Development and validation of a nomogram for predicting occurrence of severe case in children hospitalized with influenza A (H1N1) infection during the post-COVID-19 era.

Background: The significant rebound of influenza A (H1N1) virus activity, particularly among children, with rapidly growing number of hospitalized cases is of major concern in the post-COVID-19 era. The present study was performed to establish a prediction model of severe case in pediatric patients hospitalized with H1N1 infection during the post-COVID-19 era. Methods: This is a multicenter retrospective study across nine public tertiary hospitals in Yunnan, China, recruiting pediatric H1N1 inpatients hospitalized at five of these centers between February 1 and July 1, 2023, into the development dataset. Screening of 40 variables including demographic information, clinical features, and laboratory parameters were performed utilizing Least Absolute Shrinkage and Selection Operator (LASSO) regression and logistic regression to determine independent risk factors of severe H1N1 infection, thus constructing a prediction nomogram. Receiver operating characteristic (ROC) curve, calibration curve, as well as decision curve analysis (DCA) were employed to evaluate the model's performance. Data from four independent cohorts comprised of pediatric H1N1 inpatients from another four hospitals between July 25 and October 31, 2023, were utilized to externally validate this nomogram. Results: The development dataset included 527 subjects, 122 (23.1 %) of whom developed severe H1N1 infection. The external validation dataset included 352 subjects, 72 (20.5 %) of whom were eventually confirmed as severe H1N1 infection. The LASSO regression identified 19 candidate predictors, with logistic regression further narrowing down to 11 independent risk factors, including underlying conditions, prematurity, fever duration, wheezing, poor appetite, leukocyte count, neutrophil-lymphocyte ratio (NLR), erythrocyte sedimentation rate (ESR), lactate dehydrogenase (LDH), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α). By integrating these 11 factors, a predictive nomogram was established. In terms of prediction of severe H1N1 infection, excellent discriminative capacity, favorable accuracy, and satisfactory clinical usefulness of this model were internally and externally validated via ROC curve, calibration curve, and DCA, respectively. Conclusion: Our study successfully established and validated a novel nomogram model integrating underlying conditions, prematurity, fever duration, wheezing, poor appetite, leukocyte count, NLR, ESR, LDH, IL-10, and TNF-α. This nomogram can effectively predict the occurrence of serious case in pediatric H1N1 inpatients during the post-COVID-19 era, facilitating the early recognition and more efficient clinical management of such patients.

Controllable Self-Assembly of Carbon Nanotubes on Ammonium Polyphosphate as a Game-Changer for Flame Retardancy and Thermal Conductivity in Epoxy Resin.

The optimization of flame retardancy and thermal conductivity in epoxy resin (EP), utilized in critical applications such as mechanical components and electronics packaging, is a significant challenge. This study introduces a novel, ultrasound-assisted self-assembly technique to create a dual-functional filler consisting of carbon nanotubes and ammonium polyphosphate (CNTs@APP). This method, leveraging dynamic ligand interactions and strategic solvent selection, allows for precise control over the assembly and distribution of CNTs on APP surfaces, distinguishing it from conventional blending approaches. The integration of 7.5 wt.% CNTs@APP10 into EP nanocomposites results in substantial improvements in flame retardancy, as evidenced by a limiting oxygen index (LOI) value of 31.8% and achievement of the UL-94 V-0 rating. Additionally, critical fire hazard indicators, including total heat release (THR), total smoke release (TSR), and the peak intensity of CO yield (PCOY), are significantly reduced by 45.9% to 77.5%. This method also leads to a remarkable 3.6-fold increase in char yield, demonstrating its game-changing potential over traditional blending techniques. Moreover, despite minimal CNTs addition, thermal conductivity is notably enhanced, showing a 53% increase. This study introduces a novel approach in the development of multifunctional EP nanocomposites, offering potential for wide range of applications.

Evaluation of disease severity and prediction of severe cases in children hospitalized with influenza A (H1N1) infection during the post-COVID-19 era: a multicenter retrospective study.

