[Clinical advantage staging and underlying mechanisms of Wangbi Tablets against knee osteoarthritis based on "disease-formula" interaction network].

The clinical advantage staging and underlying mechanisms of Wangbi Tablets against knee osteoarthritis(KOA) were studied based on the "disease-formula" interaction network. Firstly, the clinical symptoms and related genes corresponding to Wangbi Tablets and KOA in the acute, remission, and recovery phases were collected from clinical guidelines/consensus and SoFDA database, and the putative targets of Wangbi Tablets were obtained from ETCM 2.0. Then, Jaccard similarity and cosine similarity were employed to assess the similarities of clinical symptoms, genes, and enriched pathways between Wangbi Tablets and KOA in different phases. The "disease-formula" interaction network of the drug targets and disease genes was constructed, and the key targets were screened by topological feature calculation. KEGG and Reactome database were used for the functional enrichment of the key targets, on the basis of which the functional characteristics of Wangbi Tablets against KOA in the acute, remission, and recovery phases were predicted. Finally, the SW1353 cells exposed to lipopolysaccharide were used to decipher the mechanism of Wangbi Tablets against KOA. The results showed that 92/3 921, 138/3 708, 139/3 800, and 196/3 946 clinical symptoms and the related genes corresponded to KOA in the acute, remission, and recovery phases and Wangbi Tablets were collected from SoFDA, and 260 putative targets of Wangbi Tablets were obtained from ETCM 2.0. Wangbi Tablets had highest similarity of clinical symptoms, genes, and enriched pathways with KOA in the remission phase and the secondary highest similarity with KOA in the recovery phase. The key targets of Wangbi Tablets mainly participated in the regulation of immunity-inflammation imbalance and exerted pain-relieving and bone-protecting effects to alleviate symptoms such as knee joint pain, joint swelling, soreness, fatigue, and dysfunction. Intriguingly, the key targets of Wangbi Tablets possessed antioxidant effects during KOA in the acute and remission phases, while they maintained material and energy metabolism homeostasis and protected vessels during KOA in the recovery phase. The cell experiment indicated that Wangbi Tablets down-regulated the expression of interleukin(IL)-6, IL-1ß, tumor necrosis factor-α(TNF-α), and Bcl-2-associated X protein(Bax)/B-cell lymphoma 2(Bcl-2) via regulating the phosphatidylinositol 3-kinase(PI3K)-protein kinase B(Akt) signaling pathway. The findings lay a theoretical foundation for further clarifying the clinical advantage stage and precise clinical application of Wangbi Tablets in treating KOA.

Effects of Proprioceptive Neuromuscular Facilitation Technique on Balance Function and Muscle Health in Older Adults With High Fall Risk.

PURPOSE: Older adults frequently encounter health challenges, such as impaired balance and muscle health, which increase risk of falls. The current study investigated the effectiveness of the proprioceptive neuromuscular facilitation (PNF) technique in improving balance and muscle health among older adults with high fall risk. METHOD: A total of 160 older adults with high fall risk were randomized into control and intervention groups. Over 6 months, the control group received standard interventions, while the intervention group received the same interventions and additional PNF training. RESULTS: Both groups demonstrated improvements in balance function over time, with the intervention group exhibiting significant improvements in Berg Balance Scale scores, Timed Up and Go test times, and 30-Second Chair Stand Test counts (p < 0.05). Bone density significantly increased in the intervention group compared to the control group (p < 0.05), although no substantial differences in lower limb muscle mass were observed. Satisfaction rates were higher and fall incidents fewer in the intervention group. CONCLUSION: The PNF technique is effective in enhancing balance function and muscle health in older adults with high fall risk, demonstrating potential in reducing fall risk and improving quality of life among older adults. [Journal of Gerontological Nursing, 50(8), 37-44.].

Insulin enhances acid-sensing ion channel currents in rat primary sensory neurons.

