Predicting clinically significant prostate cancer in elderly patients: A nomogram approach with shear wave elastography.

PURPOSE: This study was to construct a nomogram utilizing shear wave elastography and assess its efficacy in detecting clinically significant prostate cancer (csPCa). METHODS: 290 elderly people with suspected PCa who received prostate biopsy and shear wave elastography (SWE) imaging were respectively registered from April 2022 to December 2023. The elderly participants were stratified into two groups: those with csPCa and those without csPCa, which encompassed cases of clinically insignificant prostate cancer (cisPCa) and non-prostate cancer tissue, as determined by pathology findings. The LASSO algorithm, known as the least absolute shrinkage and selection operator, was utilized to identify features. Logistic regression analysis was utilized to establish models. Receiver operating characteristic (ROC) and calibration curves were utilized to evaluate the discriminatory ability of the nomogram. Bootstrap (1000 bootstrap iterations) was employed for internal validation and comparison with two models. A decision curve and a clinical impact curve were employed to assess the clinical usefulness. RESULTS: Our nomogram, which contained Emean, ΔEmean, prostate volume, prostate-specific antigen density (PSAD), and transrectal ultrasound (TRUS), showed better discrimination (AUC = 0.89; 95% CI: 0.83-0.94), compared to the clinical model without SWE parameters (p = 0.0007). Its accuracy, sensitivity and specificity were 0.83, 0.89 and 0.78, respectively. Based on the analysis of decision curve, the thresholds ranged from 5% to 90%. According to our nomogram, biopsying patients at a 20% probability threshold resulted in a 25% reduction in biopsies without missing any csPCa. The clinical impact curve demonstrated that the nomogram's predicted outcome is closer to the observed outcome when the probability threshold reaches 20% or greater. CONCLUSION: Our nomogram demonstrates efficacy in identifying elderly individuals with clinically significant prostate cancer, thereby facilitating informed clinical decision-making based on diagnostic outcomes and potential clinical benefits.

Association of serum cystatin C level and major adverse cardiovascular events in patients with percutaneous coronary intervention.

Background: Recurrent acute myocardial infarction requiring unplanned percutaneous coronary intervention (PCI) is one of the major adverse cardiovascular events (MACEs) in patients with acute coronary syndrome (ACS) after PCI. There is a continuing controversy about the association between serum cystatin C, a biomarker for the evaluation of renal function, and the prognosis of ACS patients following PCI. The retrospective study evaluated the association between serum cystatin C level and MACE in ACS patients after PCI. Methods: Data were retrieved for 330 patients with ACS for primary PCI in a single center. Serum cystatin C levels were measured before PCI. All patients underwent regular follow-ups after PCI, and the studied endpoint was MACE, defined as the need for a repeat revascularization in the heart. The predictive value of serum cystatin C for MACE was analyzed using univariate and multivariate analysis. Restricted cubic spline (RCS) analysis was applied to evaluate the dose-response relationship between serum cystatin C level and MACE in ACS patients following PCI. Results: After a median follow-up of 63 months (range, 1-148 months), 121 of the 330 patients experienced MACE. Compared to patients who did not have MACE, patients who had MACE showed a significant decrease in serum cystatin C levels (0.99±0.32 vs. 1.15±0.78 mg/L, P=0.03). In multivariate regression analysis, serum cystatin C level was an independent risk factor for MACE. According to the serum cystatin C level, patients were divided into 4 categories, Cox regression analysis illustrated that the second quartile of serum cystatin C level indicated an increased risk of MACE in patients with PCI for primary ACS compared to the highest quartile [Q2: adjusted hazard ratio (HR) =2.109; 95% confidence interval (CI): 1.193-3.727; P=0.01]. RCS analysis showed a significant U-shaped dose-response relationship between cystatin C level and MACE in patients with PCI for ACS (P for non-linearity =0.004). Conclusions: These results indicated an association between serum cystatin C level and post-PCI MACE in ACS patients.

