Combining chemical analysis and toxicological methods to access the ecological risk of complex contamination in Daye Lake.

As one of the nine primary non-ferrous metal smelting bases in China, Daye Lake basin was polluted due to diverse human activities. But so far the pollution status and related ecological risks of this region have not been detailly investigated. In current study, pollutants including heavy metals, polycyclic aromatic hydrocarbons (PAHs) and organochlorine pesticides (OCPs) in eight sediment samples from Daye Lake were quantified. 18S rRNA gene sequencing was employed to profile the nematode community structure within these sediments. Model organism Caenorhabditis elegans (C. elegans) were further applied for a comprehensive ecological risk assessment of Daye Lake. Notably, Cadmium (Cd) was identified as a key driver of ecological risk, reaching an index of 1287.35. At sample point S4, OCPs particularly p,p'-DDT, displayed an extreme ecological risk with a value of 23.19. Cephalobidae and Mononchida showed strong sensitivity to pollutant levels, reinforcing their suitability as robust bioindicators. The composite pollutants in sampled sediments caused oxidative stress in C. elegans, with gene Vit-2 and Mtl-1 as sensitive biomarkers. By employing the multiple analysis methods, our data can offer valuable contributions to environmental monitoring and health risk assessment for composite polluted areas.

Red nucleus mGluR1 and mGluR5 facilitate the development of neuropathic pain through stimulating the expressions of TNF-α and IL-1ß.

Our previous study has identified that glutamate in the red nucleus (RN) facilitates the development of neuropathic pain through metabotropic glutamate receptors (mGluR). Here, we further explored the actions and possible molecular mechanisms of red nucleus mGluR Ⅰ (mGluR1 and mGluR5) in the development of neuropathic pain induced by spared nerve injury (SNI). Our data indicated that both mGluR1 and mGluR5 were constitutively expressed in the RN of normal rats. Two weeks after SNI, the expressions of mGluR1 and mGluR5 were significantly boosted in the RN contralateral to the nerve injury. Administration of mGluR1 antagonist LY367385 or mGluR5 antagonist MTEP to the RN contralateral to the nerve injury at 2 weeks post-SNI significantly ameliorated SNI-induced neuropathic pain. However, unilateral administration of mGluRⅠ agonist DHPG to the RN of normal rats provoked a significant mechanical allodynia, this effect could be blocked by LY367385 or MTEP. Further studies indicated that the expressions of TNF-α and IL-1ß in the RN were also elevated at 2 weeks post-SNI. Administration of mGluR1 antagonist LY367385 or mGluR5 antagonist MTEP to the RN at 2 weeks post-SNI significantly inhibited the elevations of TNF-α and IL-1ß. However, administration of mGluR Ⅰ agonist DHPG to the RN of normal rats significantly enhanced the expressions of TNF-α and IL-1ß, these effects were blocked by LY367385 or MTEP. These results suggest that activation of red nucleus mGluR1 and mGluR5 facilitate the development of neuropathic pain by stimulating the expressions of TNF-α and IL-1ß. mGluR Ⅰ maybe potential targets for drug development and clinical treatment of neuropathic pain.

Curcumin-polydopamine nanoparticles alleviate ferroptosis by iron chelation and inhibition of oxidative stress damage.

Ferroptosis, characterized by elevated iron levels and lipid peroxidation (LPO), is a recently identified regulatory mechanism of cell death. Its substantial involvement in ischemic tissue injury, neurodegenerative disorders, and cancer positions ferroptosis inhibition as a promising strategy for managing these diverse diseases. In this study, we introduce curcumin-polydopamine nanoparticles (Cur-PDA NPs) as an innovative ferroptosis inhibitor. Cur-PDA NPs demonstrate remarkable efficacy in chelating both Fe2+ and Fe3+in vitro along with scavenging free radicals. Cur-PDA NPs were found to efficiently mitigate reactive oxygen species, reduce Fe2+ accumulation, suppress LPO, and rejuvenate mitochondrial function in PC12 cells. Thus, these NPs can act as potent therapeutic agents against ferroptosis, primarily via iron chelation and reduction of oxidative stress.