BACKGROUND: The rebound of influenza A (H1N1) infection in post-COVID-19 era recently attracted enormous attention due the rapidly increased number of pediatric hospitalizations and the changed characteristics compared to classical H1N1 infection in pre-COVID-19 era. This study aimed to evaluate the clinical characteristics and severity of children hospitalized with H1N1 infection during post-COVID-19 period, and to construct a novel prediction model for severe H1N1 infection. METHODS: A total of 757 pediatric H1N1 inpatients from nine tertiary public hospitals in Yunnan and Shanghai, China, were retrospectively included, of which 431 patients diagnosed between February 2023 and July 2023 were divided into post-COVID-19 group, while the remaining 326 patients diagnosed between November 2018 and April 2019 were divided into pre-COVID-19 group. A 1:1 propensity-score matching (PSM) was adopted to balance demographic differences between pre- and post-COVID-19 groups, and then compared the severity across these two groups based on clinical and laboratory indicators. Additionally, a subgroup analysis in the original post-COVID-19 group (without PSM) was performed to investigate the independent risk factors for severe H1N1 infection in post-COIVD-19 era. Specifically, Least Absolute Shrinkage and Selection Operator (LASSO) regression was applied to select candidate predictors, and logistic regression was used to further identify independent risk factors, thus establishing a prediction model. Receiver operating characteristic (ROC) curve and calibration curve were utilized to assess discriminative capability and accuracy of the model, while decision curve analysis (DCA) was used to determine the clinical usefulness of the model. RESULTS: After PSM, the post-COVID-19 group showed longer fever duration, higher fever peak, more frequent cough and seizures, as well as higher levels of C-reactive protein (CRP), interleukin 6 (IL-6), IL-10, creatine kinase-MB (CK-MB) and fibrinogen, higher mechanical ventilation rate, longer length of hospital stay (LOS), as well as higher proportion of severe H1N1 infection (all P < 0.05), compared to the pre-COVID-19 group. Moreover, age, BMI, fever duration, leucocyte count, lymphocyte proportion, proportion of CD3+ T cells, tumor necrosis factor α (TNF-α), and IL-10 were confirmed to be independently associated with severe H1N1 infection in post-COVID-19 era. A prediction model integrating these above eight variables was established, and this model had good discrimination, accuracy, and clinical practicability. CONCLUSIONS: Pediatric H1N1 infection during post-COVID-19 era showed a higher overall disease severity than the classical H1N1 infection in pre-COVID-19 period. Meanwhile, cough and seizures were more prominent in children with H1N1 infection during post-COVID-19 era. Clinicians should be aware of these changes in such patients in clinical work. Furthermore, a simple and practical prediction model was constructed and internally validated here, which showed a good performance for predicting severe H1N1 infection in post-COVID-19 era.

Qingfei Tongluo Mixture Attenuates Bleomycin-Induced Pulmonary Inflammation and Fibrosis through mTOR-Dependent Autophagy in Rats.

