Volumetric voltage imaging of neuronal populations in the mouse brain by confocal light-field microscopy.

Voltage imaging measures neuronal activity directly and holds promise for understanding information processing within individual neurons and across populations. However, imaging voltage over large neuronal populations has been challenging owing to the simultaneous requirements of high imaging speed and signal-to-noise ratio, large volume coverage and low photobleaching rate. Here, to overcome this challenge, we developed a confocal light-field microscope that surpassed the traditional limits in speed and noise performance by incorporating a speed-enhanced camera, a fast and robust scanning mechanism, laser-speckle-noise elimination and optimized light efficiency. With this method, we achieved simultaneous recording from more than 300 spiking neurons within an 800-µm-diameter and 180-µm-thick volume in the mouse cortex, for more than 20 min. By integrating the spatial and voltage activity profiles, we have mapped three-dimensional neural coordination patterns in awake mouse brains. Our method is robust for routine application in volumetric voltage imaging.

Case report: Mycobacterium chimaera-induced lymph node infection in a patient with chronic myeloproliferative neoplasm misdiagnosed as tuberculous lymphadenitis.

Herein, we report a case of lymphadenitis caused by Mycobacterium chimaera. A 54-year-old woman with chronic myeloproliferative neoplasm was admitted to the hospital with cervical lymphadenopathy. After preliminary exclusion of various diseases such as lymphoma, Epstein-Barr virus infection, and autoimmune disease, a lymph node biopsy specimen showed epithelioid granulomatous lymphadenitis with caseous necrosis, epithelial-like cells, and multinucleated giant cells as seen in tuberculosis (TB). Although Mycobacterium tuberculosis was never isolated, diagnostic anti-TB treatment was commenced. Following over 9 months of treatment, there was no significant reduction in the size of her cervical lymph nodes, and she continued to experience recurrent low-grade fevers. One sample from the fourth lymph node biopsy tested negative for metagenomic next-generation sequencing (mNGS), and another sample tested positive in the BACTEC MGIT960 liquid culture system, identifying the strains as Mycobacterium chimaera. Anti-non-tuberculous mycobacteria (NTM) therapy was initiated, and the patient achieved symptom improvement. In conclusion, NTM lymphoid infection is easily misdiagnosed as long-term etiologic negativity.

Plasma proteomic and polygenic profiling improve risk stratification and personalized screening for colorectal cancer.

This study aims to identify colorectal cancer (CRC)-related proteomic profiles and develop a prediction model for CRC onset by integrating proteomic profiles with genetic and non-genetic factors (QCancer-15) to improve the risk stratification and estimate of personalized initial screening age. Here, using a two-stage strategy, we prioritize 15 protein biomarkers as predictors to construct a protein risk score (ProS). The risk prediction model integrating proteomic profiles with polygenic risk score (PRS) and QCancer-15 risk score (QCancer-S) shows improved performance (C-statistic: 0.79 vs. 0.71, P = 4.94E-03 in training cohort; 0.75 vs 0.69, P = 5.49E-04 in validation cohort) and net benefit than QCancer-S alone. The combined model markedly stratifies the risk of CRC onset. Participants with high ProS, PRS, or combined risk score are proposed to start screening at age 46, 41, or before 40 years old. In this work, the integration of blood proteomics with PRS and QCancer-15 demonstrates improved performance for risk stratification and clinical implication for the derivation of risk-adapted starting ages of CRC screening, which may contribute to the decision-making process for CRC screening.

Novel insights into self-defense function of anammox sludge under magnesium ions (Mg2+) stress based on Mg2+ transport system.

Magnesium ion (Mg2+) plays an important role in the accumulation and stability of anaerobic ammonium-oxidizing bacteria (AnAOB). In this study, the response of anammox sludge to Mg2+ was comprehensively investigated by performance evaluation and metagenomics analysis. Appropriate Mg2+ (0.8 mmol/L) could improve the nitrogen removal performance, AnAOB activity, and the synthesis potential of some hydrophobic substances, while high Mg2+ (>1.6 mmol/L) has a negative effect. Meanwhile, Mg2+ transmembrane transport theory was introduced to reveal the response principle of AnAOB to Mg2+ from a novel insight. AnAOB may have a self-defense function based on the PhoQ/PhoP-MgtAB system. Low extracellular Mg2+ will activate this function to enhance Mg2+ influx, thereby improving the intracellular metabolism of AnAOB. Excessive Mg2+, however, dormant this function and induces Mg2+ efflux, which may decrease the intracellular Mg2+ and thus affect AnAOB metabolism. These findings provide valuable references for the Mg2+ regulation of anammox-based process.