Molecular characteristic, evolution, and pathogenicity analysis of avian infectious bronchitis virus isolates associated with QX type in China.

Infectious bronchitis virus (IBV) is one of the major avian pathogens plaguing the global poultry industry. Although vaccination is the primary preventive measure for IBV infection, the emergence of virus variants with mutations and recombination has resulted in IBV circulating globally, presenting a challenge for IB control. Here, we isolated 3 IBV strains (CZ200515, CZ210840, and CZ211063) from suspected sick chickens vaccinated with IBV live attenuated vaccines (H120, 4/91, or QXL87). Phylogenetic analysis of the S1 gene sequence of the spike (S) revealed that the 3 isolates belonged to the QX-type (GI-19 lineage). Whole genome sequencing and recombination analysis indicated that CZ200515 and CZ210840 contained genetic material from 4/91 and Scyz3 (QX-type), possibly due to recombination between the circulating strain and the 4/91 vaccine strain, while no evidence of recombination was found in CZ211063. Pathogenicity analysis in 1-day-old specific pathogen-free (SPF) chickens demonstrated that all 3 isolates caused severe tissue damage and varying degrees of mortality. Virus cross-neutralization assay revealed decreased antigen relatedness between the isolates and the QX-type vaccine strain (QXL87). Amino acid sequence homology analysis of S1 revealed 5%-6.5% variances between the isolates and QXL87. Analysis of the S1 subunit structure revealed that mutations of amino acid residues in the hypervariable region (HVR) and the neutralizing epitope region resulted in antigenic variation in isolates by changing the antigen conformation. Our data indicate antigenicity variances between QX isolates and QXL87 vaccine strains, potentially resulting in immune evasion occurrences. Overall, these results offer crucial insights into the epidemiology and pathogenicity of QX-type IBV, facilitating improved selection and formulation of vaccines for disease management.

Rapid discovery of natural antioxidants in Hypericum japonicum: Dual roles of the liquid phase mobile phase as extraction and separation solvent.

Hypericum japonicum is a traditional folk medicine with various bioactivities such as hepatoprotective, antioxidant, and anti-tumorous. The antioxidant effect of H. japonicum is one of the most prominent effects due to its responsibility for many of its activities. To clarify active natural substance, the antioxidant properties of H. japonicum were preliminarily assessed by ferric reducing-antioxidant power (FRAP), 2,2-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid (ABTS) and Oxygen radical absorbance capacity (ORAC), as well as superoxide dismutase (SOD). Then, a straightforward and effective method named online liquid extraction-high performance liquid chromatography combined with ABTS antioxidant assay and mass spectrometry (OLE-HPLC-ABTS/Q-TOF-MS) was developed to swiftly and directly discover the antioxidants in H. japonicum. Using mobile phase as extraction and separation reagent, coupled with online activity analysis and compounds identification by high-resolution MS, the online system enables rapid screening of natural antioxidant bioactives from complex mixture. By using it, a total of 9 compounds including flavonoids and phenolic acids characterized by retention time, precise mass, and fragmentation ions in MS/MS spectra showed antioxidant action. Finally, the antioxidant and SOD activity of main found active compounds were validated by in vitro experiment assay and molecular docking. In summary, these results suggested that H. japonicum could be considered as a potential source of natural antioxidants, and the online integrated system might become a promising candidate for the natural antioxidants discovery in the future.

Cockroach Blaptica dubia biodegrades polystyrene plastics: Insights for superior ability, microbiome and host genes.

