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1.
Int J Nanomedicine ; 19: 7399-7414, 2024.
Article in English | MEDLINE | ID: mdl-39071500

ABSTRACT

Background: Influenza A (H1N1) virus is a highly contagious respiratory disease that causes severe illness and death. Vaccines and antiviral drugs are limited by viral variation and drug resistance, so developing efficient integrated theranostic options appears significant in anti-influenza virus infection. Methods: In this study, we designed and fabricated covalent organic framework (COF) based theranostic platforms (T705@DATA-COF-Pro), which was composed of an RNA polymerase inhibitor (favipiravir, T705), the carboxyl-enriched COF (DATA-COF) nano-carrier and Cy3-labeled single DNA (ssDNA) probe. Results: The multi-porosity COF core provided an excellent micro-environment and smooth delivery for T705. The ssDNA probe coating bound to the nucleic acids of H1N1 selectively, thus controlling drug release and allowing fluorescence imaging. The combination of COF and probe triggered the synergism, promoting drug further therapeutic outcomes. With the aid of T705@DATA-COF-Pro platforms, the H1N1-infected mouse models lightly achieved diagnosis and significantly prolonged survival. Conclusion: This research underscores the distinctive benefits and immense potential of COF materials in nano-preparations for virus infection, offering novel avenues for the detection and treatment of H1N1 virus infection.


Subject(s)
Antiviral Agents , Influenza A Virus, H1N1 Subtype , Metal-Organic Frameworks , Orthomyxoviridae Infections , Theranostic Nanomedicine , Influenza A Virus, H1N1 Subtype/drug effects , Animals , Theranostic Nanomedicine/methods , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Mice , Orthomyxoviridae Infections/drug therapy , Metal-Organic Frameworks/chemistry , Metal-Organic Frameworks/pharmacology , Humans , Amides/chemistry , Amides/pharmacology , Pyrazines/chemistry , Pyrazines/pharmacology , Pyrazines/pharmacokinetics , Pyrazines/therapeutic use , Influenza, Human/drug therapy , Mice, Inbred BALB C , Madin Darby Canine Kidney Cells , Drug Carriers/chemistry , Dogs , Drug Liberation
2.
JOR Spine ; 7(3): e1354, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39071860

ABSTRACT

Background: Hypertrophy ligamentum flavum is a prevalent chronic spinal condition that affects middle-aged and older adults. However, the molecular pathways behind this disease are not well comprehended. Objective: The objective of this work is to implement bioinformatics techniques in order to identify crucial biological markers and immune infiltration that are linked to hypertrophy ligamentum flavum. Further, the study aims to experimentally confirm the molecular mechanisms that underlie the hypertrophy ligamentum flavum. Methods: The corresponding gene expression profiles (GSE113212) were selected from a comprehensive gene expression database. The gene dataset for hypertrophy ligamentum flavum was acquired from GeneCards. A network of interactions between proteins was created, and an analysis of functional enrichment was conducted using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) databases. An study of hub genes was performed to evaluate the infiltration of immune cells in patient samples compared to tissues from the control group. Finally, samples of the ligamentum flavum were taken with the purpose of validating the expression of important genes in a clinical setting. Results: Overall, 27 hub genes that were differently expressed were found through molecular biology. The hub genes were found to be enriched in immune response, chemokine-mediated signaling pathways, inflammation, ossification, and fibrosis processes, as demonstrated by GO and KEGG studies. The main signaling pathways involved include the TNF signaling pathway, cytokine-cytokine receptor interaction, and TGF-ß signaling pathway. An examination of immunocell infiltration showed notable disparities in B cells (naïve and memory) and activated T cells (CD4 memory) between patients with hypertrophic ligamentum flavum and the control group of healthy individuals. The in vitro validation revealed markedly elevated levels of ossification and fibrosis-related components in the hypertrophy ligamentum flavum group, as compared to the normal group. Conclusion: The TGF-ß signaling pathway, TNF signaling pathway, and related hub genes play crucial roles in the progression of ligamentum flavum hypertrophic. Our study may guide future research on fibrosis of the ligamentum flavum.