Insulin has been shown to modulate neuronal processes through insulin receptors. The ion channels located on neurons may be important targets for insulin/insulin receptor signaling. Both insulin receptors and acid-sensing ion channels (ASICs) are expressed in dorsal root ganglia (DRG) neurons. However, it is still unclear whether there is an interaction between them. Therefore, the purpose of this investigation was to determine the effects of insulin on the functional activity of ASICs. A 5 min application of insulin rapidly enhanced acid-evoked ASIC currents in rat DRG neurons in a concentration-dependent manner. Insulin shifted the concentration-response plot for ASIC currents upward, with an increase of 46.2 ± 7.6% in the maximal current response. The insulin-induced increase in ASIC currents was eliminated by the insulin receptor antagonist GSK1838705, the tyrosine kinase inhibitor lavendustin A, and the phosphatidylinositol-3 kinase antagonist wortmannin. Moreover, insulin increased the number of acid-triggered action potentials by activating insulin receptors. Finally, local administration of insulin exacerbated the spontaneous nociceptive behaviors induced by intraplantar acid injection and the mechanical hyperalgesia induced by intramuscular acid injections through peripheral insulin receptors. These results suggested that insulin/insulin receptor signaling enhanced the functional activity of ASICs via tyrosine kinase and phosphatidylinositol-3 kinase pathways. Our findings revealed that ASICs were targets in primary sensory neurons for insulin receptor signaling, which may underlie insulin modulation of pain.

TNKS1BP1 mediates AECII senescence and radiation induced lung injury through suppressing EEF2 degradation.

BACKGROUND: Although recent studies provide mechanistic understanding to the pathogenesis of radiation induced lung injury (RILI), rare therapeutics show definitive promise for treating this disease. Type II alveolar epithelial cells (AECII) injury in various manner results in an inflammation response to initiate RILI. RESULTS: Here, we reported that radiation (IR) up-regulated the TNKS1BP1, causing progressive accumulation of the cellular senescence by up-regulating EEF2 in AECII and lung tissue of RILI mice. Senescent AECII induced Senescence-Associated Secretory Phenotype (SASP), consequently activating fibroblasts and macrophages to promote RILI development. In response to IR, elevated TNKS1BP1 interacted with and decreased CNOT4 to suppress EEF2 degradation. Ectopic expression of EEF2 accelerated AECII senescence. Using a model system of TNKS1BP1 knockout (KO) mice, we demonstrated that TNKS1BP1 KO prevents IR-induced lung tissue senescence and RILI. CONCLUSIONS: Notably, this study suggested that a regulatory mechanism of the TNKS1BP1/CNOT4/EEF2 axis in AECII senescence may be a potential strategy for RILI.

Shirebi granules ameliorate acute gouty arthritis by inhibiting NETs-induced imbalance between immunity and inflammation.

BACKGROUND: Acute gouty arthritis (AGA) is classified as 'arthritis' in traditional Chinese medicine (TCM) theory. Shirebi granules (SGs), derived from the classic prescription SiMiaoWan, exerts satisfying therapeutic efficacy in ameliorating AGA clinically. However, the underlying mechanisms of SGs against AGA remain unclarified. METHODS: AGA-related biological processes, signal pathways and biomarker genes were mined from the GEO database through bioinformatics. SGs components were systematically recognized using the UPLC-Q-TOF-MS/MS. A correlation network was established based on the biomarker genes and the chemical components, from which the signal pathway used for further study was selected. Finally, we established an AGA model using SD rats injected with monosodium urate (MSU) in the ankle joint for experimental validation. A combination of behavioral tests, H&E, safranin O- fast green, western blotting, and immunofluorescence were employed to reveal the mechanism of action of SGs on AGA. RESULTS: The deterioration of AGA was significantly related to the imbalance between immunity and inflammation, neutrophil chemotaxis and inflammatory factor activation. HDAC5, PRKCB, NFκB1, MPO, PRKCA, PIK3CA were identified to be the candidate targets of SGs against AGA, associated with neutrophil extracellular traps (NETs) signal pathway. Animal experiments demonstrated that SGs effectively repaired cartilage damage, blocked TLR4 activation, and inhibited the expression of NETs indicators and inflammatory factors. In addition, SGs prominently alleviated joint redness and swelling, improved joint dysfunction, inhibited inflammatory infiltration of AGA rats. CONCLUSION: Our data reveal that SGs may effectively alleviate the disease severity of AGA by suppressing NETs-promoted imbalance between immunity and inflammation.