The report demonstrated that a member of cockroach family, Blaptica dubia (Blattodea: Blaberidae) biodegraded commercial polystyrene (PS) plastics with Mn of 20.3 kDa and Mw of 284.9 kDa. The cockroaches digested up to 46.6 % of ingested PS within 24 h. The biodegradation was confirmed by the 13C isotopic shift of the residual PS in feces versus pristine PS (Δ Î´13C of 2.28 ‰), reduction of molecular weight and formation of oxidative functional groups in the residual PS. Further tests found that B.dubia cockroaches degraded all eight high purity PS microplastics with low to ultra-high molecular weights (MW) at 0.88, 1.20, 3.92, 9.55, 62.5, 90.9, 524.0, and 1040 kDa, respectively, with superior biodegradation ability. PS depolymerization/biodegradation pattern was MW-dependent. Ingestion of PS shifted gut microbial communities and elevated abundances of plastic-degrading bacterial genes. Genomic, transcriptomic and metabolite analyses indicated that both gut microbes and cockroach host contributed to digestive enzymatic degradation. PS plastic diet promoted a highly cooperative model of gut digestive system. Weighted gene co-expression network analysis revealed different PS degradation patterns with distinct MW profiles in B. dubia. These results have provided strong evidences of plastic-degrading ability of cockroaches or Blaberidae family and new understanding of insect and their microbe mediated biodegradation of plastics.

The effectiveness of targeted therapy for recurrence or metastasis adenoid cystic carcinoma: a systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Several clinical studies have demonstrated the potential of molecular-targeted agents for the treatment of recurrent or metastatic adenoid cystic carcinoma (R/M ACC). However, there is currently no consensus regarding the efficacy of molecular-targeted agents for patients with R/M ACC. This study aimed to evaluate the therapeutic efficacy and safety of molecular-targeted agents in patients with R/M ACC and provide insights to guide clinical decision-making. MATERIALS AND METHODS: Five databases (PubMed, Embase, Cochrane, ProQuest, and Scopus) were searched based on the search strategy and selection criteria. Primary endpoints were objective response rate (ORR) and progression-free survival (PFS). The secondary endpoints were disease control rate (DCR), overall survival (OS), metastatic sites, and adverse events (AE). Pooled estimates were calculated using a random-effects meta-analysis. RESULTS: Finally, 28 studies, involving 849 patients, were included. The most common metastatic sites were the lungs, bones, liver, lymph nodes, and kidneys. The pooled ORR was 4.0% (95% CI, 0.7-8.8%), the pooled DCR was 80.5% (95% CI, 72.2%-87.7%). Compared with other-target drugs, multiple kinase inhibitors (MKIs) improved the ORR (pooled ORR for single-target drugs vs. MKIs: 5.9% vs. 0%). The combination of MKIs and immune checkpoint inhibitors (ICIs) had a significantly higher ORR (17.9% in the axitinib + avelumab group). The pooled median PFS and OS were 8.35 and 25.62 months, respectively. MKIs improved the median PFS compared to other-target drugs (9.43 months vs 5.06 months). In addition, the most common adverse events (AEs) were fatigue (51.6%), hypertension (44.2%), and nausea (40.0%), followed by hand-foot skin syndrome (36.8%), diarrhoea (34.4%), weight loss (34.2%), anorexia (31.8%), rash (31.7%), and headache (29.0%). CONCLUSION: The findings of this study suggest that MKIs have a better therapeutic efficacy than single-target drugs in patients with R/M ACC. Future studies are warranted to verify the synergistic role of the combination strategy of MKIs plus ICIs, given the limited number of studies on this topic conducted and published to date.

pH-Sensitive and Redox-Responsive Poly(Tetraethylene Glycol) Nanoparticle-Based Platform for Cancer Treatment.