3.
Viruses ; 16(7)2024 Jul 02.
Article in English | MEDLINE | ID: mdl-39066231

ABSTRACT

Foodborne diseases are major public health problems globally. Metagenomics has emerged as a widely used tool for pathogen screening. In this study, we conducted an updated Tn5 transposase-assisted RNA/DNA hybrid co-tagmentation (TRACE) library construction approach. To address the detection of prevalent known foodborne viruses and the discovery of unknown pathogens, we employed both specific primers and oligo-T primers during reverse transcription. The method was validated using clinical samples confirmed by RT-qPCR and compared with standard RNA-seq library construction methods. The mapping-based approach enabled the retrieval of nearly complete genomes (>95%) for the majority of virus genome segments (86 out of 88, 97.73%), with a mean coverage depth of 21,494.53× (ranging from 77.94× to 55,688.58×). Co-infection phenomena involving prevalent genotypes of Norovirus with Astrovirus and Human betaherpesvirus 6B were observed in two samples. The updated TRACE-seq exhibited superior performance in viral reads percentages compared to standard RNA-seq library preparation methods. This updated method has expanded its target pathogens beyond solely Norovirus to include other prevalent foodborne viruses. The feasibility and potential effectiveness of this approach were then evaluated as an alternative method for surveilling foodborne viruses, thus paving the way for further exploration into whole-genome sequencing of viruses.


Subject(s)
Foodborne Diseases , Genome, Viral , Metagenomics , Transposases , Transposases/genetics , Transposases/metabolism , Foodborne Diseases/virology , Humans , Metagenomics/methods , Virome/genetics , RNA, Viral/genetics , Norovirus/genetics , Norovirus/classification , Gene Library , DNA, Viral/genetics , Viruses/genetics , Viruses/classification
4.
Plants (Basel) ; 13(14)2024 Jul 14.
Article in English | MEDLINE | ID: mdl-39065462

ABSTRACT

Lycium barbarum has been widely planted in arid and semi-arid areas due to its drought-resistant ability, which is of great economic value as a medicinal and edible homology plant. In this study, the metabolome of the L. barbarum variety "Ningqi 7" under different drought stress conditions was compared and analyzed by the non-targeted UPLC-MS (ultra-high performance liquid chromatography with mass spectrometry) technique. The results showed that drought stress significantly decreased the water content of leaves, increased the activity of antioxidant enzymes in plants, and up-regulated the metabolites and pathways involved in osmoregulation, antioxidant stress, energy metabolism, and signal transduction. Under moderate drought (40-45% FC), L. barbarum accumulated osmoregulatory substances mainly through the up-regulation of the arginine metabolism pathway. At the same time, phenylalanine metabolism and cutin, suberine, and wax biosynthesis were enhanced to improve the antioxidant capacity and reduce water loss. However, in severe drought (10-15% FC), L. barbarum shifted to up-regulate purine metabolism and lysine degradation and redistributed energy and nitrogen resources. In addition, vitamin B6 metabolism was significantly upregulated in both groups of stress levels, playing a key role in antioxidant and growth regulation. These observations delineate the metabolic adaptations of L. barbarum "Ningqi 7" in response to drought stress.

