Long term online desalting analysis of MS/LC-MS using thermal assisted recrystallization ionization.

Mass spectrometric analysis of non-volatile salts containing samples remains challenging due to salt-induced ion suppression and contamination. This challenge is even more pronounced for a liquid chromatography-mass spectrometry analysis, where the accumulation of salts in the transmission system poses an ongoing problem. In this study, a novel thermal assisted recrystallization ionization mass spectrometry (TARI-MS) device was developed to achieve efficient on-line desalting and prolonged analysis of saline samples. The core component of this device was a heated plate positioned between the electrospray unit and the MS inlet. The desalting mechanism was demonstrated as the spontaneous separation of target molecules from salts during the "crystallization" process. After optimization, the angle between the nebulizer and the heated plate was 45°; the distance between the front end of the heated plate and the MS inlet was 2 mm; the distance between the front edge of the heated plate and the center of the sample spray projected onto the heating plate was 3 mm; the distance between the emitter of nebulizer and the heated plate was 3 mm. TARI-MS realized direct analysis of eight drugs dissolved in eight commonly used non-volatile salts solutions (up to 0.5 mol/L). The high sensitivity, repeatability, linearity, accuracy, and intra- and inter-day precision of TARI-MS confirm its reliability as a robust tool for the analysis of saline samples. Furthermore, TARI-MS allowed continuous analysis of salty eluates of LC for up to nearly 1 h without maintenance and verified the feasibility of LC-MS analysis through detecting a five-drug mixture and a crude aripiprazole product. Finally, six impurities in the crude aripiprazole product were successfully detected by LC-TARI-MS. The established method holds promise for applications across academic and pharmaceutical domains.

Food therapy of scutellarein ameliorates pirarubicin­induced cardiotoxicity in rats by inhibiting apoptosis and ferroptosis through regulation of NOX2­induced oxidative stress.

Pirarubicin (THP) is one of the most commonly used antineoplastic drugs in clinical practice. However, its clinical application is limited due to its toxic and heart­related side effects. It has been reported that oxidative stress, inflammation and apoptosis are closely associated with cardiotoxicity caused by pirarubicin (CTP). Additionally, it has also been reported that scutellarein (Sc) exerts anti­inflammatory, antioxidant, cardio­cerebral vascular protective and anti­apoptotic properties. Therefore, the present study aimed to investigate the effect of food therapy with Sc on CTP and its underlying molecular mechanism using echocardiography, immunofluorescence, western blot, ROS staining, and TUNEL staining. The in vivo results demonstrated that THP was associated with cardiotoxicity. Additionally, abnormal changes in the expression of indicators associated with oxidative stress, ferroptosis and apoptosis were observed, which were restored by Sc. Therefore, it was hypothesized that CTP could be associated with oxidative stress, ferroptosis and apoptosis. Furthermore, the in vitro experiments showed that Sc and the NADPH oxidase 2 (NOX2) inhibitor, GSK2795039 (GSK), upregulated glutathione peroxidase 4 (GPX4) and inhibited THP­induced oxidative stress, apoptosis and ferroptosis. However, cell treatment with the ferroptosis inhibitor, ferrostatin­1, or inducer, erastin, could not significantly reduce or promote, respectively, the expression of NOX2. However, GSK significantly affected ferroptosis and GPX4 expression. Overall, the results of the present study indicated that food therapy with Sc ameliorated CTP via inhibition of apoptosis and ferroptosis through regulation of NOX2­induced oxidative stress, thus suggesting that Sc may be a potential therapeutic drug against CTP.

Protein extraction from chlorella pyrenoidosa microalgae: Green methodologies, functional assessment, and waste stream valorization for bioenergy production.

