Effect of madecassic acid on retinal oxidative stress, inflammation and Growth Factors in streptozotocin-induced diabetic rats.

Diabetic retinopathy (DR) is the leading cause of blindness and visual loss in people with diabetes. It has been suggested that the progression of DR is associated with chronic inflammation and oxidative stress. The aim of the present work was to evaluate the ability of the natural compound madecassic acid (MEA) to reverse the negative impact of streptozotocin (STZ) on retinal injury in rats. Diabetic rats induced by STZ were treated with MEA at the doses of 10 and 20 mg/kg bw for 8 weeks. The study compared the efficacy of the drug in controlling high blood sugar levels and its impact on therapeutic targets such as SOD, CAT, GPx, NF-κB, TNF-α, IL-6, IL-1ß, VEGF, IGF, bFGF and Keap1/Nrf-2 pathway. The results showed that the treatment with MEA significantly restored the retinal SOD, CAT, and GPx levels in diabetic rats to the near-normal levels. Moreover, the level of inflammatory mediators (TNF-α, IL-1ß, IL-6) and growth factors (VEGF, IGF, bFGF) was significantly lower in retinas of animals treated with MEA as compared to retinas of diabetic animals. The study also established that MEA administration reduced the NF-κB protein and altered the Nrf-2/Keap1 pathway thereby reducing oxidative stress and inflammation. Furthermore, the use of MEA prevented the progression of the retinal capillary basement membrane thickening. It has been found that MEA offers significant protection to the retina and therefore, the compound may be useful in the treatment of DR in humans.

Altered spontaneous brain activity patterns in hypertensive retinopathy using fractional amplitude of low-frequency fluctuations: a functional magnetic resonance imaging study.

AIM: To study functional brain abnormalities in patients with hypertensive retinopathy (HR) and to discuss the pathophysiological mechanisms of HR by fractional amplitude of low-frequency fluctuations (fALFFs) method. METHODS: Twenty HR patients and 20 healthy controls (HCs) were respectively recruited. The age, gender, and educational background characteristics of the two groups were similar. After functional magnetic resonance imaging (fMRI) scanning, the subjects' spontaneous brain activity was evaluated with the fALFF method. Receiver operating characteristic (ROC) curve analysis was used to classify the data. Further, we used Pearson's correlation analysis to explore the relationship between fALFF values in specific brain regions and clinical behaviors in patients with HR. RESULTS: The brain areas of the HR group with lower fALFF values than HCs were the right orbital part of the middle frontal gyrus (RO-MFG) and right lingual gyrus. In contrast, the values of fALFFs in the left middle temporal gyrus (MTG), left superior temporal pole (STP), left middle frontal gyrus (MFG), left superior marginal gyrus (SMG), left superior parietal lobule (SPL), and right supplementary motor area (SMA) were higher in the HR group. The results of a t-test showed that the average values of fALFFs were statistically significantly different in the HR group and HC group (P<0.001). The fALFF values of the left middle frontal gyrus in HR patients were positively correlated with anxiety scores (r=0.9232; P<0.0001) and depression scores (r=0.9682; P<0.0001). CONCLUSION: fALFF values in multiple brain regions of HR patients are abnormal, suggesting that these brain regions in HR patients may be dysfunctional, which may help to reveal the pathophysiological mechanisms of HR.

[Effectiveness of reduction robot combined with navigation robot-assisted minimally invasive treatment for Tile type B pelvic fractures].

