Targeting Ras-, Rho-, and Rab-family GTPases via a conserved cryptic pocket.

The family of Ras-like GTPases consists of over 150 different members, regulated by an even larger number of guanine exchange factors (GEFs) and GTPase-activating proteins (GAPs) that comprise cellular switch networks that govern cell motility, growth, polarity, protein trafficking, and gene expression. Efforts to develop selective small molecule probes and drugs for these proteins have been hampered by the high affinity of guanosine triphosphate (GTP) and lack of allosteric regulatory sites. This paradigm was recently challenged by the discovery of a cryptic allosteric pocket in the switch II region of K-Ras. Here, we ask whether similar pockets are present in GTPases beyond K-Ras. We systematically surveyed members of the Ras, Rho, and Rab family of GTPases and found that many GTPases exhibit targetable switch II pockets. Notable differences in the composition and conservation of key residues offer potential for the development of optimized inhibitors for many members of this previously undruggable family.

Design and Optimization of Iron-Based Superionic-Like Conductor Anode for High-Performance Lithium/Sodium-Ion Batteries.

Metal selenides have received extensive research attention as anode materials for batteries due to their high theoretical capacity. However, their significant volume expansion and slow ion migration rate result in poor cycling stability and suboptimal rate performance. To address these issues, the present work utilized multivalent iron ions to construct fast pathways similar to superionic conductors (Fe-SSC) and introduced corresponding selenium vacancies to enhance its performance. Based on first-principles calculations and molecular dynamics simulations, it is demonstrated that the addition of iron ions and the presence of selenium vacancies reduced the material's work function and adsorption energy, lowered migration barriers, and enhances the migration rate of Li+ and Na+. In Li-ion half batteries, this composite material exhibites reversible capacity of 1048.3 mAh g-1 at 0.1 A g-1 after 100 cycles and 483.6 mAh g-1 at 5.0 A g-1 after 1000 cycles. In Na-ion half batteries, it is 687.7 mAh g-1 at 0.1 A g-1 after 200 cycles and 325.9 mAh g-1 at 5.0 A g-1 after 1000 cycles. It is proven that materials based on Fe-SSC and selenium vacancies have great applications in both Li-ion batteries and Na-ion batteries.

Free bone flap reconstruction in retrosigmoid approach for microvascular decompression: a comparative cohort study.

Titanium plates and screws are common material used for rigid bone flap fixation after retrosigmoid craniotomy such as microvascular decompression (MVD). We conducted this study to evaluate outcomes of the free bone flap cranioplasty without fixation in MVD and compared its postoperative complication rate with routine methods. We retrospectively reviewed all patients who underwent MVD at our institution from May 2017 to August 2022. Patients were divided into two groups according to whether the bone flap was fixed or not. Follow-ups periods spanned 6-28 months after the operation. Of 189 patients who underwent MVDs via retrosigmoid approach, 79 cases (42%) had their bone flaps replaced without titanium fixation after craniotomies (< 3 cm x 3 cm). Compared to fixed bone flap group, free bone flap group had shorter operative time (105.56 ± 15.87 min vs. 113.72 ± 17.80 min, P = 0.001), less in-patient costs (¥23059.66 ± 4488.54 vs. ¥27714.82 ± 2705.74, P < 0.001), and less proportion of postoperative headache and incisional pain (43.0% vs. 60.9%, P = 0.015). One case of incisional cerebrospinal fluid leak happened in free bone flap group while one case of incisional infection happened in fixed bone flap group. No statistical difference in bone flap displacement, duration of postoperative hospital stays or complication rate was found between the two groups. Nineteen patients in free bone flap group received long-term CT follow-up and all were proved to have good skull union. This study proves that free bone flap cranioplasty in MVD without titanium plate fixation can shorten the operation time and reduce hospitalization expenditure without increasing complication rates.

Monotropein alleviates septic acute liver injury by restricting oxidative stress, inflammation, and apoptosis via the AKT (Ser473)/GSK3ß (Ser9)/Fyn/NRF2 pathway.