C. pyrenoidosa, a species of microalgae, has been recognized as a viable protein source for human consumption. The primary challenges in this context are the development of an efficient extraction process and the valorization of the resultant waste streams. This study, situated within the paradigm of circular economy, presents an innovative extraction approach that achieved a protein extraction efficiency of 62 %. The extracted protein exhibited remarkable oil-water emulsifying performances, such as uniform morphology with high creaming stability, suggesting a sustainable alternative to conventional emulsifiers. Additionally, hydrothermal liquefaction technique was employed for converting the residual biomass and waste solution from the extraction process into biocrude. A biocrude yield exceeding 40 wt%, characterized by a carbon content of 73 % and a higher heating value of 36 MJ/kg, were obtained. These findings demonstrate the promising potential of microalgae biorefinery, which is significant for paving toward circular economy and zero-waste society.

SPARC stabilizes ApoE to induce cholesterol-dependent invasion and sorafenib resistance in hepatocellular carcinoma.

Dysregulation of cholesterol homeostasis is implicated in the development and progression of hepatocellular carcinoma (HCC) that is characterized by intrahepatic and early extrahepatic metastasis. A better understanding of the underlying mechanisms regulating cholesterol metabolism in HCC could help identify strategies to circumvent the aggressive phenotype. Here, we found that high expression of intracellular SPARC was significantly associated with elevated cholesterol levels and an enhanced invasive phenotype in HCC. SPARC potentiated cholesterol accumulation in HCC cells during tumor progression by stabilizing the ApoE protein. Mechanistically, SPARC competitively bound to ApoE, impairing its interaction with the E3 ligase tripartite motif containing 21 (TRIM21) and preventing its ubiquitylation and subsequent degradation. ApoE accumulation led to cholesterol enrichment in HCC cells, stimulating PI3K-AKT signaling and inducing epithelial-mesenchymal transition (EMT). Importantly, sorafenib-resistant HCC cells were characterized by increased expression of intracellular SPARC, elevated cholesterol levels, and enhanced invasive capacity. Inhibiting SPARC expression or reducing cholesterol levels enhanced the sensitivity of HCC cells to sorafenib treatment. Together, these findings unveil interplay between SPARC and cholesterol homeostasis. Targeting SPARC-triggered cholesterol-dependent oncogenic signaling is a potential therapeutic strategy for advanced HCC.

Simultaneous ultrasound and microwave application in myosin-chlorogenic acid conjugation: Unlocking enhanced emulsion stability.

This study investigated the grafting chlorogenic acid (CA) onto myosin, utilizing various techniques including conventional method, ultrasound, microwave, and combination of ultrasound and microwave (UM). The grafting efficiency was as follows: conventional method < microwave < ultrasound < UM. The UM technique manifested the highest CA-binding capacity (80.26 µmol/g myosin) through covalent bonding, and a much shorter time was required for conjugation than conventional method. The conjugation of polyphenol significantly increased the solubility of myosin with reduced aggregation behavior, which was accompanied by structural alterations from ordered structures (α-helix and ß-sheet) to disordered forms. The emulsion stabilized by UM-myosin-CA conjugate exhibited the most homogeneous microstructure with favorable creaming stability. Moreover, the resulting emulsion presented strong oxidation resistance and storage stability. These results illustrate the promising potential of employing CA-grafted myosin, especially when processed using the UM technique, in the development of highly efficient emulsifiers.

Resveratrol modulates the Nrf2/NF-kB pathway and inhibits TSLP-mediated atopic march