Progression of coronary artery calcium density and major adverse cardiovascular events.

BACKGROUND AND AIMS: We aimed to investigate the relationship between coronary artery calcium (CAC) density progression and major adverse cardiovascular events (MACE), and the prognostic value of CAC density progression. METHODS: Patients with serial CAC scans were enrolled in this study. CAC density was directly measured in calcified lesions. Change and rate of progression of CAC density were calculated. Cox proportional hazard regression was utilized to estimate hazard ratios (HRs) for time to MACE regarding CAC density. The incremental prognostic value and the reclassification ability of CAC density progression were evaluated using the C-index and continuous net reclassification index (NRI). RESULTS: 304 patients (57.86 ± 9.47 years, 69.4 % male) were included. There were 47 MACE over a follow-up period of 76.00 (56.00-95.00) months. After adjustment for risk factors and CAC volume, the change of CAC density was inversely associated with MACE (per 10HU: HR: 0.956, 95 % confidence interval: 0.920-0.992, p = 0.018). Adding the change of CAC density to risk factors and baseline CAC density improved the C-index (0.694 vs. 0.678, p = 0.026). Adding the change of CAC density improved reclassification of MACE compared with risk factors and baseline CAC density [NRI = 0.432 (0.016-0.789)]. CONCLUSIONS: CAC density progression is inversely associated with MACE. The addition of the change of CAC density improves prognostic value compared to baseline risk factors and CAC density and optimizes risk reclassification.

Recent advances in studies on FtsZ inhibitors.

With the abuse of antibiotics, multidrug resistant strains continue to emerge and spread rapidly. Therefore, there is an urgent need to develop new antimicrobial drugs. As a highly conserved cell division protein in bacteria, filamenting temperature-sensitive mutant Z (FtsZ) has been identified as a potential antimicrobial target. This paper reviews the structure, function, and action mechanism of FtsZ and a variety of natural and synthetic compounds targeting FtsZ, including 3-MBA derivatives, taxane derivatives, cinnamaldehyde, curcumin, quinoline and quinazoline derivatives, aromatic compounds, purpurin, and totarol. From these studies, FtsZ has a clear supporting role in the field of antimicrobial drug discovery. The urgent need and interest of antibacterial drugs will contribute to the discovery of new clinical drugs targeting FtsZ.

The role of Drp1 - Pink1 - Parkin - mediated mitophagy in perfluorobutane sulfonate- induced hepatocyte damage.

Perfluorobutane sulfonate (PFBS) is recognized as a highly persistent environmental contaminant, notorious for its chemical stability and enduring presence in ecosystems. Its propensity for persistence and environmental mobility allows PFBS to infiltrate the human body, predominantly accumulating in the liver where it poses a potential risk for hepatic damage. This investigation aimed to explore the outcomes of PFBS on the physiological functionalities of hepatocytes in vitro. To this end, hepatocytes were exposed to 750 ug/ml PFBS, followed by an analysis of various cellular phenotypes and functionalities, including assessments of cell viability and mitochondrial integrity. The findings indicated that PFBS exposure led to a suppression of cell proliferation and an increase in apoptotic cell death. Moreover, PFBS exposure was found to augment the generation of reactive oxygen species (ROS) and induce significant mitochondrial dysfunction. Gene expression analysis identified significant changes in genes associated with numerous tumor signaling pathways and autophagy signaling pathways. Further examinations revealed an increase in cellular mitophagy following PFBS exposure, coupled with the activation of the mitophagy-associated Drp1/Pink1/Parkin pathway. Inhibition of mitophagy was observed to concurrently amplify cellular damage and inhibit the Drp1/Pink1/Parkin pathway. Together, these findings highlight PFBS's capacity to inflict hepatocyte injury through mitochondrial disruption, positioning Drp1/Pink1/Parkin-mediated mitophagy as a crucial cellular defense mechanism against PFBS-induced toxicity.

Impact of nitroglycerin on machine-learning fractional flow reserve in coronary computed tomography (CT)-angiography.

