, the mapping relationship of lumbar injury between the 2 subjects was explored. The sled environment consisted of a semi-rigid seat with an adjustable seatback angle and a 3-point seat belt system with a seatback-mounted D-ring. Three seatback recline states of 25°, 45°, and 65° were designed, and the seat pan angle was maintained at 15°. A 23 g, 47 km/h pulse was used. The validity of the finite element model of the sled was verified by the comparison of ATD simulation and test results. ATD model was the test device for human occupant restraint for autonomous vehicles (THOR-AV) dummy model and HBM was the total human model for safety (THUMS) v6.1. The posture of the 2 models was adjusted to adapt to the 3 seat states. The lumbar response of THOR-AV and the mechanical and biomechanical data on L1-L5 vertebrae of THUMS were output, and the response relationship between THOR-AV and THUMS was descriptive statistically analyzed. RESULTS: Both THOR-AV and THUMS were submarined in the 65° seatback angle case. With the change of seatback angle, the lumbar spine axial compression force (Fz) of THOR-AV and THUMS changed in the similar trend. The maximum Fz ratio of THOR-AV to THUMS at 25° and 45° seatback angle cases were 1.6 and 1.7. The flexion moment (My) and the time when the maximum My occurred in the 2 subjects were very different. In particular, the form of moment experienced by the L1 - L5 vertebrae of THUMS also changed. The changing trend of My measured by THOR-AV over time can reflect the changing trend of maximum stress of L1 and L2 of THUMS. CONCLUSION: The Fz of ATD and HBM presents a certain proportional relationship, and there is a mapping relationship between the 2 subjects on Fz. The mapping function can be further clarified by applying more pulses and adopting more seatback angles. It is difficult to map My directly because they are very different in ATD and HBM. The My of ATD and stress of HBM lumbar showed a similar change trend over time, and there may be a hidden mapping relationship.
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High-altitude pulmonary edema (HAPE) is a fatal threat for sojourners who ascend rapidly without sufficient acclimatization. Acclimatized sojourners and adapted natives are both insensitive to HAPE but have different physiological traits and molecular bases. In this study, based on GSE52209, the gene expression profiles of HAPE patients were compared with those of acclimatized sojourners and adapted natives, with the common and divergent differentially expressed genes (DEGs) and their hub genes identified, respectively. Bioinformatic methodologies for functional enrichment analysis, immune infiltration, diagnostic model construction, competing endogenous RNA (ceRNA) analysis and drug prediction were performed to detect potential biological functions and molecular mechanisms. Next, an array of in vivo experiments in a HAPE rat model and in vitro experiments in HUVECs were conducted to verify the results of the bioinformatic analysis. The enriched pathways of DEGs and immune landscapes for HAPE were significantly different between sojourners and natives, and the common DEGs were enriched mainly in the pathways of development and immunity. Nomograms revealed that the upregulation of TNF-α and downregulation of RPLP0 exhibited high diagnostic efficiency for HAPE in both sojourners and natives, which was further validated in the HAPE rat model. The addition of TNF-α and RPLP0 knockdown activated apoptosis signaling in endothelial cells (ECs) and enhanced endothelial permeability. In conclusion, TNF-α and RPLP0 are shared biomarkers and molecular bases for HAPE susceptibility during the acclimatization/adaptation/maladaptation processes in sojourners and natives, inspiring new ideas for predicting and treating HAPE.
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The growing variety of RNA classes, such as mRNAs, lncRNAs, and circRNAs, plays pivotal roles in both developmental processes and various pathophysiological conditions. Nonetheless, our comprehension of RNA functions in live organisms remains limited due to the absence of durable and effective strategies for directly influencing RNA levels. In this study, we combined the CRISPR-RfxCas13d system with sperm-like stem cell-mediated semi-cloning techniques, which enabled the suppressed expression of different RNA species. This approach was employed to interfere with the expression of three types of RNA molecules: Sfmbt2 mRNA, Fendrr lncRNA, and circMan1a2(2,3,4,5,6). The results confirmed the critical roles of these RNAs in embryonic development, as their loss led to observable phenotypes, including embryonic lethality, delayed embryonic development, and embryo resorption. In summary, our methodology offers a potent toolkit for silencing specific RNA targets in living organisms without introducing genetic alterations.
