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1.
J Foot Ankle Surg ; 2024 Sep 06.
Article in English | MEDLINE | ID: mdl-39245431

ABSTRACT

Distal third tibial fractures associated with anterior soft tissue compromise are a predictor of more complications and poor prognosis. The study aimed to introduce the treatment of such fractures through the posterolateral approach. From March 2020 and January 2022, 32 patients with distal third tibial fractures were plated through the posterolateral approach due to concurrent closed anterior soft tissue compromise. There were 30 male and 2 female patients with the mean age of 33 years (range, 20-53 years). The reduction quality of diaphyseal fractures was good (n=30) and acceptable (n=2). The reduction quality of articular fragments was anatomic (n=21), good (n=6), and fair (n=1). All anterior soft tissue injuries healed without surgical intervention. Follow-ups lasted 28 months (range, 25-34 months). The mean dorsiflexion of the injured and uninjured ankles were 17.8°±5.4° and 24.5°±6.6°, respectively (P<0.05). The mean plantar flexion of the ankles were 42°±8.8° and 46°±12.9°, respectively (P>0.05). The mean inversion of the injured and uninjured ankles were 15°±13.3° and 19°±12.4°, respectively (P<0.05). The mean eversion of the injured and uninjured ankles were 27.8°±16.9° and 32.9°±14.3°, respectively (P>0.05). The mean American Orthopaedic Foot and Ankle score was 90 (range, 68-100). Distal third tibial fractures with anterior soft tissue compromise can be plated through the posterolateral approach, resulting in good functional outcomes and minimum complications. LEVEL OF EVIDENCE: Therapeutic study, Level IV.

2.
Chem Commun (Camb) ; 60(75): 10326-10329, 2024 Sep 16.
Article in English | MEDLINE | ID: mdl-39222054

ABSTRACT

Transition-metal hydroxides are a category of earth-abundant and stable electrocatalysts for energy storage and conversion devices involving sluggish oxygen evolution reaction (OER). Understanding dynamic evolution at the solid/liquid interface of transition-metal hydroxides is crucial for the rational design of high-performance OER electrocatalysts. This study implemented in situ electrochemical atomic force microscopy (EC-AFM) to directly image the dynamic structural evolution of α-Co(OH)2 platelets during the electrochemical OER. Reconstruction of α-Co(OH)2, accompanied by ion insertion from the electrolyte, results in a volume expansion, which can be well confirmed from the X-ray diffraction patterns. Our findings are important for the fundamental understanding of transition-metal hydroxide oxygen-evolution catalysts, illustrating the dynamic nature of Co-based nanostructures under electrochemical conditions.

3.
Br J Pharmacol ; 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-39238235

ABSTRACT

BACKGROUND AND PURPOSE: The emerging antidepressant effects of ketamine have inspired tremendous interest in its underlying neurobiological mechanisms, although the involvement of 5-HT in the antidepressant effects of ketamine remains unclear. EXPERIMENTAL APPROACH: The chronic restraint stress procedure was performed to induce depression-like behaviours in mice. OFT, FST, TST, and NSFT tests were used to evaluate the antidepressant-like effects of ketamine. Tph2 knockout or depletion of 5-HT by PCPA and 5,7-DHT were used to manipulate the brain 5-HT system. ELISA and fibre photometry recordings were used to measure extracellular 5-HT levels in the brain. KEY RESULTS: 60 min after injection, ketamine (10 mg·kg-1, i.p.) produced rapid antidepressant-like effects and increased brain 5-HT levels. After 24 h, ketamine significantly reduced immobility time in TST and FST tests and increased brain 5-HT levels, as measured by ELISA and fibre photometry recordings. The sustained (24 h) but not rapid (60 min) antidepressant-like effects of ketamine were abrogated by PCPA and 5,7-DHT, or by Tph2 knockout. Importantly, NBQX (10 mg·kg-1, i.p.), an AMPA receptor antagonist, significantly inhibited the effect of ketamine on brain 5-HT levels and abolished the sustained antidepressant-like effects of ketamine in naïve or CRS-treated mice. CONCLUSION AND IMPLICATIONS: This study confirms the requirement of serotonergic neurotransmission for the sustained antidepressant-like effects of ketamine, which appears to involve AMPA receptors, and provides avenues to search for antidepressant pharmacological targets.