Effective drug delivery with precise tumour targeting is crucial for cancer treatment. To address the challenges posed by the specificity and complexity of the tumour microenvironment, we developed a poly(tetraethylene glycol)-based disulfide nanoparticle platform and explored its potential in cancer treatment, focusing on drug loading and controlled release performance. Poly(tetraethylene glycol) nanoparticles were characterised using nuclear magnetic resonance spectroscopy, mass spectrometry, and ultraviolet-visible spectroscopy. Additionally, we evaluated physicochemical properties, including dynamic light scattering, zeta potential analysis, drug loading capacity, and drug loading efficiency. The impact of nanoparticles on the mouse colorectal cancer cell line (CT26) and NIH3T3 cells was assessed using a cytotoxicity assay, live/dead staining assay, flow cytometry, and confocal fluorescence microscopy. The experimental results align with the expected chemical structure and physicochemical properties of poly(tetraethylene glycol) nanoparticles. These nanoparticles exhibit high drug loading efficiency (78.7%) and drug loading capacity (12%), with minimal changes in particle size over time in different media. In vitro experiments revealed that the nanoparticles can induce significant cytotoxicity and apoptosis in CT26 cells. Cellular uptake notably increases with increasing concentration and exposure time. The confocal microscopic analysis confirmed the effective distribution and accumulation of nanoparticles within cells. In conclusion, poly(tetraethylene glycol) nanoparticles hold promise for improving drug-delivery efficiency, offering potential advancements in cancer treatment.

Effects of plastic aging on biodegradation of polystyrene by Tenebrio molitor larvae: Insights into gut microbiome and bacterial metabolism.

Plastics aging reduces resistance to microbial degradation. Plastivore Tenebrio molitor rapidly biodegrades polystyrene (PS, size: < 80 µm), but the effects of aging on PS biodegradation by T. molitor remain uncharacterized. This study examined PS biodegradation over 24 days following three pre-treatments: freezing with UV exposure (PS1), UV exposure (PS2), and freezing (PS3), compared to pristine PS (PSv) microplastic. The pretreatments deteriorated PS polymers, resulting in slightly higher specific PS consumption (602.8, 586.1, 566.7, and 563.9 mg PS·100 larvae-1·d-1, respectively) and mass reduction rates (49.6 %, 49.5 %, 49.2 %, and 48.7 %, respectively) in PS1, PS2, and PS3 compared to PSv. Improved biodegradation correlated with reduced molecular weights and the formation of oxidized functional groups. Larvae fed more aged PS exhibited greater gut microbial diversity, with microbial community and metabolic pathways shaped by PS aging, as supported by co-occurrence network analysis. These findings indicated that the aging treatments enhanced PS biodegradation by only limited extent but impacted greater on gut microbiome and bacterial metabolic genes, indicating that the T. molitor host have highly predominant capability to digest PS plastics and alters gut microbiome to adapt the PS polymers fed to them.

Alteration of ascending colon mucosal microbiota in patients after cholecystectomy.

BACKGROUND: Cholecystectomy is a successful treatment option for gallstones, although the incidence of colorectal cancer (CRC) has notably increased in post-cholecystectomy (PC) patients. However, it remains uncertain whether the altered mucosal microbiota in the ascending colon is related. AIM: To investigate the potential correlation between gut microbiota and the surgical procedure of cholecystectomy. METHODS: In total, 30 PC patients and 28 healthy controls underwent colonoscopies to collect mucosal biopsy samples. PC patients were divided based on their clinical features. Then, 16S-rRNA gene sequencing was used to analyze the amplicon, alpha diversity, beta diversity, and composition of the bacterial communities. Additionally, the Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) database, sourced from the Kyoto Encyclopedia of Genes and Genomes, was used to predict the functional capabilities of the bacteria. RESULTS: PC patients were comparable with healthy controls. However, PC patients older than 60 years had a distinct composition compared to those under 60 years old. Bacteroidetes richness was considerably higher at the phylum level in PC patients. Bacteroides, Parabacteroides, and Bilophila were more abundant in the PC group than in the control group. Furthermore, PC patients exhibited greater enrichment in metabolic pathways, specifically those related to lipopolysaccharide biosynthesis and vancomycin group antibiotic production, than controls. CONCLUSION: This study indicated that the mucosal microbiota in PC patients was altered, perhaps offering new perspectives on the treatment possibilities for CRC and diarrhea following cholecystectomy.

[Efficiency of different large language models in China in response to consultations about PCa-related perioperative nursing and health education].