Sepsis-associated acute liver injury (ALI) is a deadly condition resulting from a systemic inflammatory response to liver cell damage and malfunction. Monotropein (MON) belongs to the iris group of compounds extracted from the natural product Mollen dae officinalis radix, which has strong anti-inflammatory and antioxidant pharmacological effects. The purpose of this study was to elucidate the underlying mechanism of MON in the treatment of sepsis ALI. In this study, an in vivo caecal ligation puncture (CLP)-induced ALI model and in vitro LPS-stimulated AML12 cells and RAW264.7 cells model were established. Additionally, a variety of experimental techniques, including CCK8, H&E staining, DHE probe labelling, biochemical, QPCR, and Western blotting and blocking tests, were used to explore the role of MON in ALI. The results showed that MON improved liver morphological abnormalities, oedema, histopathological injury, and elevated ALT and AST, providing a protective effect against ALI. MON reduced CYP2E1 expression, alleviated oxidative stress (downregulation of MDA levels and upregulation of GSH, CAT, and T-AOC levels) and ROS accumulation with the involvement of the NRF2-Keap-1 pathway. MON inhibited inflammation via the TLR4/NF-κB/NLRP3 inflammasome pathway. In addition, it activated the Akt (Ser473)/GSK3ß (Ser9)/Fyn pathway and accelerated NRF2 nuclear accumulation; MK-2206 blockade reversed the NRF2 nuclear accumulation and anti-inflammatory function of MON. MON also restricted the mitochondrial apoptosis pathway, a process specifically blocked by MK-2206. In summary, we concluded that MON alleviated septic ALI by restricting oxidative stress, inflammation, and apoptosis via the AKT (Ser473)/GSK3ß (Ser9)/Fyn/NRF2 pathway.

The effect of low-temperature plasma pretreatment on the biodegradability of polyethylene films.

With the increasing focus on environmental friendliness and sustainable development, extensive research has been conducted on the biodegradation of plastics. The non-hydrolyzable, highly hydrophobic, and high-molecular-weight properties of polyethylene (PE) pose challenges for cell interaction and biodegradation of PE substrates. To overcome these obstacles, PE films were treated with low-temperature plasma before biodegradation. The morphology, surface chemistry, molecular weight, and weight loss of PE films after plasma treatment and biodegradation were studied. The plasma treatment decreased the surface water contact angle, formed C-O and C = O groups, and decreased the molecular weight of PE films. With the increased pretreatment time, the biodegradation efficiency rose to 2.6% from 0.63% after 20 days of incubation. The mechanism was proposed that the surface oxygen-containing groups formed by plasma treatment can facilitate the bio-accessibility and be further decomposed and utilised by the microbes. This study provided an effective and rapid pretreatment strategy for improving biodegradation of PE.

Exploring cuproptosis-related molecular clusters and immunological characterization in ischemic stroke through machine learning.

Objective: Ischemic stroke (IS) is a significant health concern with high disability and fatality rates despite available treatments. Immune cells and cuproptosis are associated with the onset and progression of IS. Investigating the interaction between cuproptosis-related genes (CURGs) and immune cells in IS can provide a theoretical basis for IS treatment. Methods: We obtained IS datasets from the Gene Expression Omnibus (GEO) and employed machine learning to identify CURGs. The diagnostic efficiency of the CURGs was evaluated using receiver operating characteristic (ROC) curves. KEGG and gene set enrichment analysis (GSEA) were also conducted to identify biologically relevant pathways associated with CURGs in IS patients. Single-cell analysis was used to confirm the expression of 19 CURGs, and pathway activity calculations were performed using the AUCell package. Additionally, a risk prediction model for IS patients was developed, and core modules and hub genes related to IS were identified using weighted gene coexpression network analysis (WGCNA). We classified IS patients using a method of consensus clustering. Results: We established a precise diagnostic model for IS. Enrichment analysis revealed major pathways, including oxidative phosphorylation, the NF-kappa B signaling pathway, the apoptosis pathway, and the Wnt signaling pathway. At the single-cell level, compared to those in non-IS samples, 19 CURGs were primarily overexpressed in the immune cells of IS samples and exhibited high activity in natural killer cell-mediated cytotoxicity, steroid hormone biosynthesis, and oxidative phosphorylation. Two clusters were obtained through consensus clustering. Notably, immune cell types including B cells, plasma cells, and resting NK cells, varied between the two clusters. Furthermore, the red module and hub genes associated with IS were uncovered. The expression patterns of CURGs varied over time. Conclusion: This study developed a precise diagnostic model for IS by identifying CURGs and evaluating their interaction with immune cells. Enrichment analyses revealed key pathways involved in IS, and single-cell analysis confirmed CURG overexpression in immune cells. A risk prediction model and core modules associated with IS were also identified.