4.
Sci Rep ; 14(1): 21286, 2024 09 12.
Article in English | MEDLINE | ID: mdl-39266741

ABSTRACT

In sweet potato, rational nitrogen (N) assimilation and distribution are conducive to inhibiting vine overgrowth. Nitrate (NO3-) is the main N form absorbed by roots, and cultivar is an important factor affecting N utilization. Herein, a hydroponic experiment was conducted that included four NO3- concentrations of 0 (N0), 4 (N1), 8 (N2) and 16 (N3) mmol L-1 with two cultivars of Jishu26 (J26, N-sensitive) and Xushu32 (X32, N-tolerant). For J26, with increasing NO3- concentrations, the root length and root surface area significantly decreased. However, no significant differences were observed in these parameters for X32. Higher NO3- concentrations upregulated the expression levels of the genes that encode nitrate reductase (NR2), nitrite reductase (NiR2) and nitrate transporter (NRT1.1) in roots for both cultivars. The trends in the activities of NR and NiR were subject to regulation of NR2 and NiR2 transcription, respectively. For both cultivars, N2 increased the N accumulated in leaves, growth points and roots. For J26, N3 further increased the N accumulation in these organs. Under higher NO3- nutrition, compared with X32, J26 exhibited higher expression levels of the NiR2, NR2 and NRT1.1 genes, a higher influx NO3- rate in roots, and higher activities of NR and NiR in leaves and roots. Conclusively, the regulated effects of NO3- supplies on root growth and NO3- utilization were more significant for J26. Under high NO3- conditions, J26 exhibited higher capacities of NO3- absorption and distributed more N in leaves and in growth points, which may contribute to higher growth potential in shoots and more easily cause vine overgrowth.


Subject(s)
Gene Expression Regulation, Plant , Ipomoea batatas , Nitrates , Nitrogen , Plant Roots , Nitrates/metabolism , Ipomoea batatas/metabolism , Ipomoea batatas/genetics , Ipomoea batatas/growth & development , Plant Roots/metabolism , Plant Roots/growth & development , Plant Roots/genetics , Nitrogen/metabolism , Nitrate Reductase/metabolism , Nitrate Reductase/genetics , Plant Leaves/metabolism , Plant Leaves/growth & development , Plant Leaves/genetics , Nitrate Transporters , Hydroponics , Plant Proteins/metabolism , Plant Proteins/genetics , Nitrite Reductases/metabolism , Nitrite Reductases/genetics , Anion Transport Proteins/metabolism , Anion Transport Proteins/genetics
5.
Physiol Rep ; 12(16): e70014, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39164207

ABSTRACT

Physical performance in hemodialysis patients declines and serves as a cardiovascular disease (CVD) incidence and mortality predictor. However, lower extremity function's role remains unclear. This study aimed to quantify the association between lower extremity function and CVD risk in hemodialysis patients. This was a multicenter cross-sectional study enrolling 868 participants (532 males, 336 females) from seven hemodialysis centers in Shanghai, China. Patients were divided into three groups per lower extremity function, evaluated by short physical performance battery (SPPB) scores: 0-6, 7-9, and 10-12. Upper extremity function was quantified through grip strength assessment. CVD risk was assessed using the Framingham Risk Score. Approximately 35% of hemodialysis patients had impaired lower extremity function (SPPB score < 10). Participants with high SPPB scores had stronger handgrip and lower Framingham CVD risk scores than those with low and moderate SPPB scores (p < 0.05). After adjusting clinical confounders, SPPB was independently associated with CVD risk, as a categorized variable (odds ratio: 0.577, 95% confidence interval [CI]: 0.388-0.857, p = 0.006) and as a continuous variable (odds ratio: 0.858, 95% CI: 0.772-0.953, p = 0.004). An SPPB score < 10 predicted an increased CVD risk (area under curve: 0.649, 95% CI: 0.599-0.699, p < 0.001). Causality between physical performance and CVD risk was not considered. Some upper limb results may not be generalizable to peritoneal dialysis and kidney transplant patients. Lower extremity function was significantly associated with CVD risk in hemodialysis patients. Further studies are needed to explore the long-term relationship between lower extremity function and CVD risk.


Subject(s)
Cardiovascular Diseases , Lower Extremity , Renal Dialysis , Humans , Male , Female , Renal Dialysis/adverse effects , Middle Aged , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Cardiovascular Diseases/physiopathology , Cross-Sectional Studies , Aged , Hand Strength , Adult , Heart Disease Risk Factors , Risk Factors , China/epidemiology , Kidney Failure, Chronic/therapy , Kidney Failure, Chronic/physiopathology , Kidney Failure, Chronic/epidemiology
6.
Heliyon ; 10(15): e35657, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-39170273

ABSTRACT

Background: Lung cancer is one of the malignant tumors with the highest rates of morbidity and mortality worldwide. One of the most common histological types of lung cancer is lung adenocarcinoma (LUAD). Despite the fact that development in medicine has significantly improved some patients' prognoses, the overall survival (OS) rate is still very low. In glucose-deficient SLC7A11-overexpressed cancer cells, the accumulation of disulfide molecules leads to abnormal disulfide bonding between actin cytoskeletal proteins, interferes with their tissues, and eventually leads to actin network collapse and cell death. This mode of cell death is called disulfidptosis. Studies have shown that disulfidptosis may be a new target for cancer treatment. However, the role of disulfidptosis in LUAD is still unknown. Methods: LUAD transcriptome and clinical information from The Cancer Genome Atlas (TCGA) was downloaded. The co-expression analysis, Least Absolute Shrinkage and Selection Operator (LASSO) regression, and Cox regression analysis was performed to screen the disulfidptosis-related lncRNAs (DRLs) and build the prognostic model. Kaplan-Meier curve, Cox regression analysis, and receiver operating characteristic (ROC) curve was used to validate the model. Then a nomogram is made to predict the prognosis of LUAD patients. Finally, fresh-collected clinical samples were used to verify the expression of DRLs in LUAD. Results: The prognostic model with six DRLs was developed to predict the prognosis of LUAD, with superior prognosis value compared to other clinical variables. The Cox regression analysis revealed that T stage, N stage and the risk score were identified as independent variables that affected LUAD prognosis. ROC curve revealed that the model has a moderate diagnostic value, with an AUC of 1-year 0.684, 3-year 0.664, and 5-year 0.588. Moreover, nine medications connected to LUAD treatment were acquired through drug sensitivity analysis. LUAD tissue validation showed that AC012073.1, AC012615.1, EMSLR, and SNHG12 were highly expressed, while AL606834.1 and AL365181.2 with low expression. Conclusion: Six DRLs were screened and verified to construct the prognostic model, which can accurately predict the LUAD prognosis. It establishes a basis for further exploration into the molecular mechanisms underlying LUAD and identification of potential biomarkers for diagnosis, prognosis, and therapeutic targets.