Objective: To explore the effectiveness of reduction robot combined with navigation robot-assisted minimally invasive treatment for Tile type B pelvic fractures. Methods: Between January 2022 and February 2023, 10 patients with Tile type B pelvic fractures were admitted. There were 6 males and 4 females with an average age of 45.5 years (range, 30-71 years). The fractures were caused by traffic accident in 5 cases, bruising by heavy object in 3 cases, and falling from height in 2 cases. The interval between injury and operation ranged from 4-13 days (mean, 6.8 days). There were 2 cases of Tile type B1 fractures, 1 case of Tile type B2 fracture, and 7 cases of Tile type B3 fractures. After closed reduction under assistance of reduction robot, the anterior ring was fixed with percutaneous screws with or without internal fixator, and the posterior ring was fixed with sacroiliac joint screws under assistance of navigation robot. The time of fracture reduction assisted by the reduction robot was recorded and the quality of fracture reduction was evaluated according to the Matta scoring criteria. The operation time, intraoperative fluoroscopy frequency and time, intraoperative bleeding volume, and incidence of complications were also recorded. During follow-up, the X-ray film of pelvis was taken to review the fracture healing, and the Majeed score was used to evaluate hip joint function. Results: The time of fracture reduction was 42-62 minutes (mean, 52.3 minutes). The quality of fracture reduction according to the Matta scoring criteria was rated as excellent in 4 cases, good in 5 cases, and poor in 1 case, with excellent and good rate of 90%. The operation time was 180-235 minutes (mean, 215.5 minutes). Intraoperative fluoroscopy was performed 18-66 times (mean, 31.8 times). Intraoperative fluoroscopy time was 16-59 seconds (mean, 28.6 seconds). The intraoperative bleeding volume was 50-200 mL (range, 110.0 mL). No significant vascular or nerve injury occurred during operation. All patients were followed up 13-18 months (mean, 16 months). X-ray films showed that all fractures healed with the healing time of 11-14 weeks (mean, 12.3 weeks). One case of ectopic ossification occurred during follow-up. At last follow-up, the Majeed score was 70-92 (mean, 72.7), and the hip joint function was rated as excellent in 2 cases and good in 8 cases, with the excellent and good rate of 100%. Conclusion: The reduction robot combined with navigation robot-assisted minimally invasive treatment for Tile type B pelvic fractures has the characteristics of intelligence, high safety, convenient operation, and minimally invasive treatment, which can achieve reliable effectiveness.

Plancitoxin-1 mediates extracellular trap evasion by the parasitic helminth Trichinella spiralis.

BACKGROUND: Trichinella spiralis (T. spiralis) is a parasitic helminth that causes a globally prevalent neglected zoonotic disease, and worms at different developmental stages (muscle larvae, adult worms, newborn larvae) induce immune attack at different infection sites, causing serious harm to host health. Several innate immune cells release extracellular traps (ETs) to entrap and kill most pathogens that invade the body. In response, some unicellular pathogens have evolved a strategy to escape capture by ETs through the secretion of nucleases, but few related studies have investigated multicellular helminths. RESULTS: In the present study, we observed that ETs from neutrophils capture adult worms of T. spiralis, while ETs from macrophages trap muscle larvae and newborn larvae, and ETs had a killing effect on parasites in vitro. To defend against this immune attack, T. spiralis secretes plancitoxin-1, a DNase II-like protein, to degrade ETs and escape capture, which is essential for the survival of T. spiralis in the host. CONCLUSIONS: In summary, these findings demonstrate that T. spiralis escapes ET-mediated capture by secreting deoxyribonuclease as a potential conserved immune evasion mechanism, and plancitoxin-1 could be used as a potential vaccine candidate.

Association of pyrethroids exposure with asthma in US children and adolescents: a nationally representative cross-sectional study.