Comprehensive identification of maize ZmE2F transcription factors and the positive role of ZmE2F6 in response to drought stress.

BACKGROUND: The early 2 factor (E2F) family is characterized as a kind of transcription factor that plays an important role in cell division, DNA damage repair, and cell size regulation. However, its stress response has not been well revealed. RESULTS: In this study, ZmE2F members were comprehensively identified in the maize genome, and 21 ZmE2F genes were identified, including eight E2F subclade members, seven DEL subfamily genes, and six DP genes. All ZmE2F proteins possessed the DNA-binding domain (DBD) characterized by conserved motif 1 with the RRIYD sequence. The ZmE2F genes were unevenly distributed on eight maize chromosomes, showed diversity in gene structure, expanded by gene duplication, and contained abundant stress-responsive elements in their promoter regions. Subsequently, the ZmE2F6 gene was cloned and functionally verified in drought response. The results showed that the ZmE2F6 protein interacted with ZmPP2C26, localized in the nucleus, and responded to drought treatment. The overexpression of ZmE2F6 enhanced drought tolerance in transgenic Arabidopsis with longer root length, higher survival rate, and biomass by upregulating stress-related gene transcription. CONCLUSIONS: This study provides novel insights into a greater understanding and functional study of the E2F family in the stress response.

Pharmacologic and Nutritional Interventions for Early Alzheimer's Disease: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

Background: Early intervention is essential for meaningful disease modification in Alzheimer's disease (AD). Objective: We aimed to determine the efficacy and safety of pharmacologic and nutritional interventions for early AD. Methods: PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov were searched from database inception until 1 September 2023. We included randomized controlled trials that evaluated the efficacy of interventions in early AD. Only interventions that demonstrated efficacy compared to placebo were included in the network meta-analysis (NMA). Then we performed frequentist fixed-effects NMA to rank the interventions. GRADE criteria were used to evaluate the level of evidence. Results: Fifty-eight trials including a total of 33,864 participants and 48 interventions were eligible for inclusion. Among the 48 interventions analyzed, only 6 (12.5%) treatments- ranging from low to high certainty- showed significant improvement in cognitive decline compared to placebo. High certainty evidence indicated that donanemab (standardized mean difference [SMD] -0.239, 95% confidence interval [CI] -0.343 to -0.134) and lecanemab (SMD -0.194, 95% CI -0.279 to -0.108) moderately slowed the clinical progression in patients with amyloid pathology. Additionally, methylphenidate, donepezil, LipiDiDiet, and aducanumab with low certainty showed significant improvement in cognitive decline compared to placebo. However, there was no significant difference in serious adverse events as reported between the six interventions and placebo. Conclusions: Only 12.5% of interventions studied demonstrated efficacy in reducing cognitive impairment in early AD. Donanemab and lecanemab have the potential to moderately slow the clinical progression in patients with amyloid pathology. Further evidence is required for early intervention in AD.

Chitosan/zein-based sustained-release composite films: Fabrication, physicochemical properties and release kinetics of tea polyphenols from polymer matrix.

This study investigated the properties of chitosan/zein/tea polyphenols (C/Z/T) films and analyzed the release kinetics of tea polyphenols (TP) in various food simulants to enhance the sustainability and functionality of food packaging. The results revealed that TP addition enhanced the hydrophilicity, opacity and mechanical properties of film, and improved the compatibility between film matrix. 1.5 % TP film showed the lowest lightness (76.4) and the highest chroma (29.1), while 2 % TP film had the highest hue angle (1.5). However, the excessive TP (above 1 % concentration) led to a decrease in compatibility and mechanical properties of film. The TP concentration (2 %) resulted in the highest swelling degree in aqueous (750.6 %), alcoholic (451.1 %), and fatty (6.4 %) food simulants. The cumulative release of TP decreased to 16.32 %, 47.13 %, and 5.87 % with the increase of TP load in the aqueous, alcoholic, and fatty food simulants, respectively. The Peleg model best described TP release kinetics. The 2 % TP-loaded film showed the highest DPPH (97.13 %) and ABTS (97.86 %) free radical scavenging activity. The results showed TP release influenced by many factors and obeyed Fick's law of diffusion. This study offered valuable insights and theoretical support for the practical application of active films.