7.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(8): 845-851, 2024 Aug 15.
Article in Chinese | MEDLINE | ID: mdl-39148390

ABSTRACT

OBJECTIVES: To investigate the clinical and genetic features of children with 3-methylcrotonyl-coenzyme A carboxylase deficiency (MCCD). METHODS: A retrospective analysis was conducted on the clinical manifestations and genetic testing results of six children with MCCD who attended Children's Hospital Affiliated to Zhengzhou University from January 2018 to October 2023. RESULTS: Among the six children with MCCD, there were 4 boys and 2 girls, with a mean age of 7 days at the time of attending the hospital and 45 days at the time of confirmed diagnosis. Of all children, one had abnormal urine odor and five had no clinical symptoms. All six children had increases in blood 3-hydroxyisovaleryl carnitine and urinary 3-hydroxyisovaleric acid and 3-methylcrotonoylglycine, and five of them had a reduction in free carnitine. A total of six mutations were identified in the MCCC1 gene, i.e., c.1630del(p.R544Dfs*2), c.269A>G(p.D90G), c.1609T>A(p.F537I), c.639+2T>A, c.761+1G>T, and c.1331G>A(p.R444H), and three mutations were identified in the MCCC2 gene, i.e., c.838G>T(p.D280Y), c.592C>T(p.Q198*,366), and c.1342G>A(p.G448A). Among these mutations, c.269A>G(p.D90G) and c.1609T>A(p.F537I) had not been previously reported in the literature. There was one case of maternal MCCD, and the child carried a heterozygous mutation from her mother. Five children with a reduction in free carnitine were given supplementation of L-carnitine, and free carnitine was restored to the normal level at the last follow-up visit. CONCLUSIONS: This study identifies two new mutations, c.269A>G(p.D90G) and c.1609T>A(p.F537I), thereby expanding the mutation spectrum of the MCCC1 gene. A combination of blood amino acid and acylcarnitine profiles, urine organic acid analysis, and genetic testing can facilitate early diagnosis and treatment of MCCD, and provide essential data for genetic counseling.


Subject(s)
Carnitine , Mutation , Female , Humans , Infant , Infant, Newborn , Male , Carbon-Carbon Ligases/genetics , Carbon-Carbon Ligases/deficiency , Carboxy-Lyases/genetics , Carboxy-Lyases/deficiency , Carnitine/analogs & derivatives , Carnitine/blood , Retrospective Studies , Urea Cycle Disorders, Inborn/genetics , Urea Cycle Disorders, Inborn/diagnosis
8.
Int J Biol Macromol ; 277(Pt 3): 134399, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39098682

ABSTRACT

The effect of ball milling on the physicochemical properties and gut microbiota regulation of Poria cocos pachyman (PAC) was investigated. Ball milling reduced the particle size of PAC from 102 µm to 25.19 µm after 12 h, resulting in increasing particle uniformity. Scanning electron microscopy (SEM) revealed surface roughening and fragmentation of PAC after ball milling. X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) indicated reduced crystallinity and increased hydroxyl group exposure in ball-milled PAC (BMP). Thermogravimetric analysis (TGA) showed decreased thermal stability in BMP. The optimal ball milled time was 7 h. Moisture contents in PAC and BMP-7 h were 10.30 ± 0.47 % and 10.72 ± 0.12 %, and carbohydrate contents were 81.02 ± 2.27 % and 74.54 ± 1.46 %. In vivo studies on mice demonstrated that both PAC and BMP-7 h increased diversity and reshaped the composition of gut microbiota, with BMP-7 h showing a more pronounced effect. BMP-7 h reduced the Firmicutes/Bacteroidetes ratio, and raised the abundance of Bacteroides, suggesting enhanced prebiotic potential. These findings highlight the role of ball milling in improving the physicochemical properties and prebiotic potential of water-insoluble polysaccharides and provide a theoretical basis for its broader application in the food and biopharmaceutical industries.