Pyrethroids (PYR) are among the most widely used insecticides in households, leading to substantial exposure. Children and adolescents, especially during growth spurts, have a reduced capacity to effectively metabolize these insecticides. The relationship between PYR exposure and asthma in these age groups remains poorly understood, highlighting the need for further research.We used data from the 2007-2014 National Health and Nutrition Examination Survey, which included 1181 children aged 6-11 years and 1258 adolescents aged 12-19 years. The concentration of the PYR metabolite 3-phenoxybenzoic acid (3-PBA) in urine was quantified using solid-phase extraction-high-performance liquid chromatography-heated electrospray ionization tandem mass spectrometry. Asthma was defined based on self-reported doctor diagnoses from the questionnaire. PYR exposure was measured using urine samples collected simultaneously with the questionnaire. We explored the association between PYR exposure and asthma using multiple logistic regression analyses, adjusting for potential confounders.Multiple logistic regression analyses revealed no significant association between PYR exposure and asthma in children and adolescent boys (all P > 0.05). In contrast, PYR exposure was significantly associated with asthma in adolescent girls aged 12-19 years. Specifically, for "ever asthma," the odds ratios (ORs) were 2.49 (95% CI = 1.03-5.97) in the second quartile of PYR exposure and 2.48 (95% CI = 1.04-5.91) in the third quartile, each in comparison to the first quartile. For "current asthma," in comparison to the first quartile, the ORs were 3.99 (95% CI = 1.55-10.26) in the second quartile of PYR exposure, 3.39 (95% CI = 1.32-8.70) in the third quartile, and 2.93 (95% CI = 1.24-6.90) in the fourth quartile.Conclusions:Our study found a significant association between PYR exposure and asthma in adolescent girls, whereas no significant association was observed in children and adolescent boys. These findings suggest potential sex and age differences in susceptibility to PYR exposure. Further research is warranted to confirm these results and elucidate the underlying mechanisms.

Click method preserves but EDC method compromises the therapeutic activities of the peptide-activated hydrogels for critical ischemic vessel regeneration.

Peptide-functionalized hydrogel is one of commonly used biomaterials to introduce hydrogel-induced vessel regeneration. Despite many reports about the discoveries of high-active peptides (or ligands) for regeneration, the study on the conjugating methods for the hydrogel functionalization with peptides is limited. Here, we compared the vasculogenic efficacy of the peptide-functionalized hydrogels prepared by two commonly used conjugating methods, 1-ethyl-3-(3-dimethylamino propyl) carbodiimide (EDC) and Click methods, through cell models, organ-on-chips models, animal models, and RNA sequencing analysis. Two vascular-related cell types, the human umbilical vein endothelial cells (HUVECs) and the adipose-derived stem cells (ADSCs), have been cultured on the hydrogel surfaces prepared by EDC/Click methods. It showed that the hydrogels prepared by Click method supported the higher vasculogenic activities while the ones made by EDC method compromised the peptide activities on hydrogels. The vasculogenesis assays further revealed that hydrogels prepared by Click method promoted a better vascular network formation. In a critical ischemic hindlimb model, only the peptide-functionalized hydrogels prepared by Click method successfully salvaged the ischemic limb, significantly improved blood perfusion, and enhanced the functional recoveries (through gait analysis and animal behavior studies). RNA sequencing studies revealed that the hydrogels prepared by Click method significantly promoted the PI3K-AKT pathway activation compared to the hydrogels prepared by EDC method. All the results suggested that EDC method compromised the functions of the peptides, while Click method preserved the vascular regenerating capacities of the peptides on the hydrogels, illustrating the importance of the conjugating method during the preparation of the peptide-functionalized hydrogels.

[Accuracy and clinical efficacy of robot-assisted transiliac-transsacral screw placement for posterior pelvic ring fractures].

