A Multimodal Self-Propelling Tensegrity Structure.

Tensegrity structure is composed of tensile cables and compressive rods, offering high stiffness-to-mass ratio, deploy ability, and excellent energy damping capability. The active and dynamic tensegrity designs demonstrate great potential for soft robots. In previous designs, the movement has relied on carefully controlled input power or manually controlled light irradiation, limiting their potential applications. Here, a hybrid tensegrity structure (HTS) is constructed by integrating thermally responsive cables, nonresponsive cables, and stiff rods. The HTS can self-propel continuously on a hot surface due to its unique geometry. The HTS allows for the easy achievement of multimodal self-propelled locomotive modes, which has been challenging for previously demonstrated self-propelling structures. Additionally, using Velcro tapes to adhere the rods and cables together, a modulable and reassemblable HTS is created. The HTS introduced in this study presents a new strategy and offers a large design space for constructing self-propelling and modulable robots.

Uncovering the selectivity mechanism of phosphodiesterase 7A/8A inhibitors through computational studies.

The expression of phosphodiesterase 7A (PDE7A) and phosphodiesterase 8A (PDE8) genes is integral to human signaling pathways, and the inhibition of PDE7A has been associated with the onset of various diseases, including effects on the immune system and nervous system. The development of PDE7 selective inhibitors can promote research on immune and nervous system diseases, such as multiple sclerosis, chronic inflammation, and autoimmune responses. PDE8A is expressed alongside PDE8B, and its inhibitory mechanism is still unclear. Studying the mechanisms of selective inhibitors against different PDE subtypes is crucial to prevent potential side effects, such as nausea and cardiac toxicity, and the sequence similarity of the two protein subtypes was 55.9%. Therefore, it is necessary to investigate the differences of both subtypes' ligand binding sites. Selective inhibitors of two proteins were chosen to summarize the reason for their selectivity through molecular docking, molecular dynamics simulation, alanine scanning mutagenesis, and MM-GBSA calculation. We found that Phe384PDE7A, Leu401PDE7A, Gln413PDE7A, Tyr419PDE7A, and Phe416PDE7A in the active site positively contribute to the selectivity towards PDE7A. Additionally, Asn729PDE8A, Phe767PDE8A, Gln778PDE8A, and Phe781PDE8A positively contribute to the selectivity towards PDE8A.

Value of Absolute Eosinophil Count in Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention.

Background and Aims: Elevated eosinophils typically indicate hypersensitive inflammation; however, their involvement in cardiovascular events remains incompletely understood. We investigated the association between the absolute eosinophil count (AEC) and major adverse cardiovascular and cerebrovascular events (MACCEs) in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). Additionally, we determine whether the integration of AEC with the SYNTAX II score could improve predictive ability. Methods and Results: The AECs of 1711 patients with ACS undergoing PCI from June 2016 to November 2017 were analyzed on admission. All recruitments were splitted into three groups based on AEC tertiles and 101 participants underwent one or more noteworthy outcomings. The association between AEC and MACCEs (defined as a composite of cardiovascular death, myocardial infarction [MI], and stroke) was tested by Cox proportional-hazards regression analysis. After adjusting for confounders, AEC was independently associated with MACCEs (HR 11.555, 95% CI: 3.318-40.239). Patients in the lowest AEC tertile (T1) as a reference, those in the higher tertiles had an incrementally higher risk of MACCEs (T3: HR 1.848 95% CI: 1.157-2.952; P for trend=0.008). Inclusion of AEC enhanced the predictive accuracy of the SYNTAX II score for MACCEs (AUC: from 0.701 [95% CI: 0.646-0.756] to 0.728 [95% CI: 0.677-0.780]; DeLong's test, P = 0.020). Conclusion: AEC is independently linked to MACCEs in ACS patients who underwent PCI, and adds incremental predictive information to the SYNTAX II score.

Mechanochromic Hydrogel Fibers with Multiple Fluorescent Colors.