Degradation of organic mercury in high salt environments by a marine aerobic bacterium Alteromonas macleodii KD01.

Mercury (Hg), particularly organic mercury, poses a global concern due to its pronounced toxicity and bioaccumulation. Bioremediation of organic mercury in high-salt wastewater faces challenges due to the growth limitations imposed by elevated Cl- and Na+ concentrations on microorganisms. In this study, an isolated marine bacterium Alteromonas macleodii KD01 was demonstrated to degrade methylmercury (MeHg) efficiently in seawater and then was applied to degrade organic mercury (MeHg, ethylmercury, and thimerosal) in simulated high-salt wastewater. Results showed that A. macleodii KD01 can rapidly degrade organic mercury (within 20 min) even at high concentrations (>10 ng/mL), volatilizing a portion of Hg from the wastewater. Further analysis revealed an increased transcription of organomercury lyase (merB) with rising organic mercury concentrations during the exposure process, suggesting the involvement of mer operon (merA and merB). These findings highlight A. macleodii KD01 as a promising candidate for addressing organic mercury pollution in high-salt wastewater.

Functional Connectivity-Based Searchlight Multivariate Pattern Analysis for Discriminating Schizophrenia Patients and Predicting Clinical Variables.

BACKGROUND: Schizophrenia, a multifaceted psychiatric disorder characterized by functional dysconnectivity, poses significant challenges in clinical practice. This study explores the potential of functional connectivity (FC)-based searchlight multivariate pattern analysis (CBS-MVPA) to discriminate between schizophrenia patients and healthy controls while also predicting clinical variables. STUDY DESIGN: We enrolled 112 schizophrenia patients and 119 demographically matched healthy controls. Resting-state functional magnetic resonance imaging data were collected, and whole-brain FC subnetworks were constructed. Additionally, clinical assessments and cognitive evaluations yielded a dataset comprising 36 clinical variables. Finally, CBS-MVPA was utilized to identify subnetworks capable of effectively distinguishing between the patient and control groups and predicting clinical scores. STUDY RESULTS: The CBS-MVPA approach identified 63 brain subnetworks exhibiting significantly high classification accuracies, ranging from 62.2% to 75.6%, in distinguishing individuals with schizophrenia from healthy controls. Among them, 5 specific subnetworks centered on the dorsolateral superior frontal gyrus, orbital part of inferior frontal gyrus, superior occipital gyrus, hippocampus, and parahippocampal gyrus showed predictive capabilities for clinical variables within the schizophrenia cohort. CONCLUSION: This study highlights the potential of CBS-MVPA as a valuable tool for localizing the information related to schizophrenia in terms of brain network abnormalities and capturing the relationship between these abnormalities and clinical variables, and thus, deepens our understanding of the neurological mechanisms of schizophrenia.

PTPRO inhibits LPS-induced apoptosis in alveolar epithelial cells.

