Atox1 protects hippocampal neurons after traumatic brain injury via DJ-1 mediated anti-oxidative stress and mitophagy.

Regulation of the oxidative stress response is crucial for the management and prognosis of traumatic brain injury (TBI). The copper chaperone Antioxidant 1 (Atox1) plays a crucial role in regulating intracellular copper ion balance and impacting the antioxidant capacity of mitochondria, as well as the oxidative stress state of cells. However, it remains unknown whether Atox1 is involved in modulating oxidative stress following TBI. Here, we investigated the regulatory role of Atox1 in oxidative stress on neurons both in vivo and in vitro, and elucidated the underlying mechanism through culturing hippocampal HT-22 cells with Atox1 mutation. The expression of Atox1 was significantly diminished following TBI, while mice with overexpressed Atox1 exhibited a more preserved hippocampal structure and reduced levels of oxidative stress post-TBI. Furthermore, the mice displayed notable impairments in learning and memory functions after TBI, which were ameliorated by the overexpression of Atox1. In the stretch injury model of HT-22 cells, overexpression of Atox1 mitigated oxidative stress by preserving the normal morphology and network connectivity of mitochondria, as well as facilitating the elimination of damaged mitochondria. Mechanistically, co-immunoprecipitation and mass spectrometry revealed the binding of Atox1 to DJ-1. Knockdown of DJ-1 in HT-22 cells significantly impaired the antioxidant capacity of Atox1. Mutations in the copper-binding motif or sequestration of free copper led to a substantial decrease in the interaction between Atox1 and DJ-1, with overexpression of DJ-1 failing to restore the antioxidant capacity of Atox1 mutants. The findings suggest that DJ-1 mediates the ability of Atox1 to withstand oxidative stress. And targeting Atox1 could be a potential therapeutic approach for addressing post-traumatic neurological dysfunction.

Meningioma achieves malignancy and erastin-induced ferroptosis resistance through FOXM1-AURKA-NRF2 axis.

The oncogene Aurora kinase A (AURKA) has been implicated in various tumor, yet its role in meningioma remains unexplored. Recent studies have suggested a potential link between AURKA and ferroptosis, although the underlying mechanisms are unclear. This study presented evidence of AURKA upregulation in high grade meningioma and its ability to enhance malignant characteristics. We identified AURKA as a suppressor of erastin-induced ferroptosis in meningioma. Mechanistically, AURKA directly interacted with and phosphorylated kelch-like ECH-associated protein 1 (KEAP1), thereby activating nuclear factor erythroid 2 related factor 2 (NFE2L2/NRF2) and target genes transcription. Additionally, forkhead box protein M1 (FOXM1) facilitated the transcription of AURKA. Suppression of AURKA, in conjunction with erastin, yields significant enhancements in the prognosis of a murine model of meningioma. Our study elucidates an unidentified mechanism by which AURKA governs ferroptosis, and strongly suggests that the combination of AURKA inhibition and ferroptosis-inducing agents could potentially provide therapeutic benefits for meningioma treatment.

O-GlcNAcylation of melanophilin enhances radiation resistance in glioblastoma via suppressing TRIM21 mediated ubiquitination.

The molecular mechanism of glioblastoma (GBM) radiation resistance remains poorly understood. The aim of this study was to elucidate the potential role of Melanophilin (MLPH) O-GlcNAcylation and the specific mechanism through which it regulates GBM radiotherapy resistance. We found that MLPH was significantly upregulated in recurrent GBM tumor tissues after ionizing radiation (IR). MLPH induced radiotherapy resistance in GBM cells and xenotransplanted human tumors through regulating the NF-κB pathway. MLPH was O-GlcNAcylated at the conserved serine 510, and radiation-resistant GBM cells showed higher levels of O-GlcNAcylation of MLPH. O-GlcNAcylation of MLPH protected its protein stability and tripartite motif containing 21(TRIM21) was identified as an E3 ubiquitin ligase promoting MLPH degradation whose interaction with MLPH was affected by O-GlcNAcylation. Our data demonstrate that MLPH exerts regulatory functions in GBM radiation resistance by promoting the NF-κB signaling pathway and that O-GlcNAcylation of MLPH both stabilizes and protects it from TRIM21-mediated ubiquitination. These results identify a potential mechanism of GBM radiation resistance and suggest a potential therapeutic strategy for GBM treatment.