As an interstitial fibrosis disease characterized by diffuse alveolitis and structural alveolar disorders, idiopathic pulmonary fibrosis (IPF) has high lethality but lacks limited therapeutic drugs. A hospital preparation used for the treatment of viral pneumonia, Qingfei Tongluo mixture (QFTL), is rumored to have protective effects against inflammatory and respiratory disease. This study aims to confirm whether it has a therapeutic effect on bleomycin-induced IPF in rats and to elucidate its mechanism of action. Male SD rats were randomly divided into the following groups: control, model, CQ + QFTL (84 mg/kg chloroquine (CQ) + 3.64 g/kg QFTL), QFTL-L, M, H (3.64, 7.28, and 14.56 g/kg, respectively) and pirfenidone (PFD 420 mg/kg). After induction modeling and drug intervention, blood samples and lung tissue were collected for further detection. Body weight and lung coefficient were examined, combined with hematoxylin and eosin (H&E) and Masson staining to observe lung tissue lesions. The enzyme-linked immunosorbent assay (ELISA) and the hydroxyproline (HYP) assay kit were used to detect changes in proinflammatory factors (transforming growth factor-ß (TGF-ß), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß)) and HYP. Immunohistochemistry and Western blotting were performed to observe changes in proteins related to pulmonary fibrosis (α-smooth muscle actin (α-SMA) and matrix metalloproteinase 12 (MMP12)) and autophagy (P62 and mechanistic target of rapamycin (mTOR)). Treatment with QFTL significantly improved the adverse effects of bleomycin on body weight, lung coefficient, and pathological changes. Then, QFTL reduced bleomycin-induced increases in proinflammatory mediators and HYP. The expression changes of pulmonary fibrosis and autophagy marker proteins are attenuated by QFTL. Furthermore, the autophagy inhibitor CQ significantly reversed the downward trend in HYP levels and α-SMA protein expression, which QFTL improved in BLM-induced pulmonary fibrosis rats. In conclusion, QFTL could effectively attenuate bleomycin-induced inflammation and pulmonary fibrosis through mTOR-dependent autophagy in rats. Therefore, QFTL has the potential to be an alternative treatment for IPF in clinical practice.

Bioactive substances inhibiting COX-2 and cancer cells isolated from the fibrous roots of Alangium chinense (Lour.) Harms.

Alangium chinense has been used as a traditional folk medicine for centuries to treat rheumatism, skin diseases, and diabetes by the people of Southeast Asia. However, the bioactive constituents inhibiting COX-2 and cancer cells (HepG2, Caco-2, HeLa) remain unclear. In this study one new (14) along with twenty-four known compounds (1-13, 15-25) were isolated from the fibrous roots of Alangium chinense by chromatographic methods, and identified by NMR, and Gaussian and CD calculation. Compounds 1, 2, 13, 16, 17, 19, 20, 23, and 24 were isolated from this plant for the first time. Their inhibition effects on COX-2 enzyme and cancer cells were evaluated by MTT assay. Compounds 1-4, 13-14, and 16-18 can be used as good inhibitors against COX-2 enzyme, and compounds 1, 13, 14, and 17 were stronger than the positive control (celecoxib). In addition, molecular docking suggested that compounds 13, 17, and 18 belong to ellagic acids and have good inhibition against COX-2 enzyme. While compounds 1, 5, 13 and 21 showed cytotoxicity against HepG2 cells, compounds 2 and 21 showed cytotoxicity against Caco-2 cells, and compound 20 showed cytotoxicity against HeLa cells.

Interfacial silicon­nitrogen aerogel raise flame retardancy of bamboo fiber reinforced polylactic acid composites.

A triazine derivative containing nitrogen and silicon (SiN) was synthesized and the SiN hybrid aerogel was covered on the surface of bamboo fiber (BF). The modified BF was identified as MBF. The MBF and ammonium polyphosphate (APP) were used to regulate the flame retardancy and mechanical properties of polylactic acid (PLA). The PLA/BF composites were investigated using limiting oxygen index (LOI), UL-94 vertical combustion, cone calorimetry, thermogravimetric analysis linked with infrared spectra (TG-IR) etc. The char residue of MBF at 800 °C is as high as 43.5 % which is 200 % more than that of BF. Incorporating 9 wt% APP generates a PLA9 which displays the UL-94 V2 rating and a LOI value of 28.0 vol%. PLA9/MBF composites display the UL-94 V0 rating and increased LOI values while PLA9/BF composites obtain the UL-94 V2 rating and decreased LOI. The MBF reduces the release of flammable gases during combustion, enhances charring ability and decreases the thermal conductivity of composites. Besides, the tensile and impact strength of PLA9/20MBF is 20 % and 37 % more than that of PLA9/20BF due to stronger interfacial adhesion. This work provides a good method to regulate the flame retardancy and mechanical properties of PLA/BF composites.

