The upregulation of programmed death ligand 1 (PD-L1) plays a crucial role in facilitating cancer cells to evade immune surveillance through immunosuppression. However, the precise regulatory mechanisms of PD-L1 in hepatocellular carcinoma (HCC) remain undefined. The correlation between PD-L1 and ubiquitin-like molecules (UBLs) was studied using sequencing data from 20 HCC patients in our center, combined with TCGA data. Specifically, the association between FAT10 and PD-L1 was further validated at both the protein and mRNA levels in HCC tissues from our center. Subsequently, the effect of FAT10 on tumor progression and immune suppression was examined through both in vivo and in vitro experiments. Utilizing sequencing data, qPCR, and Western blotting assays, we confirmed that FAT10 was highly expressed in HCC tissues and positively correlated with PD-L1 expression. Additionally, in vitro experiments demonstrated that the overexpression of FAT10 fostered the proliferation, migration, and invasion of HCC cells. Furthermore, the overexpression of FAT10 in HCC cells led to an increase in PD-L1 expression, resulting in the inhibition of T cell proliferation and the enhancement of HCC cell resistance to T cell-mediated cytotoxicity. Moreover, in vivo experiments utilizing the C57BL/6 mouse model revealed that overexpression of FAT10 effectively suppressed the infiltration of CD8 + GZMB + and CD8 + Ki67 + T cells, as well as reduced serum levels of TNF-α and IFN-γ. Mechanistically, we further identified that FAT10 upregulates PD-L1 expression via activating the PI3K/AKT/mTOR pathway, but not in a ubiquitin-like modification. In conclusion, our findings indicate that FAT10 promotes immune evasion of HCC via upregulating PD-L1 expression, suggesting its potential as a novel target to enhance the efficiency of immunotherapy in HCC.
BACKGROUND: Some glucoside drugs can be transported via intestinal glucose transporters (IGTs), and the presence of carbohydrate excipients in pharmaceutical formulations may influence the absorption of them. This study, using gastrodin as probe drug, aimed to explore the effects of fructose, lactose, and arabic gum on intestinal drug absorption mediated by the glucose transport pathway. METHODS: The influence of fructose, lactose, and arabic gum on gastrodin absorption was assessed via pharmacokinetic experiments and single-pass intestinal perfusion. The expression of sodium-dependent glucose transporter 1 (SGLT1) and sodium-independent glucose transporter 2 (GLUT2) was quantified via RTâqPCR and western blotting. Alterations in rat intestinal permeability were evaluated through H&E staining, RTâqPCR, and immunohistochemistry. RESULTS: Fructose reduced the area under the curve (AUC) and peak concentration (Cmax) of gastrodin by 42.7% and 63.71%, respectively (P < 0.05), and decreased the effective permeability coefficient (Peff) in the duodenum and jejunum by 58.1% and 49.2%, respectively (P < 0.05). SGLT1 and GLUT2 expression and intestinal permeability remained unchanged. Lactose enhanced the AUC and Cmax of gastrodin by 31.5% and 65.8%, respectively (P < 0.05), and increased the Peff in the duodenum and jejunum by 33.7% and 26.1%, respectively (P < 0.05). SGLT1 and GLUT2 levels did not significantly differ, intestinal permeability increased. Arabic gum had no notable effect on pharmacokinetic parameters, SGLT1 or GLUT2 expression, or intestinal permeability. CONCLUSION: Fructose, lactose, and arabic gum differentially affect intestinal drug absorption through the glucose transport pathway. Fructose competitively inhibited drug absorption, while lactose may enhance absorption by increasing intestinal permeability. Arabic gum had no significant influence.