Effect of oxycodone versus fentanyl for patient-controlled intravenous analgesia after laparoscopic hysteromyomectomy: a single-blind, randomized controlled trial.

A single-blind, randomized controlled trial comparing oxycodone and fentanyl for patient-controlled intravenous analgesia (PCIA) after laparoscopic hysteromyomectomy found comparable pain relief between the two groups. The study included 60 participants, with NRS scores for pain at rest and when moving showing no significant differences between oxycodone and fentanyl groups at various time points postoperatively. Self-rating depression scale scores were also similar between the groups at 48 h. However, patients' satisfaction with PCIA was higher in the oxycodone group, with 73.3% reporting being very satisfied compared to 36.7% in the fentanyl group. Additionally, the oxycodone group had fewer incidences of headaches within 48 h postoperatively compared to the fentanyl group. These findings suggest that oxycodone may offer comparable pain relief, higher patient satisfaction, and fewer headaches for patients undergoing laparoscopic hysteromyomectomy compared to fentanyl, making it a suitable option for postoperative pain management in this population.Clinical trial registration number The study was registered with CHICTR.org, ChiCTR2100051924.

Quercetin alleviates difenoconazole-induced growth inhibition in carp through intestinal-brain axis.

Difenoconazole (DIF) is frequently used for the management of fungal infections in fruit and vegetables and excessive residues in the aquatic environment can have adverse effects on fish such as growth inhibition. A treatment based on the dietary additive quercetin (QUE) is a promising approach to positively regulate the state of fish growth. This study focused on whether and how QUE alleviated DIF-induced growth inhibition in fish. In this study, carp were exposed to DIF (0.3906 mg/L) for consecutive 30 d, which showed growth inhibition. Disruption of the intestinal barrier led to elevated levels of intestinal lipopolysaccharide (LPS) and an inflammatory response. Through the intestinal-brain axis, LPS entered the brain where it disrupted the blood-brain barrier, triggered neuroinflammation, caused brain cell apoptosis, and damaged nerves in addition to other things. The dietary supplementation of QUE (400 mg/kg) reduced the levels of LPS in the intestinal and brain, while reducing inflammation and increasing the expression of appetite factors, thereby reducing growth inhibition in carp. This work provided evidence for QUE from the intestinal-brain axis perspective as a potential candidate for alleviating growth inhibition in fish.

Association between systemic immune-inflammation index and serum neurofilament light chain: a population-based study from the NHANES (2013-2014).

Background: The systemic immune-inflammation index (SII) is a novel inflammatory marker used to assess the immune-inflammatory status of the human body. The systemic immune inflammation has an interplay and mutual relationship with neurological disorders. Serum neurofilament light chain (sNfL) is widely regarded as a potential biomarker for various neurological diseases. The study aimed to examine the association between SII and sNfL. Methods: This cross-sectional investigation was conducted in a population with complete data on SII and sNfL from the 2013-2014 National Health and Nutrition Examination Survey (NHANES). The SII was calculated by dividing the product of platelet count and neutrophil count by the lymphocyte count. Multivariate linear regression models and smooth curves were used to explore the linear connection between SII and sNfL. Sensitivity analyses, interaction tests, and diabetes subgroup smoothing curve fitting were also performed. Results: A total of 2,025 participants were included in our present research. SII showed a significant positive association with the natural logarithm-transformed sNfL (ln-sNfL) in crude model [0.17 (0.07, 0.28)], partially adjusted model [0.13 (0.03, 0.22)], and fully adjusted model [0.12 (0.02, 0.22)]. In all participants, the positive association between SII and ln-sNfL served as a linear relationship, as indicated by a smooth curve. Interaction tests showed that age, gender, BMI, hypertension, and diabetes did not have a significant impact on this positive association (p for interaction >0.05). The subgroup analysis of diabetes was conducted using smooth curve fitting. It was found that compared to the group without diabetes and the group in a pre-diabetic state, the effect was more pronounced in the group with diabetes. Conclusion: Our findings suggest that there is a positive association between SII and sNfL. Furthermore, in comparison to individuals without diabetes and those in a pre-diabetic state, the positive association between SII and sNfL was more pronounced in individuals with diabetes. Further large-scale prospective studies are needed to confirm the association between SII and sNfL.

