Developmental relationship between junctional epithelium and epithelial rests of Malassez.

Keratin 17 (K17) is thought to be a candidate target gene for regulation by Lymphoid Enhancer Factor-1 (Lef-1). K17 is a marker that distinguishes junctional epithelium (JE) from epithelial rests of Malassez (ERM). However, the relationship of Lef-1 to K17 is not clear in this context. Moreover, the expression of other keratins such as K5, K6, K7 and K16 is not reported. Therefore, the aim of our study was to assay the expression of K5, K6, K7, K14, K16, K17 and Lef-1 in postnatal developing teeth, and clarify the corresponding immunophenotypes of the JE and ERM. Upper jaws of Wistar rats aged from postnatal (PN) day 3.5 to PN21 were used and processed for immunohistochemistry. K5 and K14 were intensely expressed in inner enamel epithelium (IEE), reduced enamel epithelium (REE), ERM and JE. There was no staining for K16 in the tissue, except for strong staining in the oral epithelium. Specifically, at PN3.5 and PN7, K17 was initially strongly expressed and then negative in the IEE. At PN16 and PN21, both REE and ERM were strongly stained for K17, whereas K17 was negative in the JE. In addition, K6, K7 and Lef-1 were not detected in any tissue investigated. REE and ERM have an identical keratin expression pattern before eruption, while JE differs from ERM in the expression of K17 after eruption. The expression of K17 does not coincide with that of Lef-1. These data indicate that JE has a unique phenotype different from ERM, which is of odontogenic origin.

TRPM7 facilitates fibroblast-like synoviocyte proliferation, metastasis and inflammation through increasing IL-6 stability via the PKCα-HuR axis in rheumatoid arthritis.

Transient receptor potential melastatin 7 (TRPM7) is a cation channel that plays a role in the progression of rheumatoid arthritis (RA), yet its involvement in synovial hyperplasia and inflammation has not been determined. We previously reported that TRPM7 affects the destruction of articular cartilage in RA. Herein, we further confirmed the involvement of TRPM7 in fibroblast-like synoviocyte (FLS) proliferation, metastasis and inflammation. We observed increased TRPM7 expression in FLSs derived from human RA patients. Pharmacological inhibition of TRPM7 protected primary RA-FLSs from proliferation, metastasis and inflammation. Furthermore, we found that TRPM7 contributes to RA-FLS proliferation, metastasis and inflammation by increasing the intracellular Ca2+ concentration. Mechanistically, the PKCα-HuR axis was demonstrated to respond to Ca2+ influx, leading to TRPM7-mediated RA-FLS proliferation, metastasis and inflammation. Moreover, HuR was shown to bind to IL-6 mRNA after nuclear translocation, which could be weakened by TRPM7 channel inhibition. Additionally, adeno-associated virus 9-mediated TRPM7 silencing is highly effective at alleviating synovial hyperplasia and inflammation in adjuvant-induced arthritis rats. In conclusion, our findings unveil a novel regulatory mechanism involved in the pathogenesis of RA and suggest that targeting TRPM7 might be a potential strategy for the prevention and treatment of RA.

Psychobiological regulation of plasma and saliva GDF15 dynamics in health and mitochondrial diseases.

GDF15 (growth differentiation factor 15) is a marker of cellular energetic stress linked to physical-mental illness, aging, and mortality. However, questions remain about its dynamic properties and measurability in human biofluids other than blood. Here, we examine the natural dynamics and psychobiological regulation of plasma and saliva GDF15 in four human studies representing 4,749 samples from 188 individuals. We show that GDF15 protein is detectable in saliva (8% of plasma concentration), likely produced by salivary glands secretory duct cells. Plasma and saliva GDF15 levels are not correlated. Using a brief laboratory socio-evaluative stressor paradigm, we find that psychological stress increases plasma (+3.4-5.3%) and saliva GDF15 (+45%) with distinct kinetics, within minutes. Moreover, saliva GDF15 exhibits a robust awakening response, declining by ∼42-92% within 30-45 minutes from its peak level at the time of waking up. Clinically, individuals with genetic mitochondrial OxPhos diseases show elevated baseline plasma and saliva GDF15, and post-stress GDF15 levels in both biofluids correlate with multi-system disease severity, exercise intolerance, and the subjective experience of fatigue. Taken together, our data establish the dynamic properties of saliva GDF15, reveal it as a stress-sensitive, and as a clinically relevant marker of mitochondrial diseases. These findings point to a shared psychobiological pathway integrating metabolic and mental stress.