Introduction of cation vacancies and iron doping into TiO2 enabling efficient uranium photoreduction.

The reduction of U(VI) to U(IV) in wastewater by semiconductor photocatalysis has become a new highly efficient and low-cost method for U(VI) removal. However, due to the weak absorption of visible light led by wide band gap and low carrier utilization rate resulted from the severe electron-holes recombination, the photoreduction performance of U(VI) is limited. Herein, the Ti vacancies and doped Fe atoms were simultaneously introduced into TiO2 nanosheet (labeled as 4%Fe-Ti1-xO2) as a highly active and stable catalysis for U(VI) photoreduction. Without adding any hole sacrifice agent, 4%Fe-Ti1-xO2 nanosheets achieved 99.7% removal efficiency for U(VI) within 120 min. And the 92.1% removal efficiency of U(VI) via 4%Fe-Ti1-xO2 nanosheets was still maintained after 5 cycles. Moreover, 4%Fe-Ti1-xO2 exhibited dramatic removal rate, 81.6% U(VI) in the solution was removed in 10 min. Further study on the mechanism showed that simultaneously introducing the Ti vacancies and doped Fe atoms in 4%Fe-Ti1-xO2 nanosheets improved the visible light utilization and decreased the recombination of photogenerated electron-hole pairs, contributing to the highly efficiency removal of U(VI).

Multiple Roles of Black Raspberry Anthocyanins Protecting against Alcoholic Liver Disease.

This study aimed to investigate the protective effect of black raspberry anthocyanins (BRAs) against acute and subacute alcoholic liver disease (ALD). Network analysis and docking study were carried out to understand the potential mechanism. Thereafter, the serum biochemical parameters and liver indexes were measured, the histopathological changes of the liver were analyzed in vivo. The results showed that all tested parameters were ameliorated after the administration of BRAs with alcohol. Meanwhile, there was increased protein expression of NF-κB and TGF-ß in extracted livers, which was associated with hepatitis and hepatic fibrosis. Furthermore, BRAs and cyanidin-3-O-rutinoside exhibited cytotoxic effects on t-HSC/Cl-6, HepG2, and Hep3B and induced the apoptosis of HepG2 cells; downregulated the protein expression level of Bcl-2; upregulated the level of Bax; and promoted the release of cytochrome C, cleaved caspase-9, cleaved caspase-3, and cleaved PARP in HepG2 cells. In addition, the antioxidant activity of BRAs was tested, and the chemical components were analyzed by FT-ICR MS. The results proved that BRAs exert preventive effect on ALD through the antioxidant and apoptosis pathways.

Investigation of Anti-Fatigue Effect and Simultaneous Determination of Eight Nucleosides in Different Parts of Velvet Antler in Red Deer and Sika Deer.

Velvet antler (VA) is crucial and precious nourishment in China and some countries in Southeast Asia and has excellent anti-fatigue effect. The incidence of fatigue syndrome has increased gradually. VA can be a potential source of anti-fatigue products. Therefore, we investigated the anti-fatigue activity of different sections (upper, middle, and basal section) of VA from different species (red deer and sika deer) via loading swimming test in mice. Furthermore, nucleosides are one kind of active components in VA which could considerably reduce fatigue in mice. In order to explore whether the nucleosides are correlated with anti-fatigue effect, the contents of eight nucleosides (uracil, cytidine, hypoxanthine, xanthine, thymine, inosine, guanosine, and adenosine) were determined simultaneously using high-performance liquid chromatography. The results indicated that the swimming time in mice was increased from basal to upper section, which was consistent with the change trend of the total contents of eight nucleosides of VA. Therefore, we speculated that the contents of nucleosides in VA may affect its anti-fatigue effect. Furthermore, the contents of nucleosides were also used as a reference for evaluating the quality of different parts of VA obtained from red and sika deer.

Identification of Anthocyanins from Four Kinds of Berries and Their Inhibition Activity to α-Glycosidase and Protein Tyrosine Phosphatase 1B by HPLC-FT-ICR MS/MS.