OBJECTIVE: To evaluate the efficiency of the four domestic language models, ERNIE Bot, ChatGLM2, Spark Desk and Qwen-14B-Chat, all with a massive user base and significant social attention, in response to consultations about PCa-related perioperative nursing and health education. METHODS: We designed a questionnaire that includes 15 questions commonly concerned by patients undergoing radical prostatectomy and 2 common nursing cases, and inputted the questions into each of the four language models for simulation consultation. Three nursing experts assessed the model responses based on a pre-designed Likert 5-point scale in terms of accuracy, comprehensiveness, understandability, humanistic care, and case analysis. We evaluated and compared the performance of the four models using visualization tools and statistical analyses. RESULTS: All the models generated high-quality texts with no misleading information and exhibited satisfactory performance. Qwen-14B-Chat scored the highest in all aspects and showed relatively stable outputs in multiple tests compared with ChatGLM2. Spark Desk performed well in terms of understandability but lacked comprehensiveness and humanistic care. Both Qwen-14B-Chat and ChatGLM2 demonstrated excellent performance in case analysis. The overall performance of ERNIE Bot was slightly inferior. All things considered, Qwen-14B-Chat was superior to the other three models in consultations about PCa-related perioperative nursing and health education. CONCLUSION: In PCa-related perioperative nursing, large language models represented by Qwen-14B-Chat are expected to become powerful auxiliary tools to provide patients with more medical expertise and information support, so as to improve the patient compliance and the quality of clinical treatment and nursing.

Urinary polycyclic aromatic hydrocarbon metabolites and their association with oxidative stress among pregnant women in Los Angeles.

BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) have been linked to adverse birth outcomes that have been reported to be induced by oxidative stress, but few epidemiological studies to date have evaluated associations between urinary PAH metabolites and oxidative stress biomarkers in pregnancy and identified critical periods for these outcomes and PAH exposures in pregnancy. METHODS: A cohort of pregnant women was recruited early in pregnancy from antenatal clinics at the University of California Los Angeles during 2016-2019. We collected urine samples up to three times during pregnancy in a total of 159 women enrolled in the cohort. A total of 7 PAH metabolites and 2 oxidative stress biomarkers [malondialdehyde (MDA), 8-hydroxy-2'-deoxyguanosine (8-OHdG)] were measured in all available urine samples. Using multiple linear regression models, we estimated the percentage change (%) and 95% confidence interval (CI) in 8-OHdG and MDA measured at each sample collection time per doubling of PAH metabolite concentrations. Furthermore, we used linear mixed models with a random intercept for participant to estimate the associations between PAH metabolite and oxidative stress biomarker concentrations across multiple time points in pregnancy. RESULTS: Most PAH metabolites were positively associated with both urinary oxidative stress biomarkers, MDA and 8-OHdG, with stronger associations in early and late pregnancy. A doubling of each urinary PAH metabolite concentration increased MDA concentrations by 5.8-41.1% and 8-OHdG concentrations by 13.8-49.7%. Linear mixed model results were consistent with those from linear regression models for each gestational sampling period. CONCLUSION: Urinary PAH metabolites are associated with increases in oxidative stress biomarkers during pregnancy, especially in early and late pregnancy.

Exploring the possible therapeutic mechanism of Danzhixiaoyao pills in depression and MAFLD based on "Homotherapy for heteropathy": A network pharmacology and molecular docking.