Analysis and risk factors of deep vein catheterization-related bloodstream infections in neonates.

To investigate the incidence, risk factors, and pathogenic characteristics of catheter-related bloodstream infection caused by peripherally inserted central venous catheter in neonates, and to provide references for reducing the infection rate of peripherally inserted central venous catheter. The clinical data of 680 neonates who underwent peripherally inserted central catheter (PICC) in the neonatal intensive care unit from June 2020 to June 2023 were retrospectively analyzed. The risk factors and independent risk factors of catheter-related bloodstream infection caused by PICC were determined by univariate and multivariate analysis, respectively. Catheter-related bloodstream infection occurred in 38 of 680 neonates who underwent PICC. The infection rate was 4.74%. The proportions of fungi, gram-positive bacteria, and gram-negative bacteria were 42.11%, 36.84%, and 21.05%, respectively. Candida parapsilosis was the main fungus (18.42%), coagulase negative Staphylococcus was the main gram-positive bacteria (23.68%), and Klebsiella pneumoniae and Escherichia coli were the main gram-negative bacteria (7.89%). Univariate analysis showed that gestational age ≤32 weeks, birth weight ≤1500 g, congenital diseases, nutritional support, catheterization time, 5-minute APGAR score ≤7, and neonatal respiratory distress syndrome were associated with catheter-related bloodstream infection caused by PICC. Multivariate analysis showed that premature delivery, low birth weight, parenteral nutrition, long catheterization time, and 5-minute APGAR score ≤7 were associated with catheter-related bloodstream infection caused by PICC. Among the pathogens detected, there were 6 cases of K pneumoniae, 5 cases of coagulase negative staphylococci, and 2 cases of fungi. Low birth weight, premature delivery, off-site nutrition, long catheterization time, and 5-minute APGAR score ≤7 are independent risk factors for catheter-related bloodstream infection in neonates with peripherally inserted central venous catheters. The pathogenic bacteria are fungi and multidrug-resistant bacteria.

Fabrication and characterization of shellac nanofibers with colon-targeted delivery of quercetin and its anticancer activity.

In this study, the feasibility of shellac nanofibers as carrier system for colonic delivery of quercetin was evaluated. Firstly, the nanofibers without and with different amounts (2.5 %, 5.0 %, and 7.5 %) of quercetin were fabricated using pure shellac as a carrier by electrospinning. The morphology of nanofibers was bead-shape confirmed by SEM. FTIR, XRD, and DSC analysis showed that quercetin was encapsulated into shellac nanofibers, forming an amorphous complex. The molecular docking simulation indicated quercetin bound well to shellac through hydrogen bonding and van der Waals forces. These nanofibers had higher thermal stability than pure quercetin, and their surface wettability exhibited a pH-responsive behavior. The loading capacity of quercetin varied from 2.25 % to 6.84 % with the increased amount of quercetin, and it affected the stability of nanofibers in food simulants by measuring the release profiles of quercetin. The shellac nanofibers had high gastrointestinal stability, with a minimum quercetin release of 16.87 % in simulated digestive fluids, while the remaining quercetin was delivered to the colon and was released gradually. Moreover, the nanofibers exerted enhanced anticancer activity against HCT-116 cells by arresting cell cycle in G0/G1 phase and inducing cell apoptosis. Overall, shellac nanofibers are promising materials for colon-targeted delivery of active compounds.

Bisphenol A induces placental ferroptosis and fetal growth restriction via the YAP/TAZ-ferritinophagy axis.