OBJECTIVE: To explore accuracy and clinical effect of robot-assisted implantation of sacroiliac penetrating screw in orthopedic surgery for posterior pelvic ring fracture. METHODS: The clinical data of 24 patients with posterior pelvic ring fracture treated with robot-assisted sacroiliac penetration screws from August 2022 to August 2023 were retrospectively analyzed, including 10 males and 14 females; aged from 21 to 73 years old with an average of (49.29±14.48) years old;according to Tile pelvic fractures, 13 patients were type B and 11 were type C. The effect of screw placement was evaluated according to Gras criteria based on postoperative CT scan results. At the final follow-up, fracture healing was evaluated according to Matta score, and functional recovery was evaluated by Majeed score. RESULTS: All patients were followed up for 3 to 13 months with an average of (6.00±3.28) months. Totally 36 sacroiliac penetrating screws, 18 S1 penetrating screws, 18 S2 penetrating screws were inserted, a total of 29 were excellent and 7 good according to Gras standard. Screw adjustment times was 0.00 (0.00, 0.75) times. At the final follow-up, Matta score was excellent in 18 patients, 5 good and 1 moderate, and the maximum displacement distance was 2.55 (0.00, 5.65) mm. Majeed score was 84.37±8.38, 15 patients were excellent, 7 good and 2 moderate. CONCLUSION: Robot could accurately and safely assist in the placement of sacroiliac joint screws for the treatment of posterior pelvic ring fractures, and promote postoperative functional recovery of patients.

Trichinella spiralis alleviates LPS-induced acute lung injury by modulating the protective Th2 immune response.

Sepsis is a disorder of immune regulation caused by pathogenic microorganisms. A large number of inflammatory factors and inflammatory mediators are released, resulting in systemic inflammatory response disorder and acute lung injury (ALI). Helminths infection activate Th2 cytokines and immunomodulatory pathways, which have the function of anti-infection effector molecules. The early infection of Trichinella spiralis (T. spiralis) was mainly intestinal phase. In this study, we explored the effect of intestinal phase infection of T. spiralis on LPS-induced ALI. Compared with control mice, the serum and lung tissues of T. spiralis infected mice had a significant decrease of Th1 inflammatory cytokines, a significant increase of Th2 anti-inflammatory cytokines, and a significant decrease of inflammatory cell infiltration in lung tissue. These results suggest that T. spiralis during the intestinal phase can act on distal organs (lung) and reduce LPS-induced lung inflammation, providing evidence for a potential new pathway for immune-mediated disease in helminths and a possible role for intestinal worms in the gut-lung axis.

Efficacy and Safety of Sacubitril/Valsartan in Chronic Type B Aortic Dissection Combined With Mild Hypertension.

BACKGROUND: Optimal antihypertensive medication for chronic type B aortic dissection (AD) remains undecided. This study compared the efficacy and safety of sacubitril/valsartan with valsartan to determine suitable antihypertensive drug combinations. METHODS: In this single-center, open-label, randomized, controlled trial, patients with chronic Stanford type B AD and mild hypertension were randomized to receive sacubitril/valsartan 100/200 mg or valsartan 80/160 mg. The primary endpoint was the reduction in mean sitting systolic blood pressure (msSBP) at week 8 in patients with sacubitril/valsartan vs. valsartan. Key secondary endpoints included changes in (i) mean sitting diastolic blood pressure (msDBP); (ii) pulse pressure (PP); and (iii) mean ambulatory blood pressure (BP) for 24-hour, daytime, and nighttime. Safety assessments included adverse events (AEs) and serious AEs. This trial was registered with the Chinese Clinical Trial Registry, identifier: ChiCTR2300073399. RESULTS: A total of 315 patients completed the study. Sacubitril/valsartan provided a significantly greater reduction in msSBP than valsartan at week 8 (between-treatment difference: -5.1 mm Hg [95% confidence interval -5.8 to -4.5], P < 0.001). Reductions in msSBP, msDBP, and PP as well as the mean ambulatory BP for 24-hour, daytime, and nighttime, were significantly greater in sacubitril/valsartan compared with valsartan (all P < 0.001). No excessive episodes of AEs occurred in the sacubitril/valsartan group. CONCLUSIONS: Sacubitril/valsartan and valsartan reduced BP compared with baseline values. However, sacubitril/valsartan improved BP control to a greater extent than valsartan. It may offer a new treatment option for patients with mild hypertension and chronic type B AD.

NhaA: A promising adjuvant target for colistin against resistant Escherichia coli.