Inflammatory Signaling via PEIZO1 Engages and Enhances the LPS-Mediated Apoptosis during Clinical Mastitis.

Bovine clinical mastitis is characterized by inflammation and immune responses, with apoptosis of mammary epithelial cells as a cellular reaction to infection. PIEZO1, identified as a mechanotransduction effector channel in nonruminant animals and sensitive to both mechanical stimuli or inflammatory signals like lipopolysaccharide (LPS). However, its role in inflammatory processes in cattle has not been well-documented. The aim of this study was to elucidate the in situ expression of PIEZO1 in bovine mammary gland and its potential involvement in clinical mastitis. We observed widespread distribution and upregulation of PIEZO1 in mammary epithelial cells in clinical mastitis cows and LPS-induced mouse models, indicating a conserved role across species. In vitro studies using mammary epithelial cells (MAC-T) revealed that LPS upregulates PIEZO1. Notably, the effects of PIEZO1 artificial activator Yoda1 increased apoptosis and NLRP3 expression, effects mitigated by PIEZO1 silencing or NLRP3 inhibition. In conclusion, the activation of the PIEZO1-NLRP3 pathway induces abnormal apoptosis in mammary epithelial cells, potentially serving as a regulatory mechanism to combat inflammatory responses to abnormal stimuli.

Directly Regenerating of Spent LiCoO2 with Gradient F-doped Subsurface towards Ultra-stable Storage Properties.

As great potential recycling strategy, the direct regeneration of spent LiCoO2 (LCO) is beneficial for lowering environmental pollutions and promoting global sustainability. However, owing to the using of binder and electrolyte, some fluorine impurities would be remained into spent materials. Considering the doping behaviors of F-elements, their suitable content introducing would facilitate the energy-storage abilities of regenerated LCO. Herein, through the tailored introduction of F-elements, spent LCO are successfully regenerated with physical-chemical evolutions. Benefitting from the existed oxygen vacancies, the diffusion energy-barrier of F-elements is reduced from 1.73 eV to 0.61 eV, facilitating the establishment of gradient F-doped subsurface, along with the formation of rigid CoO5F. Meanwhile, excess F-elements (1 wt.%, as a threshold) lead to the formation of LiF passivation layer on the surface. Thus, the as-optimized sample displays a considerable capacity of 154.4 mAh g-1 even at 5.0 C, with retention rate (88.3%) in 3.0~4.5V. Supported by detailed electrochemical and kinetic analysis, the structural advantages are confirmed to boost the improved redox activity of Co-ions and the alleviating of irreversible oxygen-release. Give this, the work is anticipated to reveal the evolutions of regenerated LCO with the introduced F-elements, whilst providing the practical regeneration strategies toward excellent high-voltage properties.

Association of Plastic Exposure with Cognitive Function Among Chinese Older Adults.

Background: The widespread exposure to plastic products and the increasing number of individuals with cognitive impairments have imposed a heavy burden on society. Objective: This study aims to investigate the relationship between plastic product exposure in daily life and cognitive function in older Chinese individuals. Methods: Data were obtained from the 2023 Ningxia Older Psychological Health Cohort, comprising 4045 participants aged 60 and above. Cognitive function was assessed using the Mini-Mental State Examination scale. A population-based plastic exposure questionnaire was used to calculate plastic exposure scores (PES). Binary logistic regression was employed to analyze the relationship between PES and cognitive function, while restricted cubic splines were used to examine the dose-response relationship between PES and cognitive function. Latent profile analysis (LPA) was employed to explore the potential patterns of plastic exposure, and logistic regression was used to investigate the relationship between different exposure patterns and cognitive function. A linear regression model was utilized to investigate the relationship between PES and different dimensions of cognitive function. Results: Among the 4045 participants, 1915 individuals were assessed with mild cognitive impairment (MCI). After adjusting for all covariates, PES (OR = 1.04, 95% CI 1.02-1.06) was significantly associated with the risk of MCI and exhibited a dose-response relationship. LPA identified two potential categories of plastic exposure, with a higher risk of MCI observed in the group using plastic utensils. Conclusions: This study indicates a positive correlation between plastic exposure levels and MCI risk, particularly among individuals who frequently use plastic tableware.