Short-term usage of proton pump inhibitors during admission was associated with increased risk of rehospitalization in critically ill patients with myocardial infarction: a cohort study.

PURPOSE: Previous studies showed that long-term use of proton pump inhibitors (PPIs) was associated with cardiovascular events. However, the impact of short-term PPI exposure on intensive care unit (ICU) patients with myocardial infarction (MI) remains largely unknown. This study aims to determine the precise correlation between short-term PPI usage during hospitalization and prognostic outcomes of ICU-admitted MI patients using Medical Information Mart for Intensive Care IV database (MIMIC-IV). METHODS: Propensity score matching (PSM) was applied to adjust confounding factors. The primary study outcome was rehospitalization with mortality and length of stay as secondary outcomes. Binary logistic, multivariable Cox, and linear regression analyses were employed to estimate the impact of short-term PPI exposure on ICU-admitted MI patients. RESULTS: A total of 7249 patients were included, involving 3628 PPI users and 3621 non-PPI users. After PSM, 2687 pairs of patients were matched. The results demonstrated a significant association between PPI exposure and increased risk of rehospitalization for MI in both univariate and multivariate [odds ratio (OR) = 1.157, 95% confidence interval (CI) 1.020-1.313] analyses through logistic regression after PSM. Furthermore, this risk was also observed in patients using PPIs > 7 days, despite decreased risk of all-cause mortality among these patients. It was also found that pantoprazole increased the risk of rehospitalization, whereas omeprazole did not. CONCLUSION: Short-term PPI usage during hospitalization was still associated with higher risk of rehospitalization for MI in ICU-admitted MI patients. Furthermore, omeprazole might be superior to pantoprazole regarding the risk of rehospitalization in ICU-admitted MI patients.

Integrated metabolome and transcriptome analysis provide insight into the biosynthesis of flavonoids in Panax japonicus.

Panax japonicus is an important medicinal plant, and flavonoids are one of its main secondary metabolites. In this study, the main roots, fibrous roots, stems, leaves and flowers of P. japonicus were analyzed using transcriptomics and widely targeted metabolomics. Through correlation analysis of transcription and metabolism, the flavonoid biosynthesis pathway in P. japonicus was analyzed, and the accumulation of flavonoid metabolites and the expression of related genes were investigated. Metabolomics revealed a total of 209 flavonoid metabolites in P. japonicus, among which flavonoids, flavonols, flavanones and flavanonols significantly accumulated in the flowers and leaves. Transcriptome sequencing revealed that key genes in the flavonoid pathway exhibited increased expression in the flowers and leaves. The expression patterns of key genes involved in flavonoid biosynthesis, including PjC4H, Pj4CL, PjCHS, PjCHI, PjF3H, PjF3'H, PjCYP, and PjPAL, are consistent with their upstream and downstream metabolites, demonstrating a significant positive correlation among them. In addition, the PjUGT gene is highly expressed in five tissues of P. japonicus, indicating that PjUGT is one of the key factors for the diversity of flavonoid glycosides. The WGCNA results showed that WRKY transcription factors exist widely in the candidate modules, and it was possible that PjWRKY transcription factors are involved in regulating the expression of key genes involved in flavonoid biosynthesis and the biosynthesis of flavonoid metabolites. This study reveals spatial differences in the accumulation patterns of flavonoid metabolites in different tissues and provides important clues for further understanding the regulatory mechanisms of flavonoid metabolism in P. japonicus, thus contributing to the optimization of germplasm resources of P. japonicus and the promotion of genetic diversity analysis.

Low-dose ionizing radiation-induced RET/PTC1 rearrangement via the non-homologous end joining pathway to drive thyroid cancer.