Acute lung injury (ALI) and its severe manifestation, acute respiratory distress syndrome (ARDS), represent critical clinical syndromes with multifactorial origins, notably stemming from sepsis within intensive care units (ICUs). Despite their high mortality rates, no selective cure is available beside ventilation support. Apoptosis plays a complex and pivotal role in the pathophysiology of acute lung injury. Excessive apoptosis of alveolar epithelial and microvascular endothelial cells can lead to disruption of lung epithelial barrier integrity, impairing the body's ability to exchange blood and gas. At the same time, apoptosis of damaged or dysfunctional cells, including endothelial and epithelial cells, can help maintain tissue integrity and accelerate recovery from organ pro-inflammatory stress. The balance between pro-survival and pro-apoptotic signals in lung injury determines patient outcomes, making the modulation of apoptosis an area of intense research in the quest for more effective therapies. Here we found that protein tyrosine phosphatase receptor type O (PTPRO), a poorly understood receptor-like protein tyrosine phosphatase, is consistently upregulated in multiple tissue types of mice under septic conditions and in the lung alveolar epithelial cells. PTPRO reduction by its selective short-interfering RNA (siRNA) leads to excessive apoptosis in lung alveolar epithelial cells without affecting cell proliferation. Consistently PTPRO overexpression by a DNA construct attenuates apoptotic signaling induced by LPS. These effects of PTPTO on cellular apoptosis are dependent on an ErbB2/PI3K/Akt/NFκB signaling pathway. Here we revealed a novel regulatory pathway of cellular apoptosis by PTPRO in lung alveolar epithelial cells during sepsis.

Onset of Alzheimer disease in apolipoprotein ɛ4 carriers is earlier in butyrylcholinesterase K variant carriers.

BACKGROUND: The authors sought to examine the impact of the K-variant of butyrylcholinesterase (BCHE-K) carrier status on age-at-diagnosis of Alzheimer disease (AD) in APOE4 carriers. METHODS: Patients aged 50-74 years with cerebrospinal fluid (CSF) biomarker-confirmed AD, were recruited to clinical trial (NCT03186989 since June 14, 2017). Baseline demographics, disease characteristics, and biomarkers were evaluated in 45 patients according to BCHE-K and APOE4 allelic status in this post-hoc study. RESULTS: In APOE4 carriers (N = 33), the mean age-at-diagnosis of AD in BCHE-K carriers (n = 11) was 6.4 years earlier than in BCHE-K noncarriers (n = 22, P < .001, ANOVA). In APOE4 noncarriers (N = 12) there was no observed influence of BCHE-K. APOE4 carriers with BCHE-K also exhibited slightly higher amyloid and tau accumulations compared to BCHE-K noncarriers. A predominantly amyloid, limited tau, and limbic-amnestic phenotype was exemplified by APOE4 homozygotes with BCHE-K. In the overall population, multiple regression analyses demonstrated an association of amyloid accumulation with APOE4 carrier status (P < .029), larger total brain ventricle volume (P < .021), less synaptic injury (Ng, P < .001), and less tau pathophysiology (p-tau181, P < .005). In contrast, tau pathophysiology was associated with more neuroaxonal damage (NfL, P = .002), more synaptic injury (Ng, P < .001), and higher levels of glial activation (YKL-40, P = .01). CONCLUSION: These findings have implications for the genetic architecture of prognosis in early AD, not the genetics of susceptibility to AD. In patients with early AD aged less than 75 years, the mean age-at-diagnosis of AD in APOE4 carriers was reduced by over 6 years in BCHE-K carriers versus noncarriers. The functional status of glia may explain many of the effects of APOE4 and BCHE-K on the early AD phenotype. TRIAL REGISTRATION: NCT03186989 since June 14, 2017.

Maize ZmLAZ1-3 gene negatively regulates drought tolerance in transgenic Arabidopsis.

