Investigating the risk factors for nonadherence to analgesic medications in cancer patients: Establishing a nomogram model.

Objective: The substantial prevalence of nonadherence to analgesic medication among individuals diagnosed with cancer imposes a significant strain on both patients and healthcare resources. The objective of this study is to develop and authenticate a nomogram model for assessing nonadherence to analgesic medication in cancer patients. Methods: Clinical information, demographic data, and medication adherence records of cancer pain patients were gathered from the Affiliated Hospital of Chengde Medical University between April 2020 and March 2023. The risk factors associated with analgesic medication nonadherence in cancer patients were analyzed using the least absolute selection operator (LASSO) regression model and multivariate logistic regression. Additionally, a nomogram model was developed. The bootstrap method was employed to internally verify the model. Discrimination and accuracy of the nomogram model were evaluated using the Concordance index (C-index), area under the receiver Operating characteristic (ROC) curve (AUC), and calibration curve. The potential clinical value of the nomogram model was established through decision curve analysis (DCA) and clinical impact curve. Results: The study included a total of 450 patients, with a nonadherence rate of 43.33%. The model incorporated seven factors: age, address, smoking history, number of comorbidities, use of nonsteroidal antiinflammatory drugs (NSAIDs), use of opioids, and PHQ-8. The C-index of the model was found to be 0.93 (95% CI: 0.907-0.953), and the ROC curve demonstrated an AUC of 0.929. Furthermore, the DCA and clinical impact curves indicate that the built model can accurately predict cancer pain patients' medication adherence performance. Conclusions: A nomogram model based on 7 risk factors has been successfully developed and validated for long-term analgesic management of cancer patients.

EFNet: enhancing feature information for 3D object detection in LiDAR point clouds.

With the development of autonomous driving, there has been considerable attention on 3D object detection using LiDAR. Pillar-based LiDAR point cloud detection algorithms are extensively employed in the industry due to their simple structure and high real-time performance. Nevertheless, the pillar-based detection network suffers from significant loss of 3D coordinate information during the feature degradation and extraction process. In the paper, we introduce a novel framework with high performance, termed EFNet. The EFNet uses the Enhancing Pillar Feature Module (EPFM) to provide more accurate representations of features from two directions: pillar internal space and pillar external space. Additionally, the Head Up Module (HUM) is utilized in the detection head to integrate multi-scale information and enhance the network's information perception ability. The EFNet achieves impressive results on the nuScenes datasets, namely, 53.3% NDS and 42.4% mAP. Compared to the baseline PointPillars, EFNet improves 8% NDS and 11.9% mAP. The results demonstrate that the proposed framework can effectively improve the network's accuracy while ensuring deployability.

The molecular subtypes of autoimmune diseases.

Autoimmune diseases (ADs) are characterized by their complexity and a wide range of clinical differences. Despite patients presenting with similar symptoms and disease patterns, their reactions to treatments may vary. The current approach of personalized medicine, which relies on molecular data, is seen as an effective method to address the variability in these diseases. This review examined the pathologic classification of ADs, such as multiple sclerosis and lupus nephritis, over time. Acknowledging the limitations inherent in pathologic classification, the focus shifted to molecular classification to achieve a deeper insight into disease heterogeneity. The study outlined the established methods and findings from the molecular classification of ADs, categorizing systemic lupus erythematosus (SLE) into four subtypes, inflammatory bowel disease (IBD) into two, rheumatoid arthritis (RA) into three, and multiple sclerosis (MS) into a single subtype. It was observed that the high inflammation subtype of IBD, the RA inflammation subtype, and the MS "inflammation & EGF" subtype share similarities. These subtypes all display a consistent pattern of inflammation that is primarily driven by the activation of the JAK-STAT pathway, with the effective drugs being those that target this signaling pathway. Additionally, by identifying markers that are uniquely associated with the various subtypes within the same disease, the study was able to describe the differences between subtypes in detail. The findings are expected to contribute to the development of personalized treatment plans for patients and establish a strong basis for tailored approaches to treating autoimmune diseases.

PPARß/δ as a promising molecular drug target for liver diseases: A focused review.