Mechanochromic polymers can change their color in response to external force and have shown promising applications in stress sensing and failure warning. They are usually obtained as thin films or bulky specimens. The mechanochromic fibers, which can be used to make smart fabrics, have been seldom reported due to the lack of efficient fabrication techniques. In this work, a general method using photo-polymerization of microgel solution in a template tube to produce mechanochromic hydrogel fibers is reported. The obtained hydrogel fibers can generate visible and fluorescent color changes upon deformation. The diameter of the mechanochromic fibers can be easily adjusted by using different template tubes. The mechanochromic fibers can be fabricated as long as 1 m. By reducing the fiber diameter or increasing the microgel concentration, the mechanical properties of the mechanochromic fibers can be improved, leading to more obvious mechanochromic behavior. The polymethacrylate (PMA) is further used to coat the hydrogel fibers, prevent the loss of water in the fibers, and increase the storage time. The mechanochromic fibers with multiple fluorescent colors are further fabricated by utilizing different microgel solutions. This work provides an easy and effective method to fabricate mechanochromic fibers with different color change abilities.

Insights into the selective mechanism of PDE2/9a inhibitors from silico aspects.

The selective design of competitive enzyme inhibitors is an extremely difficult task but necessary work for certain types of systems, such as the phosphodiesterase (PDE) system addressed in this article. In the PDE family, PDE2A and PDE9 respectively target the central nervous system and heart failure, and share many conserved amino acids at their binding sites. Therefore, gaining a deep understanding of the selective mechanisms of PDE2A/9A is crucial for designing highly selective drugs. In this study, various computer-aided drug design (CADD) methods, including molecular docking, molecular dynamics simulations (MD), and binding free energy calculations, are employed to explore the selective mechanisms of PDE2A/9A. Overall, our research results indicate a selective design strategy for PDE2A, which involves incorporating hydrophobic or aromatic moieties into the molecular structure to better accommodate the hydrophobic pocket of PDE2A. Additionally, it is recommended to introduce functional groups capable of forming connections with selective residues, such as Phe830 and Gln812 for PDE2A, or Ala452 and Tyr424 for PDE9A, to enhance the selectivity of inhibitors targeting PDE2A/9A. This achievement is anticipated to pave the way for the development of innovative and selective small molecules targeting PDE2A/9A.Communicated by Ramaswamy H. Sarma.

Impact of Climate Change on the Distribution of Three Rare Salamanders (Liua shihi, Pseudohynobius jinfo, and Tylototriton wenxianensis) in Chongqing, China, and Their Conservation Implications.

The Wushan Salamander (Liua shihi), Jinfo Salamander (Pseudohynobius jinfo), and Wenxian Knobby Salamander (Tylototriton wenxianensis) are rare national Class II protected wild animals in China. We performed MaxEnt modeling to predict and analyze the potential distribution and trends of these species in Chongqing under current and future climate conditions. Species distribution data were primarily obtained from field surveys, supplemented by museum collections and the existing literature. These efforts yielded 636 records, including 43 for P. jinfo, 23 for T. wenxianensis, and 570 for L. shihi. Duplicate records within the same 100 m × 100 m grid cell were removed using ENMTools, resulting in 10, 12, and 58 valid distribution points for P. jinfo, T. wenxianensis, and L. shihi, respectively. The optimization of feature class parameters (FC) and the regularization multiplier (RM) were applied using R package "ENMeval 2.0" to establish the optimal model with MaxEnt. The refined models were applied to simulate the suitable distribution areas for the three species. The results indicate that the current suitable habitat area for L. shihi accounted for 9.72% of the whole region of the Chongqing municipality. It is projected that, by 2050, the proportion of suitable habitat will increase to 12.54% but will decrease to 11.98% by 2070 and further decline to 8.80% by 2090. The current suitable habitat area for P. jinfo accounted for 1.08% of the whole region of the Chongqing municipality, which is expected to decrease to 0.31%% by 2050, 0.20% by 2070, and 0.07% by 2090. The current suitable habitat area for T. wenxianensis accounted for 0.81% of the whole region of the Chongqing municipality, which is anticipated to decrease to 0.37% by 2050, 0.21% by 2070, and 0.06% by 2090. Human disturbance, climate variables, and habitat characteristics are the primary factors influencing the distribution of three salamander species in Chongqing. The proximity to roads significantly impacts L. shihi, while climate conditions mainly affect P. jinfo, and the distance to water sources is crucial for T. wenxianensis. The following suggestions were made based on key variables identified for each species: (1) For L. shihi, it is imperative to minimize human disturbances and preserve areas without roads and the existing vegetation within nature reserves to ensure their continued existence. (2) For P. jinfo, the conservation of high-altitude habitats is of utmost importance, along with the reduction in disturbances caused by roads to maintain the species' ecological niche. (3) For T. wenxianensis, the protection of aquatic habitats is crucial. Additionally, efforts to mitigate the impacts of road construction and enhance public awareness are essential for the preservation of this species and the connectivity of its habitats.