The emergence and widespread of multidrug-resistant Gram-negative bacteria have posed a severe threat to human health and environmental safety, escalating into a global medical crisis. Utilization of antibiotic adjuvants is a rapid approach to combat bacterial resistance effectively since the development of new antimicrobial agents is a formidable challenge. NhaA, driven by proton motive force, is a crucial secondary transporter on the cytoplasmic membrane of Escherichia coli. We found that 2-Aminoperimidine (2-AP), which is a specific inhibitor of NhaA, could enhance the activity of colistin against sensitive E. coli and reverse the resistance in mcr-1 positive E. coli. Mechanistic studies indicated that 2-AP induced dysfunction in cytoplasmic membrane through the suppression of NhaA, leading to metabolic inhibition and ultimately enhancing the sensitivity of E. coli to colistin. Moreover, 2-AP restored the efficacy of colistin against resistant E. coli in two animal infection models. Our findings reveal the potential of NhaA as a novel target for colistin adjuvants, providing new possibilities for the clinical application of colistin.

Murine skeletal muscle satellite cells isolation and preliminary study on regulation in immune microenvironment during nurse cells formation of Trichinella spiralis infection.

As an intracellular parasitic nematode, Trichinella spiralis (T. spiralis) can induce the formation of nurse cells (NC) in host muscles and keep it to survive within the NC for an extended period. The formation of NC is similar to muscle cell injury and repair which lead to the arrest of satellite cells in the G2/M phase and build a suitable parasitic environment for the muscle larvae of T. spiralis. However, the molecular mechanisms involved in skeletal muscle repair through skeletal muscle satellite cells (SMSC) and the host immune response during T. spiralis infection have not been fully elucidated. In this study, histopathological examination revealed that the severity of damage increased as the infection progressed in the soleus muscle. SMSCs were isolated from BALB/c mice infected with T. spiralis at 4, 21 and 35 days post-infection (dpi). The immunological characteristics of these cells were analyzed by real-time PCR and flow cytometry (FCM). FCM analysis revealed a notable increase in the expression of B7 homolog 1 (B7-H1) in SMSCs following T. spiralis infection, while conversely, the expression of inducible costimulatory ligand (ICOSL) significantly decreased. Furthermore, real-time PCR results showed that toll like receptor 3 (TLR3) expression in SMSCs of the infected mice was upregulated at 21 dpi. The expression levels of three subtypes (PPARα, PPARß and PPARγ) of peroxisome proliferator-activated receptors (PPARs) also increased in the cells. This study highlights the immunological regulation significance of SMSCs host during T. spiralis infection and suggests that SMSCs actively participant in the local immune response to T. spiralis by regulating the interaction between the parasite and the host.

Non-Equivalent Donor-Acceptor Type Polymers as Dopant-Free Hole-Transporting Materials for Perovskite Solar Cells.

Electron donor (D)-electron acceptor (A) type conjugated polymers present bright prospects as dopant-free hole-transporting materials (HTMs) for perovskite solar cells (PVSCs). Most of the reported D-A polymeric HTMs contain equivalent amounts of D and A units, while the appropriate excess proportion of D units could optimize the aggregation state of polymer chains and improve the hole transport properties of the polymers. Herein, a non-equivalent D-A copolymerization strategy was utilized to develop three indacenodithiophene-benzotriazole-based polymeric HTMs for PVSCs, named as F-10, F-15, and F-20, and the equivalent D-A polymer F-00 was studied in parallel. Effects of D : A ratio on the hole transport properties of these D-A type polymeric HTMs, including energy level, molecular stacking, hole mobility, and surface morphology, were investigated by theoretical simulation and test analysis. F-15 performed best due to the appropriate D : A ratio, endowing the PVSCs a champion power conversion efficiency of 20.37 % with high stability, which confirms the fine-tuning D : A ratio via non-equivalent D-A copolymerization strategy is very helpful to construct D-A type polymeric HTMs for high-performance PVSCs.