Hsp90 induces Acsl4-dependent glioma ferroptosis via dephosphorylating Ser637 at Drp1.

Ferroptosis is a newly identified form of regulated cell death (RCD) characterized by the iron-dependent lipid reactive oxygen species (ROS) accumulation, but its mechanism in gliomas remains elusive. Acyl-coenzyme A (CoA) synthetase long-chain family member 4 (Acsl4), a pivotal enzyme in the regulation of lipid biosynthesis, benefits the initiation of ferroptosis, but its role in gliomas needs further clarification. Erastin, a classic inducer of ferroptosis, has recently been found to regulate lipid peroxidation by regulating Acsl4 other than glutathione peroxidase 4 (GPX4) in ferroptosis. In this study, we demonstrated that heat shock protein 90 (Hsp90) and dynamin-related protein 1 (Drp1) actively regulated and stabilized Acsl4 expression in erastin-induced ferroptosis in gliomas. Hsp90 overexpression and calcineurin (CN)-mediated Drp1 dephosphorylation at serine 637 (Ser637) promoted ferroptosis by altering mitochondrial morphology and increasing Acsl4-mediated lipid peroxidation. Importantly, promotion of the Hsp90-Acsl4 pathway augmented anticancer activity of erastin in vitro and in vivo. Our discovery reveals a novel and efficient approach to ferroptosis-mediated glioma therapy.

Integrated analysis reveals prognostic value and mesenchymal identity suppression by glycoprotein M6B in glioma.

Glioblastoma (GBM) stem cells (GSCs) possess multilineage differentiation potential, which is responsible for cancer progression. Glycoprotein M6B (GPM6B) is a pivotal enzyme in regulating intracranial cell differentiation and neuronal myelination, and is widely studied in several cancers. However, research on GPM6B in glioma is limited. In this study, we analyzed the clinical and molecular characteristics of GPM6B using RNA sequencing data of glioma samples from the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) datasets. Quantitative real-time PCR (qRT-PCR), western blot (WB), and immunohistochemistry (IHC) were performed for further validation. Moreover, a neurosphere formation assay, extreme limiting dilution assay, and bioluminescent imaging were employed to validate the therapeutic effects targeted on GPM6B in vitro and in vivo. We found lower expression of GPM6B in aggressive glioma. Receiver operating characteristic (ROC) analysis suggested that GPM6B is an indicator of mesenchymal subtype. Kaplan-Meier analysis also revealed that patients with glioma with high GPM6B expression levels had a tendency toward prolonged survival. The GPM6B expression level could predict favorable prognosis of patients independent of age, grade, IDH status, and 1p/19q status. Additionally, targeting GPM6B impaired the self-renewal and tumorgenicity of mesenchymal GSCs by inhibiting the activation of the Wnt pathway in vitro and in vivo. Our results demonstrated that GPM6B is a crucial predictor in glioma prognosis and represents an underlying therapeutic target in GSC therapy.

Proteomic Profile of M. longissimus thoracis from Commercial Lambs Reared in Different Forage Systems.