Various liver diseases pose great threats to humans. Although the etiologies of these liver diseases are quite diverse, they share similar pathologic phenotypes and molecular mechanisms such as oxidative stress, lipid and glucose metabolism disturbance, hepatic Kupffer cell (KC) proinflammatory polarization and inflammation, insulin resistance, and hepatic stellate cell (HSC) activation and proliferation. Peroxisome proliferator-activated receptor ß/δ (PPARß/δ) is expressed in various types of liver cells with relatively higher expression in KCs and HSCs. Accumulating evidence has revealed the versatile functions of PPARß/δ such as controlling lipid homeostasis, inhibiting inflammation, regulating glucose metabolism, and restoring insulin sensitivity, suggesting that PPARß/δ may serve as a potential molecular drug target for various liver diseases. This article aims to provide a concise review of the structure, expression pattern and biological functions of PPARß/δ in the liver and its roles in various liver diseases, and to discuss potential future research perspectives.

[Spatial-temporal Variation and Spatial Differentiation Geographic Detection of PM2.5 Concentration in the Shandong Province Based on Spatial Scale Effect].

PM2.5 remote sensing data was applied in this study, and Theil-Sen Median trend analysis and the Mann-Kendall significance test were utilized to analyze the temporal and spatial variation in PM2.5 in the Shandong Province from 2000 to 2021. The influencing power of the influencing factors on the spatial differentiation of PM2.5 concentration in the Shandong Province was detected at the provincial-city-county levels based on Geo-detector data. The results showed that:① on the temporal scale, the mean ρ(PM2.5)in the Shandong Province ranged from 38.15 to 88.63 µg·m-3 from 2000 to 2021, which was slightly higher than the secondary limit of inhalable particulate matter (35 µg·m-3) in the Ambient Air Quality Standards. On the interannual scale, 2013 was the peak year for the variation in ρ(PM2.5) with a value of 83.36 µg·m-3, according to which the trend of PM2.5 concentrations in the Shandong Province was divided into two phases:a continuous increase and a rapid decrease. On the seasonal scale, PM2.5 concentration presented the distribution characteristics of "low in summer and high in winter and moderate in spring and autumn" and the U-shaped change rule of first decreasing and then increasing. ② On the spatial scale, the PM2.5 concentration in the Shandong Province presented a spatial distribution pattern of "high in the west and low in the east." The areas with high PM2.5 concentration were distributed in the western area of the Shandong Province, whereas the areas with low PM2.5 concentration were distributed in the eastern peninsula region. The spatial variation in the changing trend of PM2.5 concentration showed significant spatial heterogeneity, and the extremely significant decrease was mainly distributed in the eastern peninsula region. ③ The results of factor detection showed that climate factor was an important factor affecting the spatial differentiation of PM2.5 concentration in the Shandong Province. Mean temperature had the highest influence on the spatial differentiation of PM2.5 concentration in the Shandong Province, with a q value of 0.512. Provincial-city-county multi-scale detection results showed that the influencing factors affecting the spatial differentiation of PM2.5 concentration and their influencing power differed at different spatial scales. At the provincial scale, mean temperature, sunshine duration, and slope were the main factors affecting the spatial differentiation of PM2.5 concentration. At the city level, precipitation, elevation, and relative humidity were the main factors affecting the spatial differentiation of PM2.5. At the county level, precipitation, mean temperature, and sunshine duration were the main factors affecting the spatial variation in PM2.5 concentration.

Assessing Aptamer-Analyte Binding Kinetics by Microfluidic Fluorescence Microscopy.

Kinetic measurement plays a crucial role in understanding aptamer binding mechanisms and identifying appropriate aptamers for clinical and research applications. Current techniques, while well established, generally require large sample volumes, bulky and expensive instruments operated by trained personnel, and are hence not readily accessible to resource-limited research laboratories. This paper presents a fluorescence microscopy-based microfluidic assay for measuring aptamer-analyte binding kinetics in a simple and cost-effective manner. Kinetic measurements are achieved by monitoring time-course fluorescence of fluorescently labeled aptamers as they bind to the targets trapped in a microfluidic chip. Fluorescence measurements are performed on a standard fluorescence microscope and are accessible to laboratories with only modest resources. Moreover, microfluidic technology allows efficient and cost-effective immobilization of small amounts of target molecules or live cells as well as flow-based manipulation of aptamers for the measurements. Kinetic measurements of aptamer binding to immunoglobulin E protein and CCRF-CEM cells have yielded results consistent with those obtained from established methods, demonstrating the potential utility of our method for exploring aptamer-target interactions and identifying aptamers that best suit specific given biomedical applications.