Regeneration of LiFePO4 from spent materials: control and influence of Al impurity.

Owing to the rapid increase of lithium iron phosphate (LiFePO4) batteries, recycling and regeneration of LiFePO4 enjoys significances for sustainable development and environmental protection. In this study, an effective regeneration method for spent LiFePO4 materials and the influence of Al impurity on the electrochemical performance of regenerated LiFePO4 were studied. Firstly, 99.26% Fe, 99.52% P, 99.58% Li, 59.36% Al and 20.24% Cu in spent LiFePO4 material were leached with 150 g•L-1 H2SO4. Subsequently, Al removal and control were achieved by simply adjusting the pH value, and FePO4•2H2O precursors with different Al contents were prepared. Specially, the LiFePO4 regenerated by FePO4•2H2O precursor containing 0.096% Al exhibits excellent electrochemical performance with discharge capacity of 145 mAh•g-1, 140.5 mAh•g-1 and 130.9 mAh•g-1 at the current density of 1C, 2C and 5C, respectively.

PTBP3 Mediates IL-18 Exon Skipping to Promote Immune Escape in Gallbladder Cancer.

Gallbladder cancer (GBC) is the most common malignant tumor of the biliary system, with poor response to current treatments. Abnormal alternative splicing has been associated with the development of a variety of tumors. Combining the GEO database and GBC mRNA-seq analysis, it is found high expression of the splicing factor polypyrimidine region- binding protein 3 (PTBP3) in GBC. Multi-omics analysis revealed that PTBP3 promoted exon skipping of interleukin-18 (IL-18), resulting in the expression of ΔIL-18, an isoform specifically expressed in tumors. That ΔIL-18 promotes GBC immune escape by down-regulating FBXO38 transcription levels in CD8+T cells to reduce PD-1 ubiquitin-mediated degradation is revealed. Using a HuPBMC mouse model, the role of PTBP3 and ΔIL-18 in promoting GBC growth is confirmed, and showed that an antisense oligonucleotide that blocked ΔIL-18 production displayed anti-tumor activity. Furthermore, that the H3K36me3 promotes exon skipping of IL-18 by recruiting PTBP3 via MRG15 is demonstrated, thereby coupling the processes of IL-18 transcription and alternative splicing. Interestingly, it is also found that the H3K36 methyltransferase SETD2 binds to hnRNPL, thereby interfering with PTBP3 binding to IL-18 pre-mRNA. Overall, this study provides new insights into how aberrant alternative splicing mechanisms affect immune escape, and provides potential new perspectives for improving GBC immunotherapy.

The splicing factor SF3B1 confers ferroptosis resistance and promotes lung adenocarcinoma progression via upregulation of SLC7A11.

This study aimed to investigate the expression of SF3B1 in non-small cell lung cancer, and its clinical significance, biological function, and molecular mechanisms. SF3B1 mRNA and protein levels were elevated in both lung squamous cell carcinoma and lung adenocarcinoma (LUAD) tissues based on TCGA data and immunohistochemistry. Notably, high SF3B1 expression in LUAD was significantly associated with increased lymph node metastasis. Functional experiments involving SF3B1 knockdown and overexpression demonstrated that SF3B1 facilitated the proliferation, invasion, and migration of LUAD cells. Additionally, the SF3B1 inhibitor pladienolide-B attenuated the aggressive behavior of LUAD cells both in vitro and in vivo. RNA sequencing analysis indicated that differentially expressed genes in the SF3B1 knockdown and SF3B1 inhibitor groups were enriched in ferroptosis-related pathways compared to their respective control groups. The antiferroptotic role of SF3B1 in LUAD cells was validated by detecting glutathione depletion, lipid peroxidation, and observing morphological changes using transmission electron microscopy. This process was confirmed to be independent of apoptosis and autophagy, as evidenced by the effects of the ferroptosis inducer erastin, the apoptosis inhibitor Z-VAD-FMK, and the autophagy inhibitor 3-methyladenine. Rescue experiments indicated that the antiferroptotic role of SF3B1 in LUAD is partially mediated by upregulating the expression of SLC7A11.