Thyroid cancer incidence increases worldwide annually, primarily due to factors such as ionizing radiation (IR), iodine intake, and genetics. Papillary carcinoma of the thyroid (PTC) accounts for about 80% of thyroid cancer cases. RET/PTC1 (coiled-coil domain containing 6 [CCDC6]-rearranged during transfection) rearrangement is a distinctive feature in over 70% of thyroid cancers who exposed to low doses of IR in Chernobyl and Hiroshima‒Nagasaki atomic bombings. This study aims to elucidate mechanism between RET/PTC1 rearrangement and IR in PTC. N-thy-ori-3-1 cells were subjected to varying doses of IR (2/1/0.5/0.2/0.1/0.05 Gy) of IR at different days, and result showed low-dose IR-induced RET/PTC1 rearrangement in a dose-dependent manner. RET/PTC1 has been observed to promote PTC both in vivo and in vitro. To delineate the role of different DNA repair pathways, SCR7, RI-1, and Olaparib were employed to inhibit non-homologous end joining (NHEJ), homologous recombination (HR), and microhomology-mediated end joining (MMEJ), respectively. Notably, inhibiting NHEJ enhanced HR repair efficiency and reduced IR-induced RET/PTC1 rearrangement. Conversely, inhibiting HR increased NHEJ repair efficiency and subsequent RET/PTC1 rearrangement. The MMEJ did not show a markable role in this progress. Additionally, inhibiting DNA-dependent protein kinase catalytic subunit (DNA-PKcs) decreased the efficiency of NHEJ and thus reduced IR-induced RET/PTC1 rearrangement. To conclude, the data suggest that NHEJ, rather than HR or MMEJ, is the critical cause of IR-induced RET/PTC1 rearrangement. Targeting DNA-PKcs to inhibit the NHEJ has emerged as a promising therapeutic strategy for addressing IR-induced RET/PTC1 rearrangement in PTC.

Al and MCPD in grain products in Gansu province, China and risk assessment.

This study conducted a dietary exposure assessment of chloropropanols and aluminium, after quantifying their content in food. The mean dietary exposure to Al from total grain products was found to be 6.4E-04 mg/kg bw/week, not exceeding the provisional tolerable weekly intake (PTWI). The results showed that the mean dietary exposure of 3-monochloro-1,2-propanediol (3-MCPD) from grain products was higher than the tolerable daily intake (TDI). Deterministic evaluations showed that the mean HQ of 1.5 to Al from fried dough twist was higher than 1. However, the HI values to Al were lower than 1 and the Monte Carlo simulation (MCS) showed that the HQ was greater than 1 at the 99% exposure level. Deterministic and probabilistic methods indicated that HQ values of 3-MCPD from grain products were above 1, whereas the mean HI value was 0.62.

Influence of Carotid Artery Stenting on the Retina and Choroid.

Purpose: The effect of carotid artery stenting in patients with unilateral carotid artery stenosis on the retina and choroid was evaluated using swept-source optical coherence tomography angiography (SS-OCTA). Methods: SS-OCTA examination was conducted before stenting and 4 days and 3 months after stenting. The retinal nerve fiber layer, ganglion cell-inner plexiform layer (GCIPL), inner nuclear layer, superficial vascular complex (SVC), deep vascular complex (DVC), choroidal vascular volume (CVV), and choroidal vascular index were measured. Repeated-measures analysis of variance was performed to assess the impact of carotid artery stenting on optical coherence tomography angiography (OCTA) metrics. Results: At baseline, 303 eyes from 160 patients (61.82 ± 9.98 years; 85.29% males) were enrolled. SVC and DVC densities and CVV were lower in ipsilateral eyes (stenosed side) compared to contralateral eyes (all P < 0.05). Four days after stenting, a significant increase was seen in SVC density in ipsilateral eyes (P < 0.05) while a significant increase was seen in CVV in ipsilateral eyes and contralateral eyes (both P < 0.05). Three months after stenting (63 patients with 114 eyes), a significant decrease was seen in the GCIPL thickness of ipsilateral and contralateral eyes (all P < 0.001). Conclusions: Short term after carotid artery stenting, ipsilateral eyes showed a rapid and significant increase in SVC density and CVV. Translational Relevance: Optical coherence tomography (OCT)/OCTA measurements may have the potential to detect retinal and choroidal changes after stenting. Future research on the long-term effect of stenting on the retina and choroid will be guided by these findings.

Childhood adversity and depression of older adults: the moderating effect of social participation.