This study compared the protein composition of M. longissimus thoracis of lambs from six commercial forage production systems in New Zealand. A total of 286 proteins were identified based on liquid chromatography-tandem mass spectrometry. First, a binomial model showed that different production groups could be distinguished based on abundances of 16 proteins. Second, pair-wise comparisons were performed to search for protein abundance differences in meat due to animal sex (ewe vs. wether), diet (perennial ryegrass vs. chicory), and age (4 vs. 6-8 months old). Greater abundance of some myofibrillar and sarcoplasmic proteins were observed in lamb loins from ewes compared to wethers. Chicory diet and older age at slaughter were associated with meat with lower abundance of some myofibrillar proteins, possibly due to a greater proportion of muscle glycolytic fibres. The proteins that showed significant differences in their abundances due to production factors could be further investigated to understand their influence on meat quality.

Loss of deubiquitylase USP2 triggers development of glioblastoma via TGF-ß signaling.

Glioblastoma (GBM) is the most aggressive primary brain tumor as one of the deadliest cancers. The TGF-ß signaling acts as an oncogenic factor in GBM, and plays vital roles in development of GBM. SMAD7 is a major inhibitor of TGF-ß signaling, while the deubiquitination of SMAD7 has been poorly studied in GBM. Here, we found USP2 as a new prominent candidate that could regulate SMAD7 stability. USP2 was lost in GBM, leading to the poor prognosis in patients. Moreover, aberrant DNA methylation mediated by DNMT3A induced the low expression of USP2 in GBM. USP2 depletion induced TGF-ß signaling and progression of GBM. In contrast, overexpressed USP2 suppressed TGF-ß signaling and GBM development. Specifically, USP2 interacted with SMAD7 and prevented SMAD7 ubiquitination. USP2 directly cleaved Lys27- and Lys48-linked poly-ubiquitin chains of SMAD7, and Lys27-linked poly-ubiquitin chains of SMAD7 K185 mediated the recruitment of SMAD7 to HERC3, which regulated Lys63-linked poly-ubiquitination of SMAD7. Moreover, we demonstrated that the DNMT3A inhibitor SGI-1027 induced USP2, suppressed TGF-ß signaling and GBM development. Thus, USP2 repressed development of GBM by inhibition TGF-ß signaling pathway via the deubiquitination of SMAD7.

A Novel lncRNA Panel Related to Ferroptosis, Tumor Progression, and Microenvironment is a Robust Prognostic Indicator for Glioma Patients.

Objective: To establish a lncRNA panel related to ferroptosis, tumor progression, and microenvironment for prognostic estimation in patients with glioma. Methods: LncRNAs associated with tumor progression and microenvironment were screened via the weighted gene co-expression network analysis (WGCNA). Overlapped lncRNAs highlighted in WGCNA, related to ferroptosis, and incorporated in Chinese Glioma Genome Atlas (CGGA) were identified as hub lncRNAs. With expression profiles of the hub lncRNA, we conducted the least absolute shrinkage and selection operator (LASSO) regression and built a ferroptosis-related lncRNA signature to separate glioma patients with distinct survival outcomes. The lncRNA signature was validated in TCGA, the CGGA_693, and CGGA_325 cohorts using Kaplan-Meier survival analysis and ROC curves. The ferroptosis-related lncRNA panel was validated with 15 glioma samples using quantitative real-time PCR (qRT-PCR). Multivariate Cox regression was performed, and a nomogram was mapped and validated. Immune infiltration correlated to the signature was explored using TIMER and CIBERSORT algorithms. Results: The present study identified 30 hub lncRNAs related to ferroptosis, tumor progression, and microenvironment. With the 30 hub lncRNAs, we developed a lncRNA signature with distinct stratification of survival chance in patients with glioma in two independent cohorts (HRs>1, p < 0.05). The lncRNA signature revealed a panel of 14 lncRNAs, i.e., APCDD1L-AS1, H19, LINC00205, LINC00346, LINC00475, LINC00484, LINC00601, LINC00664, LINC00886, LUCAT1, MIR155HG, NEAT1, PVT1, and SNHG18. These lncRNA expressions were validated in clinical specimens using qRT-PCR. Robust predictive accuracies of the signature were present across different datasets at multiple timepoints. With univariate and multivariate regressions, we demonstrated that the risk score based on the lncRNA signature is an independent prognostic indicator after clinical factors were adjusted. A nomogram was constructed with these prognostic factors, and it has demonstrated decent classification and accuracy. Additionally, the signature-based classification was observed to be correlated with multiple clinical characteristics and molecular subtypes. Further, extensive immune cells were upregulated in the high-risk group, such as CD8+ T cell, neutrophil, macrophage, and myeloid dendritic cell, indicating increased immune infiltrations. Conclusion: We established a novel ferroptosis-related lncRNA signature that could effectively stratify the prognosis of glioma patients with adequate predictive performance.