SPATS2L is a positive feedback regulator of the type I interferon signaling pathway and plays a vital role in lupus.

Through genome-wide association studies (GWAS) and integrated expression quantitative trait locus (eQTL) analyses, numerous susceptibility genes ("eGenes", whose expressions are significantly associated with common variants) associated with systemic lupus erythematosus (SLE) have been identified. Notably, a subset of these eGenes is correlated with disease activity. However, the precise mechanisms through which these genes contribute to the initiation and progression of the disease remain to be fully elucidated. In this investigation, we initially identify SPATS2L as an SLE eGene correlated with disease activity. eSignaling and transcriptomic analyses suggest its involvement in the type I interferon (IFN) pathway. We observe a significant increase in SPATS2L expression following type I IFN stimulation, and the expression levels are dependent on both the concentration and duration of stimulation. Furthermore, through dual-luciferase reporter assays, western blot analysis, and imaging flow cytometry, we confirm that SPATS2L positively modulates the type I IFN pathway, acting as a positive feedback regulator. Notably, siRNA-mediated intervention targeting SPATS2L, an interferon-inducible gene, in peripheral blood mononuclear cells (PBMCs) from patients with SLE reverses the activation of the interferon pathway. In conclusion, our research highlights the pivotal role of SPATS2L as a positive-feedback regulatory molecule within the type I IFN pathway. Our findings suggest that SPATS2L plays a critical role in the onset and progression of SLE and may serve as a promising target for disease activity assessment and intervention strategies.

Study on the Erosion Resistance of Different TiN Crystal Planes by Molecular Dynamics.

In this study, we innovatively combined the Fe-Ti-N potential function file to construct simulation models of different crystal facets of TiN/Fe ((001), (110), and (111)), which had not been previously explored. Employing molecular dynamics (MD) simulations, the research investigates the microscale differences in erosion resistance and surface properties of various TiN crystal planes under continuous impacts at varying velocities and angles. The results indicate that both surface wear and internal defects of the model increase with the impact velocity. Both TiN(110) and TiN(111) exhibit damage on their surfaces and interiors, with a larger wear range. In contrast, TiN(001), due to its superior elastic recovery capability, maintains a better surface condition, showing significantly less wear compared to TiN(110) and TiN(111). This disparity in performance among different crystal planes is attributed to variations in molecular gaps between planes, bonding points within the lattice, types of forces, and modes of action. Further research revealed that the wear volume increased with the rise in impact angle, reaching its peak at 90°. Regardless of the impact angle, TiN(001) consistently outperformed TiN(110) and TiN(111). The aim of the research is to compare the surface and internal defects of different crystal facets at the microscopic level, thereby selecting superior crystal facets and providing theoretical reference for the application of TiN materials in practical fracturing environments.

Separation and purification of nylon 54 salts from fermentation broth by an integrated process involving microfiltration, ultrafiltration, and ion exchange.

Nylon 54 is a novel, biodegradable polyamide with excellent thermal resistance and water absorption properties. It can be polymerized using bio-based cadaverine and succinic acid as monomers. Traditional separation methods isolate individual monomers from the fermentation broth through acidification or alkalization, resulting in significant amounts of waste salts; however, synchronous separation of dibasic acids and diamines has not been reported. This study investigated an integrated process for the separation and extraction of nylon 54 salts from a co-fermentation broth without acidification or alkalization. We meticulously optimized the operational parameters of the integrated process to achieve maximum separation efficiency. Following microfiltration, ultrafiltration, and decolorization, the bacterial eliminating rate was ≥99.83%, and the protein concentration was ≤40 mg/L. The absorbance of the decolorized solution was ≤0.021 at 430 nm, and the recovery rate of nylon 54 salt reached 97%. Then, the pretreated solution was passed through sequential chromatographic columns, which effectively removed organic acid by-products (such as acetic acid and lactic acid), SO4 2-, and NH4 + from the fermentation broth, resulting in a cadaverine yield of 98.01% and a succinic acid yield of 89.35%. Finally, by concentrating and crystallizing the eluent, the simulated fermentation broth yielded nylon 54 salt with a purity of 99.16% and a recovery rate of 58%, and the real fermentation broth yielded nylon 54 salt with a purity of 98.10% and a recovery rate of 56.21%. This integrated process offers a sustainable and environmentally friendly pathway for the complete biosynthesis of nylon 54 salt and has the potential to be extended to the preparation of other nylon salts.