Opportunities and challenges in perovskite-organic thin-film tandem solar cells.

Efficiency is paramount in enhancing the performance and cost-effectiveness of solar cells. Recent advancements in single-junction perovskite solar cells (PSCs) have yielded an impressive efficiency of 26.1%, nearing their theoretical limit. Meanwhile, multi-junction tandem solar cells exhibit a remarkable efficiency potential exceeding 42%, surpassing the 33% limit of single-junction cells, thereby opening avenues for ultra-high-efficiency solar cells. Tandem solar cells (TSCs) represent a groundbreaking photovoltaic technology, offering high efficiency, low cost, and a simple fabrication process. Among various TSCs, perovskite-organic TSCs (PO TSCs) are particularly promising due to their ability to leverage the complementary strengths of PSCs and organic solar cells (OSCs). PO TSCs are poised to outperform existing TSCs in terms of device performance, manufacturing cost, and diverse applications. The introduction of Y6-series non-fullerene acceptors (NFAs) over the past three years has significantly advanced the development of OSCs, leading to remarkable progress in PO TSCs. This paper commences by elucidating the advantages and potential of OSCs as bottom sub-cells in PO TSCs, followed by an in-depth review of mainstream interconnection layer (ICL) design. It then addresses key challenges in wide bandgap PSCs, including phase segregation, photovoltage loss, energy loss, and long-term stability. The paper concludes by examining critical factors influencing the future development of PO TSCs.

The deepwater oxygen deficit in stratified shallow seas is mediated by diapycnal mixing.

Seasonally stratified shelf seas are amongst the most biologically productive on the planet. A consequence is that the deeper waters can become oxygen deficient in late summer. Predictions suggest global warming will accelerate this deficiency. Here we integrate turbulence timeseries with vertical profiles of water column properties from a seasonal stratified shelf sea to estimate oxygen and biogeochemical fluxes. The profiles reveal a significant subsurface chlorophyll maximum and associated mid-water oxygen maximum. We show that the oxygen maximum supports both upward and downwards O2 fluxes. The upward flux is into the surface mixed layer, whilst the downward flux into the deep water will partially off-set the seasonal O2 deficit. The results indicate the fluxes are sensitive to both the water column structure and mixing rates implying the development of the seasonal O2 deficit is mediated by diapcynal mixing. Analysis of current shear indicate that the downward flux is supported by tidal mixing, whilst the upwards flux is dominated by wind driven near-inertial shear. Summer storminess therefore plays an important role in the development of the seasonal deep water O2 deficit.

Discovery of YFJ-36: Design, Synthesis, and Antibacterial Activities of Catechol-Conjugated ß-Lactams against Gram-Negative Bacteria.

Cefiderocol is the first approved catechol-conjugated cephalosporin against multidrug-resistant Gram-negative bacteria, while its application was limited by poor chemical stability associated with the pyrrolidinium linker, moderate potency against Klebsiella pneumoniae and Acinetobacter baumannii, intricate procedures for salt preparation, and potential hypersensitivity. To address these issues, a series of novel catechol-conjugated derivatives were designed, synthesized, and evaluated. Extensive structure-activity relationships and structure-metabolism relationships (SMR) were conducted, leading to the discovery of a promising compound 86b (Code no. YFJ-36) with a new thioether linker. 86b exhibited superior and broad-spectrum in vitro antibacterial activity, especially against A. baumannii and K. pneumoniae, compared with cefiderocol. Potent in vivo efficacy was observed in a murine systemic infection model. Furthermore, the physicochemical stability of 86b in fluid medium at pH 6-8 was enhanced. 86b also reduced potential the risk of allergy owing to the quaternary ammonium linker. The improved properties of 86b supported its further research and development.

Fourteen undescribed steroidal saponins from Solanum capsicoides leaves and their neuroprotective effects.