BACKGROUND: Molecular mechanisms in response to drought stress are important for the genetic improvement of maize. In our previous study, nine ZmLAZ1 members were identified in the maize genome, but the function of ZmLAZ1 was largely unknown. RESULTS: The ZmLAZ1-3 gene was cloned from B73, and its drought-tolerant function was elucidated by expression analysis in transgenic Arabidopsis. The expression of ZmLAZ1-3 was upregulated by drought stress in different maize inbred lines. The driving activity of the ZmLAZ1-3 promoter was induced by drought stress and related to the abiotic stress-responsive elements such as MYB, MBS, and MYC. The results of subcellular localization indicated that the ZmLAZ1-3 protein localized on the plasma membrane and chloroplast. The ectopic expression of the ZmLAZ1-3 gene in Arabidopsis significantly reduced germination ratio and root length, decreased biomass, and relative water content, but increased relative electrical conductivity and malondialdehyde content under drought stress. Moreover, transcriptomics analysis showed that the differentially expressed genes between the transgenic lines and wild-type were mainly associated with response to abiotic stress and biotic stimulus, and related to pathways of hormone signal transduction, phenylpropanoid biosynthesis, mitogen-activated protein kinase signaling, and plant-pathogen interaction. CONCLUSION: The study suggests that the ZmLAZ1-3 gene is a negative regulator in regulating drought tolerance and can be used to improve maize drought tolerance via its silencing or knockout.

Non-thyroidal disease syndrome in patients with systemic lupus erythematosus: relation to disease inflammatory activity.

OBJECTIVE: To identify risk factors for the development of non-thyroidal illness syndrome (NTIS) in patients with systemic lupus erythematosus (SLE). METHODS: A retrospective analysis of 517 SLE patients and 1034 age-and sex-matched healthy population was conducted to compare the prevalence of NTIS in these two groups, and to analyze the laboratory and clinical characteristics of SLE patients with NTIS. Finally Logistic regression analysis was used to determine the risk factors for NTIS in SLE patients. RESULTS: The prevalence of NTIS in the SLE patients was significantly higher than that in controls (39.7% vs. 1.0%, P < 0.001). In SLE patients, compared with euthyroidism patients, NTIS patients exhibited higher levels of neutrophils, hepatic enzymes, kidney damage markers, inflammatory markers and SLE disease activity index (SLEDAI). They also had a higher incidence of organ insufficiency and positive antibodies such as anti-ds-DNA antibodies and anti-SSA antibodies. However, NTIS patients had lower levels of hemoglobin, lymphocytes, platelets, serum albumin, and complement. Additionally, NTIS patients had a shorter duration of lupus and lower utilization of disease-modifying antirheumatic drugs (DMARDs) (P < 0.05). Logistic regression analysis showed that elevated SLEDAI (OR = 1.060, 95%CI 1.022-1.099, P = 0.002), elevated systemic immune-inflammation index (SII) (OR = 1.003, 95%CI 1.001-1.007, P = 0.026), elevated erythrocyte sedimentation rate (ESR) (OR = 1.019, 95%CI 1.010-1.028, P < 0.001), and hepatic insufficiency (OR = 1.916, 95% CI 1.173-3.131, P = 0.009) were independent risk factors for the development of NTIS in SLE. DMARDs treatment (OR = 0.495, 95% CI 0.306-0.799, P < 0.001) was an independent protective factor for NTIS. CONCLUSIONS: Inflammatory activity in SLE patients is associated with the development of NTIS. Key Points • Inflammatory activity indexes such as SLEDAI, SII, and ESR are independent risk factors for NTIS in SLE patients.

Flavonoids From the Aerial Parts of Sophora tonkinensis and Their Potential Anti-Inflammatory Activities.

Four undescribed prenylated flavonoids, sophoratones A-D (1-4), and 17 known flavonoids, were obtained from the aerial parts of Sophora tonkinensis. Their structures with absolute configurations were elucidated by detailed interpretation of NMR spectroscopy, mass spectrometry, and ECD calculations. Meanwhile, the ability of these compounds to inhibit the release of nitric oxide (NO) by a lipopolysaccharide induced mouse in RAW 264.7 cells was assayed. The results indicated that some compounds exhibited clear inhibitory effects, with IC50 ranging from 19.91±1.08 to 35.72±2.92 µM. These results suggest that prenylated flavonoids from the aerial parts of S. tonkinensis could potentially be used as a latent source of anti-inflammatory agents.