Background: Nitroglycerin administration prior to examination improves stenosis assessment of coronary computed tomography (CT) angiography (CCTA). However, whether nitroglycerin influences CT-derived fractional flow reserve (FFR, CT-FFR) evaluation remains unclear. This study aimed to investigate the effect of nitroglycerin on diagnostic performance of CT-FFR. Methods: In this single-center retrospective study, 107 consecutive patients suspected of coronary artery disease (CAD) with nitroglycerin administration prior to CCTA in 2019 were matched to 107 patients without nitroglycerin in 2016 from Fuwai Hospital. All patients underwent CCTA and invasive FFR in a month. Vessel-based and patient-based accuracy and diagnostic performance of CT-FFR were compared between the two groups, as well as image quality, coronary artery diameter and evaluability. Quantitative variables were compared by Kruskal-Wallis H test. Categorical variables and rates were compared by χ2 test or Fisher exact test. Results: A total of 214 patients (56.1±8.9 years, 155 male) with 237 target lesion vessels were analyzed, including 120 vessels in nitroglycerin and 117 vessels in non-nitroglycerin group. Per-vessel based accuracy of CT-FFR was higher in nitroglycerin group {80.0% [95% confidence interval (CI): 71.7-86.7%] vs. 68.4% (59.1-76.7%), P=0.041}. On a per-patient basis, nitroglycerin administration improved the accuracy [83.2% (74.7-89.7%) vs. 68.2% (58.5-76.9%), P=0.01], specificity [82.7% (69.7-91.8%) vs. 61.9% (48.8-73.9%), P=0.01], positive predictive value (PPV) [83.6% (73.6-90.4%) vs. 58.6% (50.0-66.9%), P=0.004], and area under the curve (AUC) [0.83 (0.75-0.89) vs. 0.71 (0.61-0.79), P=0.03] of CT-FFR. Vessel diameters (left main arteries: 4.3 vs. 3.8 mm, P<0.001; left anterior descending arteries: 3.1 vs. 2.9 mm, P=0.001; left circumflex arteries: 2.9 vs. 2.7 mm, P=0.01; right coronary arteries: 3.7 vs. 3.4 mm, P=0.001) and number of evaluable coronary arteries (11.0 vs. 8.0, P<0.001) were larger in nitroglycerin group. Conclusions: Nitroglycerin administration prior to CCTA has positive effects on diagnostic performance of CT-FFR.

[Research progress on treatment of unstable intertrochanteric fractures in elderly patients with bone cement type femoral head replacement].

Objective: To summarize the latest research progress of bone cement type femoral head replacement in the treatment of unstable intertrochanteric fractures in elderly patients. Methods: The literature on the application of bone cement type femoral head replacement for unstable intertrochanteric fractures in elderly patients both domestically and internationally was reviewed, and the findings in aspects of selection of prosthesis types, proximal femoral reconstruction methods, postoperative complications, and rehabilitation were summarized and analyzed. Results: The bone cement type femoral head replacement has shown significant effectiveness in the treatment of unstable intertrochanteric fractures in elderly patients. The surgery provides immediate stability, allowing patients to quickly bear weight and regain walking function, thereby reducing the incidences of postoperative complications and mortality. However, due to the generally poor physical condition and low surgical tolerance of elderly patients, the risk of postoperative complications significantly increases, which has a significant impact on patients' postoperative recovery. Common complications include deep vein thrombosis, bone cement implantation syndrome, joint dislocation, prosthesis loosening, and periprosthetic fractures. Therefore, despite the apparent short-term effectiveness of the surgery, it is crucial to emphasize the prevention and management of postoperative complications to improve the long-term prognosis of elderly patients. Conclusion: For unstable intertrochanteric fractures in elderly patients, when choosing bone cement type femoral head replacement, it is necessary to strictly adhere to surgical indications, reduce the occurrence of complications, and improve the patients' quality of life through refined preoperative evaluation, intraoperative operation, and effective postoperative management.

Enhancing drought resistance in Pinus tabuliformis seedlings through root symbiotic fungi inoculation.