Subject(s)
Gastrointestinal Microbiome , Gastrointestinal Microbiome/drug effects , Animals , Mice , Wolfiporia/chemistry , Chemical Phenomena , Prebiotics , Particle Size , Thermogravimetry , X-Ray Diffraction , Spectroscopy, Fourier Transform Infrared , Bone Morphogenetic Protein 7/chemistry
9.
Angew Chem Int Ed Engl ; : e202411292, 2024 Aug 09.
Article in English | MEDLINE | ID: mdl-39122651

ABSTRACT

Cyclopentene rings possessing a chiral quaternary center are important structural motifs found in various natural products. In this work, we disclose expedient and efficient access to this class of synthetically valuable structures via highly enantioselective desymmetrization of prochiral propargylic alcohols. The efficient chirality induction in this asymmetric gold catalysis is achieved via two-point bindings between a gold catalyst featuring a bifunctional phosphine ligand and the substrate homopropargylic alcohol moiety - an H-bonding interaction between the HO group and a ligand phosphine oxide moiety and the gold-alkyne complexation. The propargylic alcohol substrates can be prepared readily via propargylation of ketone precursors, and spirocyclic and bicyclic cyclopentenes are formed with additional neighboring chiral centers of flexible stereochemistry in addition to the quaternary center. This work represents rare gold-catalyzed highly enantioselective cycloisomerization of 1,5-enynes. Density functional theory (DFT) calculations support the chirality induction model and suggest that the rate acceleration enabled by the bifunctional ligand can be attributed to a facilitated protodeauration step at the end of the catalysis.

10.
Brain Behav Immun ; 121: 213-228, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39043349

ABSTRACT

Chronic stress enhances the risk for psychiatric disorders and induces depression and cognitive impairment. Gamma oscillations are essential for neurocircuit function, emotion, and cognition. However, the influence of gamma entrainment by sensory stimuli on specific aspects of chronic stress-induced responses remains unclear. Mice were subjected to corticosterone (CORT) administration and chronic restraint stress (CRS) for weeks, followed by rhythmic gamma frequency light flickering exposure. Local field potentials (LFPs) were recorded from the V1, CA1, and PFC regions to verify the light flicker on gamma oscillations. Behavioral tests were used to examine stress-related and memory-related behaviors. Golgi staining was performed to observe changes in spine morphology. Synaptosomes were isolated to determine the expression of synapse-related proteins through immunoblotting. RNA sequencing (RNA-seq) was applied to explore specific changes in the transcriptome. Immunofluorescence staining, real-time quantitative polymerase chain reaction (qPCR), and ELISA were used to evaluate microglial activation and cytokine levels. In this study, we demonstrated that rhythmic 40 Hz LF attenuated stress-related behavior and cognitive impairments by ameliorating the microstructural alterations in spine morphology and increasing the expression of GluN2A and GluA1 in chronically stressed mice. Transcriptome analysis revealed that significantly downregulated genes in LF-exposed CRS mice were enriched in neuroimmune-related signaling pathways. Rhythmic 40 Hz LF exposure significantly decreased the number of Iba1-positive microglia in the PFC and hippocampus, and the expression levels of the M1 markers of microglia iNOS and CD68 were reduced significantly in CRS mice. In addition, 40 Hz LF exposure suppressed the secretion of cytokines IL-12, which could regulate the production of IFN-γ and IL-10 in stressed mice. Our results demonstrate that exposure to rhythmic 40 Hz LF induces the neuroimmune response and downregulation of neuroinflammation with attenuated stress-related behaviors and cognitive function in CRS-induced mice. Our findings highlight the importance of sensory-evoked gamma entrainment as a potential therapeutic strategy for stress-related disorders treatment. Abbreviations: CORT, Chronic corticosterone treatment; CRS, Chronic restraint stress; IACUC, Institutional Animal Care and Use Committee; LF, light flickers; FST, Forced swim test; NSFT, Novelty-suppressed feeding test; SPT, Sucrose preference test; NSFT, Novelty-suppressed feeding; qPCR, Quantitative real-time polymerase chain reaction; SDS-PAGE, sodium dodecyl sulfate-polyacrylamide gel electrophoresis; PVDF, polyvinylidene fluoride; PBS, phosphate-buffered saline; PBS-T, phosphate-buffered saline plus 0.1% Tween 20; PVDF, polyvinylidene fluoride; GFAP, Glial fibrillary acidic protein; DAPI, 4',6-Diamid- ino-2-phenylindole; Iba1, Ionized calcium-binding adaptor molecule 1; iNOS, Inducible nitric oxide synthase; IL-10, Interleukin-10; IL6, Interleukin 6; IL-1ß, Interleukin 1ß; IL-12, Interleukin 12; TNF-α, Tumor necrosis factor alpha; IFN-γ, Interferon-gamma; TLR6 and 9, Toll-like Receptor 6 and 9.


Subject(s)
Cognitive Dysfunction , Cytokines , Gamma Rhythm , Stress, Psychological , Animals , Mice , Stress, Psychological/metabolism , Male , Cognitive Dysfunction/metabolism , Cognitive Dysfunction/etiology , Cytokines/metabolism , Mice, Inbred C57BL , Corticosterone/metabolism , Neuroinflammatory Diseases/metabolism , Light , Behavior, Animal , Disease Models, Animal
11.
Drug Des Devel Ther ; 18: 2681-2692, 2024.
Article in English | MEDLINE | ID: mdl-38974124