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The development of wearable electronic devices for human health monitoring requires materials with high mechanical performance and sensitivity. In this study, we present a novel transparent tissue-like ionogel-based wearable sensor based on silver nanowire-reinforced ionogel nanocomposites, P(AAm-co-AA) ionogel-Ag NWs composite. The composite exhibits a high stretchability of 605% strain and a moderate fracture stress of about 377 kPa. The sensor also demonstrates a sensitive response to temperature changes and electrostatic adsorption. By encapsulating the nanocomposite in a polyurethane transparent film dressing, we address issues such as skin irritation and enable multidirectional stretching. Measuring resistive changes of the ionogel nanocomposite in response to corresponding strain changes enables its utility as a highly stretchable wearable sensor with excellent performance in sensitivity, stability, and repeatability. The fabricated pressure sensor array exhibits great proficiency in stress distribution, capacitance sensing, and discernment of fluctuations in both external electric fields and stress. Our findings suggest that this material holds promise for applications in wearable and flexible strain sensors, temperature sensors, pressure sensors, and actuators.
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PURPOSE: To investigate the effects of erbium laser pretreatment on the bond strength of dentin and enamel,as well as microleakage at the edge of tooth defects repaired with computer-aided design (CAD) and computer-assisted manufacturing (CAM) glass-ceramic restorations for repairing dental defects. METHODS: A total of 62 fresh, nondecayed, nondiscoloration and noncracked wisdom teeth were collected from the Oral Surgery Clinic between January 2020 and January 2023. According to different pretreatment methods, they were randomly divided into two groups, erbium laser group and phosphoric acid group, with 31 teeth in each group. Each group was further divided into two subsets for bond strength testing (16 teeth) and microleakage testing (15 teeth).The shear bond strength between enamel and dentin of both groups was compared, as well as the degree and distribution of microleakage.Statistical analysis was performed with SPSS 17.0 software package. RESULTS: The shear bond strength between enamel and dentin of the erbium laser group was significantly higher than that of the phosphoric acid group (Pï¼0.05); the degree and distribution of microleakage at the lateral walls and gumline of the erbium laser group were significantly lower than those of the phosphoric acid group (Pï¼0.05). The scores of microleakage at the lateral walls of the erbium laser group mainly concentrated in grade 1 and 2, whereas those of the phosphoric acid group mainly concentrated in grade 2. There was significant difference in the distribution of lateral wall microleakage scores between the two groups (Pï¼0.05). The scores of microleakage at the gumline of the erbium laser group mainly concentrated in grade 1 and 2, whereas those of the phosphoric acid group mainly concentrated in grade 2 and 3. There was significant difference in the distribution of gumline microleakage scores between the two groups (Pï¼0.05). CONCLUSIONS: Erbium laser pretreatment can improve bonding strength between glass ionomer cement and dentin and enamel, reduce microleakage at the edge of CAD/CAM glass ionomer cement restorations, and enhance marginal fit.
