The efficacy of nutritional screening indexes in predicting the incidence of osteosarcopenia and major osteoporotic fracture in the elderly.

INTRODUCTION: The effect of nutritional status on osteosarcopenia (OS) and major osteoporotic fracture (MOF) among the elderly is still unclear. So we aimed to compare the efficacy of the Mini-Nutrition Assessment-Short Form (MNA-sf), the Geriatric Nutritional Risk Index (GNRI) and Controlling Nutritional Status (CONUT) for predicting OS and MOF among the elderly. MATERIALS AND METHODS: A total of 409 participants were enrolled in this prospective study. Blood biochemical indexes, nutritional status, and bone- and muscle-related examinations were assessed at initial visit to the outpatient. Participants were divided into 4 groups: (1) control; (2) osteopenia/osteoporosis; (3) sarcopenia; (4) osteosarcopenia, and then followed for 5 years, recording the occurrence time of MOF. RESULTS: The frequency values of osteopenia/osteoporosis, sarcopenia, and OS, at baseline, were respectively 13.4, 16.1, and 12% among the study samples. Correlation analysis showed that nutritional status scores were associated with body mass index, handgrip strength, albumin, bone mineral density, and physical functions. According to multivariate models, poor nutritional status was significantly associated with a higher risk of OS and MOF (P < 0.05). Survival analysis showed that the MOF rate in malnutrition group was significantly higher than normal nutrition group (P < 0.05). The receiver operator characteristic curve shows that the value of MNA-sf to diagnose OS and MOF is greater (P < 0.05). CONCLUSION: The poor nutritional status was associated with a higher risk of both OS and MOF. MNA-sf showed a superior diagnostic power for OS and MOF among the elderly. Early nutrition assessments and interventions may be key strategies to prevent OS and fractures.

Deciphering Anion-Modulated Solvation Structure for Calcium Intercalation into Graphite for Ca-Ion Batteries.

Co-intercalation reactions make graphite a feasible anode in Ca ion batteries, yet the correlation between Ca ion intercalation behaviors and electrolyte structure remains unclear. This study, for the first time, elucidates the pivotal role of anions in modulating the Ca ion solvation structures and their subsequent intercalation into graphite. Specifically, the electrostatic interactions between Ca ion and anions govern the configurations of solvated-Ca-ion in dimethylacetamide-based electrolytes and graphite intercalation compounds. Among the anions considered (BH4 -, ClO4 -, TFSI- and [B(hfip)4]-), the coordination of four solvent molecules per Ca ion (CN=4) leads to the highest reversible capacities and the fastest reaction kinetics in graphite. Our study illuminates the origins of the distinct Ca ion intercalation behaviors across various anion-modulated electrolytes, employing a blend of experimental and theoretical approaches. Importantly, the practical viability of graphite anodes in Ca-ion full cells is confirmed, showing significant promise for advanced energy storage systems.

α-Ketoglutaric acid ameliorates intervertebral disk degeneration by blocking the IL-6/JAK2/STAT3 pathway.

Intervertebral disk degeneration (IVDD) is the major cause of low back pain. Alpha-ketoglutaric acid (α-KG), an important intermediate in energy metabolism, has various functions, including epigenetic regulation, maintenance of redox homeostasis, and antiaging, but whether it can ameliorate IVDD has not been reported. Here, we examined the impacts of long-term administration of α-KG on aging-associated IVDD in adult rats. In vivo and in vitro experiments showed that α-KG supplementation effectively ameliorated IVDD in rats and the senescence of nucleus pulposus cells (NPCs). α-KG supplementation significantly attenuated senescence, apoptosis, and matrix metalloproteinase-13 (MMP-13) protein expression, and it increased the synthesis of aggrecan and collagen II in IL-1ß-treated NPCs. In addition, α-KG supplementation reduced the levels of IL-6, phosphorylated JAK2 and STAT3, and the nuclear translocation of p-STAT3 in IL-1ß-induced degenerating NPCs. The effects of α-KG were enhanced by AG490 in NPCs. The underlying mechanism may involve the inhibition of JAK2/STAT3 phosphorylation and the reduction of IL-6 expression. Our findings may help in the development of new therapeutic strategies for IVDD.NEW & NOTEWORTHY Alpha-ketoglutaric acid (α-KG) exerted its protective effect on nucleus pulposus cells' (NPCs) degeneration by inhibiting the senescence-associated secretory phenotype and extracellular matrix degradation. The possible mechanism may be associated with negatively regulating the JAK2/STAT3 phosphorylation and the decreased IL-6 expression, which could be explained by a blockage of the positive feedback control loop between IL-6 and JAK2/STAT3 pathway.