Nuclear receptor coactivator 4-mediated ferritinophagy contributes to cerebral ischemia-induced ferroptosis in ischemic stroke.

Ischemic stroke poses a significant health risk due to its high rate of disability and mortality. To address this problem, several therapeutic approaches have been proposed, including interruption targeting programmed cell death (PCD). Ferroptosis is a newly defined PCD characterized by iron-dependent accumulation of lipid peroxidation, and is becoming a promising target for treating numerous diseases. To explore the underlying mechanisms of the initiation and execution of ferroptosis in ischemic stroke, we established stroke models in vivo and in vitro simulating ischemia/reperfusion (I/R) neuronal injury. Different from previous reports on stroke, we tested ferroptosis by measuring the levels of core proteins, such as ACSL4, 15-LOX2, Ferritin and GPX4. In addition, I/R injury induces excessive degradation of ferritin via the autophagy pathway and subsequent increase of free iron in neurons. This phenomenon has recently been termed ferritinophagy and reported to be regulated by nuclear receptor coactivator 4 (NCOA4) in some cell lines. Increased NCOA4 in cytoplasm was detected in our study and then silenced by shRNA to investigate its function. Both in vivo and in vitro, NCOA4 deletion notably abrogated ferritinophagy caused by I/R injury and thus inhibited ferroptosis. Furthermore, we found that NCOA4 was upregulated by ubiquitin specific peptidase 14 (USP14) via a deubiquitination process in damaged neurons, and we found evidence of pharmacological inhibition of USP14 effectively reducing NCOA4 levels to protect neurons from ferritinophagy-mediated ferroptosis. These findings suggest a novel and effective target for treating ischemic stroke.

Prokineticin-2 prevents neuronal cell deaths in a model of traumatic brain injury.

Prokineticin-2 (Prok2) is an important secreted protein likely involved in the pathogenesis of several acute and chronic neurological diseases through currently unidentified regulatory mechanisms. The initial mechanical injury of neurons by traumatic brain injury triggers multiple secondary responses including various cell death programs. One of these is ferroptosis, which is associated with dysregulation of iron and thiols and culminates in fatal lipid peroxidation. Here, we explore the regulatory role of Prok2 in neuronal ferroptosis in vitro and in vivo. We show that Prok2 prevents neuronal cell death by suppressing the biosynthesis of lipid peroxidation substrates, arachidonic acid-phospholipids, via accelerated F-box only protein 10 (Fbxo10)-driven ubiquitination, degradation of long-chain-fatty-acid-CoA ligase 4 (Acsl4), and inhibition of lipid peroxidation. Mice injected with adeno-associated virus-Prok2 before controlled cortical impact injury show reduced neuronal degeneration and improved motor and cognitive functions, which could be inhibited by Fbxo10 knockdown. Our study shows that Prok2 mediates neuronal cell deaths in traumatic brain injury via ferroptosis.

Relationships among Consumer Liking, Lipid and Volatile Compounds from New Zealand Commercial Lamb Loins.