Background: Resveratrol has been found to have anti-inflammatory and anti-allergic proper-ties. The effects of resveratrol on thymic stromal lymphopoietin (TSLP)-mediated atopic march remain unclear. Purpose: To explore the potential role of resveratrol in TSLP-mediated atopic march.Methods: The atopic march mouse model was established by topical application of MC903 (a vitamin D3 analog). Following the treatment with resveratrol, airway resistance in mice was discovered by pulmonary function apparatus, and the number of total cells, neutrophils, and eosinophils in bronchoalveolar lavage fluid was counted. The histopathological features of pul-monary and ear skin tissues, inflammation, and cell infiltration were determined by hematoxy-lin and eosin staining. The messenger RNA (mRNA) levels of TSLP, immunoglobulin E, interleukin (IL)-4, IL-5, and IL-13 were measured by real-time quantitative polymerase chain reaction. The protein expression of nuclear factor kappa B (NF-κB)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling-associated molecules (p-p65, p65, p-I kappa B kinase alpha (IκBα), IκBα, Nrf2, and TSLP) in lung and ear skin tissues were assessed by Western blot analysis.Results: Resveratrol attenuated airway resistance and infiltration of total cells, eosinophils, and neutrophils in both lung and ear skin tissues. Resveratrol ameliorates serum inflammatory markers in allergic mice. Moreover, the phosphorylation levels of NF-κB pathway-related pro-teins were significantly reduced by administration of resveratrol in allergic lung and ear skin tissues. Similarly, the protein expression of TSLP in both lung and ear skin tissues was reduced by resveratrol, and Nrf2, a protector molecule, was increased with resveratrol treatment (AU)

A review: Hydrochar as potential adsorbents for wastewater treatment and CO2 adsorption.

To valorize the biomass and organic waste, hydrothermal carbonization (HTC) stands out as a highly efficient and promising pathway given its intrinsic advantages over other thermochemical processes. Hydrochar, as the main product obtained from HTC, is widely applied as a fuel source and soil conditioner. Aside from these applications, hydrochar can be either directly used or modified as bio-adsorbents for environmental remediation. This potential arises from its tunable surface chemistry and its suitability to act as a precursor for activated or engineered carbon. In view of the importance of this topic, this review offers a thorough examination of the research progress for using hydrochar and its modified forms to remove organic dyes (cationic and anionic dyes), heavy metals, herbicides/pesticides, pharmaceuticals, and CO2. The review also sheds light on the fundamental chemistry involved in HTC of biomass and the major analytical techniques applied for understanding surface chemistry of hydrochar and modified hydrochar. The knowledge gaps and potential hurdles are identified to highlight the challenges and prospects of this research field with a summary of the key findings from this review. Overall, this article provides valuable insights and directives and pinpoints the areas meriting further investigation in the application potential of hydrochar in wastewater management and CO2 capture.

Occurrence, fate, and potential impacts of wood preservatives in the environment: Challenges and environmentally friendly solutions.

Wood preservation has gained global prevalence in recent years, primarily owing to the renewable nature of wood and its capacity to act as a carbon sink. Wood, in its natural form, lacks intrinsic resilience and is prone to decay if left untreated; hence, wood preservatives (WPs) are used to improve wood's longevity. The fate and potential hazards of wood preservatives to human health, ecosystems, and the environment are complex and depend on various aspects, including the type of the preservative compounds, their physicochemical properties, application methods, exposure pathways, environmental conditions, and safety measures and guidelines. The occurrence and distribution of WPs in environmental matrices such as soil and water can result in hazardous pollutants seeping into surface water, groundwater, and soil, posing health hazards, and polluting the environment. Bioremediation is crucial to safeguarding the environment and effectively removing contaminants through hydrolytic and/or photochemical reactions. Phytoremediation, vermicomposting, and sustainable adsorption have demonstrated significant efficacy in the remediation of WPs in the natural environment. Adsorbents derived from biomass waste have been acknowledged for their ability to effectively remove WPs, while also offering cost-efficiency and environmental sustainability. This paper aims to identify wood preservatives' sources and fate in the environment and present a comprehensive overview of the latest advancements in environmentally friendly methods relevant to the removal of the commonly observed contaminants associated with WPs in environmental matrices.

Whole­exome sequencing reveals Lewis lung carcinoma is a hypermutated Kras/Nras-mutant cancer with extensive regional mutation clusters in its genome.