ABSTRACT

Purpose: Remimazolam is a novel short-acting benzodiazepine used for sedation and general anesthesia. This study aimed to evaluate the efficacy and safety of remimazolam besylate in elderly patients who underwent diagnostic gastrointestinal endoscopy. Patients and Methods: A total of 120 patients aged 60-75 years were randomly allocated to one of two groups. Remifentanil 0.3µg/kg was used for analgesia. Patients were administered remimazolam besylate 7 mg (R group) or etomidate 0.1 mg/kg combined with 1% propofol 0.5 mg/kg (EP group) for induction, supplemental repeated doses were given as needed. Some time metrics, vital signs, adverse events were evaluated. Patients' Mini-cog score and recovery questionnaires were compared. Results: Compared to the EP group, the induction time was slightly longer in the R group (1.50 VS 1.15 minutes) (P<0.05), the time spent in the post-anesthesia care unit (PACU) was shorter (15.17 VS 17.40 minutes) (P<0.05). Compare with EP group, SBP was lower in R group at T15 and T25 time point, but heart rate was higher in T2, T3, T5 (P< 0.05). The Mini-Cog score was higher after the procedure (2.83 VS 2.58) (P<0.05). The incidence of respiratory adverse events was higher in the EP group than R group (18.3% VS 5.0%, P < 0.05). The most common adverse event in R group was hiccups. The sedation satisfaction rate and degree of amnesia were higher in the R group (66.7% VS 11.7%) (P < 0.05), and the effect on patient's life within 24 hours was lower (12.0% VS 30.5%) (P < 0.05). Conclusion: The safety and efficacy of remimazolam besylate are not inferior to those of etomidate combined with propofol, rendering it a safe option for sedation during gastrointestinal endoscopy in ASA I-II elderly patients, but care should be taken to monitor the occurrence of hiccups.


Subject(s)
Endoscopy, Gastrointestinal , Etomidate , Propofol , Humans , Aged , Etomidate/administration & dosage , Etomidate/adverse effects , Male , Female , Middle Aged , Prospective Studies , Propofol/administration & dosage , Propofol/adverse effects , Hypnotics and Sedatives/administration & dosage , Hypnotics and Sedatives/adverse effects , Benzodiazepines/administration & dosage , Benzodiazepines/adverse effects
12.
Sci Total Environ ; 947: 174585, 2024 Oct 15.
Article in English | MEDLINE | ID: mdl-38986688

ABSTRACT

The focus on phytoremediation in soil cadmium (Cd) remediation is driven by its cost-effectiveness and eco-friendliness. Selecting suitable hyperaccumulators and optimizing their growth conditions are key to enhance the efficiency of heavy metal absorption and accumulation. Our research has concentrated on the role of salicylic acid (SA) and jasmonic acid (JA) in facilitating Cd phytoextraction by "Sedum alfredii (S. alfredii)" through improved soil-microbe interactions. Results showed that SA or JA significantly boosted the growth, stress resistance, and Cd extraction efficiency in S. alfredii. Moreover, these phytohormones enhanced the chemical and biochemical attributes of the rhizosphere soil, such as pH and enzyme activity, affecting soil-root interactions. High-throughput sequencing analysis has shown that Patescibacteria and Umbelopsis enhanced S. alfredii's growth and Cd extraction by modifying the bioavailability and the chemical conditions of Cd in soil. Structural Equation Model analysis further verified that phytohormones significantly enhanced the interaction between S. alfredii, soil, and microbes, leading to a marked increase in Cd accumulation in the plant. These discoveries emphasized the pivotal role of phytohormones in modulating the hyperaccumulators' response to environmental stress and offered significant scientific support for further enhancing the potential of hyperaccumulators in ecological restoration technologies using phytohormones.


Subject(s)
Biodegradation, Environmental , Cadmium , Cyclopentanes , Oxylipins , Rhizosphere , Salicylic Acid , Sedum , Soil Microbiology , Soil Pollutants , Cadmium/metabolism , Oxylipins/metabolism , Salicylic Acid/metabolism , Soil Pollutants/metabolism , Sedum/metabolism , Cyclopentanes/metabolism , Microbiota , Plant Growth Regulators/metabolism
13.
Mil Med Res ; 11(1): 39, 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38902798