6.
J Clin Anesth ; 97: 111543, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38954872

ABSTRACT

STUDY OBJECTIVE: We conducted this double-blinded randomized controlled trial to examine whether the combination of dexamethasone and dexmedetomidine as adjuvants of transversus abdominis plane (TAP) block could improve analgesia efficacy and duration for gastric cancer patients. DESIGN: Randomized controlled trial. SETTING: The preoperative area, operating room, postanesthesia recovery room and bed ward. PATIENTS: A total of 312 adult patients (104 per group) with gastric cancer were included. INTERVENTIONS: Patients received bilateral subcostal TAP block with three different anesthetics (60 ml 0.25% ropivacaine added with 10 mg dexamethasone and 1 µg·kg-1 dexmedetomidine [A] or 10 mg dexamethasone [B] or 1 µg·kg-1 dexmedetomidine [C]). MEASUREMENTS: The primary outcome was the incidence of moderate-to-severe pain 24 h on movement. Secondary outcomes included incidence of moderate-to-severe pain, pain score, opioids use, recovery quality and adverse events. MAIN RESULTS: The incidence of moderate-to-severe pain on movement 24 h postoperatively of group A was significantly lower than group B (45.19% vs 63.46%; RR 0.71; 95% CI, 0.55 to 0.92) and group C (45.19% vs 73.08%, RR 0.62; 95% CI, 0.49 to 0.79). The median moving pain scores decreased significantly at 24 h (3.00 [3.00,5.00] vs 4.00 [3.00,6.00] vs 4.00 [3.00,5.00]; P < 0.001). There were significant differences in the opioids consumption within the first 24 h (27.5 [17.0,37.2] vs 30.0 [20.0,42.0] vs 32.0 [25.0,44.0] mg; P = 0.01) and the duration to first rescue analgesia (65.5 ± 26.7 vs 45.9 ± 34.5 vs 49.2 ± 27.2 h; P = 0.04). CONCLUSIONS: The combination with dexamethasone and dexmedetomidine as adjuvants for TAP block reduced the incidence of moderate-to-severe pain and pain score both on movement and at rest at 24 h with prolonged duration to first rescue analgesia after gastric cancer surgery. TRIAL REGISTRATION NUMBER: ChiCTR2000037981.

7.
HPB (Oxford) ; 2024 Jun 16.
Article in English | MEDLINE | ID: mdl-38955633

ABSTRACT

BACKGROUND: Minimally invasive hepatectomy for difficult lesions located in posterosuperior segments (segments I, IVa, VII and VIII) remains challenging. The value of robotic liver resection (RLR) compared with laparoscopic liver resection (LLR) for posterosuperior segments is controversial. Therefore, we performed this meta-analysis to validate the safety and efficacy of RLR in posterosuperior segments. METHODS: The Medline, Embase, Web of Science, and Cochrane Library electronic databases were searched to identify available research published up to October 2023. Statistical analysis was performed with RevMan software version 5.3. RESULTS: Six studies with a total of 2289 patients (RLR: n = 749; LLR: n = 1540) were included in this meta-analysis. The RLR group had less intraoperative blood loss (WMD = -119.54 ml, 95% CI: -178.89 to -60.19, P < 0.0001), fewer blood transfusions (OR = 0.56, 95% CI: 0.39 to 0.80, P = 0.001), a lower conversion rate (OR = 0.37, 95% CI: 0.23 to 0.61, P < 0.0001), and a shorter operative time (WMD = -27.16 min, 95% CI: -35.95 to -18.36, P < 0.00001). DISCUSSION: Compared with LLR, RLR for lesions in the posterosuperior segments could be safe and effective, and it has superior surgical outcomes.

9.
Ren Fail ; 46(2): 2376929, 2024 Dec.
Article in English | MEDLINE | ID: mdl-39022902

ABSTRACT

The transient receptor potential canonical 6 (TRPC6) channel, a nonselective cation channel that allows the passage of Ca2+, plays an important role in renal diseases. TRPC6 is activated by Ca2+ influx, oxidative stress, and mechanical stress. Studies have shown that in addition to glomerular diseases, TRPC6 can contribute to renal tubular disorders, such as acute kidney injury, renal interstitial fibrosis, and renal cell carcinoma (RCC). However, the tubule-specific physiological functions of TRPC6 have not yet been elucidated. Its pathophysiological role in ischemia/reperfusion (I/R) injury is debatable. Thus, TRPC6 may have dual roles in I/R injury. TRPC6 induces renal fibrosis and immune cell infiltration in a unilateral ureteral obstruction (UUO) mouse model. Additionally, TRPC6 overexpression may modify G2 phase transition, thus altering the DNA damage checkpoint, which can cause genomic instability and RCC tumorigenesis and can control the proliferation of RCC cells. This review highlights the importance of TRPC6 in various conditions of the renal tubular system. To better understand certain renal disorders and ultimately identify new therapeutic targets to improve patient care, the pathophysiology of TRPC6 must be clarified.