Objective: Examine the effect of childhood adversity on depression in older adults and the regulatory impact that social participation has on depression. Methods: Based on 6,704 standard-compliant research subjects, single factor analysis, multiple linear regression model, and tendency score matching were used to analyze the impact of childhood adversity on depression in older adults and the regulatory effect of social participation. Results: The depression rate is higher among women, young age, low education, unmarried, in agricultural households, older adults with low annual income, pre-retirement work type in agriculture, non-drinking, and those with two or more chronic diseases (p < 0.05). Children who experienced adversity as children are more likely to suffer from depression as adults (ß = 0.513, 0.590, 0.954, 0.983, 1.221, 0.953, 0.718; p < 0.05). Through the tendency score, the result is matched with the endogenous test. As well, older adults are more likely to suffer psychological damage from a greater number of childhood adversities in their early years (ß = 1.440, 2.646, 4.122; p < 0.001). It has been shown that social participation will reduce the negative impact of low-income family economic circumstances on depression among older adults of all ages (ß = -0.459,-0.567; p < 0.01), aggravate depression resulting from "neighborhood void of mutual assistance" and "no more fun to play" for older adults of all ages (ß = 1.024, 0.894; p < 0.01), and exacerbate depression resulting from "loneliness because there are no friends" for the oldest old (ß = 0.476, 0.779; p < 0.05). Conclusion: Older adults who experience childhood adversity are more likely to suffer from depression. Social participation plays a regulatory role in the relationship between childhood adversity and depression in older adults. For older adults' mental health to improve, family and social adversity should be prevented, and moderate participation in society should be encouraged.

Clinical Predictors of Nontuberculous Mycobacteria Lung Disease and Coisolates of Potential Pathogenic Microorganisms in Noncystic Fibrosis Bronchiectasis.

Background: In bronchiectasis, nontuberculous mycobacteria (NTM) lung disease (NTM-LD) is a well-known coexisting infection. However, microorganism coisolates and clinical NTM-LD predictors are poorly studied. Methods: Patients with bronchiectasis diagnosed by means of computed tomography between January 2017 and June 2020 were screened, using the date of computed tomography as the index date. Those with a major bronchiectasis diagnosis in ≥2 follow-up visits after the index date were enrolled in the study, and NTM-LD occurrence and its association with pneumonia and hospitalization within 1 year were analyzed. Results: Of the 2717 participants, 79 (2.9%) had NTM-LD diagnosed. The factors associated with NTM-LD included hemoptysis, postinfectious bronchiectasis, a tree-in-bud score ≥2, a modified Reiff score ≥4, and chronic obstructive pulmonary disease (adjusted odds ratios, 1.80, 2.36, 1.78, 2.95, and 0.51, respectively). Compared with patients in the non-NTM group, those with NTM-LD had higher rates of hospitalization (15.9% vs 32.9%; P < .001) and pneumonia (9.8% vs 20.3%; P = .003). Pseudomonas aeruginosa was the most common microorganism in those with NTM-LD and those in the non-NTM group (10.1% vs 7.8%; P = .40). However, compared with those in the non-NTM group, Acinetobacter baumannii and Escherichia coli were more prevalent in patients with NTM-LD (0.7% vs 3.8% [P = .03%] and 1.0% vs 3.8% [P = .05], respectively). Conclusions: Postinfectious bronchiectasis with hemoptysis, higher radiological involvement, and a tree-in-bud pattern were associated with NTM-LD risk. The rate of A baumannii and E coli coisolation was higher in bronchiectasis populations with NTM-LD.