Hollow NiCo@C Nanozyme-Embedded Paper-Based Colorimetric Aptasensor for Highly Sensitive Antibiotic Detection on a Smartphone Platform.

Antibiotic residues in the environment and in foods pose a serious threat to ecosystems and human health. Developing sensitive and on-site detection methods is therefore in high demand. In this work, a portable paper-based colorimetric sensor with a smartphone platform with an ultrahigh sensitivity has been designed for on-site and quantitative analysis of antibiotic residues based on aptamer-regulated nanozyme activity. The developed excellent peroxidase-like nanozymes, carbon-protected NiCo bimetal oxides with a unique hollow nanocage structure (NiCo@C HCs), could effectively catalyze the oxidation of chromogenic substrates by H2O2. Once bound to a specific aptamer, the enzyme-mimicking activity of NiCo@C HCs is obviously inhibited as a result of the masking of active sites but could be restored via the target-aptamer recognition. Herein, the aptamer-modified NiCo@C HCs are embedded on paper pieces to construct paper-based biochips for visual detection. Meanwhile, a smartphone platform is integrated for the signal readout. Using enrofloxacin (ENR) as an analyte model, the proposed paper-based analysis platform shows a reliable and sensitive detection of ENR with an ultralow detection limit of 0.029 ng/mL. The platform also works well in various real samples. This analysis method is facile in design, showing a great application potential for on-site and mass screening of antibiotic residues in the environment and in foods.

Homologous Nitrogen-Doped Hierarchical Carbon Architectures Enabling Compatible Anode and Cathode for Potassium-Ion Hybrid Capacitors.

Potassium-ion hybrid capacitors (PIHCs) have been considered as an emerging device to render grid-scale energy storage. Nevertheless, the sluggish kinetics at the anode side and limited capacity output at the cathode side remain daunting challenges for the overall performances of PIHCs. Herein, an exquisite "homologous strategy" to devise multi-dimensional N-doped carbon nanopolyhedron@nanosheet anode and activated N-doped hierarchical carbon cathode targeting high-performance PIHCs is reported. The anode material harnessing a dual-carbon structure and the cathode candidate affording a high specific surface area (2651 m2 g-1 ) act in concert with a concentrated ether-based electrolyte, resulting in an excellent half cell performance. The related storage mechanism is systematically revealed by in situ electrokinetic characterizations. More encouragingly, the thus-derived PIHC full cell demonstrates a favorable energy output (157 Wh kg-1 ), showing distinct advantages over the state-of-the-art PIHC counterparts.

Computed tomography-based paravertebral muscle density predicts subsequent vertebral fracture risks independently of bone mineral density in postmenopausal women following percutaneous vertebral augmentation.

BACKGROUND: The risk of subsequent vertebral fractures (SVF) after the primary vertebral fracture cannot be explained by lower bone mineral density (BMD) alone. Computed tomography (CT) measurements of paravertebral muscle density (PMD) are recognized radiographic markers used to predict physical function, fragile fractures. AIMS: This study aims to investigate the relationship between PMD and the risk of SVF in cohorts of postmenopausal women, and to determine if combining both PMD and BMD measures derived from CT can improve the accuracy of predicting SVF. METHODS: This study enrolled 305 postmenopausal women between the ages of 50 and 88 for 3 years of follow-up studies. Trabecular attenuation (Hounsfield units, HU) was measured at L1 level and muscle attenuation of paravertebral muscle at L3 level on preoperative lumbar CT scans to determine the L1 BMD and L3 PMD. Kaplan-Meier analysis was applied to evaluate SVF-free survival. The hazard ratios (HRs) of PMD for SVF events were estimated with the Cox proportional hazards model. The predictive values of L1 BMD and L3 PMD for SVF were quantified using the Receiver-Operating Characteristic (ROC) curve. RESULT: During the 3 years of follow-up studies, 88 patients (28.9%) suffered an SVF. ROC curve analysis demonstrated that an L3 PMD threshold of 32 HU had a sensitivity of 89.8% and a specificity of 62% for the prediction of SVF. Kaplan-Meier analysis showed that L3 PMD ≤ 32 HU was significantly associated with lower SVF-free survival (p < 0.001; log-rank test). After adjusting for age, BMI, diabetes, postoperative osteoporosis treatment, handgrip strength, L1 BMD, multivariate analyses also indicated a persistent modest effect of L3 PMD on SVF-free survival. The area under the ROC curve of L3 PMD and L1 BMD, combined to predict the risk of SVF, was 0.790, which was significantly higher than the value for L1 BMD alone (0.735). L3 PMD and L1 BMD significantly improved the accuracy of SVF risk prediction compared with L1 BMD alone, which was confirmed by reclassification improvement measures. The inclusion of handgrip strength and postoperative osteoporosis treatment in the model further improved SVF prediction accuracy, and PMD remained significant in the model. CONCLUSION: Decreased L3 PMD is an independent risk predictor of SVF. Combined CT-based L1 BMD and L3 PMD can significantly improve the accuracy of predicting the risk of SVF in postmenopausal women who have suffered prior osteoporotic vertebral fractures.