Our previous study has identified that glutamate in the red nucleus (RN) facilitates the development of neuropathic pain through metabotropic glutamate receptors (mGluR). Here, we further explored the actions and possible molecular mechanisms of red nucleus mGluR â (mGluR1 and mGluR5) in the development of neuropathic pain induced by spared nerve injury (SNI). Our data indicated that both mGluR1 and mGluR5 were constitutively expressed in the RN of normal rats. Two weeks after SNI, the expressions of mGluR1 and mGluR5 were significantly boosted in the RN contralateral to the nerve injury. Administration of mGluR1 antagonist LY367385 or mGluR5 antagonist MTEP to the RN contralateral to the nerve injury at 2 weeks post-SNI significantly ameliorated SNI-induced neuropathic pain. However, unilateral administration of mGluRâ agonist DHPG to the RN of normal rats provoked a significant mechanical allodynia, this effect could be blocked by LY367385 or MTEP. Further studies indicated that the expressions of TNF-α and IL-1ß in the RN were also elevated at 2 weeks post-SNI. Administration of mGluR1 antagonist LY367385 or mGluR5 antagonist MTEP to the RN at 2 weeks post-SNI significantly inhibited the elevations of TNF-α and IL-1ß. However, administration of mGluR â agonist DHPG to the RN of normal rats significantly enhanced the expressions of TNF-α and IL-1ß, these effects were blocked by LY367385 or MTEP. These results suggest that activation of red nucleus mGluR1 and mGluR5 facilitate the development of neuropathic pain by stimulating the expressions of TNF-α and IL-1ß. mGluR â maybe potential targets for drug development and clinical treatment of neuropathic pain.
The production of high-demand syngas with tunable ratios by CO2 electroreduction has attracted considerable research interest. However, it is challenging to balance the evolution performance of H2 and CO with wide H2/CO ratios, while maintaining high efficiency. Herein, nitrogen-coordinated hierarchical porous carbon spheres with varying phosphorus content (PxNC-T) are assembled to regulate syngas production performance. The precise introduction of P modulates the local charge distribution of nitrogen-coordinated carbons, thereby accelerating the protonation process of ∗CO2-to-∗COOH and promoting moderate H∗ adsorption. Specifically, syngas with wide H2/CO ratios (0.60-4.98) is obtained over a low potential range (-0.46 to -0.86 V vs. RHE). As a representative, P1.0NC-900 presents a remarkable current density (-152 mA cm-2) at -1.0 V vs. RHE in flow cells and delivers a decent peak power density (1.93 mW cm-2) in reversible Zn-CO2 batteries. Our work provides valuable insights into the rational design of carbon-based catalysts for CO2 reduction.
PURPOSE: For the custom-built construction of eye plaques, the iodine (I-125) seeds of different source strengths are recycled in our eye plaque program. To return I-125 seeds to the correct lot, we developed a novel 3D-printed conical plaque QA holder for relative assay for eye plaques. MATERIALS AND METHODS: A universal 3D-printed conical plaque holder was designed to accommodate six plaque sizes and fit reproducibly in a well-type dose calibrator. A reproducibility test was used to compare the plaque placement consistency in the holder versus without the holder. Plaque assays were performed for assembled plaques both before implant and after explant. The explant reading was compared with the implant reading adjusted for decay, and the relative error was calculated. The plaque response fraction (PRF) is defined as the fraction of well chamber implant reading over the total seed strength for a plaque. The PRF was aggregated for each individual plaque to confirm the seed lot before implant. RESULTS: The reproducibility test showed the chamber reading's relative standard deviation of 0.40% with the QA holder compared to 0.68% without it. The batch relative assay was performed for 251 plaques. The absolute value of measurement deviation between explant and decay-corrected implant readings is 0.89% ± 0.86% (mean ± standard deviation). The PRFs for individual plaques range from 36.49% to 49.87%, with a maximum standard deviation of 2%. CONCLUSIONS: This novel 3D-printed QA holder provides reproducible setup for assaying assembled eye plaques in a well chamber. Batch relative assay can validate the seed batch used and plaque integrity during the implant without assaying individual seeds, saving valuable physicist time and radiation exposure from seed handling.