Lewis lung carcinoma (LLC), as a widely used preclinical cancer model, has still not been genetically and genomically characterized. Here, we performed a whole-exome sequencing analysis on the LLC cell line to elucidate its molecular characteristics and etiologies. Our data showed that LLC originated from a male mouse belonging to C57BL/6L (a transitional strain between C57BL/6J and C57BL/6N) and contains substantial somatic SNV and InDel mutations (> 20,000). Extensive regional mutation clusters are present in its genome, which were caused mainly by the mutational processes underlying the SBS1, SBS5, SBS15, SBS17a, and SBS21 signatures during frequent structural rearrangements. Thirty three deleterious mutations are present in 30 cancer genes including Kras, Nras, Trp53, Dcc, and Cacna1d. Cdkn2a and Cdkn2b are biallelically deleted from the genome. Five pathways (RTK/RAS, p53, cell cycle, TGFB, and Hippo) are oncogenically deregulated or affected. The major mutational processes in LLC include chromosomal instability, exposure to metabolic mutagens, spontaneous 5-methylcytosine deamination, defective DNA mismatch repair, and reactive oxygen species. Our data also suggest that LLC is a lung cancer similar to human lung adenocarcinoma. This study lays a molecular basis for the more targeted application of LLC in preclinical research.

Resveratrol modulates the Nrf2/NF-κB pathway and inhibits TSLP-mediated atopic march.

BACKGROUND: Resveratrol has been found to have anti-inflammatory and anti-allergic properties. The effects of resveratrol on thymic stromal lymphopoietin (TSLP)-mediated atopic march remain unclear. PURPOSE: To explore the potential role of resveratrol in TSLP-mediated atopic march. METHODS: The atopic march mouse model was established by topical application of MC903 (a vitamin D3 analog). Following the treatment with resveratrol, airway resistance in mice was discovered by pulmonary function apparatus, and the number of total cells, neutrophils, and eosinophils in bronchoalveolar lavage fluid was counted. The histopathological features of pulmonary and ear skin tissues, inflammation, and cell infiltration were determined by hematoxylin and eosin staining. The messenger RNA (mRNA) levels of TSLP, immunoglobulin E, interleukin (IL)-4, IL-5, and IL-13 were measured by real-time quantitative polymerase chain reaction. The protein expression of nuclear factor kappa B (NF-κB)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling-associated molecules (p-p65, p65, p-I kappa B kinase alpha (IκBα), IκBα, Nrf2, and TSLP) in lung and ear skin tissues were assessed by Western blot analysis. RESULTS: Resveratrol attenuated airway resistance and infiltration of total cells, eosinophils, and neutrophils in both lung and ear skin tissues. Resveratrol ameliorates serum inflammatory markers in allergic mice. Moreover, the phosphorylation levels of NF-κB pathway-related proteins were significantly reduced by administration of resveratrol in allergic lung and ear skin tissues. Similarly, the protein expression of TSLP in both lung and ear skin tissues was reduced by resveratrol, and Nrf2, a protector molecule, was increased with resveratrol treatment. CONCLUSION: Resveratrol attenuates TSLP-reduced atopic march through ameliorating inflammation and cell infiltration in pulmonary and ear skin tissues by inhibiting the abnormal activation of NF-κB signaling pathway.

Molecular design and systematic optimization of a halogen-bonding system between the asthma interleukin-5 receptor and its cyclic peptide ligand.