Subject(s)
Computer-Aided Design , Dental Bonding , Dental Enamel , Dentin , Glass Ionomer Cements , Dental Enamel/radiation effects , Humans , Dentin/chemistry , Glass Ionomer Cements/chemistry , Dental Bonding/methods , Phosphoric Acids/chemistry , Lasers, Solid-State/therapeutic use , Shear Strength , Dental Leakage/etiology , Dental Restoration, Permanent/methods , Erbium/chemistryABSTRACT
The disruptions caused by ice crystal formation during the cryopreservation of cells and tissues can cause cell and tissue damage. Thus, preventing such damage during cryopreservation is an important but challenging goal. Here, a hibernating/awakening nanomotor with magnesium/palladium covering one side of a silica platform (Mg@Pd@SiO2) is proposed. This nanomotor is used in the cultivation of live NCM460 cells to demonstrate a new method to actively limit ice crystal formation and enable highly efficient cryopreservation. Cooling Mg@Pd@SiO2 in solution releases Mg2+/H2 and promotes the adsorption of H2 at multiple Pd binding sites on the cell surface to inhibit ice crystal formation and cell/tissue damage; additionally, the Pd adsorbs and stores H2 to form a hibernating nanomotor. During laser-mediated heating, the hibernating nanomotor is activated (awakened) and releases H2, which further suppresses recrystallization and decreases cell/tissue damage. These hibernating/awakening nanomotors have great potential for promoting highly efficient cryopreservation by inhibiting ice crystal formation.
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BACKGROUND: Limited data exists on the efficacy of immune checkpoint inhibitor (ICI) combinations in non-small-cell lung cancer (NSCLC) with uncommon driver alterations in genes such as ERBB2, BRAF, RET, and MET. This study retrospectively assessed ICI-combination therapy outcomes in this molecular subset of NSCLC. METHODS: We retrospectively analyzed patients with advanced NSCLC confirmed with driver alterations in genes including ERBB2, BRAF, RET or MET, and received ICI combined with chemotherapy (ICI + chemo) and/or targeted therapy (ICI + chemo/TT) as first-line (1L) or second- or third-line (≥ 2L) treatment at Hunan Cancer Hospital between January 2018 and May 2024. RESULTS: Of the 181 patients included in the study, 131 patients received 1L-ICI + chemo (ERBB2, n = 64; BRAF, n = 34; RET, n = 23; and MET, n = 10), and 50 patients received ≥ 2L-ICI + chemo/TT (ERBB2, n = 16; BRAF, n = 7; RET, n = 14; MET, n = 13). The full cohort had an overall response rate (ORR) of 45.9% and disease control rate of 84.0%. Among patients who received 1L-ICI + chemo, ORR ranged between 51.6% and 60.0%, with the median progression-free survival (mPFS) and overall survival (mOS) of 8.2 and 21.0 months for those with ERBB2-altered tumors, 10.0 and 15.0 months for BRAF-altered tumors, 12.1 months and OS not reached for RET-altered tumors, and 6.2 and 28.0 months for MET-altered tumors, respectively. Additionally, ORR ranged between 14.3% and 30.8% for ≥ 2L-ICI + chemo/TT; mPFS and mOS were 5.4 and 16.2 months for patients with ERBB2-altered tumors, 2.7 and 5.0 months for BRAF-altered tumors, 6.2 and 14.3 months for RET-altered tumors, and 5.7 and 11.5 months for MET-altered tumors, respectively. CONCLUSION: ICI-based combination therapies, regardless of treatment line, were effective in treating patients with advanced NSCLC harboring driver alterations in ERBB2, BRAF, RET, or MET. This suggests their potential as alternative treatment options in this patient population.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Carcinoma, Non-Small-Cell Lung , Immune Checkpoint Inhibitors , Lung Neoplasms , Receptor, ErbB-2 , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/pathology , Immune Checkpoint Inhibitors/therapeutic use , Male , Female , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Middle Aged , Aged , Retrospective Studies , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Adult , Receptor, ErbB-2/genetics , Receptor, ErbB-2/metabolism , Aged, 80 and over , Proto-Oncogene Proteins B-raf/genetics , Proto-Oncogene Proteins c-ret/genetics , Treatment Outcome , Mutation , Proto-Oncogene Proteins c-met/geneticsABSTRACT