Activates B lymphocytes and enhanced immune response: A promising adjuvant based on PLGA nanoparticle to improve the sensitivity of ZEN monoclonal antibody.

In preparing monoclonal antibodies by hybridoma cell technology, the quality of B lymphocytes used for cell fusion directly affects the sensitivity of monoclonal antibodies. To obtain B-lymphocytes producing high-quality specific antibodies for cell fusion during the immunization phase of the antigen, we prepared a TH2-Cell stimulatory delivery system as a novel adjuvant. Astragalus polysaccharide has a good ability to enhance antigenic immune response, and it was encapsulated in biocompatible materials PLGA as an immunostimulatory factor to form the delivery system (APS-PLGA). The preparation conditions of APSP were optimized using RSM to attain the highest utilization of APS. Immunization against ZEN-BSA antigen using APSP as an adjuvant to obtain B lymphocytes producing ZEN-specific antibodies for cell fusion. As results present, APSP could induce a stronger TH2 immune response through differentiating CD4 T cells and promoting IL-4 and IL-6 cytokines. Moreover, it could slow down the release efficiency of ZEN-BSA and enhance the targeting of ZEN-BSA to lymph nodes in vivo experiments. Ultimately, the sensitivity of mouse serum ZEN-specific antibodies was enhanced upon completion of immunization, indicating a significant upregulation of high-quality B lymphocyte expression. In the preparation of monoclonal antibodies, the proportion of positive wells for the first screening was 60%, and the inhibition rates of the antibodies were all similar (>50%). Then we obtained the ZEN monoclonal antibody with IC50 of 0.049 ng/mL, which was more sensitive than most antibodies prepared under conventional adjuvants. Finally, a TRFIAS strip assay was preliminarily established with a LOD value of 0.246 ng/mL.

Four-in-one multifunctional self-driven photoelectrocatalytic system for water purification: Organics degradation, U(VI) reduction, electricity generation and disinfection against bacteria.

This study addresses the energy-intensive nature of conventional wastewater treatment processes and proposes a solution through the development of a green, low-energy, and multifunctional wastewater treatment technology. The research focuses on a multifunctional self-driven photoelectrocatalytic (PEC) system, exploring its four-in-one applications in eliminating organic pollutants, reducing U(VI), generating electrical energy, and disinfecting pathogenic microorganisms. A TiO2-decorated carbon felt (CF@TiO2) cathode is synthesized to enhance interfacial charge transfer, with TiO2 coating improving surface binding sites (edge TiO and adsorbed -OH) for UO22+ adsorption and reduction. The self-driven PEC system, illuminated solely with simulated sunlight, exhibits remarkable efficiency in removing nearly 100 % of uranium within 0.5 h and simultaneously degrading 99.9 % of sulfamethoxazole (SMX) within 1.5 h, all while generating a maximum power output density (Pmax) of approximately 1065 µW·cm-2. The system demonstrates significant anti-interference properties across a wide pH range and coexisting ions. Moreover, 49.4 % of the fixed uranium on the cathode is reduced into U(IV) species, limiting its migration. The self-driven PEC system also excels in detoxifying various toxic organic compounds, including tetracycline, chlortetracycline, and oxytetracycline, and exhibits exceptional sterilization ability by disinfecting nearly 100 % of Escherichia coli within 0.5 h. This work presents an energy-saving, sustainable, and easily recyclable wastewater purification system with four-in-one capabilities, relying solely on sunlight for operation.

Yu Linzhu alleviates primary ovarian insufficiency in a rat model by improving proliferation and energy metabolism of granulosa cells through hif1α/cx43 pathway.