Recombinant human erythropoietin (rhEPO) is a glycoprotein that acts as the main hormone involved in regulating red blood cell production to treat anemia caused by chronic kidney disease or chemotherapy, which has three N-glycosylation sites and one O-glycosylation site. It contains a variety of different glycosylation modifications, such as sialyation, O-acetylation on sialic acids, etc., which causes a big challenge for the glycosylation analysis of rhEPO. In this study, a liquid chromatography-mass spectrometry (LC-MS) method combined with electron-activated dissociation (EAD) technology was used in qualitative and quantitative characterization of rhEPO N-glycosylation and O-glycosylation in just one injection. The usage of EAD not only generated abundant MS/MS fragment ions of glycopeptides and improved the MS/MS sequence coverage but also preserved the glycan structures in the MS/MS fragment ions and the integrity of the glycosidic bond between the glycans and peptides. Three N-glycosylation sites (N24, N38, and N83) and one O-glycosylation site (S126) of rhEPO samples were successfully identified. Among them, the glycosylation ratios of N24, N38, and N83 sites were 82.7%, 100%, and 100% respectively, and 15, 10, and 12 different N-glycans could be identified at the glycopeptide level. The total average number of sialic acids, N-hydroxyacetylneuraminoic acid, and O-acetylation on sialic acid were 7.28, 4.21, and 0.66 at the intact protein level, respectively. For O-glycosylation site S126, O-glycosylation ratios analyzed at the intact protein level and the glycopeptide level were 80.2% and 80.3%, respectively, and two O-glycans were identified, including Core1_S1 and Core1_S2. This study also compared the difference of the glycans and their relative contents in batch-to-batch rhEPO samples. The results proved that the workflow using EAD fragmentation in LC-MS method could be effectively applied for characterizing the glycosylation analysis of rhEPO samples and batch-to-batch consistency analysis, which would help to reasonably guide the optimization of rhEPO production process.
BACKGROUND: This study aimed to investigate the potential association between the circadian rhythm of blood pressure and deceleration capacity (DC)/acceleration capacity (AC) in patients with essential hypertension. METHODS: This study included 318 patients with essential hypertension, whether or not they were being treated with anti-hypertensive drugs, who underwent 24-hour ambulatory blood pressure monitoring (ABPM). Patients were categorized into three groups based on the percentage of nocturnal systolic blood pressure (SBP) dipping: the dipper, non-dipper and reverse dipper groups. Baseline demographic characteristics, ambulatory blood pressure monitoring parameters, Holter recordings (including DC and AC), and echocardiographic parameters were collected. RESULTS: In this study, the lowest DC values were observed in the reverse dipper group, followed by the non-dipper and dipper groups (6.46 ± 2.06 vs. 6.65 ± 1.95 vs. 8.07 ± 1.79 ms, P < .001). Additionally, the AC gradually decreased (-6.32 ± 2.02 vs. -6.55 ± 1.95 vs. -7.80 ± 1.73 ms, P < .001). There was a significant association between DC (r = .307, P < .001), AC (r=-.303, P < .001) and nocturnal SBP decline. Furthermore, DC (ß = 0.785, P = .001) was positively associated with nocturnal SBP decline, whereas AC was negatively associated with nocturnal SBP (ß = -0.753, P = .002). By multivariate logistic regression analysis, deceleration capacity [OR (95% CI): 0.705 (0.594-0.836), p < .001], and acceleration capacity [OR (95% CI): 1.357 (1.141-1.614), p = .001] were identified as independent risk factors for blood pressure nondipper status. The analysis of ROC curves revealed that the area under the curve for DC/AC in predicting the circadian rhythm of blood pressure was 0.711/0.697, with a sensitivity of 73.4%/65.1% and specificity of 66.7%/71.2%. CONCLUSIONS: Abnormal DC and AC density were correlated with a blunted decline in nighttime SBP, suggesting a potential association between the circadian rhythm of blood pressure in essential hypertension patients and autonomic nervous dysfunction.
Antihypertensive Agents , Blood Pressure Monitoring, Ambulatory , Blood Pressure , Circadian Rhythm , Essential Hypertension , Heart Rate , Humans , Male , Female , Middle Aged , Essential Hypertension/physiopathology , Essential Hypertension/diagnosis , Essential Hypertension/drug therapy , Time Factors , Antihypertensive Agents/therapeutic use , Aged , Predictive Value of Tests , Adult , Risk Factors , Electrocardiography, Ambulatory , Acceleration , Deceleration
Vitamin D3 (VD3) is a steroid hormone that plays pivotal roles in pathophysiology, and 1,25(OH)2D3 is the most active form of VD3. In the current study, the crucial role of VD3 in maintaining energy homeostasis under short-term fasting conditions was investigated. Our results confirmed that glucose-depriving pathways were inhibited while glucose-producing pathways were strengthened in zebrafish after fasting for 24 or 48 h. Moreover, VD3 anabolism in zebrafish was significantly suppressed in a time-dependent manner under short-fasting conditions. After fasting for 24 or 48 h, zebrafish fed with VD3 displayed a higher gluconeogenesis level and lower glycolysis level in the liver, and the serum glucose was maintained at higher levels, compared to those fed without VD3. Additionally, VD3 augmented the expression of fatty acids (FAs) transporter cd36 and lipogenesis in the liver, while enhancing lipolysis in the dorsal muscle. Similar results were obtained in cyp2r1-/- zebrafish, in which VD3 metabolism is obstructed. Importantly, it was observed that VD3 induced the production of gut GLP-1, which is considered to possess a potent gluconeogenic function in zebrafish. Meanwhile, the gene expression of proprotein convertase subtilisin/kexin type 1 (pcsk1), a GLP-1 processing enzyme, was also induced in the intestine of short-term fasted zebrafish. Notably, gut microbiota and its metabolite acetate were involved in VD3-regulated pcsk1 expression and GLP-1 production under short-term fasting conditions. In summary, our study demonstrated that VD3 regulated GLP-1 production in zebrafish by influencing gut microbiota and its metabolite, contributing to energy homeostasis and ameliorating hypoglycemia under short-term fasting conditions.