Human interleukin-5 (IL-5) functions as an important pro-inflammatory factor by binding to its specific receptor, IL-5Rα, which has been implicated in the pathogenesis of asthma. Previously, a disulfide-bonded cyclic peptide AF17121 obtained from random library screening and sequence variation was found to competitively disrupt the cognate IL-5Rα/IL-5 interaction with moderate potency. In this study, the crystal complex of IL-5Rα with AF17121 was investigated at structural and energetic levels. It is revealed that the side-chain indole moiety of the AF17121 Trp5 residue is a potential site for a stem putative halogen bond (X-bond) with IL-5Rα, which is just located within the key 3 EXXR6 motif region recognized specifically by IL-5Rα. We systematically examined four halogen substitution types at five positions of the indole moiety; QM/MM calculations theoretically unraveled that only halogenations at 5 and 6 positions can form effective X-bonds with the side-chain hydroxyl oxygen of the IL-5Rα Thr21 residue and the backbone carbonyl oxygen of Ala66 residue, respectively. Binding assays observed that I-substitution at the 5 position and Br-substitution at the 6 position can result in two potent halogenated peptides, [5I]AF17121 and [6Br]AF17121, which are improved by 1.6-fold and 3.5-fold relative to the native AF17121, respectively. 5I/6Br-double substitution, resulting in [5I/6Br]AF17121, can further enhance the peptide affinity by 7.5-fold. Structural analysis revealed that the X-bond stemming from 6Br-substitution is also involved in an orthogonal interaction system with a H-bond; they share a common backbone carbonyl oxygen acceptor of IL-5Rα Ala66 residue and exhibit a significant synergistic effect between them.

Resolution of trans-1,2-cyclohexanedicarboxylic acid containing two carboxylic groups by forming diastereomeric salts based on feeding molar ratio control.

To investigate the thermodynamic and molecular self-assembly mechanism of trans-1,2-cyclohexane dicarboxylic acid containing two carboxylic acid groups in the chiral resolution process, (S)-phenylethylamine was used as the chiral resolving agent. Two stoichiometric salts were formed when the raw materials were fed at different molar ratios: cyclohexane dicarboxylate monophenylethylamine salt and cyclohexane dicarboxylate diphenylethylamine salt. When the molar ratio of the (S)-phenylethylamine to trans-1,2-cyclohexane dicarboxylic acid was less than 3:1, trans-(1S,2S)-cyclohexane dicarboxylic acid was obtained with 97 e.e% purity. But when the molar ratio exceeded 3:1, the product was the racemic trans-(1,2)-cyclohexane dicarboxylic acid. In addition, single crystal structures of more soluble mono-salt, less soluble mono-salt, and less soluble di-salt were obtained. The weak intermolecular interactions and the way of the molecules packing in the crystals were analyzed. The hydrogen bond was stronger in the less soluble salt than that in the more soluble salt. And a "lock-and-key" structure in the hydrophobic layers makes it more tightly packed through the van der Waals interaction, which is responsible for the stability of less soluble salts.

Manifestations and Outcomes of Intracerebral Hemorrhage During the COVID-19 Pandemic in China: Multicenter, Longitudinal Cohort Study.

BACKGROUND: The COVID-19 pandemic has inevitably affected the distribution of medical resources, and epidemic lockdowns have had a significant impact on the nursing and treatment of patients with other acute diseases, including intracerebral hemorrhage (ICH). OBJECTIVE: This study aimed to investigate how the COVID-19 pandemic affected the manifestations and outcomes of patients with ICH. METHODS: Patients with acute ICH before (December 1, 2018-November 30, 2019) and during (December 1, 2019-November 30, 2020) the COVID-19 pandemic at 31 centers in China from the Chinese Cerebral Hemorrhage: Mechanism and Intervention (CHEERY) study were entered into the analysis. Demographic information and clinical manifestations and outcomes were collected and compared between the 2 groups. RESULTS: From December 1, 2018, to November 30, 2020, a total of 3460 patients with ICH from the CHEERY study were enrolled and eventually analyzed. The results showed that during the COVID-19 pandemic, patients with ICH were more likely to be older (P<.001) with a history of ischemic stroke (P=.04), shorter time from onset to admission (P<.001), higher blood pressure (P<.001), higher fasting blood glucose (P=.003), larger hematoma volume (P<.001), and more common deep ICH (P=.01) and intraventricular hemorrhage (P=.02). These patients required more intensive care unit treatment (P<.001) and preferred to go to the hospital directly rather than call an ambulance (P<.001). In addition, the COVID-19 pandemic was associated with an increased risk of pulmonary infection during hospitalization (adjusted risk ratio [RRadjusted] 1.267, 95% CI 1.065-1.509), lower probability of a 3-month good outcome (RRadjusted 0.975, 95% CI 0.956-0.995), and a higher probability of in-hospital (RRadjusted 3.103, 95% CI 2.156-4.465), 1-month (RRadjusted 1.064, 95% CI 1.042-1.087), and 3-month (RRadjusted 1.069, 95% CI 1.045-1.093) mortality. CONCLUSIONS: Our study indicated that the cloud of COVID-19 has adversely impacted the presentation and outcomes of ICH. Medical workers may pay more attention to patients with ICH, while the public should pay more attention to hypertension control and ICH prevention. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900020872; https://www.chictr.org.cn/showprojEN.html?proj=33817.