Chinese formula Guben-Jiannao Ye alleviates the dysfunction of circadian and sleep rhythms in APP/PS1 mice implicated in activation of the PI3K/AKT/mTOR signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The Chinese formula Guben-Jiannao Ye (GBJNY) formula has a long history of usage in traditional Chinese medicine (TCM) for the treatment of learning and memory disorders as well as senile insomnia. This formulation is derived from Sun Simiao's five tonic pills. Furthermore, modern pharmacological investigations have revealed its ability to improve cognitive impairment and ameliorate sleep-wake circadian rhythm disorders. However, the precise mechanism underlying its efficacy remains elusive. AIM OF THE STUDY: The current research explored the modulatory effects and possible mechanisms of GBJNY in circadian rhythm sleep-wake disorders and cognitive dysfunction in Alzheimer's disease using transcriptome sequencing and experimental validation. MATERIALS AND METHODS: The LC-MS/MS tandem technology was utilized to qualitatively discern the active components present in GBJNY. The APP/PS1 mice received continuous treatment with GBJNY or Melatonin for 3 months. The learning and memory abilities of mice were assessed utilizing the Morris water maze (MWM) test, while sleep changes were studied utilizing the electroencephalogram (EEG) and electromyogram (EMG). Concurrently, mice's hippocampus clock gene rhythmicity was investigated. Subsequently, we employed HE staining, Golgi staining, and immunofluorescence to observe GBJNY's impact on synaptic damage and neuronal loss. We performed high-throughput sequencing to analyze the mRNA expression profiles of mice, aiming to identify differentially expressed genes (DEGs). Subsequently, we conducted GO and KEGG enrichment analyses to explore associated signaling pathways. Furthermore, we evaluated the expression levels of proteins involved in the PI3K/AKT/mTOR pathway and Aß deposition in the hippocampus of mice. Through this comprehensive approach, we sought to elucidate and validate the potential mechanisms of action of GBJNY in APP/PS1 mice. RESULTS: Results showed 216 DEGs. Following this, we conducted GO enrichment and KEGG pathway analyses to delve deeper into the distinctions and fundamental functions of the mRNA target genes. The enrichment analysis underscored the prominence of the PI3K/Akt/mTOR signaling pathway as the most pivotal among them. Through in vivo experiments, it was further demonstrated that the administration of GBJNY enhanced memory and learning capacities in APP/PS1 mice. Additionally, GBJNY treatment resulted in alterations in the sleep-wake circadian rhythm, characterized by reduced wakefulness and an increase in non-rapid eye movement (NREM) sleep. Moreover, alterations in the peak expression of Per1, Per2, Clock, Cry1, Cry2, and Bmal1 mRNA were noted in the hippocampus of treated mice. Particularly noteworthy were the observed reductions in amyloid-beta (Aß) deposition within the hippocampus, improvements in neuronal synaptic integrity, and upregulation of mTOR, Akt, and PI3K protein expression in the hippocampal region. These findings underscore the critical involvement of the PI3K/Akt/mTOR signaling pathway in mitigating disturbances in sleep-wake circadian rhythms. CONCLUSIONS: GBJNY enhanced the cognitive performance of APP/PS1 mice and altered clock gene expression patterns, alleviating sleep-wake circadian rhythm disruptions. The fundamental mechanism appears to be linked to the PI3K/Akt/mTOR pathway regulation, offering a foundation for potential clinical applications.

1α,25-hydroxyvitamin D/VDR suppresses stem-like properties of ovarian cancer cells by restraining nuclear translocation of ß-catenin.

Several studies have indicated that 1α,25-hydroxyvitamin D [1α,25(OH)2D3] inhibits the proliferation and metastasis of cancer cells through suppressing epithelial-mesenchymal transition. However, its influence on the translocation of ß-catenin remains unclear. In the present study, ovarian cancer stem-like cells (CSCs), including side population (SP) and CD44+/CD117+, were isolated from mouse ovarian surface epithelial (MOSE) cells with malignant transformation. The findings revealed that 1α,25(OH)2D3 obviously reduced the sphere-forming ability, as well as Notch1 and Klf levels. Moreover, the limiting dilution assay demonstrated that 1α,25(OH)2D3 effectively hindered the tumorigenesis of ovarian CSCs in vitro. Notably, treatment with 1α,25(OH)2D3 led to a substantial increase in the cell population of CD44+/CD117+ forming one tumor from ≤ 100 to 445 in orthotopic transplanted model, indicating a pronounced suppression of stemness of ovarian CSCs. Additionally, 1α,25(OH)2D3 robustly promoted the translocation of ß-catenin from the nuclear to the cytoplasm through directly binding to VDR, which resulted in decreased levels of c-Myc and CyclinD1 within late MOSE cells. Taken together, these results strongly supported the role of 1α,25(OH)2D3 in inhibiting stem-like properties in ovarian cancer cells by restraining nuclear translocation of ß-catenin, thereby offering a promising target for cancer therapeutics.