Cholecalciferol , Energy Metabolism , Fasting , Homeostasis , Zebrafish , Animals , Cholecalciferol/metabolism , Cholecalciferol/pharmacology , Liver/metabolism , Gluconeogenesis , Gastrointestinal Microbiome/physiology , Blood Glucose/metabolism , Glucagon-Like Peptide 1/metabolism , Glucagon-Like Peptide 1/blood
Spontaneous cerebral vasomotion, characterized by â¼0.1 Hz rhythmic contractility, is crucial for brain homeostasis. However, our understanding of vasomotion is limited due to a lack of high-precision analytical methods to determine single vasomotion events at basal levels. Here, we developed a novel strategy that integrates a baseline smoothing algorithm, allowing precise measurements of vasodynamics and concomitant Ca2+ dynamics in mouse cerebral vasculature imaged by two-photon microscopy. We identified several previously unrecognized vasomotion properties under different physiological and pathological conditions, especially in ischemic stroke, which is a highly harmful brain disease that results from vessel occlusion. First, the dynamic characteristics between SMCs Ca2+ and corresponding arteriolar vasomotion are correlated. Second, compared to previous diameter-based estimations, our radius-based measurements reveal anisotropic vascular movements, enabling a more precise determination of the latency between smooth muscle cell (SMC) Ca2+ activity and vasoconstriction. Third, we characterized single vasomotion event kinetics at scales of less than 4 seconds. Finally, following pathological vasoconstrictions induced by ischemic stroke, vasoactive arterioles entered an inert state and persisted despite recanalization. In summary, we developed a highly accurate technique for analyzing spontaneous vasomotion, and our data suggested a potential strategy to reduce stroke damage by promoting vasomotion recovery.
Oxidative rancidity of food products and massive consumption of plastic packaging have put the necessity in manufacturing novel antioxidant biodegradable packaging films. A comprehensive investigation was conducted on starch/poly(butylene adipate-co-terephthalate) (PBAT) antioxidant blown films, in which starch acted as a gatekeeper for the controlled release of propyl gallate (PG). PG was well integrated into the matrices and bound to starch molecules by hydrogen bonding. All films showed strong anti-ultraviolet performance, and higher oxygen barrier than the traditional polyethylene film. Increasing starch proportions promoted the swelling of films and the release of PG, thereby causing higher antioxidant activity at the same contact time to free radical solutions. Similar polarity made PG prone to partition and rapid migration into the food simulants with higher ethanol concentration and the high-fat-content peanut butter. The film with 20:80 w/w starch/PBAT proportion and 3% w/w PG content effectively suppressed the oxidation of peanut butter within 300-day storage. Findings demonstrated this strategy for manufacturing starch/PBAT antioxidant films as a long-term active packaging in food industry.