Background: Drought constitutes a major abiotic stress factor adversely affecting plant growth and productivity. Plant-microbe symbiotic associations have evolved regulatory mechanisms to adapt to environmental stress conditions. However, the interactive effects of different fungi on host growth and stress tolerance under drought conditions remain unclear. Objective: This study explored the effects of varying polyethylene glycol (PEG-6000) concentrations (0%, 15%, 25%, and 35%) on the growth and physiological responses of two ectomycorrhizal fungi (Suillus granulatus (Sg) and Pisolithus tinctorius (Pt)) and two dark septate endophytes (Pleotrichocladium opacum (Po) and Pseudopyrenochaeta sp. (Ps)) isolated from the root system of Pinus tabuliformis. Specifically, the study aimed to evaluate six inoculation treatments, including no inoculation (CK), single inoculations with Sg, Pt, Po, Ps, and a mixed inoculation (Sg: Pt : Po: Ps = 1:1:1:1), on the growth and physiological characteristics of P. tabuliformis seedlings under different water regimes: well-watered at 70% ± 5%, light drought at 50% ± 5%, and severe drought at 30% ± 5% of the maximum field water holding capacity. Results: All four fungi exhibited the capacity to cope with drought stress by enhancing antioxidant activities and regulating osmotic balance. Upon successful root colonization, they increased plant height, shoot biomass, root biomass, total biomass, and mycorrhizal growth response in P. tabuliformis seedlings. Under drought stress conditions, fungal inoculation improved seedling drought resistance by increasing superoxide dismutase and catalase activities, free proline and soluble protein contents, and promoting nitrogen and phosphorus uptake. Notably, mixed inoculation treatments significantly enhanced antioxidant capacity, osmotic adjustment, and nutrient acquisition abilities, leading to superior growth promotion effects under drought stress compared to single inoculation treatments. Conclusion: All four fungi tolerated PEG-induced drought stress, with increased antioxidant enzyme activities and osmotic adjustment substances and they promoted the growth and enhanced drought resistance of P. tabuliformis seedlings.

Evaluation of long-term benefits and cost-effectiveness of nation-wide colorectal cancer screening strategies in China in 2020-2060: a modelling analysis.

Background: Evidence on the long-term benefits and cost-effectiveness of colorectal cancer (CRC) screening strategies in China remains limited. This modelling study aims to address this issue for various CRC screening strategies in China between 2020 and 2060. Methods: Using a previously developed microsimulation model (MIMIC-CRC) with Chinese epidemiological data, we evaluated four CRC screening strategies targeting population aged 45-74 years: no screening, colonoscopy every 10 years, biennial faecal immunochemical testing (FIT), and a roll-out FIT screening strategy. Screening coverage (invitation) rates from 5% to 100% were analysed. Single-cohort analysis of 100,000 individuals was conducted to estimate the relative cost-effectiveness of each strategy. A multiple-cohort analysis of 100,000 people aged 40+ over 2020-2060 was conducted to project nation-wide long-term benefits and cost-effectiveness. Findings: In single-cohort analysis, all strategies yielded reductions in CRC incidence and mortality compared to no screening, with colonoscopy outperforming FIT-based strategies at the same invitation rates. In multiple-cohort analysis, among people over 40 years of age in China over 2020-2060, compared to no screening, at invitation rate of 5%, screening by colonoscopy, biennial FIT and roll-out FIT-based approach were estimated to avert 1.2, 0.4, and 0.3 million incident CRCs and 0.2, 0.1, and 0.1 million CRC-related deaths, respectively, compared to no screening (25.4 million incident CRCs and 4.4 million CRC-related deaths), and this preventive effect enlarged as the screening coverage rate increased. At full coverage, colonoscopy achieved the largest reductions (38.2% lower incidence and 43.2% lower mortality) but required the most resources. Biennial FIT and roll-out FIT-based approach screening was slightly less effective but had significant reduced colonoscopy needs (reduction of 83.8% and 85.2%, respectively) and overall cost (reduction of 23.4% and 37.8%, respectively) compared to colonoscopy screening. Interpretation: Nation-wide implementation of screening would be effective in reducing the burden of CRC in China. Biennial FIT and roll-out FIT-based screening strategies could prevent incident CRC cases and CRC-related deaths with considerably fewer resources than colonoscopy screening. Efforts should be made to increase the screening coverage in China. Funding: Chinese Academy of Medical Science Innovation Fund for Medical Science (2022-I2M-1-0031); National Natural Science Foundation of China (82173606; 82273726); Beijing Nova Program of Science and Technology (20230484397).