Metallic Transition Metal Dichalcogenides of Group VIB: Preparation, Stabilization, and Energy Applications.

Layered transition metal dichalcogenides (TMDs) of group VIB have been widely used in the realms of energy storage and conversions. Along with the existence of semiconducting states, their metallic phases have recently attracted numerous attentions owing to their fascinating physical and chemical properties. Many efforts have been devoted to obtain metallic TMDs with high purity and yield. Nevertheless, such metallic phase is thermodynamically metastable and tends to convert into semiconducting phase, which necessitates the exploration over effective strategies to ensure the stability. In this review, typical fabrication routes are introduced and those critical factors during preparation are elaborately discussed. Moreover, the stabilized strategies are summarized with concrete examples highlighting the key mechanisms toward efficient stabilization. Finally, emerging energy applications are overviewed. This review presents comprehensive research status of metallic group VIB TMDs, aiming to facilitate further scientific investigations and promote future practical applications in the fields of energy storage and conversion.

Association between handgrip strength and subsequent vertebral-fracture risk following percutaneous vertebral augmentation.

INTRODUCTION: The aim of this study was to investigate the association between handgrip strength (HGS) and the risk of subsequent vertebral fracture (SVF) after percutaneous vertebral augmentation (PVA). MATERIALS AND METHODS: A total of 340 patients aged over 50 years with osteoporotic vertebral fracture were enrolled in this 3-year follow-up investigation. HGS was measured with a hand-held dynamometer before PVA. Female patients and male patients were grouped using the HGS threshold recommended by the Asian Working Group for Sarcopenia (AWGS). Kaplan-Meier analysis was used to evaluate SVF-free survival. The hazard ratios (HRs) of HGS for SVF events were estimated with the Cox proportional hazards model. RESULTS: During the follow-up period, a total of 93 patients (27.4%) experienced SVF. Kaplan-Meier analysis showed that the HGS of female patients < 18.0 kg and male patients < 28 kg was significantly associated with lower SVF-free survival (female patients: p < 0.001, male patients: p = 0.038; log-rank test). Among women, each 1-kg increase in HGS was associated with a 9% lower risk of SVF (HR 0.91, p = 0.035) after adjustment for potential risk factors. Among men, although the associations between low HGS and increased risk of SVF were significant in the crude model (HR 0.79, p < 0.001), this significance disappeared after adjustment for bone mineral density of the femoral neck. CONCLUSIONS: Low HGS was significantly associated with lower SVF-free survival among elderly patients who underwent single-level PVA for osteoporotic vertebral fracture.

Kindness is rewarded! The impact of corporate social responsibility on Chinese market reactions to the COVID-19 pandemic.

This study takes the COVID-19 outbreak as a quasi-natural experiment to investigate whether corporate social responsibility (CSR) performance can help firms mitigate drops in their share prices. The results show that CSR ratings are positively associated with cumulative abnormal return (CAR) during the COVID-19 outbreaks periods. Further, the positive role of CSR is more significant for non-state-owned enterprises (non-SOE) and those located in regions with lower levels of marketization.

ZIF-8@ZIF-67-Derived Nitrogen-Doped Porous Carbon Confined CoP Polyhedron Targeting Superior Potassium-Ion Storage.