Hierarchical porous MOF-199 mediated cellulosic paper for selective CO2 capture.

MOF-199 is considered to be an excellent CO2 adsorbent owing to its substantial specific surface area, suitable pore structure and abundant sorption sites. However, powdered MOF-199 is prone to agglomeration and has poor recyclability. Herein, we proposed a MOF-199-based adsorbent by combining the MOF synthesis process with traditional papermaking process. Through such a design, MOF-199 particles are adhered on the surface of wood pulp fiber. The sufficient hydroxyl groups and electrostatic forces of cellulose facilitates the homogeneous and tight adhesion of MOF crystals. The optimal MP-4 sample demonstrated a high CO2 adsorption capacity (1.80 mmol·g-1 at 25 °C) and good CO2/N2 selectivity (30.06). Moreover, the composite sorbent can be easily regenerated. The adsorption mechanism was analyzed by the density functional theory approach. The simulation results showed that the carboxyl functional groups with a large number of oxygen atoms and active metal sites are the key to boost the CO2 adsorption performance.

Engineering a universal and fully automatic analyzer for multichannel and on-site biochemical detection in body fluids.

OBJECTIVE: Rising concerns over wellness and aging have heightened the demand for convenient and efficient on-site health monitoring and disease screening. Current research, focused on specific biomarker detection, often neglects the complexities of sample matrix interference and the absence of a comprehensive, automated platform. To address these issues, we have developed a universal, fully automated analyzer for multifaceted, on-site biochemical analysis of body fluids. METHODS: This analyzer integrates automated sample pretreatment, automatic dilution, detection, and self-cleaning functionalities seamlessly. It is designed to detect a wide range of analytes, from small molecules to macromolecules, including ions and proteins, utilizing spectrophotometric sensing. After optimization, the analyzer achieves performance comparable to traditional Enzyme-Linked Immunosorbent Assay (ELISA), while significantly expanding its detection range through automated dilution. RESULTS: Demonstrations of small molecule detection include the simultaneous assessment of citric acid (CA) and oxalic acid (OA) in urine, achieving recovery rates between 96.65%-106.42% and 93.13%-112.50%, respectively. For protein detection, the analyzer successfully identified Cyfra21-1 in saliva with a recovery rate of 104.93%-111.31%. The pre-treatment process requires only 8.8 minutes, showing enhanced recovery rates for CA and OA at 97.8% and 97.6% respectively, which are superior and more rapid than manual methods. CONCLUSION: The exemplary pretreatment and detection performance of the analyzer underlines its effectiveness in multifaceted, on-site biomarker detection, establishing it as a promising and versatile tool for disease screening and health monitoring. SIGNIFICANCE: This analyzer offers a powerful technological solution for on-site fluid testing, advancing community health care by facilitating more reliable and rapid diagnostics.

Health-risk assessment of mercury in main market-sold foods in the Pingliang region of Gansu province, China, from 2013 to 2021.

In the present study, we analyzed mercury concentrations in 742 samples across five main food categories from 2013 to 2021 using direct mercury analysis (DMA) to understand mercury pollution in major market-sold foods in the Pingliang region of Gansu Province and assess the health risks of mercury dietary exposure in adults. Health risks of adult dietary exposure were assessed through deterministic evaluation. Total mercury content ranged from non-detectable (ND) to 0.13 mg/kg, with a detection rate of 90.70% (673/742), the highest detection rates being in fresh edible mushrooms and nuts. The overall exceedance rate was 0.13% (1/742), with one sample of fresh edible mushrooms exceeding the regulatory limit for total mercury content. Additionally, we incorporated the average mercury content and consumption levels of meat and seafood from regions geographically close to Pingliang, as reported in the Fifth National Total Diet Study, to calculate the Estimated Daily Intake (EDI) by a deterministic evaluation. For adult males, the exposure was 0.120 µg/(kg BW), while for adult females, it was 0.141 µg/(kg BW). Both values are significantly lower than the provisional tolerable weekly intake (PTWI) of 4 µg/(kg BW) established by JECFA in 2010, indicating that the total mercury concentration from food intake does not pose a significant health risk to the residents of the Pingliang area. These findings offer valuable scientific data to inform food safety regulations in the region and can serve as a benchmark for future mercury pollution risk assessments in other locations.