A total of 14 previously undescribed steroidal saponins named capsicsaponins A-N were isolated from the leaves of Solanum capsicoides, encompassing various types, including cholesterol derivatives and pseudospirostanol saponins. The structures of all compounds were determined through comprehensive analysis of spectroscopic data (1D NMR and 2D NMR), along with physicochemical analysis methods (acid hydrolysis, OR, and UV). Moreover, in the H2O2-induced pheochromocytoma cell line model, compounds 1-14 were screened for their neuroprotective effects on cells. The bioassay results demonstrated compounds 8-14 were able to revive cell viability compared to the positive control edaravone. The damage neuroprotection of the most active compound was further explored.

Downregulation of GPX8 in hepatocellular carcinoma: impact on tumor stemness and migration.

PURPOSE: GPX8, which is found in the endoplasmic reticulum lumen, is a member of the Glutathione Peroxidases (GPXs) family. Its role in hepatocellular carcinoma (HCC) is unknown. METHODS: Immunohistochemical staining was used to detect the protein levels of GPX8 in HCC tissue microarrays. A short hairpin RNA lentivirus was used to knock down GPX8, and the main signaling pathways were investigated using transcriptome sequencing and a phosphorylated kinase array. The sphere formation assays, cloning-formation assays and cell migration assays were used to evaluate the stemness and migration ability of HCC cells. Identifying the GPX8-interacting proteins was accomplished through immunoprecipitation and protein mass spectrometry. RESULTS: The GPX8 protein levels were downregulated in HCC patients. Low expression of GPX8 protein was related to early recurrence and poor prognosis in HCC patients. GPX8 knockdown could enhance the stemness and migration ability of HCC cells. Consistently, Based on transcriptome analysis, multiple signaling pathways that include the PI3K-AKT and signaling pathways that regulate the pluripotency of stem cells, were activated after GPX8 knockdown. The downregulation of GPX8 could increase the expression of the tumor stemness markers KLF4, OCT4, and CD133. The in vivo downregulation of GPX8 could also promote the subcutaneous tumor-forming and migration ability of HCC cells. MK-2206, which is a small-molecule inhibitor of AKT, could reverse the tumor-promoting effects both in vivo and in vitro. We discovered that GPX8 and the 71-kDa heat shock cognate protein (Hsc70) have a direct interaction. The phosphorylation of AKT encouraged the translocation of Hsc70 into the nucleus and the expression of the PI3K p110 subunit, thereby increasing the downregulation of GPX8. CONCLUSION: The findings from this study demonstrate the anticancer activity of GPX8 in HCC by inactivating the Hsc70/AKT pathway. The results suggest a possible therapeutic target for HCC.

Thy1-ApoE4/C/EBPß double transgenic mice act as a sporadic model with Alzheimer's disease.

Early onset familial Alzheimer's disease (FAD) with APP, PS1/2 (presenilins) mutation accounts for only a small portion of AD cases, and most are late-onset sporadic. However, majority of AD mouse models are developed to mimic the genetic cause of human AD by overexpressing mutated forms of human APP, PS1/2, and/or Tau protein, though there is no Tau mutation in AD, and no single mouse model recapitulates all aspects of AD pathology. Here, we report Thy1-ApoE4/C/EBPß double transgenic mouse model that demonstrates key AD pathologies in an age-dependent manner in absence of any human APP or PS1/2 mutation. Using the clinical diagnosis criteria, we show that this mouse model exhibits tempo-spatial features in AD patient brains, including progressive cognitive decline associated with brain atrophy, which is accompanied with extensive neuronal degeneration. Remarkably, the mice display gradual Aß aggregation and neurofibrillary tangles formation in the brain validated by Aß PET and Tau PET. Moreover, the mice reveal widespread neuroinflammation as shown in AD brains. Hence, Thy1-ApoE4/C/EBPß mouse model acts as a sporadic AD mouse model, reconstituting the major AD pathologies.

Design, Synthesis, and Biological Evaluation of Novel Arylomycins against Multidrug-Resistant Gram-Negative Bacteria.