The polyphenolic profiles of four berries (blueberry, bilberry, mulberry, and cranberry) in China were investigated using Fourier transform-ion cyclotron resonance mass spectrometry (FT-ICR MS). Thirty-nine polyphenols including 26 anthocyanins, 9 flavonoids, and 4 phenolic acids were identified accurately. Cyanidin aglycones are common in four berries, and malvidin aglycones are the main compounds found in bilberry and cranberry. The anthocyanin level in blueberry are the highest with 739.6 ± 17.14 mg/g DW and presented the strongest antioxidant capacity in DPPH, ABTS, FRAP, and ORAC assay. In α-glycosidase, the inhibition activity was in the following order: mulberry > bilberry > blueberry > cranberry. For the PTP1B inhibition assay, blueberry demonstrated the highest inhibitory effect with IC50 3.06 ± 0.02 µg/mL, followed by bilberry, mulberry, and cranberry. Molecular docking results showed that cyanidin aglycones had the highest inhibition activity to PTP1B.

Dammarane triterpenoids for pharmaceutical use: a patent review (2005 - 2014).

INTRODUCTION: Dammarane triterpenoids, the main secondary metabolites of Panax ginseng, are very important natural compounds with remarkable biological activity. They could be isolated from the plants of Panax or other genus, as well as through the modifications of certain natural products. This review is a collection of a number of patents (2005 - 2014) that describe the dammarane triterpenoids for therapeutic or preventive uses on numerous common diseases. AREAS COVERED: In this review, patents from 2005 to 2014 on chemical structures and treatment of different diseases by dammarane triterpenoids have been summarized. The SciFinder and the World Intellectual Property Organisation databases have been used as main sources for the search. EXPERT OPINION: In the last decade, over 90 patents concerning dammarane derivatives for pharmaceutical have been published. These types of compounds could be used as agents for prevention and treatment of various kinds of diseases, such as cancer, diabetes mellitus and metabolic syndrome, hyperlipidemia, cardiovascular and cerebrovascular disease, aging, neurodegenerative disease, bone disease, liver disease, kidney disease, gastrointestinal disease, depression-type mental illness and skin aging. Rare plants, except for Panax genus, which contain dammarane triterpenoids should be studied extensively. In addition, more dammarane triterpenoids with good biological activity, especially the aglycones possessing novel side chain, should be prepared using chemical modification. Finally, pharmacological effects of dammarane triterpenoids should be further studied.

Fabrication of fullerene-decorated carbon nanotubes and their application in flame-retarding polypropylene.

Multi-walled carbon nanotubes were decorated with fullerene (C(60)) via a three-step chemical functionalization, with the goal of combining their unique physical and chemical characteristics and simultaneously improving the solubility of CNTs in organic solvents. C(60) molecules, about 0.67% by molecule, were homogeneously bonded onto the surface of the CNTs. Electron microscopy clearly shows that C(60) molecules are introduced onto the surface of the CNTs, and this is also evidenced by their UV-VIS absorption spectra. Cone calorimetry measurements showed that compared with pristine CNTs, fullerene-decorated CNTs further reduced the flammability of polypropylene, which may be due to the free-radical-trapping effect of C(60) and the barrier effect of the CNT network.

Notch1 signaling inhibits growth of human hepatocellular carcinoma through induction of cell cycle arrest and apoptosis.