Exposure to bisphenol A (BPA) during gestation leads to fetal growth restriction (FGR), whereby the underlying mechanisms remain unknown. Here, we found that FGR patients showed higher levels of BPA in the urine, serum, and placenta; meanwhile, trophoblast ferroptosis was observed in FGR placentas, as indicated by accumulated intracellular iron, impaired antioxidant molecules, and increased lipid peroxidation products. To investigate the role of ferroptosis in placental and fetal growth, BPA stimulation was performed both in vivo and in vitro. BPA exposure during gestation was associated with FGR in mice; also, it induces ferroptosis in mouse placentas and human placental trophoblast. Pretreatment with ferroptosis inhibitor ferritin-1 (Fer-1) alleviated BPA-induced oxidative damage and cell death. Notably, BPA reduced the trophoblastic expression of Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), which regulated tissue growth and organ size. YAP or TAZ siRNA enhanced BPA-induced ferroptosis, suggesting that trophoblast ferroptosis is dependent on YAP/TAZ downregulation after BPA stimulation. Consistently, the protein levels of YAP/TAZ were also reduced in FGR placentas. Further results revealed that silencing YAP/TAZ promoted BPA-induced ferroptosis through autophagy. Pretreatment with autophagy inhibitor chloroquine (CQ) attenuated BPA-induced trophoblast ferroptosis. Ferritinophagy, an autophagic degradation of ferritin (FTH1), was observed in FGR placentas. Similarly, BPA reduced the protein level of FTH1 in placental trophoblast. Pretreatment with iron chelator desferrioxamine (DFO) and NCOA4 (an autophagy cargo receptor) siRNA weakened the ferroptosis of trophoblast after exposure to BPA, indicating that autophagy mediates ferroptosis in BPA-stimulated trophoblast by degrading ferritin. In summary, ferroptosis was featured in BPA-associated FGR and trophoblast injury; the regulation of ferroptosis involved the YAP/TAZ-autophagy-ferritin axis.

[C(NH2)3][B(C2O2H4)2]: An Organic-Inorganic Hybrid Borate Containing Nonlinear-Optical Active Unit [B(C2O2H4)2]- with Solar-Blind-Region Optical Nonlinearity.

We herein report an unprecedented organic-inorganic hybrid borate incorporating a novel nonlinear-optical (NLO) active unit, namely, [C(NH2)3][B(C2O2H4)2]. The novel NLO active unit was derived from the condensation reaction between two glycol molecules and one (BO4)5- group. The title compound exhibits a moderate second-harmonic-generation effect (0.7 × KDP), a significant band gap (5.76 eV), and a suitable birefringence (0.078 at 550 nm). The optical properties are determined by the synergistic interaction between the C(NH2)3+ cation and the [B(C2O2H4)2]- group, as indicated by theoretical calculations.

[C(NH2)3]6Mo7O24: A Guanidinium Molybdate as a UV Nonlinear Optical Crystal with Large Birefringence.

The key to searching novel nonlinear optical (NLO) crystals was effectively combining the NLO-active units to obtain a noncentrosymmetric structure. Nevertheless, the present predicament lies in the growing challenge of discovering novel crystals within conventional inorganic frameworks that surpass the properties of the current NLO materials. In view of this, researchers expanded their research focus to the organic-inorganic hybridization system; it is foreseeable to concentrate the advantages from several kinds of NLO-active units to acquire novel NLO crystals with superior properties. We herein report an organic-inorganic hybrid molybdate crystal, namely, [C(NH2)3]6Mo7O24 (GMO). It was successfully obtained via combining inorganic NLO-active MoO6 octahedra and organic π-conjugated [C(NH2)3]+ groups. GMO demonstrates a moderate second-harmonic-generation response, specifically measuring about 1.3 times the value of KDP. Additionally, it exhibits a significant birefringence value of 0.203 at the wavelength of 550 nm and possesses a wide band gap of 3.31 eV. Theoretical calculations suggest that the optical properties of the GMO are primarily influenced by the synergy effect of [C(NH2)3]+ groups between MoO6 octahedra.

Artificial intelligence for segmentation and classification of lobar, lobular, and interstitial pneumonia using case-specific CT information.