Smooth muscle cell-specific matrix metalloproteinase 3 deletion reduces osteogenic transformation and medial artery calcification.

AIMS: Vascular calcification is highly prevalent in atherosclerosis, diabetes, and chronic kidney disease. It is associated with increased morbidity and mortality in patients with cardiovascular disease. Matrix metalloproteinase 3 (MMP-3), also known as stromelysin-1, is part of the large matrix metalloproteinase family. It can degrade extracellular matrix components of the arterial wall including elastin, which plays a central role in medial calcification. In this study, we sought to determine the role of MMP-3 in medial calcification. METHODS AND RESULTS: We found that MMP-3 was increased in rodent models of medial calcification as well as in vascular smooth muscle cells (SMCs) cultured in a phosphate calcification medium. It was also highly expressed in calcified tibial arteries in patients with peripheral arterial disease (PAD). Knockdown and inhibition of MMP-3 suppressed phosphate-induced SMC osteogenic transformation and calcification, whereas the addition of a recombinant MMP-3 protein facilitated SMC calcification. In an ex vivo organ culture model and a rodent model of medial calcification induced by vitamin D3, we found that MMP-3 deficiency significantly suppressed medial calcification in the aorta. We further found that medial calcification and osteogenic transformation were significantly reduced in SMC-specific MMP-3-deficient mice, suggesting that MMP-3 in SMCs is an important factor in this process. CONCLUSION: These findings suggest that MMP-3 expression in vascular SMCs is an important regulator of medial calcification and that targeting MMP-3 could provide a therapeutic strategy to reduce it and address its consequences in patients with PAD.

[Impact of extracorporeal carbon dioxide removal combined with continuous renal replacement therapy on diaphragmatic function in patients with acute respiratory distress syndrome].