Objective: Danzhixiaoyao pills (DXP) is a traditional Chinese medicine formula that has been effectively used in clinical practice to treat depression and metabolic associated fatty liver disease (MAFLD), but its therapeutic mechanism is not yet clear. The purpose of this study is to explore the possible mechanisms of DXP in treating depression and MAFLD using network pharmacology and molecular docking techniques based on existing literature reports. Methods: By combining TCMSP, Swiss ADME, Swiss TargetPrediction, and UniProt databases, the active ingredients and potential targets of DXP were screened and obtained. By searching for relevant disease targets through Gene Cards, OMIM, and TTD databases, intersection targets between drugs and diseases were obtained. The network of "Disease - Potential targets - Active ingredients - Traditional Chinese medicine - Prescriptions" was constructed using Cytoscape 3.9.1 software, and the PPI network was constructed using STRING 12.0 database. The core targets were obtained through topology analysis. GO function enrichment and KEGG pathway enrichment analysis were conducted based on DAVID. The above results were validated by molecular docking using PyMol 2.5 and AutoDock Tool 1.5.7 software, and their possible therapeutic mechanisms were discussed. Results: Network pharmacology analysis obtained 130 main active ingredients of drugs, 173 intersection targets between drugs and diseases, and 37 core targets. Enrichment analysis obtained 1390 GO functional enrichment results, of which 922 were related to biological process, 107 were related to cellular component, 174 were related to molecular function, and obtained 180 KEGG pathways. Molecular docking has confirmed the good binding ability between relevant components and targets, and the literature discussion has preliminarily verified the above results. Conclusion: DXP can act on targets such as TNF, AKT1, ALB, IL1B, TP53 through active ingredients such as kaempferol, quercetin, naringenin, isorhamnetin, glyuranolide, etc, and by regulating signaling pathways such as pathways in cancer, MAPK signaling pathway, lipid and atherosclerosis, to exert its effect of "homotherapy for heteropathy" on depression and MAFLD. In addition, glyuranolide showed the strongest affinity with TNF (-7.88 kcal/mol), suggesting that it may play a key role in the treatment process. The research results provide a theoretical basis for elucidating the scientific connotation and mechanism of action of traditional Chinese medicine compound DXP, and provide new directions for its clinical application.

Nucleation and growth process of a softened-spark layer during microarc oxidation on a selective laser melted Ti alloy.

A two-step method for preparing composite coatings with different composition on Ti alloys using softened spark microarc oxidation technology was proposed. The nucleation and growth processes of a softened spark layer, as well as the influence of softened sparks on the deposition of anions in electrolytes, were studied. The results show that the process voltage of the softened spark discharge on the selective laser-melted Ti6Al4V alloy was lower than the breakdown voltage of its anodic oxide film. The softened sparks prioritized nucleation at the coating/substrate interface in the initial spark discharge area rather than in the microarc discharge area. On one hand, the softened spark layer grew towards the Ti6Al4V substrate, and on the other hand, the molten oxide generated by the softened sparking was transferred into the external porous layer. The softened sparks generated inside the coating promoted the rutile phase formation and linear growth in the thickness of the softened spark layer. Ca and P are mainly distributed in the external porous layer or at the interface between the softened-spark and external porous layers. Nevertheless, softened sparking had little effect on the initial micro/nanoporous structures of the coatings.

Constructing the Electron-Rich Microenvironment of an All-Polymer-Based S-Scheme Homostructure for Accelerating Uranium Capture from Nuclear Wastewater.

Large quantities of uranium-containing radioactive wastewater are typically generated during nuclear fuel cycle processes. Despite significant efforts, efficient capture of migratable hexavalent uranium U(VI) is still a huge challenge due to its acidity, radioactivity, coexisting organics, and high impurity cation abundance in wastewater. Herein, we have fabricated all-polymer-based 0D/2D C4N/C6N7 homostructure hybrids with an S-scheme electronic configuration by coordinating the band engineering of semiconductors to enrich uranium species from the complex wastewater environment. The sample can capture over 97% of U(VI) in the actual concentration of nuclear industrial reprocessing wastewater; also, the U(VI) enrichment ratio still exceeds 95% when the irradiation dose (including α, ß, and γ) is up to 100 kGy. Density functional theory and X-ray absorption spectroscopy demonstrate that the aggregation of charge carriers on the surface of the sample regulates the electron-rich microenvironment, thus accelerating the reduction conversion of single electron reaction uranium disproportionation. It is expected that this work can provide more insight into other functional materials, thereby promoting uranium removal advancements in nuclear wastewater.

Apolipoprotein E deficiency leads to the polarization of splenic macrophages towards M1 phenotype by increasing iron content.