G0775, an arylomycin-type SPase I inhibitor that is being evaluated in a preclinical study, exhibited potent antibacterial activities against some Gram-negative bacteria but meanwhile suffered defects such as a narrow antibacterial spectrum and poor pharmacokinetic properties. Herein, systematic structural modifications were carried out, including optimization of the macrocyclic skeleton, warheads, and lipophilic regions. The optimization culminated in the discovery of 138f, which showed more potent activity and a broader spectrum against clinically isolated carbapenem-resistant Gram-negative bacteria, especially against Acinetobacter baumannii and Pseudomonas aeruginosa. 162, the free amine of 138f, exhibited an excellent pharmacokinetic profile in rats. In a neutropenic mouse thigh model of infection with multidrug-resistant P. aeruginosa, the potent in vivo antibacterial efficacy of 162 was confirmed and superior to that of G0775 (3.5-log decrease vs 1.1-log decrease in colony-forming unit (CFU)). These results support 162 as a potential antimicrobial agent for further research.

Physical exercise frequency and cognition: a multicenter cross-sectional cohort study.

Background and aims: Dementia imposes a heavy burden on society and families, therefore, effective drug treatments, exploring and preventing factors associated with dementia, are paramount. To provide reference points for the best frequency of physical exercise (physical exercise), we investigated the association between frequency of PE and cognition in Chinese old adults. Methods: 16,181 Chinese participants aged 65 years or older were included in this study. Associations between PE and cognition were estimated multivariate logistic and linear regression analyses. Associations were further investigated across dementia subtypes (Alzheimer dementia, vascular dementia, and other types of dementia). Subgroup analyses were performed in different age groups, in populations with and without stroke, and those with and without hypertension. Results: PE associated with dementia after adjusting for full covariates (OR: 0.5414, 95% CI: 0.4536-0.6491, p < 0.001). Exercise performed at ≥3 times/week associated with lower risk of dementia (OR: 0.4794-0.6619, all p value <0.001). PE was associated with improved cognition (ß: 12851, p < 0.001), and any PE frequency contributed to cognitive improvement (p values for exercise performed ≥1 time/week were <0.001). Similar conclusions were identified when we repeated analyses in different dementia subtypes and age groups. Subgroup analyses suggested that the cognition of individuals without hypertension also benefitted from exercising 1-2 times/week (OR: 0.6168, 95% CI: 0.4379-0.8668, p = 0.005). Conclusion: The best exercise frequency is exercising ≥3 times/week for individuals from different dementia subtypes and age groups. While for those without hypertension, PE at 1-2 times /week is also beneficial.

Interventions to Improve Endoscopic Screening Adherence of Cancer in High-Risk Populations: A Scoping Review.

Background: Colorectal, and gastric cancers have the second, and fourth mortality rates worldwide, respectively. Endoscopic screening is a crucial diagnostic tool for colorectal, and gastric cancers. Effective interventions can improve adherence to endoscopic screening in high-risk populations, which is important for cancer prevention and mortality reduction. This study aimed to identify interventions that could improve adherence to endoscopic screening for cancer in high-risk populations. Methods: Combination keywords including colorectal cancer, gastric cancer, screening adherence, and interventions were used to search for articles in PubMed, Web of Science, Cochrane Library, and MEDLINE Complete. The review methodology was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-SCR). Results: A total of 12 articles were included in this review: 9 randomized controlled trials(RCT) and 3 quasi-experimental studies(QEDs). Among the extracted studies, 11 were about colorectal cancer, and 1 was about gastric cancer. Most studies used lecture-based or Information Technology-based health education interventions. Narrative interventions have proven to be novel and effective approaches for promoting adherence to endoscopic screening. Health education interventions included cancer epidemiology, cancer risk factors, warning symptoms, and screening methods. Conclusion: All interventions involved were effective in increasing individual knowledge of cancer-related endoscopic screening, willingness to undergo screening, and screening behaviors. These findings provide a reference for designing endoscopy-related cancer screening interventions.

Boosted Sacrificial-Agent-Free Selective Photoreduction of CO2 to CH3OH by Rhenium Atomically Dispersed on Indium Oxide.