Potassium ion batteries (KIB) have become a compelling energy-storage system owing to their cost effectiveness and the high abundance of potassium in comparison with lithium. However, its practical applications have been thwarted by a series of challenges, including marked volume expansion and sluggish reaction kinetics caused by the large radius of potassium ions. In line with this, the exploration of reliable anode materials affording high electrical conductivity, sufficient active sites, and structural robustness is the key. The synthesis of ZIF-8@ZIF-67 derived nitrogen-doped porous carbon confined CoP polyhedron architectures (NC@CoP/NC) to function as innovative KIB anode materials is reported. Such composites enable an outstanding rate performance to harvest a capacity of ≈200 mAh g-1 at 2000 mA g-1 . Additionally, a high cycling stability can be gained by maintaining a high capacity retention of 93% after 100 cycles at 100 mA g-1 . Furthermore, the potassium ion storage mechanism of the NC@CoP/NC anode is systematically probed through theoretical simulations and experimental characterization. This contribution may offer an innovative and feasible route of emerging anode design toward high performance KIBs.

Estimation of the ideal correction of lumbar lordosis to prevent reoperation for symptomatic adjacent segment disease after lumbar fusion in older people.

BACKGROUND: Symptomatic adjacent segment disease (ASDis) is a major complication following spinal fusion. Sagittal spinopelvic imbalance may contribute to the development of ASDis. However, the exact ideal correction of lumbar lordosis (LL) is unknown for different ages of people to prevent ASDis. The purpose of this study was to estimate the ideal correction of LL required to prevent symptomatic ASDis requiring revision surgery in patients of various ages, and to determine the radiographic risk factors for ASDis. METHODS: 468 patients who underwent lumbar fusion between January 2014 and December 2016, were enrolled in the present study. The patients were classified into the ASDis and N-ASD group. These two matched groups were compared regarding surgery-related factors and radiographic features. Multivariate logistic regression analysis was used to evaluate the risk factors for ASDis. RESULTS: Sixty-two patients (13.25%) underwent reoperation for ASDis during a mean follow-up duration of 38.07 months. Receiver operating characteristic curve analysis showed that the postoperative LL - preoperative LL (△LL) cutoff value was 11.7°for the development of ASDis. Logistic regression analysis revealed that the risk factors for symptomatic ASDis were a smaller LL angle, △LL > 12°, and PI-LL > 10° (p <  0.05). For patients > 60 years, the incidence of ASDis was higher in patients with a LL correction of ≥10° and a lumbar-pelvic mismatch (PI-LL) of > 20°. CONCLUSIONS: The significant predictors of the occurrence of ASDis were a smaller LL angle, △LL > 12°, and PI-LL > 10°. However, in patients older than 60 years, the incidence of ASDis after lumbar fusion was higher in those with a LL correction of ≥10° and PI-LL of > 20°. More attention should be paid to patient age and the angle of correction of LL before lumbar fusion.

Sagittal imbalance, muscle atrophy, and osteoporosis: risk factors for revision posterior lumbar fusion surgery in patients with Parkinson's disease.

OBJECTIVE: The aim of our study was to evaluate features and complications of patients with Parkinson's disease (PD) who underwent posterior lumbar fusion surgery for lumbar degenerative diseases (LDD), as well as the risk factors for revision. METHODS: Between January 2010 and December 2016, 132 patients were retrospectively identified for inclusion. Patients were divided into a 29 revision PD group and a 103 non-revision PD group. Patient factors included bone mineral density (BMD) and severity of PD using the Hoehn and Yahr staging system. Surgical factors included surgical levels and fusion methods. Radiographic measurements included pre-operative spinopelvic parameters, paraspinal muscle atrophy, and fatty infiltration. Logistic regression analysis was used to determine independent predictors for revision posterior lumbar fusion. RESULTS: The average age of the PD patients was 67.96 years, and the follow-up time was 49.01 months. R-PD patients accounted for 21.97% of all PD patients who underwent lumbar fusion surgery. Multivariable analysis indicated that low BMD (p = 0.012), fatty infiltration (p = 0.038), a smaller relative cross-sectional area (rCSA) of the paraspinal muscle (p = 0.008), larger pelvic incidence-lumbar lordosis (PI-LL) (p = 0.01), and sagittal vertical axis (SVA) (p = 0.004) were significant independent risk factors for revision posterior lumbar fusion in PD patients. CONCLUSION: PD patients with low pre-operative BMD, fatty infiltration, a smaller rCSA of the paraspinal muscle, and larger PI-LL and SVA had a higher rate of revision lumbar fusion. Maintaining sagittal balance, functional exercises, and anti-osteoporosis treatment were important in preventing complications in PD patients.