Apolipoprotein E (ApoE) plays a crucial role in iron homeostasis in the body, while macrophages are the principal cells responsible for handling iron in mammals. However, it is unknown whether ApoE can affect the functional subtypes and the iron handling capacity of splenic macrophages (SM). Here, we investigated the effects of ApoE deficiency (ApoE-/-) on the polarization and iron content of SM and its potential mechanisms. ApoE-/- was found to induce a significant increase in the expressions of M1 marker genes CD86, IL-1ß, IL-6, IL-12, TNF-α and iNOS and a reduction in M2 marker genes CD206, Arg-1, IL-10 and Ym-1 in SM of mice aged 28 weeks, Meanwhile, ApoE-/- caused a significant increase in iron content and expression of ferritin, transferrin receptor 1 (TfR1), iron regulatory protein 1 (IRP1) and heme oxygenase-1 (HO-1) and a reduction in ferroportin1 (Fpn1) in spleen and/or SM of mice aged 28 weeks. It was concluded that ApoE-/- can increase iron content through increased iron uptake mediated by TfR/ IRPs and decreased iron release mediated by Fpn1, leading to polarization of the SM to M1 phenotype.

Osteocalcin: A potential marker to identify and monitor girls with rapidly progressive central precocious puberty.

AIM: To evaluate the suitability of serum osteocalcin (OC) as a marker to distinguish between rapidly and non-rapidly progressive central precocious puberty (RP-CPP and NRP-CPP), as well as its potential to assess growth rates following treatment with gonadotropin-releasing hormone agonist (GnRHa). METHODS: Serum levels of OC were measured using enzyme-linked immunosorbent assays in girls diagnosed with either RP-CPP or NRP-CPP as well as in normal control subjects. Receiver operating characteristic (ROC) curve analysis was performed to determine the cut-off value for OC. Multivariate linear regression analysis was used to analyse the main influencing factors associated with OC. RESULTS: Serum OC levels were higher in the CPP girls when compared to normal controls (110.76 ± 43.69 vs 55.97 ± 20.96 ng/mL, P < 0.001). The level in the RP-CPP group was higher than the NRP-CPP group (153.28 ± 33.89 vs 88.33 ± 29.26 ng/mL, P < 0.001). The cut-off value of OC levels for distinguishing between RP-CPP and NRP-CPP was 107.05 ng/mL, the sensitivity was 94.7% and the specificity was 77.8%, which was superior to using the basal luteinising hormone (B-LH) levels, and the area under ROC curve (AUC) were 0.933 versus 0.695, respectively. Following 1-2 years of treatment with GnRHa for girls with CPP, both OC levels and the growth rates decreased to pre-pubertal values. B-LH levels, bone age and body weight were also significant factors, which affected OC levels. CONCLUSIONS: Serum OC levels may be a useful marker for distinguishing RP-CPP from NRP-CPP. In addition, it was also found to be a useful predictor for growth rate during GnRHa treatment.

[Antibiotic Pollution and Its Effects on the Spatiotemporal Variation in Microbial Community Structure and Functional Genes in Sediment of Baiyangdian Lake].