Solar-energy-driven photoreduction of CO2 is promising in alleviating environment burden, but suffers from low efficiency and over-reliance on sacrificial agents. Herein, rhenium (Re) is atomically dispersed in In2O3 to fabricate a 2Re-In2O3 photocatalyst. In sacrificial-agent-free photoreduction of CO2 with H2O, 2Re-In2O3 shows a long-term stable efficiency which is enhanced by 3.5 times than that of pure In2O3 and is also higher than those on Au-In2O3, Ag-In2O3, Cu-In2O3, Ir-In2O3, Ru-In2O3, Rh-In2O3 and Pt-In2O3 photocatalysts. Moreover, carbon-based product of the photoreduction overturns from CO on pure In2O3 to CH3OH on 2Re-In2O3. Re promotes charge separation, H2O dissociation and CO2 activation, thus enhancing photoreduction efficiency of CO2 on 2Re-In2O3. During the photoreduction, CO is a key intermediate. CO prefers to desorption rather than hydrogenation on pure In2O3, as CO binds to pure In2O3 very weakly. Re strengthens the interaction of CO with 2Re-In2O3 by 5.0 times, thus limiting CO desorption but enhancing CO hydrogenation to CH3OH. This could be the origin for photoreduction product overturn from CO on pure In2O3 to CH3OH on 2Re-In2O3. The present work opens a new way to boost sacrificial-agent-free photoreduction of CO2.

Factors affecting the compliance of hepatocellular carcinoma screening among high-risk populations: A systematic review and meta-analysis.

BACKGROUND: Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and the third leading cause of cancer mortality. HCC has high morbidity, high mortality, and low survival rates. Screening is one of the most significant methods of lowering incidence and death while also increasing survival. OBJECTIVES: The aim of this study was to identify the facilitators and barriers to participation in HCC screening among high-risk populations. METHODS: A comprehensive and systematic search was undertaken in PubMed, Web of Science, MEDLINE, EMBACE, EBSCOhost and the Cochrane Library. A combination of synonyms of the keywords including HCC, screening, factors and adherence were used for searching. Studies addressing the facilitators and barriers to HCC screening compliance in at-risk individuals were included. Data were synthesized using Review Manager version 5.4. A random/fixed effects model meta-analysis was performed to estimate the pooled data and expressed with odds ratio (OR) and 95% confidence interval (CI). RESULTS: A total of seven articles met the inclusion criteria. Qualitative (n = 1) and quantitative (n = 6) studies using various types of surgery were conducted. The most commonly mentioned barriers were insufficient knowledge and awareness of HCC screening, unawareness of the necessity for early detection of HCC and lack of physician recommendation. A meta-analysis of seven studies showed that individuals with a family history of HCC increased screening uptake by nearly three times (OR: 2.69, 95% CI: 1.93, 3.75). Other most frequently reported facilitators include age, education level, and perceived risk et al. CONCLUSIONS: Many barriers to HCC screening were found. Meanwhile, this review points out that improving the awareness of high-risk populations toward HCC screening is expected to enhance compliance, thereby promoting early diagnosis of liver cancer, reducing mortality, and alleviating the burden of HCC.

Mature compost promotes biodegradable plastic degradation and reduces greenhouse gas emission during food waste composting.

Mature compost can promote the transformation of organic matter (OM) and reduce the emission of polluting gases during composting, which provides a viable approach to reduce the environmental impacts of biodegradable plastics (BPs). This study investigated the impact of mature compost on polybutylene adipate terephthalate (PBAT) degradation, greenhouse gas (GHG) emission, and microbial community structure during composting under two treatments with mature compost (MC) and without (CK). Under MC, visible plastic rupture was advanced from day 14 to day 10, and a more pronounced rupture was observed at the end of composting. Compared with CK, the degradation rate of PBAT in MC was increased by 4.44 % during 21 days of composting. Thermobifida, Ureibacillus, and Bacillus, as indicator species under MC treatment, played an important role in PBAT decomposition. Mature compost reduced the total global warming potential (GWP) by 25.91 % via inhibiting the activity of bacteria related to the production of CH4 and N2O. Functional Annotation of Prokaryotic Taxa (FAPROTAX) further revealed that mature compost addition increased relative abundance of bacteria related to multiple carbon (C) cycle functions such as methylotrophy, hydrocarbon degradation and cellulolysis, inhibited nitrite denitrification and denitrification, thus alleviating the emission of GHGs. Overall, mature compost, as an effective additive, exhibits great potential to simultaneously mitigate BP and GHG secondary pollution in co-composting of food waste and PBAT.