Subject(s)
TRPC6 Cation Channel , Humans , TRPC6 Cation Channel/metabolism , TRPC6 Cation Channel/genetics , Animals , Kidney Tubules/pathology , Kidney Tubules/metabolism , Acute Kidney Injury/metabolism , Acute Kidney Injury/etiology , Carcinoma, Renal Cell/metabolism , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/pathology , Reperfusion Injury/metabolism , Fibrosis , Kidney Neoplasms/metabolism , Kidney Neoplasms/pathology , Kidney Neoplasms/genetics , Mice , TRPC Cation Channels/metabolism , TRPC Cation Channels/genetics , Oxidative Stress , Kidney Diseases/metabolism , Kidney Diseases/etiology
10.
World J Microbiol Biotechnol ; 40(9): 268, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39007987

ABSTRACT

Bacillus subtilis is a widespread Gram-positive facultative aerobic bacterium that is recognized as generally safe. It has shown significant application value and great development potential in the animal farming industry. As a probiotic, it is frequently used as a feed growth supplement to effectively replace antibiotics due to its favourable effects on regulating the intestinal flora, improving intestinal immunity, inhibiting harmful microorganisms, and secreting bioactive substances. Consequently, the gut health and disease resistance of farmed animals can be improved. Both vegetative and spore forms of B. subtilis have also been utilized as vaccine carriers for delivering the antigens of infectious pathogens for over a decade. Notably, its spore form is regarded as one of the most prospective for displaying heterologous antigens with high activity and stability. Previously published reviews have predominantly focused on the development and applications of B. subtilis spore surface display techniques. However, this review aims to summarize recent studies highlighting the important role of B. subtilis as a probiotic and vaccine carrier in maintaining animal health. Specifically, we focus on the beneficial effects and underlying mechanisms of B. subtilis in enhancing disease resistance among farmed animals as well as its potential application as mucosal vaccine carriers. It is anticipated that B. subtilis will assume an even more prominent role in promoting animal health with in-depth research on its characteristics and genetic manipulation tools.


Subject(s)
Bacillus subtilis , Probiotics , Probiotics/administration & dosage , Bacillus subtilis/genetics , Animals , Spores, Bacterial/immunology , Gastrointestinal Microbiome , Disease Resistance , Vaccines/immunology
11.
Front Pharmacol ; 15: 1408304, 2024.
Article in English | MEDLINE | ID: mdl-38989153

ABSTRACT

Introduction: Pycnogenol (PYC), a standardized extract from French maritime pine, has traditionally been used to treat inflammation. However, its primary active components and their mechanisms of action have not yet been determined. Methods: This study employed UPLC-MS/MS (Ultra-high performance liquid chromatography-tandem mass spectrometry) and network pharmacology to identify the potential active components of PYC and elucidate their anti-inflammatory mechanisms by cell experiments. Results: 768 PYC compounds were identified and 19 anti-inflammatory compounds were screened with 85 target proteins directly involved in the inflammation. PPI (protein-protein interaction) analysis identified IL6, TNF, MMP9, IL1B, AKT1, IFNG, CXCL8, NFKB1, CCL2, IL10, and PTGS2 as core targets. KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis suggested that the compound in PYC might exert anti-inflammatory effects through the IL17 and TNF signal pathways. Cell experiments determined that PYC treatment can reduce the expression of IL6 and IL1ß to relieve inflammation in LPS (lipopolysaccharide)-induced BV2 cells. Conclusion: PYC could affect inflammation via multi-components, -targets, and -mechanisms.