Liver impairment caused by VCM has been linked to irreversible damage such as fibrosis, necrosis, hepatocellular carcinoma, and liver angiosarcoma. However, the ability to detect abnormalities during initial phase have not been achieved so far. Thus, this study aimed to investigate the effect of interleukin 8 (IL-8) and C-X-C chemokines 2 (CXCR2) on screening for a VCM-exposed group (n = 227) from a PVC manufacturing factory compared to a control group (n = 110) in Tianjin City in 2020 with influence factors evaluation. Ambient concentrations of VCM and health archives from 2012 to 2018 were collected for establishing the dose-effect trend. A cross-sectional survey in 2020 was performed to measure TDGA, IL-8, CXCR2, 8-OHdG, SOD, GPX, CAT, MDA, and ROS levels. Results indicated a continuous increased incidence on liver abnormalities despite a fluctuated downward trend in cumulative time-weighted average (CTWA) VCM concentrations over the years. ALT, AST, and AST/ALT ratio all contributed to liver abnormalities that contained fatty liver, liver calcification, and liver cysts, IL-8 and CXCR2 correlated with each other strongly and showed significant associations with oxidative stress markers, even AST/ALT ratio. IL-8 (>1547 µg/m3) or CXCR2 (<139 µg/m3) influenced the AST/ALT ratio through reciprocal interactions under oxidative stress injury, CXCR2 (>222 µg/m3), working years of 21 to 30 (a) and 11 to 20 (a), TDGA (>1.52 mg/L), alcohol consumption, smoking habit, and a less sleeping duration of <4 h per day would also be potential factors affecting the AST/ALT ratio. In conclusion (1) even with decreased VCM concentrations in PVC manufacturing factories liver abnormalities that contained fatty liver, liver calcification, and liver cysts could still occur due to oxidative stress injury with involvement of IL-8 and CXCR2. The status of protective measure and appropriate mask types also play a role; (2) the AST/ALT ratio could be a specific indicator for detecting abnormalities when combined with liver B ultrasonography results before impairment altered from bad to worse; and (3) factors such as definite medication history, fully broken protective facilities, alcohol consumption, less sleeping duration, inappropriate mask types, and longer working years could also influence AST/ALT ratio alterations through complex interactions.
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The objective of this study was to investigate the potential targets and mechanisms of UA in the treatment of PD. The efficacy of UA in PD was assessed through network pharmacology, molecular docking, and experimental methods. Common target protein-protein interaction (PPI) networks were constructed and visualized using Cytoscape. As a result, 9 key genes, namely CASP3, IL6, IL1B, PTGS2, CREB1, TNF, MAPK3, JUN, and CASP8, were selected. Molecular docking simulations were performed using Discovery Studio 2019 to validate the correlation between UA and the core targets. The results demonstrated a favorable binding affinity between UA and CASP8, IL1B, CASP3, TNF, MAPK3 and IL6. In vivo studies showed UA ameliorated motor dysfunction, and UA can significantly increase the protein expression of tyrosine hydroxylase (TH) in PD mice model. In addition, in vitro experiments confirmed that UA effectively reduced the protein expression of CASP8, CASP3 and MAPK3 in PD cell models and suppressed the gene expression of TNF-α, IL-6, and IL-1ß. These findings indicate that the therapeutic effects of UA on PD could be due to its influence on various targets within both the apoptosis and neuroinflammatory signaling pathways. Consequently, this study provides a methodological and theoretical foundation for further elucidating the pharmacological mechanism of UA.
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Isochrysis galbana is valuable in aquaculture due to its production of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). However, achieving high yields of polyunsaturated fatty acids (PUFAs) presents challenges, leading to exploration of innovative approaches. This study investigated the influence of Bacillus jeotgali on the growth of I. galbana and its fatty acid composition. Co-culturing I. galbana with B. jeotgali significantly increased chlorophyll a content and cell abundance, particularly at higher bacterial population densities (algae-to-bacteria ratio of 1:10). Physiological and biochemical analyses found elevated soluble protein content in microalgae co-cultured with B. jeotgali, accompanied by decreased superoxide dismutase (SOD) activity. Fatty acid composition analysis demonstrated a distinctive profile in co-cultured I. galbana, characterized by increased PUFAs, especially EPA and DHA. Gene expression analysis indicated an upregulation of desaturase genes (d4FAD, d5FAD, d6FAD, and d8FAD) associated with PUFA synthesis pathway in I. galbana during co-culturing with B. jeotgali. This study advances our understanding of bacteria-microalgae interactions and presents a promising strategy for enhancing the production of DHA and EPA.