Enzymatic digestibility of lignocellulosic wood biomass: Effect of enzyme treatment in supercritical carbon dioxide and biomass pretreatment.

Energy and resource intensive mechanical and chemical pretreatment along with the use of hazardous chemicals are major bottlenecks in widespread lignocellulosic biomass utilization. Herein, the study investigated different pretreatment methods on spruce wood namely supercritical CO2 (scCO2) pretreatment, ultrasound-assisted alkaline pretreatment, and acetosolv pulping-alkaline hydrogen peroxide bleaching, to enhance the enzymatic digestibility of wood using optimized enzyme cocktail. Also, the effect of scCO2 pretreatment on enzyme cocktail was investigated after optimizing the concentration and temperature of cellulolytic enzymes. The impact of scCO2 and ultrasound-assisted alkaline pretreatments of wood were insignificant for the enzymatic digestibility, and acetosolv pulping-alkaline hydrogen peroxide bleaching was the most effective pretreatment that showed the release of total reducing sugar yield (TRS) of ∼95.0 wt% of total hydrolyzable sugars (THS) in enzymatic hydrolysis. The optimized enzyme cocktail showed higher yield than individual enzymes with degree of synergism 1.34 among the enzymes, and scCO2 pretreatment of cocktail for 0.5-1.0 h at 10.0-22.0 MPa and 38.0-54.0 °C had insignificant effect on the enzyme's primary and global secondary structure of cocktail and its activity.

Addition of transarterial chemoembolization improves outcome of tyrosine kinase and immune checkpoint inhibitors regime in patients with unresectable hepatocellular carcinoma.

Background: Transarterial chemoembolization (TACE) is the standard treatment for hepatocellular carcinoma (HCC); the value of its combination with systemic therapy is worthy of further exploration. This study aimed to investigate the efficacy and safety of TACE combined with tyrosine kinase inhibitor (TKI) and immune checkpoint inhibitor (ICI) in the treatment of unresectable HCC. Methods: In this retrospective observational, single-center study, 147 patients with unresectable HCC were divided into a TACE group (n=98) and a non-TACE group (n=49) based on whether TACE was performed during TKI plus ICI therapy. The survival outcomes and adverse events (AEs) of the two groups were compared. Results: Data from patients with unresectable HCC who received TKI plus ICI treatment between July 2017 and April 2020 were collected. The median intrahepatic tumor size was 8.7 cm [interquartile range (IQR), 5.9-12.4 cm]. At data cut-off, overall survival (OS) of the TACE group was significantly longer than that of the non-TACE group (19.5 and 10.8 months, respectively, P=0.005). In the high-risk cohort (with main or contralateral portal vein tumor thrombi and/or bile duct invasion and/or a tumor burden >50% of liver), the OS of the TACE group was still longer than that of the non-TACE group (14.9 and 8.7 months, respectively, P=0.031). Major AEs were tolerated in both groups, and there was no significant difference in their incidence (34.7% and 30.6%, respectively, P=0.621). Conclusions: TACE treatment combined with TKI plus ICI regime resulted in longer OS than treatment with TKI plus ICI alone for patients with unresectable HCC.