Anionic Sublattices in Halide Solid Electrolytes: A Case Study with the High-Pressure Phase of Li3ScCl6.

The Li3MX6 compounds (M=Sc, Y, In; X=Cl, Br) are known as promising ionic conductors due to their compatibility with typical metal oxide cathode materials. In this study, we have successfully synthesized γ-Li3ScCl6 using high pressure for the first time in this family. Structural analysis revealed that the high-pressure polymorph crystallizes in the polar and chiral space group P63mc with hexagonal close-packing (hcp) of anions, unlike the ambient-pressure α-Li3ScCl6 and its spinel analog with cubic closed packing (ccp) of anions. Investigation of the known Li3MX6 family further revealed that the cation/anion radius ratio, rM/rX, is the factor that determines which anion sublattice is formed and that in γ-Li3ScCl6, the difference in compressibility between Sc and Cl exceeds the ccp rM/rX threshold under pressure, enabling the ccp-to-hcp conversion. Electrochemical tests of γ-Li3ScCl6 demonstrate improved electrochemical reduction stability. These findings open up new avenues and design principles for lithium solid electrolytes, enabling routes for materials exploration and tuning electrochemical stability without compositional changes or the use of coatings.

Comparing the severity of second preeclampsia with first preeclampsia: a multicenter retrospective longitudinal cohort study.

OBJECTIVE: Compare the clinical severity of second preeclampsia with the first preeclampsia. METHODS: This retrospective longitudinal cohort study was conducted in three teaching hospitals in Guangzhou, where there were a total of 296 405 deliveries between 2010 and 2021. Two consecutive singleton deliveries complicated with preeclampsia were included. Clinical features, laboratory results within 1 week before delivery, and maternal and neonatal outcomes of both deliveries were collected. Univariate analyses were made using paired Wilcoxon tests and McNemar tests. Multivariable logistic regression and generalized linear models were performed to assess the association of adverse maternal and neonatal outcomes with second preeclampsia. RESULTS: A total of 151 women were included in the study. The mean maternal age was 28 and 33 years for the first and second deliveries, respectively. The proportion of preventive acetylsalicylic acid use was 4.6% for the first delivery and 15.2% for the second delivery. No significant differences were observed in terms of blood pressure on admission, gestational weeks of admission and delivery, application of perinatal antihypertensive agents, rates of preterm delivery, and severe features between the two occurrences. However, the rates of heart disease, edema, and admission to the ICU were lower, and hospital stays were shorter in the second preeclampsia compared with the first preeclampsia. Sensitivity analysis conducted among women who did not use preventive acetylsalicylic acid yielded similar results. After adjusting for potential confounding variables, the occurrence of second preeclampsia was associated with significantly decreased risks of heart disease, edema, complications, and admission to the NICU, with odds ratios ranging between 0.157 and 0.336. CONCLUSION: Contrary to expectations, the second preeclampsia did not exhibit worse manifestations or outcomes to the first occurrence. In fact, some clinical features and outcomes appeared to be better in the second preeclampsia.

Preliminary study of the effect of low-intensity focused ultrasound on postpartum uterine involution and breast pain in puerperal women: a randomised controlled trial.