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The electrochemical regeneration of reduced nicotinamide adenine dinucleotide (NADH) using [Rh(Cp*)(bpy)Cl]+ holds significant promise for the industrial synthesis of chiral chemicals. However, challenges persist due to the high consumption of NADH and the limited efficiency of its cyclic regeneration, which currently hinder widespread application. To address these obstacles, based on in-situ growth of 3D ordered metal-organic framework (NU-1000) on the surface of graphite felt, [Rh(Cp*)(bpy)Cl]+ were immobilized on the Zr6 nodes of NU-1000 by solvent-assisted ligand incorporation (SALI), and applied in a flow bioreactor. Moreover, we employ a gas diffusion electrode (GDE) to oxidize H2, providing a clean proton source for the electrochemical regeneration of NADH. Consequently, highly efficient enzymatic electrocatalytic synthesis of L-lactate was achieved when coupled with L-lactate dehydrogenases (LDH) as a model reaction, and the total turnover number (TTN) reached 19600 and 1750 for [Rh(Cp*)(bpy)Cl]+ and NAD+ after 48 h, corresponding to a high turnover frequency (TOF) of 2350 h-1 and 210 h-1 for [Rh(Cp*)(bpy)Cl]+ and NAD+, respectively. This work provides new insights for the construction of efficient enzymatic electrosynthesis systems in industrial production.
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Posttraumatic epilepsy (PTE) is considered to be one of the most severe and enduring outcomes that can arise from traumatic brain injury (TBI). The authors' study aims to create and authenticate a prognostic model for forecasting the PTE occurrence after TBI. The clinical prognostic model was developed in 475 people who had a TBI history in Nanning using a multivariate logistic regression model. The score in the authors' prognostic model participants was subjected to external validation from other cities in Guangxi and assessed its performance with the area under the receiver operating characteristic curve (area under the curve), calibration plots, and decision curve analysis. Six variables were selected to establish the nomogram for PTE, including time, Glasgow Coma Scale, location, cranial imaging (midline shift), intracranial infection, and titanium mesh cranioplasty. The area under the curve was found to be 0.860 in the training cohort and 0.735 in the validation cohort, revealing that the nomogram exhibited a satisfactory level of discriminative ability. The calibration plots exhibited a substantial degree of concordance between the prognostic predictions generated by the nomogram and the observed outcomes in both the training and validation groups. In addition, the decision curve analysis demonstrated the clinical utility of the nomogram. The cutoff value for the training cohort was determined to be 0.381, whereas for the validation cohort, it was 0.380. This suggests that patients with a probability >0.381 should be given special consideration. A prognostic nomogram was formulated and verified to aid health care clinicians in assessing the prognosis of patients with PTE.
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With the successive release of the CONSORT extensions for acupuncture, moxibustion, cupping, and Tuina/massage, this review aims to assess the reporting characteristics and quality of randomized controlled trials (RCTs) based on these specific guidelines. A comprehensive review was conducted by searching multiple databases, including Embase, Ovid MEDLINE(R), All EBM Reviews, AMED, CNKI, VIP Chinese Medical Journal Database, and Wanfang Data, for publications from January 1 to December 31, 2022. Two reviewers independently evaluated the eligibility of the records, extracted predetermined information, and assessed the reporting based on the STRICTA, STRICTOM, STRICTOC, and STRICTOTM checklists. Among the included 387 studies (acupuncture, 213; Tuina/massage, 85; moxibustion, 73; cupping, 16), the overall reporting compliance averaged 56.0%, with acupuncture leading at 62.6%, followed by cupping (60.2%), moxibustion (53.1%), and Tuina/massage (47.9%). About half of the evaluated items showed poor reporting (compliance rate < 65%). Notably, international journals demonstrated significantly higher reporting quality than Chinese journals (P < 0.05). Although acupuncture trials had relatively higher compliance rates, deficiencies persist in reporting non-pharmacological therapies of Chinese medicine, particularly in areas like treatment environment details and provider background information.