Background: Pneumonia can be anatomically classified into lobar, lobular, and interstitial types, with each type associated with different pathogens. Utilizing artificial intelligence (AI) to determine the anatomical classifications of pneumonia and assist in refining the differential diagnosis may offer a more viable and clinically relevant solution. This study aimed to develop a multi-classification model capable of identifying the occurrence of pneumonia in patients by utilizing case-specific computed tomography (CT) information, categorizing the pneumonia type (lobar, lobular, and interstitial pneumonia), and performing segmentation of the associated lesions. Methods: A total of 61 lobar pneumonia patients, 60 lobular pneumonia patients, and 60 interstitial pneumonia patients were consecutively enrolled at our local hospital from June 2020 and May 2022. All selected cases were divided into a training cohort (n=135) and an independent testing cohort (n=46). To generate the ground truth labels for the training process, manual segmentation and labeling were performed by three junior radiologists. Subsequently, the segmentations were manually reviewed and edited by a senior radiologist. AI models were developed to automatically segment the infected lung regions and classify the pneumonia. The accuracy of pneumonia lesion segmentation was analyzed and evaluated using the Dice coefficient. Receiver operating characteristic curves were plotted, and the area under the curve (AUC), accuracy, precision, sensitivity, and specificity were calculated to assess the efficacy of pneumonia classification. Results: Our AI model achieved a Dice coefficient of 0.743 [95% confidence interval (CI): 0.657-0.826] for lesion segmentation in the training set and 0.723 (95% CI: 0.602-0.845) in the test set. In the test set, our model achieved an accuracy of 0.927 (95% CI: 0.876-0.978), precision of 0.889 (95% CI: 0.827-0.951), sensitivity of 0.889 (95% CI: 0.827-0.951), specificity of 0.946 (95% CI: 0.902-0.990), and AUC of 0.989 (95% CI: 0.969-1.000) for pneumonia classification. We trained the model using labels annotated by senior physicians and compared it to a model trained using labels annotated by junior physicians. The Dice coefficient of the model's segmentation improved by 0.014, increasing from 0.709 (95% CI: 0.589-0.830) to 0.723 (95% CI: 0.602-0.845), and the AUC improved by 0.042, rising from 0.947 to 0.989. Conclusions: Our study presents a robust multi-task learning model with substantial promise in enhancing the segmentation and classification of pneumonia in medical imaging.

Effects of Sophora alopecuroides in a High-Concentrate Diet on the Liver Immunity and Antioxidant Function of Lambs According to Transcriptome Analysis.

The purpose of this study was to determine the effects of Sophora alopecuroides (SA) on liver function, liver inflammatory factor levels, antioxidant indexes and transcriptome in sheep. Twenty-four 3-month-old healthy Dumont hybrid lambs weighing 25.73 ± 2.17 kg were randomly divided into three groups: C1 (the control group), fed a concentrate-to-forage ratio of 50:50; H2 (the high-concentration group), fed a concentrate-to-forage ratio of 70:30; and S3 (the SA group), fed a concentrate-to-forage ratio of 70:30 + 0.1% SA. The results showed that the rumen pH values of the C1 and S3 groups were significant or significantly higher than that of the H2 group (p < 0.05 or p < 0.01). The serum ALT, AST and LDH activities and the LPS and LBP concentrations in the sheep serum and liver in the H2 group were significantly or extremely significantly higher than those in the C1 and S3 groups (p < 0.01), and the IL-10 content and SOD, GPX-PX and T-AOC activities showed the opposite trend (p < 0.05 or p < 0.01). KEGG enrichment analysis showed that the differentially expressed genes were significantly enriched in the ECM-receptor interaction and focal adhesion pathways, which are closely related to immune and antioxidant functions (p-adjust < 0.1). In summary, SA could improve the immune and antioxidant functions of lamb livers under high-concentrate conditions and regulate the mechanism of damage on sheep livers, which is caused by high-concentrate diets and through the expression of related genes in the ECM/FAs pathway.

Extracellular CIRP induces abnormal activation of fibroblast-like synoviocytes from patients with RA via the TLR4-mediated HDAC3 pathways.

The development of rheumatoid arthritis (RA) is closely related to the excessive activation of fibroblast-like synoviocytes (FLSs), which are regulated by a variety of endogenous proinflammatory molecules. Extracellular cold-inducible RNA-binding protein (CIRP), as a novel endogenous proinflammatory molecule, plays an important role in inflammatory diseases. More importantly, the synovial concentration of CIRP in patients with RA was significantly higher than that in patients with osteoarthritis (OA). Thus, this study aimed to investigate the role of extracellular CIRP in the abnormal activation of RA-FLSs and its related mechanisms. Our study showed that extracellular CIRP induced proliferation, migration and invasion of RA-FLSs, increased the expression of N-cadherin and MMP-3, and promoted the release of IL-1ß and IL-33. However, blocking of extracellular CIRP with C23 inhibited CIRP-induced abnormal activation of RA-FLSs and alleviated the arthritis severity in AA rats. Accumulating evidence suggests that the activity and proinflammatory effects of CIRP are mediated through Toll-like receptor 4 (TLR4). Further studies demonstrated that the TLR4 knockdown inhibited CIRP-induced abnormal activation, and histone deacetylase 3 (HDAC3) expression in RA-FLSs. In addition, we found that HDAC3 knockdown and the specific inhibitor RGFP966 significantly suppressed CIRP-induced abnormal activation of RA-FLSs. We further found that treatment with HDAC3 specific inhibitor effectively alleviated the severity of arthritis in AA rats. Taken together, these findings indicate that extracellular CIRP induces abnormal activation of RA-FLSs via the TLR4-mediated HDAC3 pathways.