Causal relationship between systemic circulatory inflammatory regulators and intervertebral disc degeneration: A bidirectional 2-sample Mendelian randomization study.

In the context of the development of intervertebral disc degeneration (IDD), inflammatory mediators play a pivotal role. Nevertheless, due to the influence of the inflammatory microenvironment, the causal relationship between specific inflammatory mediators and the development of IDD remains uncertain. The understanding of the causal relationship between inflammatory mediators and IDD is of great importance in preventing and delaying disc degeneration in the future. We utilized genetic data concerning systemic circulating inflammatory regulators obtained from a Genome-Wide Association Study (GWAS) analyzing 41 serum cytokines in a cohort of 8293 individuals from Finland. The genetic data for IDD were derived from the most recent GWAS summary statistics conducted within the FinnGen consortium, encompassing 37,636 IDD cases and 270,964 controls. Our analysis employed bidirectional 2-sample Mendelian randomization (MR) techniques, which included several MR methods such as MR Egger, weighted median, inverse variance weighted, weighted mode, and simple mode. Additionally, the MR-PRESSO method was employed to identify horizontal pleiotropy, heterogeneity was quantified using the Cochran Q statistic, and MR-Egger intercept analysis was performed to assess pleiotropy. We established causal relationships between 3 specific inflammatory factors and IDD. Elevated levels of MIP-1ß (OR = 0.956, 95% CI: -0.08 to -0.006; P = .02) and IFN-G (OR = 0.915, 95% CI: -0.16 to -0.02; P = .01) expression were associated with a reduced risk of IDD. Conversely, genetic susceptibility to IDD was linked to a decrease in IL-13 levels (OR = 0.967, 95% CI: -0.063 to -0.004; P = .03). In this study, we have identified inflammatory factors that exhibit a causal relationship with the onset and progression of IDD, as supported by genetic predictions.

The molecular mechanism of ferroptosis-induced spontaneous abortion based on bioinformatics approach.

Spontaneous abortion (SA) is a prevalent placental dysfunction, and ferroptosis may play a crucial role in placental dysfunction and the development of SA. In this study, we employed data mining and analysis techniques to investigate the biological mechanism of SA induced by ferroptosis, resulting in the identification of a total of 79 ferroptosis-related genes in SA were identified. Among them, 3 co-expression modules of ferroptosis risk genes, ten significant functions and six biologically significant pathways were obtained 61 pairs of differentially expressed miRNA-ferroptosis factor relationships were identified, and WIPI1 and GSN were expressed at significantly higher levels in SA. This is extremely helpful for future research on SA.

Insight into Mocha Diffusion Occurring during Ethanol Droplet Spreading on Acrylic Paint.

Mocha diffusion, a significant interfacial phenomenon in pottery painting, remains insufficiently understood in the documented literature regarding its dynamics. This study experimentally investigates Mocha patterns by quantitatively dripping ethanol droplets onto an acrylic paint surface. Results indicate that the spreading radius increases with the ethanol mass fraction, while the fractal period decreases. The fractal dimension of all Mocha patterns approximates 1.4087. Marangoni flow, generated by the volatilization of ethanol, is crucial for the growth and fractal formation of the "dendrites" in this spreading. The scaling analysis is used to interpret the spreading dynamics. This work encourages the interface science community to develop a comprehensive theory for the dynamics of Mocha diffusion and highlights the potential of this intriguing decorative technique.

The Differences in Parameters in Ultrasound Imaging and Biomechanical Properties of the Quadriceps Femoris with Unilateral Knee Osteoarthritis in the Elderly: A Preliminary Observational Study.