12.
Lancet Reg Health West Pac ; 48: 101122, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38993541

ABSTRACT

Background: Furmonertinib showed superior efficacy compared with gefitinib as first-line therapy in patients with epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) in the FURLONG study. Here we present prespecified secondary endpoints of patient-reported outcomes (PRO). Methods: In this multicentre, double-blind, double-dummy, randomised phase 3 study, patients were 1:1 randomly assigned to receive furmonertinib 80 mg once daily or gefitinib 250 mg once daily. PROs assessed by the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 and Quality-of-Life Questionnaire Lung Cancer 13 were analysed using a mixed model for repeated measures and time-to-event analyses. A difference in score of 10 points or more was deemed clinically relevant. Findings: Three hundred and fifty-seven patients (furmonertinib group, n = 178; gefitinib group, n = 179) received at least one dose of the study drug, all of whom completed at least one PRO assessment. Statistically significant difference of overall score changes from baseline favoured furmonertinib in physical functioning (between-group difference 2.14 [95% CI 0.25-4.04], p = 0.027), nausea/vomiting (-1.56 [95% CI -2.62 to -0.49], p = 0.004), appetite loss (-2.24 [95% CI -4.26 to -0.23], p = 0.029), diarrhoea (-3.36 [95% CI -5.19 to -1.54], p < 0.001), alopecia (-2.62 [95% CI -4.54 to -0.71], p = 0.007), and pain in other parts (-4.55 [95% CI -7.37 to -1.74], p = 0.002), but not reached clinical relevance. Time to deterioration in physical functioning (hazard ratio 0.63 [95% CI 0.42-0.94], p = 0.021), cognitive functioning (0.73 [95% CI 0.54-0.98], p = 0.034), nausea/vomiting (0.64 [95% CI 0.41-0.99], p = 0.042), appetite loss (0.63 [95% CI 0.43-0.92], p = 0.016), diarrhoea (0.63 [95% CI 0.46-0.85], p = 0.002), dyspnoea (0.72 [95% CI 0.53-0.98], p = 0.034), cough (0.67 [95% CI 0.44-1.00], p = 0.049), dysphagia (0.54 [95% CI 0.35-0.83], p = 0.004), and alopecia (0.62 [95% CI 0.42-0.90], p = 0.012) was longer with furmonertinib versus gefitinib. Interpretation: In patients with locally advanced or metastatic EGFR mutation-positive NSCLC, furmonertinib showed improved scores and delayed deterioration in several functioning and symptoms compared to gefitinib. Funding: Shanghai Allist Pharmaceutical Technology Co., Ltd and the National Science and Technology Major Project for Key New Drug Development (2017ZX09304015).

13.
Ecotoxicol Environ Saf ; 282: 116704, 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38996646

ABSTRACT

Hyperaccumulators are the material basis and key to the phytoremediation of heavy metal contaminated soils. Conventional methods for screening hyperaccumulators are highly dependent on the time- and labor-consuming sampling and chemical analysis. In this study, a novel spectral approach assisted with multi-task deep learning was proposed to streamline accumulating ecotype screening, heavy metal stress discrimination, and heavy metals quantification in plants. The significant Cd/Zn co-hyperaccumulator Sedum alfredii and its non-accumulating ecotype were stressed by Cd, Zn, and Pb. Spectral images of leaves were rapidly acquired by hyperspectral imaging. The self-designed deep learning architecture was composed of a shallow network (ENet) for accumulating ecotype identification, and a multi-task network (HMNet) for heavy metal stress type and accumulation prediction simultaneously. To further assess the robustness of the networks, they were compared with conventional machine learning models (i.e., partial least squares (PLS) and support vector machine (SVM)) on a series of evaluation metrics of classification, multi-label classification, and regression. S. alfredii with heavy metals accumulation capability was identified by ENet with 100 % accuracy. HMNet reduced overfitting and outperformed machine learning models with the average exact match ratio (EMR) of heavy metal stress discrimination increased by 7.46 %, and residual prediction deviations (RPD) of heavy metal concentrations prediction increased by 53.59 %. The method succeeded in rapidly and accurately discriminating heavy metal stress with EMRs over 91 % and accuracies over 96 %, and in predicting heavy metals accumulation with an average RPD of 3.29 for Zn, 2.57 for Cd, and 2.53 for Pb, indicating the satisfactory practicability and potential for sensing heavy metals accumulation. This study provides a relatively novel spectral method to facilitate hyperaccumulator screening and heavy metals accumulation prediction in the phytoremediation process.