Loin sections (m. Longissimus lumborum) were collected at slaughter from forty-eight lamb carcasses to evaluate consumer-liking scores of six types of typical New Zealand commercial lamb and to understand the possible underlying reasons for those ratings. A consumer panel (n = 160) evaluated tenderness, juiciness, flavor liking, and overall liking of the different types of lamb loins. Consumer scores differed among the types of lamb meat for all the evaluated attributes (p < 0.05). Further segmentation based on overall liking scores showed two consumer clusters with distinct ratings. Correlation and external preference map analyses indicated that one consumer cluster (n = 75) liked lamb types that had lower total lipid content, a lower proportion of branched-chain fatty acids, oleic and heptadecanoic acids; and a higher proportion of polyunsaturated fatty acids and volatile compounds (green and fruity descriptors). Consumer liking of the other segment (n = 85) was less influenced by fatty acids and volatiles, except hexanoic, heptanoic and octanoic acids (rancid, fatty, and sweaty descriptors). Thus, the fatty acid profile and the volatile compounds derived from their oxidation upon cooking seem to be a stronger driver of consumer liking of lamb for some consumers than others.

MEF2C silencing downregulates NF2 and E-cadherin and enhances Erastin-induced ferroptosis in meningioma.

BACKGROUND: Ferroptosis, a programmed cell death characterized by lipid peroxidation, is implicated in various diseases including cancer. Although cell density-dependent E-cadherin and Merlin/Neurofibromin (NF2) loss can modulate ferroptosis, the role of ferroptosis and its potential link to NF2 status and E-cadherin expression in meningioma remain unknown. METHODS: Relationship between ferroptosis modulators expression and NF2 mutational status was examined in 35 meningiomas (10 NF2 loss and 25 NF2 wild type). The impact of NF2 and E-cadherin on ferroptosis were examined by lactate dehydrogenase (LDH) release, lipid peroxidation, and western blot assays in IOMM-Lee, CH157, and patient-derived meningioma cell models. Luciferase reporter and chromatin immunoprecipitation assays were used to assess the ability of MEF2C (myocyte enhancer factor 2C) to drive expression of NF2 and CDH1 (E-cadherin). Therapeutic efficacy of Erastin-induced ferroptosis was tested in xenograft mouse models. RESULTS: Meningioma cells with NF2 inactivation were susceptible to Erastin-induced ferroptosis. Meningioma cells grown at higher density increased expression of E-cadherin, which suppressed Erastin-induced ferroptosis. Maintaining NF2 and E-cadherin inhibited ferroptosis-related lipid peroxidation and meningioma cell death. MEF2C was found to drive the expression of both NF2 and E-cadherin. MEF2C silencing enhanced Erastin-induced ferroptotic meningioma cell death and lipid peroxidation levels in vitro, which was limited by forced expression of MEF2C targets, NF2 and E-cadherin. In vivo, anti-meningioma effect of Erastin was augmented by MEF2C knockdown and was counteracted by NF2 or E-cadherin. CONCLUSIONS: NF2 loss and low E-cadherin create susceptibility to ferroptosis in meningioma. MEF2C could be a new molecular target in ferroptosis-inducing therapies for meningioma.

Fatty Acid Composition and Volatile Profile of M. longissimus thoracis from Commercial Lambs Reared in Different Forage Systems.