BACKGROUND: Yu Linzhu (YLZ) is a classical Chinese traditional formula, which has been used for more than 600 years to regulate menstruation to help pregnancy. However, the mechanism of modern scientific action of YLZ needs to be further studied. METHODS: Thirty SD female rats were divided into three groups to prepare the blank serum and drug-containing serum, and then using UHPLC-QE-MS to identify the ingredients of YLZ and its drug-containing serum. Twenty-four SD female rats were divided into four groups, except the control group, 4-vinylcyclohexene dicycloxide (VCD) was intraperitoneally injected to establish a primary ovarian insufficiency (POI) model of all groups. Using vaginal smear to show that the estrous cycle of rats was disturbed after modeling, indicates that the POI model was successfully established. The ELISA test was used to measure the follicle-stimulating hormone (FSH), estradiol (E2), and anti-Mullerian hormone (AMH) levels in the serum of rats. HE stain was used to assess the morphology of ovarian tissue. The localization and relative expression levels of CX43 protein were detected by tissue immunofluorescence. Primary ovarian granulosa cells (GCs) were identified by cellular immunofluorescence. CCK8 was used to screen time and concentration of drug-containing serum and evaluate the proliferation effect of YLZ on VCD-induced GCs. ATP kit and Seahorse XFe24 were used to detect energy production and real-time glycolytic metabolism rate of GCs. mRNA and protein expression levels of HIF1α, CX43, PEK, LDH, HK1 were detected by RT-PCR and WB. RESULTS: UHPLC-QE-MS found 1702 ingredients of YLZ and 80 constituents migrating to blood. YLZ reduced the FSH while increasing the AMH and E2 levels. In ovarian tissues, YLZ improved ovarian morphology, follicle development, and the relative expression of CX43. In vitro studies, we found that YLZ increased the proliferative activity of GCs, ATP levels, glycolytic metabolic rate, HIF1α, CX43, PEK, HK1, LDH mRNA, and protein levels. CONCLUSIONS: The study indicated that YLZ increased the proliferation and glycolytic energy metabolism of GCs to improve follicular development further alleviating ovarian function.

Relationship between Thyroid Feedback Quantile-based Index and cardiovascular diseases in a population with normal thyroid function: Evidence from the National Health and Nutrition Examination Survey 2007-2012.

BACKGROUND: Previous study has demonstrated a link between TFQI, indicating the central sensitivity of thyroid hormones, and conditions like obesity, diabetes, and metabolic syndrome. HYPOTHESIS: Nevertheless, the potential relationship between TFQI and cardiovascular disease (CVD) in individuals with normal thyroid function has yet to be established. METHODS: The present research is a retrospective cohort investigation that included a total of 6297 individuals who had normal function of the thyroid and no history of thyroid disorders. These participants were selected from National Health and Nutrition Examination Survey data set, covering the years 2007-2012. The calculation of TFQI was performed depending on FT4 and TSH. Given the complex survey design and sample weights, we used multivariate linear regression models and stratified analysis to evaluate TFQI's correlation with CVD. RESULTS: Subjects with CVD had greater levels of TFQI than those with no CVD. After adjusting for other covariates, TFQI exhibited a positive association with CVD risk, and the OR was 1.706 (p = .005). In subgroup analyses that were stratified by sex and BMI, it was shown that female individuals who had CVD had greater levels of TFQI in comparison to female participants without CVD (p = .002). Furthermore, elevated levels of TFQI were consistently connected to a raised incidence of CVD in the BMI (>28 kg/m2) group after regulating for different covariates. Furthermore, correlation analysis showed an association between TFQI and metabolic biomarkers. CONCLUSIONS: The levels of TFQI are strongly connected to the prevalence of CVD, indicating that energy metabolism may be related to the occurrence of CVD.

Access to innovative anticancer medicines in China: a national survey on availability, price and affordability.