To evaluate the safety and efficacy of low-intensity focused ultrasound (LIFU) therapy in facilitating fundus descent and relieving postpartum breast pain compared with sham treatment. A multicentre, randomised, sham-controlled, blinded trial was conducted. A cohort of 176 eligible participants, who had normal prenatal check-ups and met the inclusion and exclusion criteria, were recruited from three medical centres and subsequently randomized into either the LIFU or sham group. All participants received three treatment sessions, wherein LIFU signal was applied to the uterus and breast sites using coupling gel, with the absence of ultrasound signal output in the sham group. Fundal height measurement and breast pain score were performed after each treatment. The primary outcome, uterine involution, was presented by measuring the fundal height of the uterus. The visual analogue scale (VAS) score, as a secondary outcome, was used to assess breast pain and determine the correlation between breast pain and fundal height as the outcome simultaneously. All participants were randomly assigned to either the LIFU group (n = 88) or sham group (n = 88), with seven individuals not completing the treatment. Overall, a statistically significant difference was noted in the rate and index of fundus descent after each treatment. The rate and index of fundus descent showed greater significance following the second treatment (rate: 1.5 (1.0, 2.0) cm/d; index: 0.15 (0.1, 0.18), P < 0.001) and third treatment (rate: 1.67 (1.33, 2.0) cm/d; index: 0.26 (0.23, 0.3), P < 0.001) in the LIFU group. VAS scores, which were based on the continuous variables for the baseline, first, second, and third treatments in the LIFU group (2.0 (2.0, 3.0), 1.0 (0.0, 2.0), 0.0 (0.0, 1.0), and 0.0 (0.0, 0.0) points, respectively), and the sham group (2.0 (2.0, 2.0), 2.0 (1.0, 2.0), 2.0 (1.0, 3.0), and 3.0 (1.0, 3.0) points, respectively), showed a statistically significant difference between the two groups. Meanwhile, the discrepancies in VAS score classification variables between the two groups were statistically significant. After the third treatment, a notable correlation was observed between the VAS score decrease and fundus descent rate; the more the VAS score decreased, the faster was the fundal decline rate in the LIFU group. LIFU therapy is safe and effective, contributing to the acceleration of uterine involution and the relief of postpartum breast pain.Trial ID The study has registered in the Chinese Clinical Trial Registry (ChiCTR2100049586) at 05/08/2021.

Prognosis of Elevated Mitral Valve Pressure Gradient After Transcatheter Edge-to-Edge Repair: Systematic Review and Meta-Analysis.

Elevation in mitral valve pressure gradient (MVPG) after mitral valve transcatheter edge-to-edge repair (M-TEER) is common, however, evidence on its prognosis is scarce and debatable. Thus, this study aims to investigate the impact of increased MVPG after M-TEER on outcomes. Studies reporting the associations between the elevated MVPG after M-TEER and outcomes were identified in a systematic search of published literatures. Associations were pooled by meta-analysis using a random-effects model. The primary outcome was the composite of all-cause mortality and heart failure (HF) hospitalization. Seven observational studies with 2,730 patients (mean age, 77.7 ± 9.3 years; male, 64.4%; functional mitral regurgitation [MR], 65.2%) were eligible for the present analysis. M-TEER was performed entirely using the MitraClip system (Abbott), followed by 29.7% of patients having increased MVPG. Elevated postprocedural MVPG was not associated with a higher risk of the primary outcome, compared to low MVPG [hazard ratio (HR) = 1.22; 95% confidence interval (CI) 0.95-1.58; p = 0.12; I2 = 53.5%). However, the prognosis of elevated MVPG was observed in degenerative MR patients (HR = 1.37; 95% CI 1.03-1.84; p = 0.03; I2 = 0%), whereas not in functional MR patients. Patients with low MVPG + high residual MR had a higher risk of the primary outcome than those with high MVPG + low residual MR after M-TEER (HR = 1.50; 95% CI 1.10-2.03; p = 0.01; I2 = 13%). In conclusion, elevated MVPG seems to predict adverse outcomes mainly in patients with degenerative MR. Future studies are needed to prove these findings.

Development, validation, and clinical utility of a risk prediction model for recurrent preeclampsia.