ABSTRACT

BACKGROUND: Despite the efficacy of absolute ethanol (EtOH), its radiolucency introduces several risks in interventional therapy for treating vascular malformations. This study aims to develop a novel radiopaque ethanol injection (REI) to address this issue. METHODS: Iopromide is mixed with ethanol to achieve radiopacity and improve the physicochemical properties of the solution. Overall, 82 male New Zealand white rabbits are selected for in vivo radiopacity testing, peripheral vein sclerosis [animals were divided into the following 5 groups (n = 6): negative control (NC, saline, 0.250 ml/kg), positive control (EtOH, 0.250 ml/kg), low-dose REI (L-D REI, 0.125 ml/kg), moderate-dose REI (M-D REI, 0.250 ml/kg), and high-dose REI (H-D REI 0.375 ml/kg)], pharmacokinetic analyses (the blood sample was harvested before injection, 5 min, 10 min, 20 min, 40 min, 1 h, 2 h, 4 h, and 8 h after injection in peripheral vein sclerosis experiment), peripheral artery embolization [animals were divided into the following 5 groups (n = 3): NC (saline, 0.250 ml/kg), positive control (EtOH, 0.250 ml/kg), L-D REI (0.125 ml/kg), M-D REI (0.250 ml/kg), and H-D REI (0.375 ml/kg)], kidney transcatheter arterial embolization [animals were divided into the following 4 groups (n = 3): positive control (EtOH, 0.250 ml/kg), L-D REI (0.125 ml/kg), M-D REI (0.250 ml/kg), and H-D REI (0.375 ml/kg); each healthy kidney was injected with saline as negative control], and biosafety evaluations [animals were divided into the following 5 groups (n = 3): NC (0.250 ml/kg), high-dose EtOH (0.375 ml/kg), L-D REI (0.125 ml/kg), M-D REI (0.250 ml/kg), and H-D REI (0.375 ml/kg)]. Then, a prospective cohort study involving 6 patients with peripheral venous malformations (VMs) is performed to explore the clinical safety and effectiveness of REI. From Jun 1, 2023 to August 31, 2023, 6 patients [age: (33.3 ± 17.2) years] with lingual VMs received sclerotherapy of REI and 2-month follow-up. Adverse events and serious adverse events were evaluated, whereas the efficacy of REI was determined by both the traceability of the REI under DSA throughout the entire injection and the therapeutic effect 2 months after a single injection. RESULTS: The REI contains 81.4% ethanol (v/v) and 111.3 mg/ml iodine, which can be traced throughout the injection in the animals and patients. The REI also exerts a similar effect as EtOH on peripheral venous sclerosis, peripheral arterial embolization, and renal embolization. Furthermore, the REI can be metabolized at a similar rate compared to EtOH and Ultravist® and did not cause injury to the animals' heart, liver, spleen, lungs, kidneys and brain. No REI-related adverse effects have occurred during sclerotherapy of VMs, and 4/6 patients (66.7%) have achieved complete response at follow-up. CONCLUSION: In conclusion, REI is safe, exerts therapeutic effects, and compensates for the radiolucency of EtOH in treating VMs. TRIAL REGISTRATION: The clinical trial was registered as No. ChiCTR2300071751 on May 24 2023.


Subject(s)
Ethanol , Vascular Malformations , Animals , Rabbits , Ethanol/therapeutic use , Ethanol/pharmacology , Male , Vascular Malformations/therapy , Vascular Malformations/drug therapy , Humans , Contrast Media/pharmacokinetics , Contrast Media/pharmacology , Contrast Media/therapeutic use , Iohexol/analogs & derivatives
14.
PLoS One ; 19(6): e0300056, 2024.
Article in English | MEDLINE | ID: mdl-38905187

ABSTRACT

Accurate, non-destructive and cost-effective estimation of crop canopy Soil Plant Analysis De-velopment(SPAD) is crucial for precision agriculture and cultivation management. Unmanned aerial vehicle (UAV) platforms have shown tremendous potential in predicting crop canopy SPAD. This was because they can rapidly and accurately acquire remote sensing spectral data of the crop canopy in real-time. In this study, a UAV equipped with a five-channel multispectral camera (Blue, Green, Red, Red_edge, Nir) was used to acquire multispectral images of sugar beets. These images were then combined with five machine learning models, namely K-Nearest Neighbor, Lasso, Random Forest, RidgeCV and Support Vector Machine (SVM), as well as ground measurement data to predict the canopy SPAD of sugar beets. The results showed that under both normal irrigation and drought stress conditions, the SPAD values in the normal ir-rigation treatment were higher than those in the water-limited treatment. Multiple vegetation indices showed a significant correlation with SPAD, with the highest correlation coefficient reaching 0.60. Among the SPAD prediction models, different models showed high estimation accuracy under both normal irrigation and water-limited conditions. The SVM model demon-strated a good performance with a correlation coefficient (R2) of 0.635, root mean square error (Rmse) of 2.13, and relative error (Re) of 0.80% for the prediction and testing values under normal irrigation. Similarly, for the prediction and testing values under drought stress, the SVM model exhibited a correlation coefficient (R2) of 0.609, root mean square error (Rmse) of 2.71, and rela-tive error (Re) of 0.10%. Overall, the SVM model showed good accuracy and stability in the pre-diction model, greatly facilitating high-throughput phenotyping research of sugar beet canopy SPAD.


Subject(s)
Beta vulgaris , Remote Sensing Technology , Remote Sensing Technology/methods , Remote Sensing Technology/instrumentation , Unmanned Aerial Devices , Support Vector Machine , Soil/chemistry , Machine Learning , Crops, Agricultural/growth & development , Agriculture/methods , Droughts
15.
Brain Behav ; 14(6): e3602, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38898641