Analysis of Magnetic Resonance Imaging Perfusion Parameters for the Identification of Spinal Metastatic Tumors with Rich Blood Supply.

PURPOSE: To determine the reliability of dynamic magnetic resonance imaging (MRI) perfusion parameters for the evaluation of blood supply to spinal metastatic tumors. METHODS: A total of 36 patients with spinal metastasis who underwent dynamic contrast-enhanced magnetic resonance spinal perfusion imaging at Tianjin Hospital from December 2018 to December 2020 were reviewed. Subsequently, the patients underwent corresponding preoperative examination using digital subtraction angiography of the spine at the hospital and were divided into 2 groups accordingly. Differences in dynamic MRI perfusion parameters between the 2 groups were analyzed. RESULTS: There were statistically significant differences between the 2 groups in the quantitative dynamic contrast-enhanced MRI perfusion parameters vascular permeability and plasma volume, as well as semi-quantitative peak enhancement and blood flow ratio parameters. CONCLUSIONS: Dynamic MRI perfusion may distinguish spinal metastatic lesions with rich blood supply from those with poor blood supply and may help clinicians identify patients that can benefit from invasive spinal angiography and preoperative embolization. This technique may also provide guidance on decision taking for surgery basing on dynamic MRI perfusion parameters.

Living Alone Increases the Risk of Hypertension in Older Chinese Adults: A Population-Based Longitudinal Study.

Background and Objectives: Cross-sectional studies have suggested a potential association between living alone and hypertension risk, but longitudinal evidence remains limited. We aimed to investigate the correlation between living alone, alterations in living arrangements, and hypertension risk among older adults utilizing a population-based longitudinal design. Research Design and Methods: The study included 8 782 older adults (≥65 years) without hypertension from the Chinese Longitudinal Healthy Longevity Survey. Participants were surveyed during the 2008 and 2011/2012 waves and were subsequently followed up in the next wave. Hypertension was defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg, or a self-reported diagnosis of hypertension by a physician. Cox proportional hazards model was used to explore the association between living alone and hypertension. Additionally, we analyzed how switching living arrangements during the follow-up period affects hypertension. Results: During a median follow-up of 2.8 (1.7-3.0) years, 2 750 hypertension events occurred. Compared with living with family, the hazard ratio (HR) (95% confidence interval [CI]) of living alone was 1.19 (1.06-1.33) for hypertension. Similarly, persisting in living alone during follow-up increased the risk of hypertension compared to continuing to live with family (HR 1.24; 95% CI: 1.06-1.45). Compared to married participants who continued to live with family, widowed/divorced participants who transitioned from living with family to living alone experienced a higher risk of hypertension (HR 1.21; 95% CI: 1.00-1.47). Stratified analyses showed that living alone was only associated with an increased hypertension risk for participants aged >80, men, and rural residents. Discussion and Implications: Living alone at baseline or persisting in living alone during follow-up correlated with increased hypertension risk. Divorced or widowed individuals who transitioned from living with family to living alone were still at risk. These results indicate that social support and living arrangements may be important in preventing hypertension in older adults.

Influence of elevated pressure and pressurized fluids on microenvironment and activity of enzymes.

Enzymes have great potential in bioprocess engineering due to their green and mild reaction conditions. However, there are challenges to their application, such as enzyme extraction and purification costs, enzyme recovery, and long reaction time. Enzymatic reaction rate enhancement and enzyme immobilization have the potential to overcome some of these challenges. Application of high pressure (e.g., hydrostatic pressure, supercritical carbon dioxide) has been shown to increase the activity of some enzymes, such as lipases and cellulases. Under high pressure, enzymes undergo multiple alterations simultaneously. High pressure reduces the bond lengths of molecules of reaction components and causes a reduction in the activation volume of enzyme-substrate complex. Supercritical CO2 interacts with enzyme molecules, catalyzes structural changes, and removes some water molecules from the enzyme's hydration layer. Interaction of scCO2 with the enzyme also leads to an overall change in secondary structure content. In the extreme, such changes may lead to enzyme denaturation, but enzyme activation and stabilization have also been observed. Immobilization of enzymes onto silica and zeolite-based supports has been shown to further stabilize the enzyme and provide resistance towards perturbation under subjection to high pressure and scCO2.