Purpose: Our study aims to evaluate differences in muscle parameters of the quadriceps muscles in patients with knee osteoarthritis (KOA) in older adults. Methods: The study included 40 patients diagnosed with unilateral knee osteoarthritis in the KOA group (KG) and 40 asymptomatic elderly individuals in the control group (CG). Muscle ultrasonic mean echo intensity and shear modulus, as well as tone and stiffness of the rectus femoris (RF), vastus medialis (VM), and vastus lateralis (VL) were analyzed. Additionally, clinical correlations were performed. Results: In the KG group, there were significant differences in echo intensity, shear modulus, and tone between the affected and unaffected sides for RF (p=0.003, 0.019, 0.014), while VM showed significant differences in shear modulus and tone (p=0.006, 0.002). Additionally, VL exhibited significant differences in echo intensity, shear modulus, and stiffness (p=0.007, 0.006, 0.010). Compared to the CG group, the KG group showed significant differences in echo intensity of the affected side RF (p=0.001). VM exhibited statistically significant differences in echo intensity and shear modulus (p < 0.001, p=0.008), while VL showed statistically significant differences in echo intensity, tone, and stiffness (p < 0.001, p=0.028, p < 0.001). The correlation results showed that patients with unilateral KOA, VM, and VL echo intensity were correlated with K-L grade (r = 0.443, p=0.004; r = 0.469, p=0.002). The tone of VL was correlated with VAS and WOMAC (r = 0.327, p=0.039; r = 0.344, p=0.030). Conclusion: The parameters of the quadriceps femoris muscle exhibit asymmetry between the affected and unaffected sides in patients with unilateral KOA, as well as a difference between the dominant side of healthy older individuals and the affected side of KOA.

Metabolic-associated steatotic liver disease and risk of Alzheimer's disease: a real-world retrospective cohort study.

Objective: Alzheimer's Disease (AD) is increasingly recognized as being associated with metabolic disorders, including Metabolic Associated Steatotic Liver Disease (MASLD). This study aimed to assess the relative risk of AD in individuals with MASLD. Methods: In this retrospective cohort study, we analyzed data from individuals aged over 65 who underwent health check-ups between January 2018 and June 2023. MASLD was diagnosed based on ultrasound findings and cardiometabolic criteria. AD incidence was identified using ICD-10 codes and self-reports. Poisson regression models estimated the relative risk of AD in relation to MASLD, adjusting for age, BMI, sex, SBP, HbA1c, HDL-c, triglycerides, hs-CRP, GGT, and estimated GFR. Results: The study included 4,582 MASLD patients and 6,318 controls. MASLD patients showed a higher incidence of AD (127 cases) compared to controls (61 cases). The fully adjusted Poisson regression model indicated an increased AD risk in MASLD patients [RR: 2.80 (95% CI: 1.79-4.38)]. Conclusion: Our findings suggested MASLD as an independent risk factor for AD, underlining the role of metabolic dysfunctions in AD pathogenesis. The study emphasized the need for comprehensive metabolic health management in AD prevention strategies, particularly among high-risk groups.

The mRNA and microRNA Landscape of the Blastema Niche in Regenerating Newt Limbs.

Newts are excellent vertebrate models for investigating tissue regeneration due to their remarkable regenerative capabilities. To investigate the mRNA and microRNAs (miRNAs) profiles within the blastema niche of regenerating newt limbs, we amputated the limbs of Chinese fire belly newts (Cynops orientalis) and conducted comprehensive analyses of the transcriptome and microRNA profiles at five distinct time points post-amputation (0 hours, 1 day, 5 days 10 days and 20 days). We identified 24 significantly differentially expressed (DE) genes and 20 significantly DE miRNAs. Utilizing weighted gene co-expression network analysis (WGCNA) and gene ontology (GO) enrichment analysis, we identified four genes likely to playing crucial roles in the early stages of limb regeneration: Cemip, Rhou, Gpd2 and Pcna. Moreover, mRNA-miRNA integration analysis uncovered seven human miRNAs (miR-19b-1, miR-19b-2, miR-21-5p, miR-127-5p, miR-150-5p, miR-194-5p, and miR-210-5p) may regulate the expression of these four key genes. The temporal expression patterns of these key genes and miRNAs further validated the robustness of the identified mRNA-miRNA landscape. Our study successfully identified candidate key genes and elucidated a portion of the genetic regulatory mechanisms involved in newt limb regeneration. These findings offer valuable insights for further exploration of the intricate processes of tissue regeneration.

Characterization of the Metabolic Proteome of Serum From Patients With Diabetic Distal Symmetric Polyneuropathy.