Does the C3/4 disc play a role in cervical spondylosis with dizziness? A retrospective study.

PURPOSE: To investigate the effect of C3/4 disc degeneration on cervical spondylosis with dizziness (CSD) and to assess the curative effect of anterior cervical decompression and fusion (ACDF) in patients with CSD. METHOD: Four hundred nineteen patients who underwent ACDF for treatment of myelopathy or radiculopathy were divided into dizziness and non-dizziness group. The visual analog scale (VAS) score and Japanese Orthopaedic Association (JOA) score were used to determine the intensity of dizziness and neurological symptoms, respectively. Cervical disc degeneration was evaluated using Miyazaki's classification system. Some parameters were measured using cervical radiographs. The surgical effects on CSD were compared between surgery with and without C3/4 level. Multivariate logistic regression analysis was used to determine the risk factors for CSD. RESULTS: The pre-operative incidence of CSD was 33.9%. Women were more likely to develop dizziness than men (p < 0.05), CSD was significantly associated with C3/4 disc degeneration (69.7%, p < 0.001), and smokers were more subject to dizziness (p < 0.05). Regression analysis showed that female (OR = 1.611, p = 0.031), smoking (OR = 1.719, p = 0.032), Miyazaki grade of C3/4 ≥ IV (OR = 2.648, p < 0.001), and instability on C3/4 (OR = 1.672, p = 0.024) were risk factors for CSD. Treatment of CSD by ACDF involving C3/4 was more effective than not involving C3/4 (efficacy rate, 73.2% vs 51.7%, p < 0.05). CONCLUSION: The CSD is a common clinical manifestation in elderly patients, especially patients with cervical spondylosis at the C3/4 level. Female, smoking, instability on C3/4, and C3/4 Miyazaki grade ≥ IV could be considered significant risk factors for CSD. CSD is more likely to be alleviated by ACDF involving C3/4.

A versatile CuCo@PDA nanozyme-based aptamer-mediated lateral flow assay for highly sensitive, on-site and dual-readout detection of Aflatoxin B1.

Mycotoxin contaminations in food and environment seriously harms human health. Constructing sensitive and point-of-test early-warning tools for mycotoxin determination is in high demand. In this study, a CuCo@PDA nanozyme-based aptamer-mediated lateral flow assay (Apt-LFA) has been elaborately designed for on-site and sensitive determination of mycotoxin Aflatoxin B1 (AFB1). Benefiting from the rich functional groups and excellent peroxidase-like activity, the CuCo@PDA with original dark color can be conjugated with the specific recognition probe (i.e., aptamer), generating colorimetric signal on the test lines of Apt-LFA via a competitive sensing strategy. The signal can further be amplified in-situ by catalytic chromogenic reaction. Therefore, a visual and dual-readout detection of AFB1 has been realized. The developed Apt-LFA provides a flexible detection mode for qualitative and quantitative analysis of AFB1 by naked-eyes observation or smartphone readout. The smartphone-based LFA platform shows a reliable and ultrasensitive determination of AFB1 with the limit of detection (LOD) of 2.2 pg/mL. The recoveries in the real samples are in the range of 95.11-113.77% with coefficients of variations less than 9.84%. This study provides a new approach to realize point-of-test and sensitive detection of mycotoxins in food and environment using nanozyme-based Apt-LFAs.

Inhibition of Mettl3 ameliorates osteoblastic senescence by mitigating m6A modifications on Slc1a5 via Igf2bp2-dependent mechanisms.