OBJECTIVES: We aim to establish a predictive model for recurrent preeclampsia. METHODS: A retrospective review of medical records from three hospitals between 2010 and 2021 was conducted. The study included women who had two consecutive singleton deliveries at the same hospital, with the first delivery complicated by preeclampsia. A multivariable logistic regression model was constructed using a training cohort, and subsequently cross-validated and tested using an independent cohort. The model's performance was assessed in terms of discrimination and calibration, and its clinical utility was evaluated using decision curve analysis (DCA). RESULTS: Among 296 405 deliveries, 694 women met the inclusion criteria, with 151 (21.8%) experiencing recurrent preeclampsia. The predictive model incorporated 10 risk factors from previous preeclampsia, including gestational weeks with elevated blood pressure, gestational diabetes mellitus (GDM), pericardial effusion, heart failure, limb edema, serum creatinine, white blood cell count, low platelet counts within one week before delivery, SBP on the first postpartum day, and postpartum antihypertensive use. Additionally, one risk factor from the index pregnancy was included, which was antihypertensive use before 20 weeks. The model demonstrated better discrimination, calibration, and a net benefit across a wide range of recurrent preeclampsia risk thresholds. Furthermore, the model has been translated into a clinical risk calculator, enabling clinicians to calculate individualized risks of recurrent preeclampsia. CONCLUSION: Our study demonstrates that a predictive tool utilizing routine clinical and laboratory factors can accurately estimate the risk of recurrent preeclampsia. This predictive model has the potential to facilitate shared decision-making by providing personalized and risk-stratified care.

Diallyl disulfide synergizes with melphalan to increase apoptosis and DNA damage through elevation of reactive oxygen species in multiple myeloma cells.

Diallyl disulfide (DADS), one of the main components of garlic, is well known to have anticancer effects on multiple cancers. However, its efficacy in treating multiple myeloma (MM) is yet to be determined. We explored the effects of DADS on MM cells and investigated the synergistic effects of DADS when combined with five anti-MM drugs, including melphalan, bortezomib, carfilzomib, doxorubicin, and lenalidomide. We analyzed cell viability, cell apoptosis, and DNA damage to determine the efficacy of DADS and the drug combinations. Our findings revealed that DADS induces apoptosis in MM cells through the mitochondria-dependent pathway and increases the levels of γ-H2AX, a DNA damage marker. Combination index (CI) measurements indicated that the combination of DADS with melphalan has a significant synergistic effect on MM cells. This was further confirmed by the increases in apoptotic cells and DNA damage in MM cells treated with the two drug combinations compared with those cells treated with a single drug alone. The synergy between DADS and melphalan was also observed in primary MM cells. Furthermore, mechanistic investigations showed that DADS decreases reduced glutathione (GSH) levels and increases reactive oxygen species (ROS) production in MM cells. The addition of GSH is effective in neutralizing DADS cytotoxicity and inhibiting the synergy between DADS and melphalan in MM cells. Taken together, our study highlights the effectiveness of DADS in treating MM cells and the promising therapeutic potential of combining DADS and melphalan for MM treatment.

Reduced graphene oxide/SiC nanowire composite aerogel prepared by a hydrothermal method with excellent thermal insulation performance and electromagnetic wave absorption performance.

In aerospace and downhole exploration, materials must function reliably in challenging environments characterized by high temperatures and complex electromagnetic (EM) interference. Graphene oxide (GO) aerogels are promising materials for thermal insulation, and the incorporation of silicon carbide nanowires can enhance their mechanical properties, thermal stability and EM absorption efficiency. In this context, citric acid acts as both a cross-linking and reducing agent, facilitating the formation of a composite aerogel comprising GO and SiC nanowires (rGO/m-SiC NWs). Compared with GO aerogels, the representative composite aerogel sample rGS4 demonstrated significantly improved mechanical properties (yield strength increased by 0.031 MPa), outstanding thermal stability (ability to withstand temperatures up to 800 °C) and remarkably low thermal conductivity (measuring just 0.061 W m-1K-1). Importantly, the composite aerogels displayed impressive EM absorption characteristics, including a slim profile (2.5 mm), high absorption capacity (-42.23 dB) and an exceptionally broad effective absorption bandwidth (7.47 GHz). Notably, the specific effective absorption bandwidth of composite aerogels exceeded that of similar composite materials. In conclusion, rGO/m-SiC NWs exhibited exceptional mechanical properties, remarkable thermal stability, efficient thermal insulation and outstanding microwave absorption capabilities. These findings highlight their potential for use in high-temperature and electromagnetically challenging environments.

Comparison of percutaneous coronary intervention of native coronary artery versus bypass graft in patients with prior coronary artery bypass grafting.