Microbial communities play an important role in water quality regulation and biogeochemical cycles in lakes, and their community structure and function are affected by environmental factors. Therein, antibiotics affect the abundance, diversity, composition, and function of microbial communities. In this study, Baiyangdian Lake was selected as the study area. Sediment samples of 16 sites were collected in August 2018 and April 2019, respectively. Ultra-high performance liquid chromatography-mass spectrometry （HPLC-MS/MS） was used to determine the content of typical antibiotics-quinolones （QNs） in sediment. Through high-throughput sequencing technology, the structure and function of microbial communities was analyzed in the sediments to explore the spatiotemporal variation. Thereinto, redundancy analysis （RDA） was used to identify the key influencing factors of spatiotemporal variation of microbial communities. The results showed that： ① From August to April, the average ω（QNs） showed an increasing trend, and its mean value changed from 3.91 ng·g-1 to 6.34 ng·g-1, with significant seasonal differences in oxolinic acid （OXO） and total QNs content （P < 0.05）. ② In terms of temporal variation, the dominant bacteria were Proteobacteria and Chloroflexi. The relative abundance of Proteobacteria showed a decreasing trend, whereas Chloroflexi showed an increasing trend； at the genus level, the dominant bacteria genera in August were norank_ f__Anaerolineaceae and Thiobacilus, and the dominant bacteria genera in April were Acinetobacter and norank_ f_Anaerolineaceae, and the dominant bacteria genera had significant seasonal differences （P < 0.05）. ③ In terms of temporal variation, the index of Simpson, Chao, Ace, and OTU number all showed an increasing trend, and the seasonal differences were significant （P < 0.05）. ④ In terms of spatial variation, there were no significant spatial differences among functional genes of COG. In terms of temporal variation, there were significant seasonal differences in functional genes of energy production and conversion, carbohydrate transport and metabolism, transcription, cell wall/membrane/envelope biogenesis, and signal transduction mechanisms （P < 0.01 and P < 0.05）. ⑤ Microbial community structure and functional genes were significantly correlated with QNs （P < 0.01 and P < 0.05）, and QNs were the main influencing factors. Therefore, QNs were the main factor affecting the changes in microbial community structure and functional genes in sediments of Baiyangdian Lake. Thus, comprehensive control of antibiotic pollution in sediments should be further strengthened.

Fatty links between multisystem proteinopathy and small VCP-interacting protein.

Multisystem proteinopathy (MSP) is a rare, dominantly inherited disorder that includes a cluster of diseases, including frontotemporal dementia, inclusion body myopathy, and Paget's disease of bone. MSP is caused by mutations in the gene encoding valosin-containing protein (VCP). Patients with the same mutation, even within the same family, can present with a different combination of any or all of the above diseases, along with amyotrophic lateral sclerosis (ALS). The pleiotropic effects may be linked to the greater than 50 VCP co-factors that direct VCP's many roles in the cell. Small VCP-interacting protein (SVIP) is a small protein that directs VCP to autophagosomes and lysosomes. We found that SVIP directs VCP localization to lysosomes in an acylation-dependent manner. We demonstrate that SVIP is myristoylated at Glycine 2 and palmitoylated at Cysteines 4 and 7. Acylation of SVIP is required to mediate cell death in the presence of the MSP-associated VCP variant (R155H-VCP), whereas blocking SVIP myristoylation prevents cytotoxicity. Therefore, SVIP acylation may present a novel target in MSP.

Crebanine mitigates glucocorticoid-induced osteonecrosis of the femoral head by restoring bone remodelling homeostasis via attenuating oxidative stress.

The onset of osteonecrosis of the femoral head (ONFH) is intimately associated with the extensive administration of glucocorticoids (GCs). Long-term stimulation of GCs can induce oxidative stress in both osteoclasts (OCs) and osteoblasts (OBs), resulting in the disturbance of bone remodelling. An alkaloid named crebanine (CN) demonstrates pharmacological properties including anti-inflammation and reactive oxygen species (ROS) modulation. Our objective is to assess the therapeutic potential of CN in treating ONFH and elucidate the associated underlying mechanisms. The network pharmacology analysis uncovered that CN played a role in regulating ROS metabolism. In vitro, CN demonstrated its ability to reduce the dexamethasone (DEX)-stimulated generation of OCs and suppress their resorptive function by downregulating the level of osteoclast marker genes. Concurrently, CN also mitigated DEX-induced damage to OBs, facilitating the restoration of osteoblast marker gene expression, cellular differentiation and function. These effects were achieved by CN augmenting the antioxidant system to reduce intracellular ROS levels. Furthermore, in vitro results were corroborated by micro-CT and histological data, which also showed that CN attenuated MPS-induced ONFH in mice. This study highlights the therapeutic potential of CN in counteracting GCs-induced ONFH.