AIMS: The pathophysiological of diabetic distal symmetric polyneuropathy (DSPN) remains to be elucidated and there are no diagnostic or prognostic biomarkers for the condition. In this explorative proteomic study, metabolic proteome profiling of serum in patients with/without DSPN was analyzed. We aimed to discover proteins with different abundance ranges through proximity extension assay (PEA) technology. METHODS: Temperature quantitative sensory testing (QST) and electromyography (EMG) were used to access the small- and large-fiber function of all participants, respectively. The metabolic proteome profile of serum was analyzed using PEA technology (Olink Target 96 METABOLISM panel). RESULTS: We evaluated serum from patients without DSPN (n = 27), with small-fiber neuropathy (SFN, n = 25) and with mixed small- and large-fiber neuropathy (MSLFN, n = 24). Fifteen proteins, which were especially related to immune response, insulin resistance, and lipid metabolism, were significantly different between patients without DSPN and with MSLFN. Besides, seven proteins, especially related to extracellular structure organization, were significantly different between serum from patients with SFN and with MSLFN. What's more, serum from patients without DSPN showed that three proteins, related to immune response, altered significantly compared to serum from patients with SFN. CONCLUSIONS: This was the first study that characterized the metabolic proteomic profile of serum in DSPN patients by analyzing a panel of 92 metabolic proteins using PEA technology.

Immunotoxic response of bio-based plastic on early life stage zebrafish (Danio rerio): A safe alternative to petroleum-based plastics?

Bio-based plastics are marketed as environmentally friendly alternatives to petroleum-based plastics, although they require specific composting conditions for degradation, which leads to their accumulation in the environment and potential risks to aquatic organisms. We hypothesized that the accumulation of bio-based plastics may induce immunotoxic responses in fish. Our research focused on the accumulation and immunotoxicity of 80 nm polylactic acid (PLA) and polystyrene (PS) (0.1-10 mg/L) on early life stage zebrafish (Danio rerio) exposed for 7 days. Compared to PS, there was a higher accumulation of PLA in larvae. Exposure to PLA resulted in a significant increase in neutrophils and macrophages, while immune protein levels such as Complement 3 (C3), Immunoglobulin M (IgM), and C-reactive protein (CRP) were significantly reduced. Furthermore, the mRNA expression of pro-inflammatory cytokines, including tnf-α and il-6, were significantly elevated in PLA treatments. Additionally, PLA-exposed zebrafish were more susceptible to infection by Vibrio parahaemolyticus. Interestingly, at the same concentration, exposures to PS did not induce significant changes in macrophages or immune protein levels, C3 and IgM. This suggests that PLA has a greater immunotoxic response relative to PS. Our research findings contradict the popular belief that bio-based plastics are non-toxic and harmless, which may have potential risk to aquatic organisms.

Associations between blood glucose and early- and late-onset colorectal cancer: evidence from two prospective cohorts and Mendelian randomization analyses.

Background: The incidence of early-onset colorectal cancer (EOCRC), which exhibits differential clinical, pathological, and molecular features compared to late-onset CRC (LOCRC), is rising globally. The potential differential effects of blood glucose on EOCRC compared to LOCRC have not been investigated. Methods: This study analyzed 374,568 participants from the UK Biobank cohort and 172,809 participants from the Kailuan cohort. The linear associations between blood glucose and EOCRC/LOCRC were estimated using Cox regression models. Restricted cubic spline (RCS) analysis and non-linear Mendelian randomization (MR) analysis using a 70-SNPs genetic instrument for fasting glucose were used to explore the potential non-linear associations. Results: Participants in the highest quintile of blood glucose had higher overall CRC risk compared to the lowest quintile (HR = 1.10 in the UK Biobank cohort, 95% CI: 1.01-1.21, P-trend = 0.012; HR = 1.23 in the Kailuan cohort, 95% CI: 1.01-1.51, P-trend = 0.036). Elevated glucose (>7.0 mmol/L) was more strongly associated with increased risk of EOCRC (HR = 1.61, 95% CI: 1.07-2.44) than with LOCRC (HR = 1.14, 95% CI: 1.02-1.27) in the UK Biobank cohort (P-heterogeneity = 0.014). Elevated glucose (>7.0 mmol/L) was associated with increased risk of LOCRC (HR = 1.25, 95% CI: 1.04-1.65) in the Kailuan cohort as well. There was no evidence for non-linear associations between blood glucose and risks of EOCRC/LOCRC. Conclusions: This study showed a positive association between blood glucose and CRC risk in a dose-response manner, particularly for EOCRC, suggesting that tighter glucose control should be a priority for younger age groups.