Antioxidants , Food Packaging , Propyl Gallate , Starch , Food Packaging/instrumentation , Antioxidants/chemistry , Propyl Gallate/chemistry , Starch/chemistry , Delayed-Action Preparations/chemistry , Oxidation-Reduction , Polyesters/chemistry
Intervertebral disc degeneration (IVDD) is the primary factor contributing to low back pain (LBP). Unlike elderly patients, many young IVDD patients usually have a history of trauma or long-term abnormal stress, which may lead to local inflammatory reaction causing by immune cells, and ultimately accelerates degeneration. Research has shown the significance of M1-type macrophages in IVDD; nevertheless, the precise mechanism and the route by which it influences the function of nucleus pulposus cell (NPC) remain unknown. Utilizing a rat acupuncture IVDD model and an NPC degeneration model induced by lipopolysaccharide (LPS), we investigated the function of M1 macrophage-derived exosomes (M1-Exos) in IVDD both in vivo and in vitro in this study. We found that M1-Exos enhanced LPS-induced NPC senescence, increased the number of SA-ß-gal-positive cells, blocked the cell cycle, and promoted the activation of P21 and P53. M1-Exos derived from supernatant pretreated with the exosome inhibitor GW4869 reversed this result in vivo and in vitro. RNA-seq showed that Lipocalin2 (LCN2) was enriched in M1-Exos and targeted the NF-κB pathway. The quantity of SA-ß-gal-positive cells was significantly reduced with the inhibition of LCN2, and the expression of P21 and P53 in NPCs was decreased. The same results were obtained in the acupuncture-induced IVDD model. In addition, inhibition of LCN2 promotes the expression of type II collagen (Col-2) and inhibits the expression of matrix metalloproteinase 13 (MMP13), thereby restoring the equilibrium of metabolism inside the extracellular matrix (ECM) in vitro and in vivo. In addition, the NF-κB pathway is crucial for regulating M1-Exo-mediated NPC senescence. After the addition of M1-Exos to LPS-treated NPCs, p-p65 activity was significantly activated, while si-LCN2 treatment significantly inhibited p-p65 activity. Therefore, this paper demonstrates that M1 macrophage-derived exosomes have the ability to deliver LCN2, which activates the NF-κB signaling pathway, and exacerbates IVDD by accelerating NPC senescence. This may shed new light on the mechanism of IVDD and bring a fresh approach to IVDD therapy.
Cellular Senescence , Exosomes , Intervertebral Disc Degeneration , Lipocalin-2 , Macrophages , NF-kappa B , Nucleus Pulposus , Rats, Sprague-Dawley , Signal Transduction , Animals , Exosomes/metabolism , Nucleus Pulposus/metabolism , Intervertebral Disc Degeneration/metabolism , Lipocalin-2/metabolism , Lipocalin-2/genetics , Rats , NF-kappa B/metabolism , Signal Transduction/drug effects , Macrophages/metabolism , Macrophages/drug effects , Male , Lipopolysaccharides/pharmacology , Disease Models, Animal
The aim of this study was to investigate the association between hypothyroidism in early pregnancy and small intestinal bacterial overgrowth (SIBO) and the effect of probiotics. Patients with hypothyroidism in early pregnancy and normal pregnant women during the same period were included in the methane-hydrogen breath test to compare the incidence of SIBO, smoothed curve fit, and differences in clinical symptoms. For those who combined with SIBO, the rate of clinical symptom conversion, thyroid hormones, and changes in associated inflammatory indexes were compared after 21 days of treatment with probiotics on top of conventional levothyroxine sodium tablets. The results are as follows: (1) The incidence of combined SIBO in patients with hypothyroidism in pregnancy was 56.0%, significantly higher than the 28.0% of normal pregnant women during the same period. (2) The highest value of hydrogen plus methane gas in 90 min in pregnancy hypothyroid patients showed a significant negative correlation with FT4 (p < .001, SD = 0.169). (3) Abdominal distension symptoms were significantly increased in both groups after combined SIBO (p = .036, p = .025), and the conversion rate after treatment was 69.2% and 75.0%, respectively. (4) In hypothyroidism, pregnancy combined with SIBO, TSH, and CRP was higher before treatment (p = .001, p = .012) and decreased significantly after treatment (p = .001, p = .008). Hypothyroidism in early pregnancy is associated with SIBO, and probiotic treatment is significantly effective.
This study aimed to investigate the effects of polydimethylsiloxane (PDMS) with a low surface energy on the structure and physicochemical properties of starch/poly (butylene adipate-co-terephthalate) (PBAT) blown films. The film's appearance was not significantly changed after the addition of PDMS. Compared with the films without PDMS, the films with PDMS displayed a smoother surface. A 2% w/w PDMS addition resulted in the maximum mechanical properties (8.10 MPa of strength, 211.00% of modulus) and surface hydrophobicity (87°) of the films. By contrast, the film with 3% w/w PDMS showed the lowest light transmittance, water vapor (2.73 × 10-11 g·cm·cm2·s-1·Pa-1) and oxygen permeability (9.73 × 10-13·cm3·cm·cm-2·s-1·Pa-1), owing to the improved tightness of the matrix, which increased the zigzag path for molecules to pass through. Films with higher PDMS contents effectively extended the shelf life of packaged bananas and shiitake mushrooms, benefiting from the outstanding and appropriate barrier properties, according to principal component analysis results. Findings supported that high-content starch/PBAT films containing PDMS had potential in the preservation of fresh agricultural products.