14.
Mol Neurobiol ; 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38976127

ABSTRACT

Temporomandibular joint osteoarthritis (TMJOA) is a severe form of temporomandibular joint disorders (TMD), and orofacial inflammatory allodynia is one of its common symptoms which lacks effective treatment. N-methyl-D-aspartate receptor (NMDAR), particularly its subtypes GluN2A and GluN2B, along with gap junctions (GJs), are key players in the mediation of inflammatory pain. However, the precise regulatory mechanisms of GluN2A, GluN2B, and GJs in orofacial inflammatory allodynia during TMJ inflammation still remain unclear. Here, we established the TMJ inflammation model by injecting Complete Freund's adjuvant (CFA) into the TMJ and used Cre/loxp site-specific recombination system to conditionally knock out (CKO) GluN2A and GluN2B in the trigeminal ganglion (TG). Von-frey test results indicated that CFA-induced mechanical allodynia in the TMJ region was relieved in GluN2A and GluN2B deficient mice. In vivo, CFA significantly up-regulated the expression of GluN2A and GluN2B, Gjb1, Gjb2, Gjc2 and Panx3 in the TG, and GluN2A and GluN2B CKO played different roles in mediating the expression of Gjb1, Gjb2, Gjc2 and Panx3. In vitro, NMDA up-regulated the expression of Gjb1, Gjb2, Gjc2 and Panx3 in satellite glial cells (SGCs) as well as promoted the intercellular communication between SGCs, and GluN2A and GluN2B knocking down (KD) altered the expression and function differently. NMDAR regulated Gjb1 and Panx3 through ERK1/2 pathway, and mediated Gjb2 and Gjc2 through MAPK, PKA, and PKC intracellular signaling pathways. These findings shed light on the distinct functions of GluN2A and GluN2B in mediating peripheral sensitization induced by TMJ inflammation in the TG, offering potential therapeutic targets for managing orofacial inflammatory allodynia.

15.
Cancer Med ; 13(13): e7342, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38967142

ABSTRACT

OBJECTIVE: Our study aims to evaluate the predictive accuracy of functional liver remnant volume (FLRV) in post-hepatectomy liver failure (PHLF) among surgically-treated jaundiced patients with hilar cholangiocarcinoma (HCCA). METHODS: We retrospectively reviewed surgically-treated jaundiced patients with HCCA between June, 2000 and June, 2018. The correlation between FRLV and PHLF were analyzed. The optimal cut off value of FLRV in jaundiced HCCA patients was also identified and its impact was furtherly evaluated. RESULTS: A total of 224 jaundiced HCCA patients who received a standard curative resection (43 patients developed PHLF) were identified. Patients with PHLF shared more aggressive clinic-pathological features and were generally in a more advanced stage than those without PHLF. An obvious inconsistent distribution of FLRV in patients with PHLF and those without PHLF were detected. FLRV (continuous data) had a high predictive accuracy in PHLF. The newly-acquired cut off value (FLRV = 53.5%, sensitivity = 81.22%, specificity = 81.4%) showed a significantly higher predictive accuracy than conventional FLRV cut off value (AUC: 0.81 vs. 0.60, p < 0.05). Moreover, patients with FLRV lower than 53.5% also shared a significantly higher major morbidity rate as well as a worse prognosis, which were not detected for FLRV of 40%. CONCLUSION: For jaundiced patients with HCCA, a modified FLRV of 53.5% is recommended due to its great impact on PHLF, as well as its correlation with postoperative major morbidities as well as overall prognosis, which might help clinicians to stratify patients with different therapeutic regimes and outcomes. Future multi-center studies for training and validation are required for further validation.