One-pot preparation of magnetic composite containing boronic acid groups and aminated multwalled carbon nanotubes for the speciation of Se(IV) and Se(VI) in water and milk samples by combination with chromatographic quantification.

Speciation of Se(IV) and Se(VI) is essential due to their significant differences in reactivity, toxicity and bioavailability. Efficient extraction is the pivotal step in the quantification of inorganic selenium species. In this work, a new magnetic nano-composite (MNC) containing boronic acid group and aminated multwalled carbon nanotubes was facilely fabricated by means of one-pot hydrothermal strategy. The prepared MNC contained abundant functional groups and satisfactory magnetic saturation value. Combining with magnetic solid phase extraction (MSPE) format, the MNC displayed satisfactory capture performance towards the complex formed by the coordination of Se(IV) and o-phenylenediamine (OPA). Adsorption isotherm and adsorption kinetics were studied in detail to investigate the adsorption procedure of Se(IV)/OPA complex on MNC. Under the optimal preparation conditions of MNC and extraction parameters, the MNC/MSPE was connected with HPLC equipped with a diode array detector (DAD) to quantify trace Se(IV) and Se(VI) species in water and milk samples. Se(VI) was reduced to Se(IV) and then the total inorganic Se was quantified by the developed method. Subtraction method was used to measure the concentration of Se(VI). The achieved limits of detection were in the ranges of 0.0082-0.013 µg/L and 0.041-0.13 µg/kg for water and milk samples, respectively. Recoveries in actual samples spiked with different amounts of analytes varied from 81.0 % and 117 %, and the RSDs for repeatability varied from 1.0 % to 10 %. In comparison with existing studies based on MSPE, the established method presents some merits such as greenness in the preparation of magnetic adsorbent, rapid extraction procedure, low cost and satisfactory sensitivity in the speciation of inorganic Se species.

Th1 cell immune response in Talaromyces marneffei infection with anti-interferon-γ autoantibody syndrome.

Anti-interferon-γ autoantibody (AIGA) syndrome may be the basis of disseminated Talaromyces marneffei infection in human immunodeficiency virus (HIV)-negative adults. However, the pathogenesis of Th1 cell immunity in T. marneffei infection with AIGA syndrome is unknown. A multicenter study of HIV-negative individuals with T. marneffei infection was conducted between September 2018 and September 2020 in Guangdong and Guangxi, China. Patients were divided into AIGA-positive (AP) and AIGA-negative (AN) groups according to the AIGA titer and neutralizing activity. The relationship between AIGA syndrome and Th1 immune deficiency was investigated by using AP patient serum and purification of AIGA. Fifty-five HIV-negative adults with disseminated T. marneffei infection who were otherwise healthy were included. The prevalence of AIGA positivity was 83.6%. Based on their AIGA status, 46 and 9 patients were assigned to the AP and AN groups, respectively. The levels of Th1 cells, IFN-γ, and T-bet were higher in T. marneffei-infected patients than in healthy controls. However, the levels of CD4+ T-cell STAT-1 phosphorylation (pSTAT1) and Th1 cells were lower in the AP group than in the AN group. Both the serum of patients with AIGA syndrome and the AIGA purified from the serum of patients with AIGA syndrome could reduce CD4+ T-cell pSTAT1, Th1 cell differentiation and T-bet mRNA, and protein expression. The Th1 cell immune response plays a pivotal role in defense against T. marneffei infection in HIV-negative patients. Inhibition of the Th1 cell immune response may be an important pathological effect of AIGA syndrome.IMPORTANCEThe pathogenesis of Th1 cell immunity in Talaromyces marneffei infection with anti-interferon-γ autoantibody (AIGA) syndrome is unknown. This is an interesting study addressing an important knowledge gap regarding the pathogenesis of T. marneffei in non-HIV positive patients; in particular patients with AIGA. The finding of the Th1 cell immune response plays a pivotal role in defense against T. marneffei infection in HIV-negative patients, and inhibition of the Th1 cell immune response may be an important pathological effect of AIGA syndrome, which presented in this research could help bridge the current knowledge gap.