Animal production factors can affect the fatty acid and volatile profile of lamb meat. The fatty acid and volatile composition of the M. longissimus thoracis was evaluated from 150 lambs from 10 groups of commercial lambs that differed in age, sex, diet and breed, from three farms, which represent typical forage lamb production systems in New Zealand. The meat from 4-month-old composite lambs slaughtered at weaning had a similar polyunsaturated to saturated fatty acid ratio compared to 6- to 8-month-old composite lambs, but a greater ratio than that of 12-month-old Merino lambs (p < 0.05), with all ratios being lower than the recommended ≥0.45. All lamb production systems produced meat with an omega-6 to omega-3 ratio below 1.5, well below the recommended ratio ≤ 4.0. Meat from 4-month-old lambs had higher C12:0, C14:0 and C16:0 and lower C18:0, reflecting the composition of the milk diet, resulting in higher atherogenic index than meat from other animal groups, while meat from 12-month-old Merino lambs, with lower content of polyunsaturated fatty acids, showed higher thrombogenic index. Meat from lambs processed at weaning contained the greatest concentration of eicosapentaenoic and docosahexaenoic acids, which would qualify as a 'source' or 'good source' of these target fatty acids based on the Commission of Regulation of the European Union or the Food Standards Australia New Zealand guidelines, respectively. Volatiles were extracted from the headspace of raw lean meat and 36 volatile compounds were identified. The abundance of carbon disulphide, isododecane, heptanal, 2,5-hexanediol and 3-octanone and pentanoic, octanoic, nonanoic and heptanoic acids was similar between all groups of lambs. Meat from 12-month-old Merino lambs had low abundance of acetic, propanoic, butanoic and hexanoic acids, and hexanal, octanal and dimethyl sulphide. For 6- to 8-month-old composite lambs, hexanal, octanal and nonanal were present at higher relative abundance in meat from lambs that grazed on chicory than perennial ryegrass. The significant differences in the fatty acid and volatile profiles in meat from 12-month-old Merino lambs compared with lambs slaughtered at weaning or further grazed on red clover, chicory or mixed pasture may result in distinctive nutritional value and lamb flavour.

Curcumin alleviates neuroinflammation, enhances hippocampal neurogenesis, and improves spatial memory after traumatic brain injury.

Cognitive decline is one of the most obvious symptoms of traumatic brain injury (TBI). Previous studies have demonstrated that cognitive decline is related to substantially increased neuroinflammation and decreased neurogenesis in the hippocampus in a rat model of TBI. Using this model, we explored the role of curcumin (Cur) in ameliorating TBI-impaired spatial memory because Cur has been shown to exhibit anti-chronic-neuroinflammatory, neurogenesis-promoting, and memory-improving properties. Animals received daily Cur or vehicle treatment for 28 days after TBI and also received 50-bromodeoxyuridine(BrdU) for the first 7 days of the treatment for assaying neurogenesis. An optimal Cur dose of 30 mg/kg, selected from a range of 10-50 mg/kg, was used for the present study. Neuroinflammation was evaluated by astrocyte hypertrophy, activated microglia, and inflammatory factors in the hippocampus. Behavioral water-maze studies were conducted for 5 days, starting at 35-day post-TBI. The tropomyosin receptor kinase B (Trkb) inhibitor, ANA-12, was used to test the role of the brain-derived neurotrophic factor (BDNF)/ TrkB/Phosphoinositide 3-kinase (PI3K)/Akt signaling pathway in regulating inflammation and neurogenesis in the hippocampus. Treatment with Cur ameliorated the spatial memory of TBI rats, reduced TBI-induced chronic inflammation, typified by diminished astrocyte hypertrophy, reduction in activated microglia, declined inflammatory factors, and increased neurogenesis in the hippocampus. We also found that BDNF/Trkb/PI3K/Akt signaling was involved in the effects of Cur in TBI rats. Thus, Cur treatment can ameliorate the spatial memory in a murine model of TBI, which may be attributable to decreased chronic neuroinflammation, increased hippocampal neurogenesis, and/or BDNF/Trkb/PI3K/Akt signaling.

The relationship between urinary kidney injury molecule-1 and blood bone metabolism markers in patients with chronic kidney disease
.