Automatic measurement of anatomical parameters of the lumbar vertebral body and the intervertebral disc on radiographs by deep learning.

Background: Lumbar spine disorders are one of the common causes of low back pain (LBP). Objective and reliable measurement of anatomical parameters of the lumbar spine is essential in the clinical diagnosis and evaluation of lumbar disorders. However, manual measurements are time-consuming and laborious, with poor consistency and repeatability. Here, we aim to develop and evaluate an automatic measurement model for measuring the anatomical parameters of the vertebral body and intervertebral disc based on lateral lumbar radiographs and deep learning (DL). Methods: A model based on DL was developed with a dataset consisting of 1,318 lateral lumbar radiographs for the prediction of anatomical parameters, including vertebral body heights (VBH), intervertebral disc heights (IDH), and intervertebral disc angles (IDA). The mean of the values obtained by 3 radiologists was used as a reference standard. Statistical analysis was performed in terms of standard deviation (SD), mean absolute error (MAE), Percentage of correct keypoints (PCK), intraclass correlation coefficient (ICC), regression analysis, and Bland-Altman plot to evaluate the performance of the model compared with the reference standard. Results: The percentage of intra-observer landmark distance within the 3 mm threshold was 96%. The percentage of inter-observer landmark distance within the 3 mm threshold was 94% (R1 and R2), 92% (R1 and R3), and 93% (R2 and R3), respectively. The PCK of the model within the 3 mm distance threshold was 94-99%. The model-predicted values were 30.22±3.01 mm, 10.40±3.91 mm, and 10.63°±4.74° for VBH, IDH, and IDA, respectively. There were good correlation and consistency in anatomical parameters of the lumbar vertebral body and disc between the model and the reference standard in most cases (R2=0.89-0.95, ICC =0.93-0.98, MAE =0.61-1.15, and SD =0.89-1.64). Conclusions: The newly proposed model based on a DL algorithm can accurately measure various anatomical parameters on lateral lumbar radiographs. This could provide an accurate and efficient measurement tool for the quantitative evaluation of spinal disorders.

Vitamin D receptor attenuates carbon tetrachloride-induced liver fibrosis via downregulation of YAP.

Liver fibrosis is characterized by the excessive accumulation of extracellular matrix proteins, which can lead to cirrhosis and liver cancer. Metabolic dysfunction-associated steatosis liver diseases are common causes of liver fibrosis, sharing a similar pathogenesis with carbon tetrachloride (CCl4) exposure. This process involves the activation of hepatic stellate cells (HSCs) into myofibroblasts. However, the detailed mechanism and effective treatment strategies require further investigation. In this study, we uncovered a negative correlation between VDR expression and YAP within HSCs. Subsequently, we demonstrated that VDR exerted a downregulatory influence on YAP transcriptional activity in HSCs. Intriguingly, activation VDR effectively inhibited the culture induced activation of primary HSCs by suppressing the transcriptional activity of early YAP. Furthermore, in vivo results manifested that hepatic-specific deletion of YAP/TAZ ameliorates CCl4-induced liver fibrosis, and nullified the antifibrotic efficacy of VDR. Importantly, a YAP inhibitor rescued the exacerbation of liver fibrosis induced by hepatic-specific VDR knockout. Moreover, the combined pharmacological of VDR agonist and YAP inhibitor demonstrated a synergistic effect in diminishing CCl4-induced liver fibrosis, primary HSCs activation and hepatic injury in vivo. These effects were underpinned by their collective ability to inhibit HSC activation through AMPK activation, consequently curbing ATP synthesis and HSCs proliferation. In conclusion, our results not only revealed the inhibition of VDR on YAP-activated liver stellate cells but also identified a synergistic effect of VDR agonist and YAP inhibitor in an AMPKα-dependent manner, providing a practical foundation for integration of multi-targeted drugs in the therapy of CCl4-induced hepatic fibrosis.