OBJECTIVE: To investigate the effects of extracorporeal carbon dioxide removal (ECCO2R) combined with continuous renal replacement therapy (CRRT) on respiratory efficiency and diaphragm function in patients with acute respiratory distress syndrome (ARDS) received mechanical ventilation. METHODS: A prospective randomized controlled study was conducted. Sixty patients with mild to moderate ARDS admitted to the department of respiratory and critical care medicine of Henan Provincial People's Hospital from January 2019 to January 2021 were enrolled, and they were divided into observation group and control group according to the random number table method, with 30 cases in each group. All patients received antibiotics, anti-inflammatory, and mechanical ventilation therapy. On this basis, the observation group received ECCO2R and CRRT, while the control group received bedside CRRT. Baseline data including gender, age, etiology, acute physiology and chronic health evaluation II (APACHE II), etc., were recorded. Arterial blood gas analysis [including arterial partial pressure of oxygen (PaO2), arterial partial pressure of carbon dioxide (PaCO2), and oxygenation index (PaO2/FiO2)] was performed at 12 hours and 24 hours during the treatment, and respiratory mechanics parameters [including tidal volume, respiratory rate, maximum expiratory pressure (MEP), and maximum inspiratory pressure (MIP)] were recorded, and rapid shallow breathing index (RSBI) was calculated. The levels of glutathione peroxidase (GSH-Px), malondialdehyde (MDA), and superoxide dismutase (SOD) in serum were detected by enzyme-linked immunosorbent assay (ELISA). Diaphragm thickness and diaphragm activity were measured by ultrasonography at 24 hours during the treatment. RESULTS: There were no significantly differences in age, gender, etiology, and APACHE II score between the two groups, indicating that the baseline data of the two groups were balanced and comparable. Compared with the 12 hours after treatment, the PaO2 and PaO2/FiO2 in the observation group significantly increased, PaCO2 significantly decreased, RSBI significantly decreased, MEP and MIP significantly increased, and serum GSH-Px and MDA significantly decreased, while SOD significantly increased at 24 hours during the treatment. In the control group, only PaCO2 significantly decreased. Compared with the control group, the PaCO2 significantly decreased in the observation group at 12 hours and 24 hours [mmHg (1 mmHg≈0.133 kPa): 55.05±7.57 vs. 59.49±6.95, 52.77±7.88 vs. 58.25±6.92, both P < 0.05], but no significantly differences in PaO2 and PaO2/FiO2. Compared with the control group, the observation group showed significant decreases in RSBI at 12 hours and 24 hours (times×min-1×L-1: 85.92±8.83 vs. 90.38±3.78, 75.73±3.86 vs. 90.05±3.66, both P < 0.05), significant increases in MEP and MIP [MEP (mmH2O, 1 mmH2O≈0.01 kPa): 86.64±5.99 vs. 83.88±4.18, 93.70±5.59 vs. 85.04±3.73; MIP (mmH2O): 44.19±6.66 vs. 41.17±3.13, 57.52±5.28 vs. 42.34±5.39, all P < 0.05], and significant decreases in serum GSH-Px and MDA [GSH-Px (mg/L): 78.52±8.72 vs. 82.10±3.37, 57.11±4.67 vs. 81.17±5.13; MDA (µmol/L): 7.84±1.97 vs. 8.71±0.83, 3.67±0.78 vs. 8.41±1.09, all P < 0.05], as well as a significant increase in SOD (U/L: 681.85±49.24 vs. 659.40±26.47, 782.32±40.56 vs. 676.65±51.97, both P < 0.05). Compared with the control group, the observation group showed significant increases in diaphragm thickness and diaphragm activity at 24 hours of treatment [diaphragm thickness (cm): 1.93±0.28 vs. 1.40±0.24, diaphragmatic thickening fraction: (0.22±0.04)% vs. (0.19±0.02)%, quiet breathing diaphragm displacement (cm): 1.42±0.13 vs. 1.36±0.06, deep breathing diaphragm displacement (cm): 5.11±0.75 vs. 2.64±0.59, all P < 0.05]. CONCLUSIONS: ECCO2R combined with CRRT can reduce work of breathing and oxidative stress levels in ARDS patients receiving non-invasive ventilation, and protect diaphragm function.

Serum proteomics identifies novel diagnostic biomarkers for asthma in preschool children.

Background: Asthma is characterized by airway hyperresponsiveness, reversible airway obstruction, and chronic airway inflammation. It is the most common chronic disease in childhood. However, the diagnosis of childhood asthma remains challenging, and there is an urgent need to develop new diagnostic methods. Methods: To identify biomarkers of asthma in children, we adopted the Orbitrap-based data-independent acquisition (DIA) mass spectrometry proteomics method to analyze the serum proteomic signatures of children with acute asthma and convalescent children. Results: We identified 747 proteins in 46 serum samples and 50 differentially expressed proteins (DEPs) that distinguished between asthmatic and healthy children. Next, functional enrichment analysis of the DEPs was conducted, it was indicated that the DEPs were significantly enriched in immune-related and function terms and pathways. Furthermore, we performed statistical analysis and identified MMP14, ABHD12B, PCYOX1, LTBP1, CFHR4, APOA1, IGHG4, ANG and IGFALS proteins as the diagnostic biomarker candidates. Ultimately, a promising asthma diagnostic model for preschool children based on IGFALS was built and evaluated. The area under the curve (AUC) of the IGFALS model was 0.959. Conclusions: In this study, the DIA proteome strategy was used and the largest number of proteins of asthmatic children serum proteomics was identified. The proteomics results showed that the DEPs play the central role of the inflammation-immune mechanism in asthma pathogenesis, suggesting that these proteins may be used in asthma diagnosis, prognosis, or therapy, and suggested biomarkers for asthma of preschool children. In conclusion, our results provide insight into the pathophysiology of asthma. We believe that the diagnostic model will facilitate clinical decision-making regarding asthma in preschool children.