Subject(s)
Bile Duct Neoplasms , Hepatectomy , Jaundice , Klatskin Tumor , Liver Failure , Humans , Male , Hepatectomy/adverse effects , Female , Middle Aged , Klatskin Tumor/surgery , Klatskin Tumor/pathology , Retrospective Studies , Bile Duct Neoplasms/surgery , Bile Duct Neoplasms/pathology , Liver Failure/etiology , Liver Failure/prevention & control , China/epidemiology , Jaundice/etiology , Liver/surgery , Liver/pathology , Aged , Postoperative Complications/etiology , Postoperative Complications/prevention & control , Postoperative Complications/epidemiology , Prognosis , Adult , Organ Size
16.
MedComm (2020) ; 5(8): e627, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39015557

ABSTRACT

Minimal hepatic encephalopathy (MHE) has a substantial impact on the clinical outcomes and quality of life (QOL) of patients with cirrhosis. However, timely diagnosis and intervention are challenging due to sophisticated diagnostic methods. In this study, 673 healthy controls and 905 patients with cirrhosis were screened, and 660 healthy controls and 757 patients with cirrhosis, divided into the test (292 patients) and validation (465 patients) cohort, were analyzed after screening. A diagnostic model of the Stroop test (Stroop-CN) was constructed by multivariate linear regression based on the results of healthy controls. The prevalence of MHE and the comparison results with psychometric hepatic encephalopathy score through the Stroop-CN model were stable in the test and validation cohorts. Moreover, the prevalence of MHE remained significantly higher in patients with worse disease conditions marked as high Child-Pugh grades and the Model for End-stage Liver Disease and Sodium (MELD-Na) scores in the test and validation cohort. The EuroQol 5-D questionnaire revealed that patients with MHE had a worse QOL than those without MHE both in the test and validation cohort. In conclusion, an easy and practical Stroop-CN model for MHE diagnosis based on the EncephalApp is established. It is found that a considerable number of Chinese patients with cirrhosis experience MHE, which significantly impacts their QOL.

17.
Expert Opin Drug Saf ; : 1-10, 2024 Jul 18.
Article in English | MEDLINE | ID: mdl-39016171

ABSTRACT

BACKGROUND: Osteoporosis (OP), characterized by low bone mass and increased fracture risk, is a prevalent skeletal disorder. Teriparatide (TP) and abaloparatide (ABL) are anabolic agents that may reduce fracture incidence, but their impact on musculoskeletal and connective tissue disorders (MCTD) risk is uncertain. RESEARCH DESIGN AND METHODS: A retrospective, observational disproportionality analysis was conducted utilizing FAERS data from Q1 2004 to Q3 2023, where TP or ABL was identified as the primary suspect drug. Multiple data mining algorithms, including reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS), were employed to detect MCTD safety signals. RESULTS: A total of 366,747 TP-related and 422,377 ABL-related cases were identified, predominantly among female patients aged ≥45 years. The top specific AEs involved musculoskeletal, connective tissue, and administration site disorders. Comparative analysis revealed a higher frequency of AEs related to the nervous, cardiovascular, and gastrointestinal systems for ABL compared to TP. Both drugs exhibited strong signals for arthralgia, limb pain, back pain, muscle spasms, bone pain, muscle pain, and muscle weakness. CONCLUSION: The analysis suggests a potential MCTD risk with TP and ABL treatment in OP patients, highlighting the need for AE monitoring and management in clinical practice. This contributes to a better understanding of the safety profiles of these anabolic medications.

18.
Int J Biol Macromol ; : 133729, 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-39019699

ABSTRACT

Microfibrillated cellulose (MFC) as an attractive green bio-based material has attracted widespread attention in recent years due to its non-toxicity, degradability, excellent performance, and high aspect ratio. In this study, the g-C3N5 with a high nitrogen/carbon ratio was prepared as a catalyst through the self-polymerization of a nitrogen-rich precursor. The triazole groups at the edges of g-C3N5 were proven to exhibit strong adsorption to biomass and strong alkalinity. In a low-acidic aqueous system with g-C3N5, MFC with diameters of 100-200 nm and lengths up to 100 µm was fabricated from various biomasses within 5 min under microwave radiation. The ultimate yield of the MFC produced from viscose reached 90 %. Young's modulus of the MFC reaches 3.7 GPa. This work provides a particular method with high efficiency to prepare MFC with excellent properties from biomass by chemical method.