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Background: Chemically modified therapeutic mRNAs have gained momentum recently. In addition to commonly used modifications (e.g., pseudouridine), 5moU is considered a promising substitution for uridine in therapeutic mRNAs. Accurate identification of 5-methoxyuridine (5moU) would be crucial for the study and quality control of relevant in vitro-transcribed (IVT) mRNAs. However, current methods exhibit deficiencies in providing quantitative methodologies for detecting such modification. Utilizing the capabilities of Oxford nanopore direct RNA sequencing, in this study, we present NanoML-5moU, a machine-learning framework designed specifically for the read-level detection and quantification of 5moU modification for IVT data. Materials and Methods: Nanopore direct RNA sequencing data from both 5moU-modified and unmodified control samples were collected. Subsequently, a comprehensive analysis and modeling of signal event characteristics (mean, median current intensities, standard deviations, and dwell times) were performed. Furthermore, classical machine learning algorithms, notably the Support Vector Machine (SVM), Random Forest (RF), and XGBoost were employed to discern 5moU modifications within NNUNN (where N represents A, C, U, or G) 5-mers. Results: Notably, the signal event attributes pertaining to each constituent base of the NNUNN 5-mers, in conjunction with the utilization of the XGBoost algorithm, exhibited remarkable performance levels (with a maximum AUROC of 0.9567 in the "AGTTC" reference 5-mer dataset and a minimum AUROC of 0.8113 in the "TGTGC" reference 5-mer dataset). This accomplishment markedly exceeded the efficacy of the prevailing background error comparison model (ELIGOs AUC 0.751 for site-level prediction). The model's performance was further validated through a series of curated datasets, which featured customized modification ratios designed to emulate broader data patterns, demonstrating its general applicability in quality control of IVT mRNA vaccines. The NanoML-5moU framework is publicly available on GitHub (https://github.com/JiayiLi21/NanoML-5moU). Conclusion: NanoML-5moU enables accurate read-level profiling of 5moU modification with nanopore direct RNA-sequencing, which is a powerful tool specialized in unveiling signal patterns in in vitro-transcribed (IVT) mRNAs.
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OBJECTIVE: We aimed to investigate the clinical findings of hospitalized paediatric COVID-19 patients by the end of 2022. METHOD: All confirmed children with COVID-19 infection admitted into Chaozhou Central Hospital during the COVID-19 outbreak from 19 December 2022 to 1 February 2023 were included. Detailed clinical data of those children were evaluated retrospectively. RESULTS: A total of 286 children, ranging in age from 1 month to 13 years old, were diagnosed with SARS-CoV-2 infection. Among these cases, 138 (48.3%) were categorized as mild, 126 (44.0%) as moderate and 22 (7.7%) as severe/critical. Symptoms varied among the children and included fever, upper respiratory tract symptoms, convulsions, sore throat, poor appetite, dyspnoea and gastrointestinal symptoms. Notably, febrile convulsions were observed in 96 (33.6%) patients, while acute laryngitis was documented in 50 (17.5%) cases. Among the severe/critical patients, eight developed multisystem inflammatory syndrome in children (MIS-C), and tragically, one patient's condition worsened and resulted in death. Furthermore, MRI scans revealed abnormal brain signals in six severe/critical patients. The severe/critical group also exhibited more pronounced laboratory abnormalities, including decreased haemoglobin and elevated ALT, AST, LDH and CK levels. CONCLUSIONS: Febrile convulsions and acute laryngitis are frequently observed in children diagnosed with SARS-CoV-2 Omicron infection. Moreover, MIS-C and abnormal neuroimaging appear to be relatively common phenomena in severe/critical cases.