Environmental exposure to per- and polyfluoroalkyl substances mixture and asthma in adolescents.

BACKGROUND: Previous epidemiological studies about the relationship between per- and polyfluoroalkyl substances (PFAS) concentrations and adolescent asthma have typically examined single PFAS, without considering the mixtures effects of PFAS. METHODS: Using data from the 2013-2018 National Health and Nutrition Examination Survey (NHANES), 886 adolescents aged 12-19 years were included in this study. We explored the association between PFAS mixture concentrations and adolescent asthma using weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) models, respectively. RESULTS: After adjusting for confounders, the results of the WQS regression and BKMR models were consistent, with mixed exposure to the five PFAS not significantly associated with asthma in all adolescents. The association remained nonsignificant in the subgroup analysis by sex. CONCLUSIONS: Our study demonstrated no significant association between mixed exposure to PFAS and adolescent asthma, and more large cohort studies are needed to confirm this in the future.

Large-scale gene expression alterations introduced by structural variation drive morphotype diversification in Brassica oleracea.

Brassica oleracea, globally cultivated for its vegetable crops, consists of very diverse morphotypes, characterized by specialized enlarged organs as harvested products. This makes B. oleracea an ideal model for studying rapid evolution and domestication. We constructed a B. oleracea pan-genome from 27 high-quality genomes representing all morphotypes and their wild relatives. We identified structural variations (SVs) among these genomes and characterized these in 704 B. oleracea accessions using graph-based genome tools. We show that SVs exert bidirectional effects on the expression of numerous genes, either suppressing through DNA methylation or promoting probably by harboring transcription factor-binding elements. The following examples illustrate the role of SVs modulating gene expression: SVs promoting BoPNY and suppressing BoCKX3 in cauliflower/broccoli, suppressing BoKAN1 and BoACS4 in cabbage and promoting BoMYBtf in ornamental kale. These results provide solid evidence for the role of SVs as dosage regulators of gene expression, driving B. oleracea domestication and diversification.

Risk factor analysis and risk prediction study of obesity in steelworkers: model development based on an occupational health examination cohort dataset.

BACKGROUND: Obesity is increasingly recognized as a grave public health concern globally. It is associated with prevalent diseases including coronary heart disease, fatty liver, type 2 diabetes, and dyslipidemia. Prior research has identified demographic, socioeconomic, lifestyle, and genetic factors as contributors to obesity. Nevertheless, the influence of occupational risk factors on obesity among workers remains under-explored. Investigating risk factors specific to steelworkers is crucial for early detection, prediction, and effective intervention, thereby safeguarding their health. METHODS: This research utilized a cohort study examining health impacts on workers in an iron and steel company in Hebei Province, China. The study involved 5469 participants. By univariate analysis, multifactor analysis, and review of relevant literature, predictor variables were found. Three predictive models-XG Boost, Support Vector Machine (SVM), and Random Forest (RF)-were employed. RESULTS: Univariate analysis and cox proportional hazard regression modeling identified age, gender, smoking and drinking habits, dietary score, physical activity, shift work, exposure to high temperatures, occupational stress, and carbon monoxide exposure as key factors in the development of obesity in steelworkers. Test results indicated accuracies of 0.819, 0.868, and 0.872 for XG Boost, SVM, and RF respectively. Precision rates were 0.571, 0.696, and 0.765, while recall rates were 0.333, 0.592, and 0.481. The models achieved AUCs of 0.849, 0.908, and 0.912, with Brier scores of 0.128, 0.105, and 0.104, log losses of 0.409, 0.349, and 0.345, and calibration-in-the-large of 0.058, 0.054, and 0.051, respectively. Among these, the Random Forest model demonstrated superior performance. CONCLUSIONS: The research indicates that obesity in steelworkers results from a combination of occupational and lifestyle factors. Of the models tested, the Random Forest model exhibited superior predictive ability, highlighting its significant practical application.