This work proposed a novel strategy for manufacturing biodegradable pH-response packaging. Briefly, to minimize the amount and thermal processing times of blueberry extract (BE), ethanol-dissolved BE (≤ 3 w/w) was sprayed onto the starch/poly(butylene adipate-co-terephthalate) (PBAT) pellets before extrusion blowing. BE was well-integrated into the matrix, forming uniformly colored films. The films with BE exhibited superior mechanical (7.85 MPa of strength, 606.53% of elongation) and enhanced barrier capabilities against ultraviolet light, moisture, and gas. Additionally, they exhibited good antioxidant capacity (68.69%), antibacterial activity (72.40%), and maintained color stability. The film with 3 w/w BE presented excellent color responsiveness (ΔEâ ≥ 15) in the alkaline range, and successfully monitored the spoilage of shrimp. The pigments in the film had the maximum migration degree (≥ 70%) and rate in 50% ethanol simulation, following a first-order kinetic behavior dominated by Fickian diffusion. Findings supported the application of this strategy in the fabrication of starch/PBAT/BE films for pH-response intelligent packaging.
Anti-Bacterial Agents , Blueberry Plants , Food Packaging , Plant Extracts , Food Packaging/instrumentation , Blueberry Plants/chemistry , Plant Extracts/chemistry , Plant Extracts/pharmacology , Hydrogen-Ion Concentration , Kinetics , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Antioxidants/chemistry , Antioxidants/pharmacology , Animals , Polyesters/chemistry , Food Preservation/methods , Food Preservation/instrumentation , Color
BACKGROUND CONTEXT: Thoracic spinal stenosis (TSS) is secondary to different pathologies that differ in clinical characteristics and surgical outcomes. PURPOSE: This study aimed to determine the optimal warning thresholds for combined somatosensory-evoked potentials (SSEP) and motor-evoked potentials (MEP) for predicting postoperative neurological deterioration in surgical treatment for TSS based on different pathologies. Additionally, we explored the correlation between SSEP/MEP monitoring and postoperative spinal neurological function. STUDY SETTING: Retrospective study. PATIENT SAMPLE: Two hundred and five patients. OUTCOME MEASURES: We obtained perioperative modified Japanese Orthopedic Association (mJOA) scores to assess spinal neurological function. METHODS: The data collected in this study included demographic data, intraoperative neurophysiological monitoring (IONM) signals, and perioperative neurological function assessments. To determine the optimal IONM warning threshold, a receiver operating characteristic (ROC) curve was used. Additionally, Pearson correlation analysis was conducted to determine the correlation between IONM signals and clinical neurological conditions. RESULTS: A total of 205 consecutive patients were eligible. Forty-one patients had thoracic disc herniation (TDH), 14 had ossification of the posterior longitudinal ligament (OPLL), 124 had ossification of the ligamentum flavum (OLF), and 26 had OPLL+OLF. The mean mJOA scores before surgery and 3 months after surgery were 7.0 and 7.9, respectively, resulting in a mean mJOA recovery rate (RR) of 23.1%. The average postoperative mJOA RRs for patients with TDH, OPLL, OLF, and OPLL+OLF were 24.8%, 10.4%, 26.8%, and 11.2%, respectively. Patients with OPLL+OLF exhibited a more stringent threshold for IONM changes. This included a lower amplitude cutoff value (a decrease of 49.0% in the SSEP amplitude and 57.5% in the MEP amplitude for short-term prediction) and a shorter duration of waveform change (19.5 minutes for SSEP and 22.5 minutes for MEP for short-term prediction). On the other hand, patients with TDH had more lenient IONM warning criteria (a decrease of 49.0% in SSEP amplitude and 77.5% in MEP amplitude for short-term prediction; durations of change of 25.5 minutes for SSEP and 32.5 minutes for MEP). However, OPLL patients or OLF patients had moderate and similar IONM warning thresholds. Additionally, there was a stronger correlation between the SSEP amplitude variability ratio and the JOA RR in OPLL+OLF patients, while the correlation was stronger between the MEP amplitude variability ratio and the JOA RR for the other three TSS pathologies. CONCLUSIONS: Optimal IONM change criteria for prediction vary depending on different TSS pathologies. The optimal monitoring strategy for prediction varies depending on TSS pathologies.