OBJECTIVE: The aim of this study was to evaluate the changes of urinary kidney injury molecule-1(uKIM-1) in chronic kidney disease (CKD) at different stages, and to determine the relationships between uKIM-1 and circulating bone metabolism markers. MATERIALS AND METHODS: This cross-sectional study included CKD patients (n = 121) and controls (n = 65). CKD stages were assigned to each individual according to their estimated glomerular filtration rate (eGFR), which was calculated with the modification of diet in renal disease (MDRD) equation. We evaluated the relationships of bone metabolism markers (including calcium, phosphorus, intact parathyroid hormone (iPTH), 25 hydroxy vitamin D (25(OH)D), alkaline phosphatase (ALP), fibroblast growth factor 23 (FGF23), and α-Klotho), uKIM-1, and eGFR. We also compared the levels of bone metabolism markers and uKIM-1 at different CKD stages. The uKIM-1 level was standardized with urine creatinine (uCr). RESULTS: Compared with healthy controls, CKD patients had higher levels of uKIM-1/uCr, serum creatinine, urea, phosphorus, iPTH, and plasma FGF23, whereas they had lower levels of serum calcium, α-Klotho, and plasma 25(OH)D. In CKD patients, eGFR was positively correlated with levels of serum calcium, α-Klotho, and plasma 25(OH)D, whereas it was negatively correlated with serum phosphorus, iPTH, plasma FGF23, and uKIM-1/uCr. Serum calcium and α-Klotho were significantly decreased in patients with stage 5 CKD compared to those with stage 1 CKD. Serum phosphorus, iPTH, and plasma FGF23 were significantly elevated in patients with stage 4 CKD when compared to those with stage 1 CKD. UKIM-1/uCr was significantly elevated in patients with stage 5 CKD when compared to those with stage 1 CKD. In CKD patients, uKIM-1/uCr levels were positively correlated with levels of serum phosphorus and plasma FGF23, whereas they were negatively correlated with serum calcium and plasma 25(OH)D. CONCLUSION: UKIM-1/uCr levels are increased with the deterioration of CKD stage and are correlated with the development of CKD-mineral and bone disorder (CKD-MBD).

Parathyroid Hormone Fragments: New Targets for the Diagnosis and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder.

As a common disorder, chronic kidney disease (CKD) poses a great threat to human health. Chronic kidney disease-mineral and bone disorder (CKD-MBD) is a complication of CKD characterized by disturbances in the levels of calcium, phosphorus, parathyroid hormone (PTH), and vitamin D; abnormal bone formation affecting the mineralization and linear growth of bone; and vascular and soft tissue calcification. PTH reflects the function of the parathyroid gland and also takes part in the metabolism of minerals. The accurate measurement of PTH plays a vital role in the clinical diagnosis, treatment, and prognosis of patients with secondary hyperparathyroidism (SHPT). Previous studies have shown that there are different fragments of PTH in the body's circulation, causing antagonistic effects on bone and the kidney. Here we review the metabolism of PTH fragments; the progress being made in PTH measurement assays; the effects of PTH fragments on bone, kidney, and the cardiovascular system in CKD; and the predictive value of PTH measurement in assessing the effectiveness of parathyroidectomy (PTX). We hope that this review will help to clarify the value of accurate PTH measurements in CKD-MBD and promote the further development of multidisciplinary diagnosis and treatment.

Preparation and characterization of cellulose regenerated from phosphoric acid.

Native cellulose has a highly crystalline structure stabilized by a strong intra- and intermolecular hydrogen-bond network. It is usually not considered as a good gelling material and emulsion stabilizer due to its insolubility in water. Chemical modification is generally necessary to obtain cellulose derivatives for these applications. In this study, we have shown that, by simply disrupting the hydrogen-bond network of cellulose with phosphoric acid treatment, the regenerated cellulose can be a good gelling material and emulsion stabilizer. Microscopy, X-ray diffraction, and Fourier transform infrared spectroscopy analysis have confirmed that the regenerated cellulose is primarily amorphous with low crystallinity in the structure of cellulose II. Stable aqueous suspensions and opaque gels that resist flowing can be obtained with the regenerated cellulose at concentrations higher than 0.6% and 1.6%, respectively. Moreover, it can effectively stabilize oil-in-water emulsions at concentrations less than 1% by a mechanism that combines network and Pickering stabilization.