Background: Large number of patients with prior coronary artery bypass grafting (CABG) need repeat revascularization yearly, and percutaneous coronary intervention (PCI) is the optimal treatment strategy for such patients. However, it is still controversial whether PCI of native coronary artery or bypass graft is more beneficial. The aim of the study was to compare the clinical outcomes between native coronary artery vs. bypass graft PCI in patients with prior CABG. Methods: A total of 1,276 patients with prior CABG who underwent index PCI of native coronary artery (n=1,072) or bypass graft (n=204) were retrospectively examined. Patients were divided into native group and graft group according to the target vessel. The outcomes of the two groups were compared by using inverse probability of treatment weighting (IPTW) and Cox regression analysis. The primary endpoint was the composite of major adverse cardiac and cerebrovascular events (MACCEs), which included all-cause death, non-fatal stroke, non-fatal myocardial infarction (MI), or target vessel revascularization (TVR). Results: Compared with native group, patients in graft group had higher risk of slow-flow/no-reflow phenomenon (1.5% vs. 0.1%, P=0.011 before IPTW, and 2.2% vs. 0.1%, P<0.001 after IPTW) and peri-procedural stroke (0.3% vs. 0, P=0.021 after IPTW). During a median follow-up period of 43 months, there was similar risk of MACCE between two groups. Notably, patients in graft group had a significantly higher incidence of non-fatal MI compared with native group regardless with or without IPTW (7.8% vs. 3.8%, P=0.018 and 8.3% vs. 3.9%, P=0.030, separately). After adjusting for confounding by using Cox regression, bypass graft PCI was associated with a higher risk of non-fatal MI (HR: 2.091, 95% CI: 1.069-4.089; P=0.031), but similar results in MACCE (HR: 1.077, 95% CI: 0.817-1.419; P=0.599) compared with native group. Conclusions: This study found that native coronary artery might be preferred for PCI in patients with prior CABG because of lower rates of slow-flow/no-reflow, peri-procedural stroke, and non-fatal MI at follow-up.

Triglyceride-glucose index is associated with poor prognosis in acute coronary syndrome patients with prior coronary artery bypass grafting undergoing percutaneous coronary intervention.

BACKGROUND: The triglyceride-glucose (TyG) index, which is a reliable substitute indicator for insulin resistance, has been considered an independent risk factor for long-term outcomes in patients with cardiovascular disease. However, it remains unknown whether the TyG index is associated with poor prognosis in acute coronary syndrome (ACS) patients with prior coronary artery bypass grafting (CABG) undergoing percutaneous coronary intervention (PCI). METHODS: A total of 1158 ACS patients with prior CABG undergoing PCI were retrospectively studied. The TyG index was calculated by ln[fasting triglyceride (mg/dL) × fasting blood glucose (mg/dL)/2]. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE), a composite of all-cause death, nonfatal myocardial infarction, nonfatal stroke, and unplanned repeat revascularization. RESULTS: During a median of 42-month follow-up, 350 patients (30.2%) experienced at least one endpoint event. Based on the optimal cut-off value of the TyG index, patients were divided into the high TyG index group and the low TyG index group. Patients in the high TyG index group had higher risks of MACCE (35.3% vs. 25.3%, p < 0.001), major adverse cardiovascular events (MACE) (31.1% vs. 23.4%, p = 0.003), nonfatal stroke (4.2% vs. 1.9%, p = 0.022) and unplanned repeat revascularization (19.4% vs. 11.3%, p < 0.001) than those in the low TyG index group. Cox regression analysis demonstrated that there was an independent association between the TyG index and MACCE regardless of whether the TyG index was a continuous or categorical variable (HR 1.42, 95% CI 1.09-1.86, p = 0.009; HR 1.53, 95% CI 1.16-2.01, p = 0.003, respectively). Restricted cubic spline curve exhibited that the relationship between the TyG index and MACCE was linear (p for non-linear = 0.595, p for overall = 0.005). By incorporating the TyG index groups into baseline risk model, the accuracy of predicting MACCE was improved [AUC: baseline risk model, 0.618 vs. baseline risk model + TyG index groups, 0.636, p for comparison = 0.042]. CONCLUSIONS: The TyG index is independently associated with MACCE, suggesting that the TyG index may serve as a valid indicator for predicting poor prognosis in ACS patients with prior CABG undergoing PCI.

[Retracted] Role of microRNA­210 in human intervertebral disc degeneration.

[This retracts the article DOI: 10.3892/etm.2016.3176.].

Identification of pyroptosis-related genes in NASH based on bioinformatic analysis.