Hearing loss (HL) is a health burden that seriously affects the quality of life of cancer patients receiving platinum-based chemotherapy, and few FDA-approved treatment specifically targets this condition. The main mechanisms that contribute to cisplatin-induced hearing loss are oxidative stress and subsequent cell death, including ferroptosis revealed by us as a new mechanism recently. In this study, we employed the frontier molecular orbital (FMO) theory approach as a convenient prediction method for the glutathione peroxidase (GPx)-like activity of isoselenazolones and discovered new isoselenazolones with great GPx-like activity. Notably, compound 19 exhibited significant protective effects against cisplatin-induced hair cell (HC) damage in vitro and in vivo and effectively reverses cisplatin-induced hearing loss through oral administration. Further investigations revealed that this compound effectively alleviated hair cell oxidative stress, apoptosis and ferroptosis. This research highlights the potential of GPx mimics as a therapeutic strategy against cisplatin-induced hearing loss. The application of quantum chemistry (QC) calculations in the study of GPx mimics sheds light on the development of new, innovative treatments for hearing loss.
Cisplatin , Glutathione Peroxidase , Hearing Loss , Cisplatin/pharmacology , Glutathione Peroxidase/metabolism , Animals , Hearing Loss/drug therapy , Hearing Loss/chemically induced , Humans , Quantum Theory , Molecular Structure , Mice , Structure-Activity Relationship , Small Molecule Libraries/chemistry , Small Molecule Libraries/pharmacology , Small Molecule Libraries/chemical synthesis , Oxidative Stress/drug effects , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Drug Discovery , Dose-Response Relationship, Drug , Apoptosis/drug effects
Cells are the fundamental units of life. The cell membrane primarily composed of two layers of phospholipids (a bilayer) structurally defines the boundary of a cell, which can protect its interior from external disturbances and also selectively exchange substances and conduct signals from the extracellular environment. The complexity and particularity of transmembrane proteins provide the foundation for versatile cellular functions. Nanomedicine as an emerging therapeutic strategy holds tremendous potential in the healthcare field. However, it is susceptible to recognition and clearance by the immune system. To overcome this bottleneck, the technology of cell membrane coating has been extensively used in nanomedicines for their enhanced therapeutic efficacy, attributed to the favorable fluidity and biocompatibility of cell membranes with various membrane-anchored proteins. Meanwhile, some engineering strategies of cell membranes through various chemical, physical and biological ways have been progressively developed to enable their versatile therapeutic functions against complex diseases. In this review, we summarized the potential clinical applications of four typical cell membranes, elucidated their underlying therapeutic mechanisms, and outlined their current engineering approaches. In addition, we further discussed the limitation of this technology of cell membrane coating in clinical applications, and possible solutions to address these challenges.
Cell Membrane , Nanomedicine , Humans , Cell Membrane/metabolism , Cell Membrane/chemistry , Animals , Membrane Proteins/chemistry , Membrane Proteins/metabolism
BACKGROUND: The current study reported a case with a history of neuroradiculitis. Within 2 months of the COVID-19 vaccine, critical Guillain-Barre Syndrome (GBS) appeared after acute diarrhea, progressive myasthenia, and sudden respiratory and cardiac symptoms. METHODS: The syndrome was addressed with measures, such as endotracheal intubation and cardiopulmonary resuscitation vasoactive drugs. Next, we conducted six cycles of human immunoglobulin treatment (dose of 400 mg/kg·d intravenously for 5 days consecutively) and three times plasma exchange (PE, 30 ml/kg), followed by methylprednisolone sodium succinate. Rehabilitation training was carried out continuously. RESULTS: The consciousness of the patient returned to normal, wherein he carried out normal communication. The muscle strength recovered gradually but still could not stand independently. Presently, he is recovering at home. CONCLUSIONS: For patients with previous radiculitis, COVID-19 vaccination may increase the susceptibility to GBS. Thus, it is recommended to extend the vaccination interval for these patients and ensure that any potential increased risk is continually assessed.