19.
Microbiol Spectr ; : e0021924, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39012118

ABSTRACT

Interactions between photosynthetic microalgae and bacteria impact the physiology of both partners, which influence the fitness and ecological trajectories of each partner in an environmental context-dependent manner. Thermal tolerance of Chlamydomonas reinhardtii can be enhanced through a mutualistic interaction with vitamin B12 (cobalamin)-producing Sinorhizobium meliloti. Here, we used label-free quantitative proteomics to reveal the metabolic networks altered by the interaction under normal and high temperatures. We created a scenario where the growth of Sinorhizobium requires carbon provided by Chlamydomonas for growth in co-cultures, and survival of Chlamydomonas under high temperatures relies on cobalamin and possibly other metabolites produced by Sinorhizobium. Differential abundance analysis identified proteins produced by each partner in co-cultures compared to mono-cultures at each temperature. Proteins involved in cobalamin production by Sinorhizobium increased in the presence of Chlamydomonas under elevated temperatures, whereas in Chlamydomonas, there was an increase in cobalamin-dependent methionine synthase and certain proteins associated with methylation reactions. Co-cultivation and heat stress strongly modulated the central metabolism of both partners as well as various transporters that could facilitate nutrient cross-utilization. Co-cultivation modulated expression of various components of two- or one-component signal transduction systems, transcriptional activators/regulators, or sigma factors, suggesting complex regulatory networks modulate the interaction in a temperature-dependent manner. Notably, heat and general stress-response and antioxidant proteins were upregulated in co-cultures, suggesting that the interaction is inherently stressful to each partner despite the benefits of mutualism. Our results shed insight into the metabolic tradeoffs required for mutualism and how metabolic networks are modulated by elevated temperature. IMPORTANCE: Photosynthetic microalgae are key primary producers in aquatic ecosystems, playing an important role in the global carbon cycle. Nearly every alga lives in association with a diverse community of microorganisms that influence each other and their metabolic activities or survival. One chemical produced by bacteria that influence algae is vitamin B12, an enzyme cofactor used for a variety of metabolic functions. The alga Chlamydomonas reinhardtii benefits from vitamin B12 produced by Sinorhizobium meliloti by producing the amino acid methionine under high temperatures which are required for Chlamydomonas thermotolerance. Yet, our understanding of this interaction under normal and stressful temperatures is poor. Here, we used quantitative proteomics to identify differentially expressed proteins to reveal metabolic adjustments made by Chlamydomonas and Sinorhizobium that could facilitate this mutualism. These findings will enhance our understanding of how photosynthetic algae and their associated microbiomes will respond as global temperatures increase.

20.
Plant Sci ; 347: 112174, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38960071

ABSTRACT

Common flue-cured tobacco (Nicotiana tabacum L.) primarily accumulates nicotine, and its flue-cured leaves exhibit a lemon appearance. In contrast, a spontaneous cherry-red variant (CR60) primarily accumulates nornicotine, accompanied by distinctive red dapples on the cured leaves. In this study, suppression of conversion of nicotine to nornicotine by genome editing resulted in decreased nornicotine and N-acyl nornicotines (NacNNs), and the subsequent disappearance of red dapples in CR60. Conversely, overexpression of CYP82E4 increased nornicotine and NacNNs accumulation, inducing a red dapple phenotype in common tobacco. Notably, nicotine conversion triggered significant alterations in leaf total sugars, alkaloids, and nitrogens. Metabolome analyses using 1352 identified compounds indicated nicotine conversion dramatically affected the entire metabolic network and induced unique metabolic responses across diverse genetic backgrounds. Further WGCNA analysis revealed that nicotine conversion caused substantial contents variation of alkaloids, flavonoids and amino acids and derivatives in cured leaves. Overall, this research provides valuable insights into the mechanisms underlying red dapple formation in cherry-red tobacco, elucidating profound influence of nicotine conversion on entire metabolic network.

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