An Anatomy- and Topology-Preserving Framework for Coronary Artery Segmentation.

Coronary artery segmentation is critical for coronary artery disease diagnosis but challenging due to its tortuous course with numerous small branches and inter-subject variations. Most existing studies ignore important anatomical information and vascular topologies, leading to less desirable segmentation performance that usually cannot satisfy clinical demands. To deal with these challenges, in this paper we propose an anatomy- and topology-preserving two-stage framework for coronary artery segmentation. The proposed framework consists of an anatomical dependency encoding (ADE) module and a hierarchical topology learning (HTL) module for coarse-to-fine segmentation, respectively. Specifically, the ADE module segments four heart chambers and aorta, and thus five distance field maps are obtained to encode distance between chamber surfaces and coarsely segmented coronary artery. Meanwhile, ADE also performs coronary artery detection to crop region-of-interest and eliminate foreground-background imbalance. The follow-up HTL module performs fine segmentation by exploiting three hierarchical vascular topologies, i.e., key points, centerlines, and neighbor connectivity using a multi-task learning scheme. In addition, we adopt a bottom-up attention interaction (BAI) module to integrate the feature representations extracted across hierarchical topologies. Extensive experiments on public and in-house datasets show that the proposed framework achieves state-of-the-art performance for coronary artery segmentation.

Preconception or prenatal acceptance of SMN1 gene carrier screening and carrier rate of spinal muscular atrophy: a retrospective study in 18,818 reproductive age women in Wuhan area of China.

OBJECTIVE: Spinal muscular atrophy (SMA) is an autosomal recessive disorder mainly affecting the neuromuscular system, which seriously threatens the life and health of patients. But few studies have reported the acceptance rate of SMA gene screening and SMA carrier rate in China. The present study aimed to clarify the two issues in China through a retrospective analysis of 18,818 reproductive age women in Wuhan area of China. METHODS: The copy number (CN) of exons 7 and 8 in survival motor neuron 1 (SMN1) gene was detected by real-time quantitative PCR, and the results were verified by multiplex ligation-dependent probe amplification. RESULTS: Carrier screening was offered to 44,953 women of childbearing age in our medical center from March, 2018, to February, 2022, of whom 18,818 were enrolled in the program. A total of 336 women were identified as carriers (1.73%; 326/18,808; without fertility history of the children with SMA). Among 18,818 reproductive age women, 286 spouses (85.12%; 286/336) were successfully recalled for screening. The results showed 17 couples at high risk of having children with SMA, of whom prenatal diagnosis was implemented in 11, and 6 fetuses were identified with SMA. All the 5 pregnant women bearing the 6 SMA fetuses chose to terminate the pregnancy by artificial abortion. CONCLUSION: Reproductive age women and their spouses in Wuhan area showed a positive attitude toward general screening for SMA carriers. Given the high early mortality of children with SMA, screening for SMA carriers in women of reproductive age is necessary and feasible.

Serum interleukin-33 combined with FEF75% z-score and FeNO improves the diagnostic accuracy of asthma in children.

OBJECTIVE: To investigate the diagnostic efficacy of serum IL-33 single indicator and combined indicators for asthma in children. METHODS: 132 children were initially diagnosed with asthma during acute exacerbation and 100 healthy children were included. Serum IL-33 concentration differences were compared between asthmatic and normal children. Correlations between IL-33 with pulmonary function parameters, FeNO, peripheral blood EOS counts and serum total IgE were analyzed in asthmatic children. ROC curves were used to assess IL-33 diagnostic efficacy and its combined indicators. To prevent overfitting of the predictive model, the hold-out cross-validation method was used. RESULTS: (1) Serum IL-33 concentrations were significantly higher in children with asthma than in normal children (p < 0.001). (2) IL-33 concentration was negatively correlated with FVC z-score, FEV1 z-score and FEF75% z-score in asthmatic children (p < 0.05). (3) The area under the ROC curve of IL-33 was 0.821, which was higher than those of FeNO, FVC z-score, and FEV1 z-score. (4) Cross-validation of the combined indicators showed that IL-33 significantly improved asthma diagnostic efficacy. The combination of IL-33, FEF75% z-score, and FeNO showed the highest diagnostic efficacy, with the AUC, sensitivity, and specificity of the combined indicator being 0.954, 90.1%, and 89. 0%, respectively, and good extrapolation of the predictive model. CONCLUSION: Serum IL-33 is higher in children with asthma and increases with the severity of pulmonary ventilation obstruction. A single indicator of serum IL-33 demonstrates moderate diagnostic accuracy, and its combination with FEF75% z-score and FeNO significantly improves the diagnostic accuracy in childhood asthma.