ABSTRACT

OBJECTIVE: The causes and triggering factors of epilepsy are still unknown. The results of genome-wide association studies can be utilized for a phenome-wide association study using Mendelian randomization (MR) to identify potential risk factors for epilepsy. METHODS: This study utilizes two-sample MR analysis to investigate whether 316 phenotypes, including lifestyle, environmental factors, blood biomarker, and more, are causally associated with the occurrence of epilepsy. The primary analysis employed the inverse variance weighted (IVW) model, while complementary MR analysis methods (MR Egger, Wald ratio) were also employed. Sensitivity analyses were also conducted to evaluate heterogeneity and pleiotropy. RESULTS: There was no evidence of a statistically significant causal association between the examined phenotypes and epilepsy following Bonferroni correction (p < 1.58 × 10-4) or false discovery rate correction. The results of the MR analysis indicate that the frequency of tiredness or lethargy in the last 2 weeks (p = 0.042), blood uridine (p = 0.003), blood propionylcarnitine (p = 0.041), and free cholesterol (p = 0.044) are suggestive causal risks for epilepsy. Lifestyle choices, such as sleep duration and alcohol consumption, as well as biomarkers including steroid hormone levels, hippocampal volume, and amygdala volume were not identified as causal factors for developing epilepsy (p > 0.05). CONCLUSIONS: Our study provides additional insights into the underlying causes of epilepsy, which will serve as evidence for the prevention and control of epilepsy. The associations observed in epidemiological studies may be partially attributed to shared biological factors or lifestyle confounders.


Subject(s)
Epilepsy , Genome-Wide Association Study , Mendelian Randomization Analysis , Humans , Epilepsy/genetics , Epilepsy/epidemiology , Phenotype , Risk Factors , Phenomics , Biomarkers/blood
16.
Genes (Basel) ; 15(6)2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38927696

ABSTRACT

Small auxin-upregulated RNAs (SAURs), as the largest family of early auxin-responsive genes, play important roles in plant growth and development processes, such as auxin signaling and transport, hypocotyl development, and tolerance to environmental stresses. However, the functions of few SAUR genes are known in the root development of sweet potatoes. In this study, an IbSAUR36 gene was cloned and functionally analyzed. The IbSAUR36 protein was localized to the nucleus and plasma membrane. The transcriptional level of this gene was significantly higher in the pencil root and leaf.This gene was strongly induced by indole-3-acetic acid (IAA), but it was downregulated under methyl-jasmonate(MeJA) treatment. The promoter of IbSAUR36 contained the core cis-elements for phytohormone responsiveness. Promoter ß-glucuronidase (GUS) analysis in Arabidopsis showed that IbSAUR36 is highly expressed in the young tissues of plants, such as young leaves, roots, and buds. IbSAUR36-overexpressing sweet potato roots were obtained by an efficient Agrobacterium rhizogenes-mediated root transgenic system. We demonstrated that overexpression of IbSAUR36 promoted the accumulation of IAA, upregulated the genes encoding IAA synthesis and its signaling pathways, and downregulated the genes encoding lignin synthesis and JA signaling pathways. Taken together, these results show that IbSAUR36 plays an important role in adventitious root (AR) development by regulating IAA signaling, lignin synthesis, and JA signaling pathways in transgenic sweet potatoes.


Subject(s)
Gene Expression Regulation, Plant , Indoleacetic Acids , Ipomoea batatas , Plant Proteins , Plant Roots , Plants, Genetically Modified , Ipomoea batatas/genetics , Ipomoea batatas/growth & development , Ipomoea batatas/metabolism , Plant Roots/growth & development , Plant Roots/genetics , Plant Roots/metabolism , Plants, Genetically Modified/genetics , Plants, Genetically Modified/growth & development , Indoleacetic Acids/metabolism , Indoleacetic Acids/pharmacology , Plant Proteins/genetics , Plant Proteins/metabolism , Plant Growth Regulators/pharmacology , Plant Growth Regulators/metabolism , Plant Growth Regulators/genetics , Promoter Regions, Genetic , Cyclopentanes/pharmacology , Cyclopentanes/metabolism
17.
J Cancer Res Clin Oncol ; 150(6): 287, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38833016

ABSTRACT

BACKGROUND: Butyrate is a common short-chain fatty acids (SCFA), and it has been demonstrated to regulate the development of breast cancer (BC), while the underlying mechanism is still unreported. METHODS: Gas chromatography was used to measure the amounts of SCFA (acetate, propionate, and butyrate) in the feces. Cell viability was measured by the CCK-8 assay. The wound healing assay demonstrated cell migration, and the transwell assay demonstrated cell invasion. The levels of protein and gene were determined by western blot assay and RT-qPCR assay, respectively. RESULTS: The levels of SCFA were lower in the faecal samples from BC patients compared to control samples. In cellular experiments, butyrate significantly suppressed the cell viability, migration and invasion of T47D in a dose-dependent manner. In animal experiments, butyrate effectively impeded the growth of BC tumors. Toll like receptor 4 (TLR4) was highly expressed in the tumors from BC patients. Butyrate inhibited the expression of TLR4. In addition, butyrate promoted the expression of cuproptosis-related genes including PDXK (pyridoxal kinase) and SLC25A28 (solute carrier family 25 member 28), which was lowly expressed in BC tumors. Importantly, overexpression of TLR4 can reverses the promotion of butyrate to PDXK and SLC25A28 expression and the prevention of butyrate to the malignant biological behaviors of T47D cells. CONCLUSION: In summary, butyrate inhibits the development of BC by facilitating the expression of PDXK and SLC25A28 through inhibition of TLR4. Our investigation first identified a connection among butyrate, TLR4 and cuproptosis-related genes in BC progression. These findings may provide novel target for the treatment of BC.