OBJECTIVES: This study aimed to investigate the availability, price, and affordability of nationally negotiated innovative anticancer medicines in China. DESIGN: Retrospective observational study based on data from a nationwide medical database. DATA SOURCES/SETTING: Quarterly data about the use of innovative anticancer medicines from 2020 to 2022 were collected from the Chinese Medicine Economic Information Network. This study covered 895 public general hospitals in 30 provincial administrative regions in China. Of the total hospitals, 299 (33.41%) were secondary and 596 (66.59%) were tertiary. MAIN OUTCOME MEASURES: The adjusted WHO and Health Action International methodology was used to calculate the availability and affordability of 33 nationally negotiated innovative anticancer medicines in the investigated hospitals. Price is expressed as the defined daily dose cost. RESULTS: On average, the total availability of 33 innovative anticancer medicines increased annually from 2020 to 2022. The median availability of all investigated medicines in tertiary hospitals from 2020 to 2022 was 24.04%, 33.60% and 37.61%, respectively, while the indicators in secondary hospitals were 4.90%, 12.54% and 16.48%, respectively. The adjusted prices of the medicines newly put in Medicare (in March 2021) decreased noticeably, with the decline rate ranging from 39.98% to 82.45% in 2021 compared with those in 2020. Most generic brands were priced much lower than the originator brands. The affordability of anticancer medicines has improved year by year from 2020 to 2022. In comparison, rural residents had lower affordability than urban residents. CONCLUSIONS: The overall accessibility of 33 nationally negotiated innovative anticancer medicines improved from 2020 to 2022. However, the overall availability of most anticancer medicines in China remained at a low level (less than 50%). Further efforts should be made to sufficiently and equally benefit patients with cancer.

Rapid duplex flap probe-based isothermal assay to identify the Cryptococcus neoformans and Cryptococcus gattii.

Cryptococcosis is a life-threatening invasive fungal infection with significantly increasing mortality worldwide, which is mainly caused by Cryptococcus neoformans and Cryptococcus gattii. These two species complexes have different epidemiological and clinical characteristics, indicating the importance of accurate differential diagnosis. However, the clinically used culture method and cryptococcal capsular antigen detection couldn't achieve the above goals. Herein, we established a novel duplex flap probe-based isothermal assay to identify the Cryptococcus neoformans and Cryptococcus gattii within 1 hour. This assay combined the highly sensitive nucleic acid isothermal amplification and highly specific fluorescence probe method, which could effectively distinguish the sequence differences of the two species complexes using two different fluorescence flap probes in a single reaction system. This novel method showed excellent detection performance with sensitivity (10 copies/µL each) and specificity (100%) compared to traditional culture and sequencing methods. Furthermore, we applied this method to spiked clinical samples, 30 cerebrospinal fluids and 30 bronchoalveolar lavage fluids, which kept good detection performance. This novel rapid duplex flap probe-based isothermal assay is a promising and robust tool for applications in differential diagnosis of the Cryptococcus neoformans and Cryptococcus gattii in clinical settings, especially when clinical suspicion for cryptococcal disease is high and epidemiological studies.

Reverse design of haptens based on antigen spatial conformation to prepare anti-capsaicinoids&gingerols antibodies for monitoring of gutter cooking oil.

Rapid simultaneous detection of multi-component adulteration markers can improve the accuracy of identification of gutter cooking oil in edible oil, which is made possible by broad-spectrum antibody (bs-mAb). This study used capsaicinoids (CPCs) and gingerol derivatives (GDs) as adulteration markers, and two broad-spectrum haptens (bs-haptens) were designed and synthesized based on a reverse design strategy of molecular docking. Electrostatic potential (ESP) and monoclonal antibodies (mAbs) preparation verified the strategy's feasibility. To further investigate the recognition mechanism, five other reported antigens and mAbs were also used. Finally, the optimal combination (Hapten 5-OVA/1-F12) and key functional groups (f-groups) were determined. The half maximal inhibitory concentration (IC50) for CPCs-GDs was between 88.13 and 499.16 ng/mL. Meanwhile, a preliminary lateral flow immunoassay (LFIA) study made practical monitoring possible. The study provided a theoretical basis for the virtual screening of bs-haptens and simultaneous immunoassay of multiple exogenous markers to monitor gutter oil rapidly and accurately.