Bisphenol A induces placental ferroptosis and fetal growth restriction via the YAP/TAZ-ferritinophagy axis.

Exposure to bisphenol A (BPA) during gestation leads to fetal growth restriction (FGR), whereby the underlying mechanisms remain unknown. Here, we found that FGR patients showed higher levels of BPA in the urine, serum, and placenta; meanwhile, trophoblast ferroptosis was observed in FGR placentas, as indicated by accumulated intracellular iron, impaired antioxidant molecules, and increased lipid peroxidation products. To investigate the role of ferroptosis in placental and fetal growth, BPA stimulation was performed both in vivo and in vitro. BPA exposure during gestation was associated with FGR in mice; also, it induces ferroptosis in mouse placentas and human placental trophoblast. Pretreatment with ferroptosis inhibitor ferritin-1 (Fer-1) alleviated BPA-induced oxidative damage and cell death. Notably, BPA reduced the trophoblastic expression of Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), which regulated tissue growth and organ size. YAP or TAZ siRNA enhanced BPA-induced ferroptosis, suggesting that trophoblast ferroptosis is dependent on YAP/TAZ downregulation after BPA stimulation. Consistently, the protein levels of YAP/TAZ were also reduced in FGR placentas. Further results revealed that silencing YAP/TAZ promoted BPA-induced ferroptosis through autophagy. Pretreatment with autophagy inhibitor chloroquine (CQ) attenuated BPA-induced trophoblast ferroptosis. Ferritinophagy, an autophagic degradation of ferritin (FTH1), was observed in FGR placentas. Similarly, BPA reduced the protein level of FTH1 in placental trophoblast. Pretreatment with iron chelator desferrioxamine (DFO) and NCOA4 (an autophagy cargo receptor) siRNA weakened the ferroptosis of trophoblast after exposure to BPA, indicating that autophagy mediates ferroptosis in BPA-stimulated trophoblast by degrading ferritin. In summary, ferroptosis was featured in BPA-associated FGR and trophoblast injury; the regulation of ferroptosis involved the YAP/TAZ-autophagy-ferritin axis.

Serum interleukin-33 combined with FEF75% z-score and FeNO improves the diagnostic accuracy of asthma in children

Abstract Objective To investigate the diagnostic efficacy of serum IL-33 single indicator and combined indicators for asthma in children. Methods 132 children were initially diagnosed with asthma during acute exacerbation and 100 healthy children were included. Serum IL-33 concentration differences were compared between asthmatic and normal children. Correlations between IL-33 with pulmonary function parameters, FeNO, peripheral blood EOS counts and serum total IgE were analyzed in asthmatic children. ROC curves were used to assess IL-33 diagnostic efficacy and its combined indicators. To prevent overfitting of the predictive model, the hold-out cross-validation method was used. Results (1) Serum IL-33 concentrations were significantly higher in children with asthma than in normal children (p < 0.001). (2) IL-33 concentration was negatively correlated with FVC z-score, FEV1 z-score and FEF75% z-score in asthmatic children (p < 0.05). (3) The area under the ROC curve of IL-33 was 0.821, which was higher than those of FeNO, FVC z-score, and FEV1 z-score. (4) Cross-validation of the combined indicators showed that IL-33 significantly improved asthma diagnostic efficacy. The combination of IL-33, FEF75% z-score, and FeNO showed the highest diagnostic efficacy, with the AUC, sensitivity, and specificity of the combined indicator being 0.954, 90.1%, and 89. 0%, respectively, and good extrapolation of the predictive model. Conclusion Serum IL-33 is higher in children with asthma and increases with the severity of pulmonary ventilation obstruction. A single indicator of serum IL-33 demonstrates moderate diagnostic accuracy, and its combination with FEF75% z-score and FeNO significantly improves the diagnostic accuracy in childhood asthma.