Age-related osteoporosis is characterized by a marked decrease in the number of osteoblasts, which has been partly attributed to the senescence of cells of the osteoblastic lineage. Epigenetic studies have provided new insights into the mechanisms of current osteoporosis treatments and bone repair pathophysiology. N6-methyladenosine (m6A) is a novel transcript modification that plays a major role in cellular senescence and is essential for skeletal development and internal environmental stability. Bioinformatics analysis revealed that the expression of the m6A reading protein Igf2bp2 was significantly higher in osteoporosis patients. However, the role of Igf2bp2 in osteoblast senescence has not been elucidated. In this study, we found that Igf2bp2 levels are increased in ageing osteoblasts induced by multiple repetition and H2O2. Increasing Igf2bp2 expression promotes osteoblast senescence by increasing the stability of Slc1a5 mRNA and inhibiting cell cycle progression. Additionally, Mettl3 was identified as Slc1a5 m6A-methylated protein with increased m6A modification. The knockdown of Mettl3 in osteoblasts inhibits the reduction of senescence, whereas the overexpression of Mettl3 promotes the senescence of osteoblasts. We found that administering Cpd-564, a specific inhibitor of Mettl3, induced increased bone mass and decreased bone marrow fat accumulation in aged rats. Notably, in an OVX rat model, Igf2bp2 small interfering RNA delivery also induced an increase in bone mass and decreased fat accumulation in the bone marrow. In conclusion, our study demonstrated that the Mettl3/Igf2bp2-Slc1a5 axis plays a key role in the promotion of osteoblast senescence and age-related bone loss.

Vitamin D delays intervertebral disc degeneration and improves bone quality in ovariectomized rats.

Known to be involved in bone-cartilage metabolism, Vitamin D (VD) may play a role in human's disc pathophysiology. Given that postmenopausal women are prone to suffer VD deficiency and intervertebral disc degeneration (IDD), this study is intended to investigate whether VD can delay IDD in ovariectomized rats by improving bone microstructure and antioxidant stress. Female Sprague-Dawley rats were randomly allocated into four groups: sham, oophorectomy (OVX)+VD deficiency (VDD), OVX, and OVX+VD supplementation (VDS). In vivo, after a 6-month intervention, imaging and pathology slice examinations showed that IDD induced by OVX was significantly alleviated in VDS and deteriorated by VDD. The expressions of aggrecan and Collagen II in intervertebral disc were reduced by OVX and VDD, and elevated by VDS. Compared with the OVX+VDD and OVX group vertebrae, OVX+VDS group vertebrae showed significantly improved endplate porosity and lumbar bone mineral density with increased percent bone volume and trabecular thickness. Furthermore, 1α,25(OH)2D3 restored the redox balance (total antioxidant capacity, ratio of oxidized glutathione/glutathione) in the disc. The cocultivation of 1α,25(OH)2D3 and nucleus pulposus cells (NPCs) was conducted to observe its potential ability to resist excessive oxidative stress damage induced by H2O2. In vitro experiments revealed that 1α,25(OH)2D3 reduced the senescence, apoptosis, and extracellular matrix degradation induced by H2O2 in NPCs. In conclusion, VDS exhibits protective effects in OVX-induced IDD, partly by regulating the redox balance and preserving the microstructure of endplate. This finding provides a new idea for the prevention and treatment of IDD.

Dendrite-Free and High-Rate Potassium Metal Batteries Sustained by an Inorganic-Rich SEI.

Potassium metal battery is an appealing candidate for future energy storage. However, its application is plagued by the notorious dendrite proliferation at the anode side, which entails the formation of vulnerable solid electrolyte interphase (SEI) and non-uniform potassium deposition on the current collector. Here, this work reports a dual-modification design of aluminum current collector to render dendrite-free potassium anodes with favorable reversibility. This work achieves to modulate the electronic structure of the designed current collector and accordingly attain an SEI architecture with robust inorganic-rich constituents, which is evidenced by detailed cryo-EM inspection and X-ray depth profiling. The thus-produced SEI manages to expedite ionic conductivity and guide homogeneous potassium deposition. Compared to the potassium metal cells assembled using typical aluminum current collector, cells based on the designed current collector realize improved rate capability (maintaining 400 h under 50 mA cm-2 ) and low-temperature durability (stable operation at -50 °C). Moreover, scalable production of the current collector allows for the sustainable construction of high-safety potassium metal batteries, with the potential for reducing the manufacturing cost.

LC-MS/MS determination of pogostone in rat plasma and its application in pharmacokinetic studies.