COVID-19 Vaccines , COVID-19 , Guillain-Barre Syndrome , Humans , Guillain-Barre Syndrome/therapy , Guillain-Barre Syndrome/etiology , Male , COVID-19/complications , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Plasma Exchange , Middle Aged , Immunoglobulins, Intravenous/therapeutic use , SARS-CoV-2
BACKGROUND: The aim of this study was to assess the microbial variations and biomarkers in the vaginal and oral environments of patients with human papillomavirus (HPV) and cervical cancer (CC) and to develop novel prediction models. MATERIALS AND METHODS: This study included 164 samples collected from both the vaginal tract and oral subgingival plaque of 82 women. The participants were divided into four distinct groups based on their vaginal and oral samples: the control group (Z/KZ, n = 22), abortion group (AB/KAB, n = 17), HPV-infected group (HP/KHP, n = 21), and cervical cancer group (CC/KCC, n = 22). Microbiota analysis was conducted using full-length 16S rDNA gene sequencing with the PacBio platform. RESULTS: The vaginal bacterial community in the Z and AB groups exhibited a relatively simple structure predominantly dominated by Lactobacillus. However, CC group shows high abundances of anaerobic bacteria and alpha diversity. Biomarkers such as Bacteroides, Mycoplasma, Bacillus, Dialister, Porphyromonas, Anaerococcus, and Prevotella were identified as indicators of CC. Correlations were established between elevated blood C-reactive protein (CRP) levels and local/systemic inflammation, pregnancy, childbirth, and abortion, which contribute to unevenness in the vaginal microenvironment. The altered microbial diversity in the CC group was confirmed by amino acid metabolism. Oral microbial diversity exhibited an inverse pattern to that of the vaginal microbiome, indicating a unique relationship. The microbial diversity of the KCC group was significantly lower than that of the KZ group, indicating a link between oral health and cancer development. Several microbes, including Fusobacterium, Campylobacter, Capnocytophaga, Veillonella, Streptococcus, Lachnoanaerobaculum, Propionibacterium, Prevotella, Lactobacillus, and Neisseria, were identified as CC biomarkers. Moreover, periodontal pathogens were associated with blood CRP levels and oral hygiene conditions. Elevated oral microbial amino acid metabolism in the CC group was closely linked to the presence of pathogens. Positive correlations indicated a synergistic relationship between vaginal and oral bacteria. CONCLUSION: HPV infection and CC impact both the vaginal and oral microenvironments, affecting systemic metabolism and the synergy between bacteria. This suggests that the use of oral flora markers is a potential screening tool for the diagnosis of CC.
Microbiota , Mouth , Papillomavirus Infections , Uterine Cervical Neoplasms , Vagina , Humans , Female , Vagina/microbiology , Vagina/virology , Uterine Cervical Neoplasms/microbiology , Uterine Cervical Neoplasms/virology , Papillomavirus Infections/virology , Papillomavirus Infections/microbiology , Mouth/microbiology , Mouth/virology , Adult , Middle Aged , Papillomaviridae/isolation & purification , Papillomaviridae/genetics , RNA, Ribosomal, 16S/genetics , Human Papillomavirus Viruses
In real terrain and dynamic obstacle scenarios, the complexity of the 3D UAV path planning problem greatly increases. Thus, to procure the optimal flight path for UAVs in such scenarios, an augmented Artificial Gorilla Troops Optimizer, denoted as OQMGTO, is proposed. The proposed OQMGTO algorithm introduces three strategies: combination mutation, quadratic interpolation, and random opposition-based learning, aiming to enhance the ability to timely escape from local optimal path areas and rapidly converge to the global optimal path. Given the flight distance, smoothness, terrain collision, and other five realistic factors of UAVs, specific constraint conditions are proposed to address complex scenarios, aiming to construct a path planning model. By optimizing this model, OQMGTO algorithm solves the path planning problem in complex scenarios. The extensive validation of OQMGTO algorithm on CEC2017 test suite enhances its credibility as a powerful optimization tool. Comparison experiments are conducted in simulated terrain scenarios, including six multi-obstacle terrain scenarios and three dynamic obstacle scenarios. The experimental findings validate OOMGTO algorithm can assist UAV in searching for excellent flight paths, featuring high safety and reliability characteristics, which confirms the superiority of OOMGTO algorithm for path planning in simulated terrain scenarios. Furthermore, in four flight missions carried out in real terrains, OQMGTO algorithm demonstrates superior search performance, planning smooth trajectories without mountain collision.