Bioinformatic Analysis of the Mechanism of Action of COL3A1 in Pan-Cancer and Design of Specific Inhibitors for Its Conformation.

In this study, we investigated the mechanism of action of COL3A1 in various types of cancers by bioinformatics analysis and designed some specific inhibitors aimed at the treatment of this gene. We found that COL3A1 was highly expressed in several cancer types and correlated with tumor progression and prognosis. Through systems biology analysis, we identified a central role for COL3A1 in cancer development, including cell proliferation, metastasis and invasion. We also used molecular dynamics simulations and drug screening techniques to design anticancer drugs with potential COL3A1 inhibitory functions. These results provide a strong rationale for the development and use of COL3A1 as a therapeutic target.

Fabrication of colon-targeted ethyl cellulose/gelatin hybrid nanofibers: Regulation of quercetin release and its anticancer activity.

A colon-targeted delivery system that can efficiently deliver and release quercetin is essential to improve its bioavailability. We previously found that hydrophobic ethyl cellulose (EC) nanofibers could efficiently deliver quercetin to colon, but the release of quercetin was limited. To address this problem, hydrophilic gelatin (GN) was used as a regulator, and quercetin-loaded nanofibers with different mass ratios of EC to GN (3:1, 1:1, 1:2, 1:3) were fabricated by electrospinning. All nanofibers had a cylindrical morphology and high encapsulation efficiency (over 94 %), and there existed molecular interactions among quercetin, EC, and GN. The high GN content reduced the thermal stability of nanofibers but increased their surface wettability. Besides, these nanofibers had good stability in acidic and aqueous foods. Importantly, the release of quercetin in the simulated gastrointestinal fluid was <3 %. The addition of GN was beneficial to the release of quercetin in colon, and nanofibers with EC to GN being 1:3 had a more preferable release performance. The anticancer activity of nanofibers against HCT-116 cells was proved by inhibiting cell viability through the induction of apoptosis. Therefore, these nanofibers are potential carriers for efficient colon-targeted delivery of bioactive compounds in the food industry.

Can the Chinese study on the normal range of FeNO in children evaluate standardized asthma treatment efficacy in 6- to 12-year-old children?

Objective: By examining fractional exhaled nitric oxide (FeNO) levels and performing pulmonary function testing, this study explored whether the multicenter study on the normal range of FeNO in children in China can be used to evaluate standardized treatment efficacy in 6- to 12-year-old children with asthma. Methods: A total of 115 children aged 6-12 years old who were first diagnosed with asthma and received standardized asthma treatment from April 2018 to July 2022 were selected. According to the FeNO level at the first visit, the subjects were divided into different high- and low-FeNO groups according to the American Thoracic Society (ATS) guidelines and the Chinese multicenter study recommendations. The consistency of the two grouping methods and the differences between the high- and low-FeNO groups were compared after standardized treatment. The grouping method that was the most suitable for children in the cross group was discussed. Results: (i) There was fair consistency between the Chinese multicenter study recommendations and the ATS guidelines regarding the classification of high- and low-FeNO groups (Kappa = 0.338). (ii) Repeated-measures ANOVA showed that the level of improvement in FVC%, FEV1%, FEF25%, FEF50%, and FeNO in the American high- and low-FeNO groups differed with the duration of therapy (P < 0.05), however, there was no significant difference between the Chinese groups. (iii) FEV1% and FeNO improved more after treatment in the fixed high-FeNO group than in the cross group (P < 0.05). Conclusion: The Chinese multicenter study on the normal range of FeNO in children in China has a limited role in evaluating standardized asthma treatment efficacy in 6- to 12-year-old children. The ATS guidelines are currently recommended for clinical assessment of asthma treatment efficacy.

Recent Advances in the Synthesis and Analysis of Atorvastatin and its Intermediates.

Atorvastatin, a lipid-lowering drug that is widely used in the treatment of cardiovascular diseases, has significant clinical significance. This article focuses on the synthetic procedures of atorvastatin, including Paal-Knorr synthesis and several new synthetic strategies. It also outlines chemical and chemo-enzymatic methods for synthesizing optically active side chain of atorvastatin. In addition, a comprehensive overview of the analytical monitoring techniques for atorvastatin and its metabolites and impurities is reported, alongside a discussion of their strengths and limitations.