Pogostone is an important constituent of Pogostemon cablin (Blanco) Benth., and possesses various known bioactivities. A rapid, simple and sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed for the analysis of pogostone in rat plasma using chrysophanol as internal standard (IS). The analytes were extracted with methanol and separated using a reversed-phase YMC-UltraHT Pro C18 column. Elution was achieved with a mobile phase consisting of methanol-water (75:25, v/v) for 5 min at a flow rate of 400 µL/min. The precursor/product transitions (m/z) under MS/MS detection with negative electrospray ionization (ESI) were 223.0 → 139.0 and 253.1 → 224.9 for pogostone and IS, respectively. The calibration curve was linear over the concentration range 0.05-160 µg/mL (r = 0.9996). The intra- and inter-day accuracy and precision were within ±10%. The validated method was successfully applied to the preclinical pharmacokinetic investigation of pogostone in rats after intravenous (5, 10 and 20 mg/kg) and oral administration (5, 10 and 20 mg/kg). Finally, the oral absolute bioavailability of pogostone in rats was calculated to be 70.39, 78.18 and 83.99% for 5, 10 and 20 mg/kg, respectively.

Role of ferroptosis and immune infiltration in intervertebral disc degeneration: novel insights from bioinformatics analyses.

Background: Intervertebral disc degeneration (IVDD), which contributes to stenosis of the spinal segment, commonly causes lower back pain. The process of IVDD degradation entails gradual structural adjustments accompanied by extreme transformations in metabolic homeostasis. However, the molecular and cellular mechanisms associated with IVDD are poorly understood. Methods: The RNA-sequencing datasets GSE34095 and GSE56081 were obtained from the Gene Expression Omnibus (GEO) database. Ferroptosis-related differentially expressed genes (DEGs) were identified from these gene sets. The protein-protein interaction (PPI) network was established and visualized using the STRING database and Cytoscape software, and the key functional modules of ferroptosis-related genes were identified. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on the DEGs. Weighted gene co-expression network analysis (WGCNA), immune infiltration analysis in the GEO database, and other GSE series were used as validation datasets. The xCELL algorithm was performed to investigate the immune cell infiltration differences between the degenerated IVDD and control groups. Results: The major genes involved in nucleus pulposus tissue immune infiltration and ferroptosis-related genes were mined by bioinformatics analysis. A total of 3,056 DEGs were obtained between the IVDD tissue and control groups. The DEGs were enriched in the cell cycle; apoptosis; necroptosis; and the PI3K-Akt, Hippo, and HIF-1 signaling pathways. PCR and Western blot techniques were utilized to confirm the differential ferroptosis-related genes. The results indicated that the protein expression levels of NCOA4 and PCBP1 were elevated, while the protein expression level of GPX4 was reduced in NPCs following IL-1ß treatment. Our study has found that severe disc tissue degeneration leads to a noteworthy increase in the expression of CD8A in naive T cells, CCR7 in memory CD4+ cells, GZMB in natural killer (NK) cells, and CD163 and CD45 in macrophages. Conclusion: Our data demonstrate that ferroptosis occurs in IVDD, suggesting that ferroptosis may also increase IVDD improvement by triggering immune infiltration. This work was conducted to further understand IVDD pathogenesis and identify new treatment strategies.

Fingerprinting and simultaneous determination of alkaloids in Picrasma quassioides from different locations by high performance liquid chromatography with photodiode array detection.

A simple and sensitive method was developed and validated for profiling and simultaneous quantitation of seven alkaloids (6-hydroxy-ß-carboline-1-carboxylic acid, ß-carboline-1-carboxylic acid, ß-carboline-1-propanoic acid, 3-methylcanthin-5,6-dione, 5-hydroxy-4-methoxycanthin-6-one, 1-methoxycarbony-ß-carboline, and 4,5-dimethoxycanthin-6-one) in Picrasma quassioide grown in different locations by high-performance liquid chromatography with photodiode array detection. The analysis was conducted on a Phenomenex Gemini C(18) column at 35°C with mobile phase of 25 mM aqueous ammonium acetate (pH 4.0, adjusted by glacial acetate acid) and acetonitrile. A common fingerprint chromatograph under 254 nm consisting of 27 peaks was constructed for the evaluation of the similarities among 31 P. quassioide samples. Samples from Guangdong and Guangxi Provinces were found to be within group linkage and showed significant difference from that of Jiangxi Province origin by using principal component analysis and hierarchical clustering analysis. In addition, the seven alkaloids were identified by electrospray ionization mass spectrometry and comparing with reference standards and literature data. All of them were determined simultaneously using the established HPLC method. This rapid and effective analytical method could be employed for quality assessment of P. quassioide, as well as pharmaceutical products containing this herbal material.