Serum ceruloplasmin oxidase activity: A neglected diagnostic biomarker for Wilson disease.

BACKGROUND: Low serum ceruloplasmin concentration is considered robust marker for Wilson disease (WD) screening, measuring serum ceruloplasmin oxidase activity might be an even more valuable diagnostic tool, but it has not been sufficiently studied. METHODS: All patients who were assessed for serum ceruloplasmin oxidase activity between January 1, 2016, and September 2, 2019, were enrolled in this study. The diagnostic performance of serum ceruloplasmin oxidase activity was analyzed using receiver operating characteristic curve analysis (ROC), Spearman's rank correlation, and Mann-Whitney U test. RESULTS: Serum ceruloplasmin oxidase activity was significantly decreased in WD patients (0.87 U/L, IQR 0.61-1.54). The optimal cut-off of serum ceruloplasmin oxidase activity to identified WD is 7 U/L, with sensitivity and specificity of 97.03 % and 98.19 %, respectively. Furthermore, this study revealed a positive correlation between enzymatic and immunoreactive serum ceruloplasmin tests. As primary diagnostic methods, serum ceruloplasmin levels below the diagnostic cut-offs for either the enzymatic or immunoreactive tests were observed in 818 out of 842 WD patients (97.15 %). Compared with the presence of K-F rings in asymptomatic patients, the accuracy of serum ceruloplasmin tests was significantly higher (56.12 % VS 95.08 %). Moreover, the positive rate of cranial MRI in neurological patients was similar to the tests of serum ceruloplasmin (92.91 % VS 97.40 %). Moreover, 71 patients had ambiguous genetic results, complicating the diagnosis. However, serum ceruloplasmin tests successfully identified 65 out of these 71 patients (91.55 %). CONCLUSION: Serum ceruloplasmin oxidase activity has excellent performance in diagnosing WD, which should be widely used as preferred test in WD patients.

Exploring Cancer Incidence Trends by Age and Sex Among 14.14 Million Individuals in China From 2007 to 2021: Population-Based Study.

BACKGROUND: Sex is a crucial factor in the development, progression, and treatment of cancer, making it vital to examine cancer incidence trends by sex for effective prevention strategies. OBJECTIVE: This study aimed to assess the incidence of cancer in China between 2007 and 2021, with a focus on sex-based trends. METHODS: A population-based cancer registry comprising 14.14 million individuals was maintained between 2007 and 2021 by the Beijing Municipal Health Big Data and Policy Research Center. The age-standardized rates (ASRs) of cancers were calculated using the Segi population. The average annual percentage of change (AAPC) was evaluated using the joinpoint regression model, while the Bayesian age-period-cohort model was used to predict cancer incidence in the next 10 years. RESULTS: From 2007 to 2021, the study included 651,342 incident patients with cancer, of whom 51.2% (n=333,577) were women. The incidence indicated by the ASR for all cancers combined was 200.8 per 100,000 for women and 184.4 per 100,000 for men. The increase in incidence indicated by AAPC for all malignancies combined significantly increased in women between 2007 and 2021 (AAPC=3.1%; P<.001), whereas it remained constant in men (AAPC=0.3%; P=.30). Although the overall incidence of all cancers indicated by AAPC increased in young men (AAPC=3.2%; P=.01), the greatest increase was observed among young women (AAPC=6.1%; P<.001). The incidence rate ratio for cancer in women increased among subsequent younger generations compared with patients born in the 1962-1966 cohort. The ASR in women will increase 1.6-fold over the next 10 years, with women having twice the incidence rate of men by 2031. CONCLUSIONS: The rising incidence of cancer among women in China has become a growing concern, emphasizing the need for increased efforts in cancer prevention and early screening, especially among young women.