The objective of this research was to investigate whether or if there is a connection between genes associated with pyroptosis and novel approaches to the diagnosis and treatment of NASH. The mRNA expression patterns of the gene expression dataset GSE135251 integrated (GEO) database were analyzed, and a total of 60 genes related to scorch death were extracted and included in the PubMed database. Methods from the field of bioinformatics were utilized to investigate the degrees to which differentially expressed genes and pyroptosis-related genes differed between NASH patients and healthy controls. As a result of this, the Centre for Genetic Research has now come around to accepting enrichment and PPI interaction analyses. GSE89632 and NASH models were evaluated, trained, qualified, and validated by 18 of the links between the expression of hub genes. PLCG1 expression raised NASH in the progress of the disease. PLCG1 expression levels were then validated by Western Blot and qRT-PCR in FFA-induced HepG2 cells and mouse liver tissues. An analysis of mRNA expression of cleaved-caspase 3, GSDMD, and GSDME in NASH models. In addition, the PLCG1based diagnostic model successfully discriminated NASH from normal samples. Collectively, our results imply that PLCG1 is significantly associated with NASH and may be a biomarker for pyroptosis-related disease.

Based on disulfidptosis-related glycolytic genes to construct a signature for predicting prognosis and immune infiltration analysis of hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) comprises several distinct molecular subtypes with varying prognostic implications. However, a comprehensive analysis of a prognostic signature for HCC based on molecular subtypes related to disulfidptosis and glycolysis, as well as associated metabolomics and the immune microenvironment, is yet to be fully explored. Methods: Based on the differences in the expression of disulfide-related glycolytic genes (DRGGs), patients with HCC were divided into different subtypes by consensus clustering. Establish and verify a risk prognosis signature. Finally, the expression level of the key gene SLCO1B1 in the signature was evaluated using immunohistochemistry (IHC) and quantitative real-time PCR (qRT-PCR) in HCC. The association between this gene and immune cells was explored using multiplex immunofluorescence. The biological functions of the cell counting kit-8, wound healing, and colony formation assays were studied. Results: Different subtypes of patients have specific clinicopathological features, prognosis and immune microenvironment. We identified seven valuable genes and constructed a risk-prognosis signature. Analysis of the risk score revealed that compared to the high-risk group, the low-risk group had a better prognosis, higher immune scores, and more abundant immune-related pathways, consistent with the tumor subtypes. Furthermore, IHC and qRT-PCR analyses showed decreased expression of SLCO1B1 in HCC tissues. Functional experiments revealed that SLCO1B1 overexpression inhibited the proliferation, migration, and invasion of HCC cells. Conclusion: We developed a prognostic signature that can assist clinicians in predicting the overall survival of patients with HCC and provides a reference value for targeted therapy.

Universal response method for accurate quantitative analysis of the impurities in quinolone antibiotics using liquid chromatography coupled with diode array detector and charged aerosol detector.

HPLC method is the standard method for the separation and quantification of impurities from quinolone antibiotics. However, due to the large differences in the UV absorption of the impurities in quinolone antibiotics, quantitative analysis without the availability of corresponding reference substances currently poses a challenge. A sensitive and direct method using high performance liquid chromatography coupled with diode array detector and charged aerosol detector (HPLC-DAD-CAD) was developed for the analysis of impurities in quinolone antibiotics. The chromatographic conditions were optimized for good separation and output signal of CAD detector by response surface method (RSM). The systematic variation of CAD parameter settings, such as nebulization temperature, filter constant and power function value (PFV), were used to study the effect of on the detector response of signal-to-noise ratios (S/N) and linearity for ofloxacin, ciprofloxacin and their impurities. In the method validation, good linearity of each component was obtained with coefficient of determination (r) greater than 0.999 in the range of 0.5-300 µg mL-1. The average recoveries of each component were 99.02-102.39 % by DAD, were 98.22-101.91 % by CAD, RSDs were less than 2.5 % for intra-day and inter-day precision by DAD-CAD, with good precision and accuracy. The correction factor experimental results showed that the developed method provided a uniform response to the impurities with differences chromophores and could unbiasedly and directly detect the impurities in quinolone antibiotics. The method is first reported application of HPLC-DAD-CAD method for the analysis of impurities in quinolone antibiotics and it can be used for quality control of quinolone antibiotics.