Subject(s)
Breast Neoplasms , Butyrates , Humans , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Female , Butyrates/pharmacology , Animals , Mice , Cell Movement/drug effects , Gene Expression Regulation, Neoplastic/drug effects , Xenograft Model Antitumor Assays , Cell Proliferation/drug effects , Cell Line, Tumor , Mice, Nude , Toll-Like Receptor 4/metabolism , Toll-Like Receptor 4/genetics , Cell Survival/drug effects , Mice, Inbred BALB C
18.
Langmuir ; 40(27): 14007-14015, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38916446

ABSTRACT

Allograft transplantation is an important method for tendon reconstruction after injury, and its clinical success highly relies on the storage and transportation of the grafts. Cryopreservation is a promising strategy for tendon storage. In this study, we report a novel cryopreservation agent (CPA) formulation with a high biocompatibility for tendon cryopreservation. Mainly composed of natural zwitterionic betaine and the biocompatible polymer poly(vinylpyrrolidone) (PVP), it exhibited ideal abilities to depress the freezing point and inhibit ice growth and recrystallization. Notably, after cryopreservation via plunge-freezing for 1 month, Young's modulus (144 MPa, 98% of fresh tendons) and ultimate stress (46.7 MPa, 99% of fresh tendons) remained stable, and the cross-linking of collagen microfibers, protein structures, and glycosaminoglycan (GAG) contents changed slightly. These results indicate that the formulation (5 wt % betaine and 5 wt % PVP in phosphate-buffered saline, PBS solution) effectively maintains the biomechanical properties and tissue structure. This work offers a novel cryopreservation method for tendons and may also provide insights into the long-term preservation of various other tissues.


Subject(s)
Betaine , Cryopreservation , Tendons , Cryopreservation/methods , Tendons/drug effects , Betaine/chemistry , Animals , Freezing , Cryoprotective Agents/chemistry , Cryoprotective Agents/pharmacology , Povidone/chemistry , Collagen/chemistry , Glycosaminoglycans/chemistry , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology
19.
Cell Death Dis ; 15(6): 447, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38918360

ABSTRACT

There is a paucity of comprehensive knowledge pertaining to the underlying mechanisms leading to gefitinib resistance in individuals diagnosed NSCLC harboring EGFR-sensitive mutations who inevitably develop resistance to gefitinib treatment within six months to one year. In our preceding investigations, we have noted a marked upregulation of IGFBP2 in the neoplastic tissues of NSCLC, predominantly in the periphery of the tissue, implying its plausible significance in NSCLC. Consequently, in the current research, we delved into the matter and ascertained the molecular mechanisms that underlie the participation of IGFBP2 in the emergence of gefitinib resistance in NSCLC cells. Firstly, the expression of IGFBP2 in the bronchoalveolar lavage fluid and lung cancer tissues of 20 NSCLC patients with gefitinib tolerance was found to be significantly higher than that of non-tolerant patients. Furthermore, in vitro and in vivo experiments demonstrated that IGFBP2 plays a significant role in the acquisition of gefitinib resistance. Mechanistically, IGFBP2 can activate STAT3 to enhance the transcriptional activity of CXCL1, thereby increasing the intracellular expression level of CXCL1, which contributes to the survival of lung cancer cells in the gefitinib environment. Additionally, we identified ITGA5 as a key player in IGFBP2-mediated gefitinib resistance, but it does not function as a membrane receptor in the process of linking IGFBP2 to intracellular signaling transduction. In conclusion, this study demonstrates the promoting role and mechanism of IGFBP2 in acquired gefitinib resistance caused by non-EGFR secondary mutations, suggesting the potential of IGFBP2 as a biomarker for gefitinib resistance and a potential intervention target.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Chemokine CXCL1 , Drug Resistance, Neoplasm , Gefitinib , Insulin-Like Growth Factor Binding Protein 2 , Lung Neoplasms , STAT3 Transcription Factor , Animals , Female , Humans , Male , Mice , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/pathology , Cell Line, Tumor , Chemokine CXCL1/metabolism , Chemokine CXCL1/genetics , Drug Resistance, Neoplasm/genetics , Drug Resistance, Neoplasm/drug effects , Gefitinib/pharmacology , Gefitinib/therapeutic use , Gene Expression Regulation, Neoplastic/drug effects , Insulin-Like Growth Factor Binding Protein 2/metabolism , Insulin-Like Growth Factor Binding Protein 2/genetics , Lung Neoplasms/metabolism , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Mice, Nude , Signal Transduction/drug effects , STAT3 Transcription Factor/metabolism
20.
Org Lett ; 26(27): 5736-5740, 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38935932

ABSTRACT

Gold-catalyzed dimerization of terminal alkynes is achieved under mild reaction conditions and in excellent yields. In addition to homodimerizations, heterodimerizations between TBS acetylene and a range of terminal alkynes were realized using the syringe pump technique. The reaction tolerates various functional groups. The rate acceleration experienced in the reactions is enabled by metal-ligand cooperation. A binaphthyl-2-ylphosphine ligand featuring a 3'-diisopropylphosphoryl group plays a pivotal role in facilitating alkyne attack by accommodating and/or deprotonating its terminal proton.

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