Effect of nalbuphine plus ropivacaine on vaginal labor in epidural analgesia.

BACKGROUND: Various approaches using epidural analgesia have been employed for relieving labor pain and promoting spontaneous delivery. We aimed to evaluate the effect of nalbuphine and ropivacaine versus fentanyl and ropivacaine on the duration of delivery in parturients. METHODS: Clinical data of 160 full-term primiparous women who received either nalbuphine or fentanyl in combination with ropivacaine infusion for epidural labor analgesia in our hospital from December 2020 to May 2022 were retrospectively analyzed. The participants were divided into two groups based on anesthesia methods: nalbuphine group (NR group, n = 78) received 0.2 mg/mL nalbuphine combined with 0.1% ropivacaine hydrochloride for patient-controlled epidural analgesia (PCEA) and fentanyl group (FR group, n = 82) received 2 ug/mL fentanyl citrate and 0.1% ropivacaine hydrochloride for PCEA. Both groups received an epidural blockade for labor analgesia at lumbar 2-3 interspace. The duration of the first, second, and third stages of labor, the onset of analgesia, and time before delivery (T0), 15 min of analgesia (T1), 30 min of analgesia (T2), full opening of the uterine opening (T3),exerts force during childbirth(T4), heart rate (HR), blood pressure (BP), blood saturation (SpO2), visual analogue pain scale (VAS) score, Ramsay sedation score, and modified Bromage score, and 5 min were recorded at 2 h postpartum (T5). The neonatal Apgar score, neonatal behavioral neurological assessment (NBNA) score, maternal nausea, vomiting, and itchy skin were recorded. RESULTS: Compared with the FR group, the first stage of labor duration (p < 0.05) and total duration of labor (p < 0.05) were shortened and the onset of analgesia (p < 0.05) was increased in the NR group. NR group had lower incidence of urinary retention than FR group (p < 0.05). The maternal and neonatal investigational parameters and scores had no significant difference between the two groups. CONCLUSIONS: Nalbuphine combined with ropivacaine in epidural block labor has a faster onset of analgesia and has a lower incidence of urinary retention than fentanyl combined with ropivacaine, and nalbuphine shortens the duration of the first and total stages of labor. Both nalbuphine and fentanyl can reduce pain during labor, have little effect on maternal hemodynamics, and have no significant effect on neonatal Apgar or NBNA scores.

Inhibit ALDH3A2 reduce ovarian cancer cells survival via elevating ferroptosis sensitivity.

Ovarian cancer (OC) is a malignant gynecologic tumor with high morbidity and mortality. As a newly discovered mode of programmed cell death, ferroptosis has been involved in various pathological processes of kinds of tumors in recent years. Aldehyde dehydrogenase 3 family member A2 (ALDH3A2) catalyzes the oxidation of long-chain aliphatic aldehydes to fatty acid. ALDH3A2 has been shown to be associated with ferroptosis in acute myeloid leukemia (AML), but the mechanism remains unclear. In this study, we analyzed the TCGA and GTEx databases and showed that high ALDH3A2 expression predicted poor prognosis in ovarian cancer. Further studies found that knockout or overexpression of ALDH3A2 correspondingly increased or attenuated the ferroptosis sensitivity of ovarian cancer cells. And sequencing revealed that ALDH3A2 knockout led to the activation of lipid metabolic, GSH metabolic, phospholipid metabolic, and aldehyde metabolic pathways, suggesting that ALDH3A2 induced changes in the sensitivity of ovarian cancer cells to ferroptosis by affecting these metabolic processes. Our results provide a new promising therapeutic strategy for the treatment of OC.