Notch signaling plays a critical role in maintaining the balance between cell proliferation, differentiation, and apoptosis; hence, perturbed Notch signaling may contribute to tumorigenesis. Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in Africa and Asia. The mechanisms that orchestrate the multiple oncogenic insults required for initiation and progression of HCC are not clear. We constitutively overexpressed active Notch1 in human HCC to explore the effects of Notch1 signaling on HCC cell growth and to investigate the underlying molecular mechanisms. We show here that overexpression of Notch1 was able to inhibit the growth of HCC cells in vitro and in vivo. Biochemical analysis revealed the involvement of cell cycle regulated proteins in Notch1-mediated G(0)/G(1) arrest of HCC cells. Compared with green fluorescent protein (GFP) control, transient transfection of Notch1 ICN decreased expression of cyclin A (3.5-fold), cyclin D1 (2-fold), cyclin E (4.5-fold), CDK2 (2.8-fold), and the phosphorylated form of retinoblastoma protein (3-fold). Up-regulation of p21(waf/cip1) protein expression was observed in SMMC7721-ICN cells stably expressing active Notch1 but not in SMMC7721-GFP cells, which only express GFP. Furthermore, a 12-fold increase in p53 expression and an increase (4.8-fold) in Jun-NH(2)-terminal kinase activation were induced in SMMC7721-ICN cells compared with SMMC7721-GFP cells. In contrast, expression of the antiapoptotic Bcl-2 protein could not be detected in SMMC7721-ICN cells. These findings suggest that Notch1 signaling may participate in the development of HCC cells, affecting multiple pathways that control both cell proliferation and apoptosis.

Up-regulation of TLR9 gene expression by LPS in mouse macrophages via activation of NF-kappaB, ERK and p38 MAPK signal pathways.

Toll-like receptors (TLR) are critical in the activation of macrophages by bacterial products. It has been shown that TLR2 and TLR4 mediate lipopolysaccharide (LPS) and lipoproteins signal transduction, respectively. Regulation of TLR2 and TLR4 expression by LPS was considered to be one of the mechanisms to control the overall responses of immune cells to bacteria. However, little is known about whether the other members of TLR family are regulated by LPS. Recently, TLR9 was demonstrated to be essential for CpG DNA signaling. Given the effective immune modulation by CpG DNA, regulation of TLR9 expression might play important role in controlling the overall responses of immune cells to bacteria. In this study, regulation of TLR9 gene expression in mouse macrophage cell line RAW264.7 by LPS was investigated. Semiquantitative RT-PCR was performed to determine gene expression of TLR9. Following LPS stimulation, TLR9 gene expression was upregulated within 1 h and reached peak level at about 3 h. LPS stimulation activated NF-kappaB, ERK and p38 MAPK signal pathways. Pretreatment of macrophages with inhibitors of NF-kappaB, ERK and p38 MAPK signal pathways inhibited LPS-induced upregulation of TLR9 mRNA expression. Our results demonstrated that LPS stimulation could upregulate gene expression of TLR9 via NF-kappaB, ERK, and p38 MAPK signal pathways in macrophages, indicating that macrophages with increased TLR9 expression induced by LPS might respond to invading bacteria more effectively.

Involvement of ERK, p38 and NF-kappaB signal transduction in regulation of TLR2, TLR4 and TLR9 gene expression induced by lipopolysaccharide in mouse dendritic cells.

Toll-like receptors (TLR) are sentinel receptors capable of recognizing pathogen-associated molecule patterns (PAMP) such as lipopolysaccharide (LPS) and CpG-containing oligonucleotides (CpG ODN). TLR2 and TLR4 are major receptors for Gram-positive and Gram-negative bacterial cell wall components, respectively. TLR9 is necessary for CpG signalling. LPS or CpG ODN can activate immature dendritic cells (DC) and induce DC maturation characterized by production of cytokines, up-regulation of co-stimulatory molecules, and increased ability to activate T cells. However, little is known regarding the regulation of TLR gene expression in mouse DC. In this study, we investigated the regulation of TLR2, TLR4 and TLR9 gene expression by LPS in murine immature DC. TLR2, TLR4 and TLR9 mRNA were up-regulated following LPS stimulation. The up-regulation of TLR9 expression coincided with significantly increased production of tumour necrosis factor-alpha induced by LPS plus CpG ODN. While inhibition of extracellular signal-related kinase and NF-kappaB activation suppressed the up-regulation of the expression of TLR2, TLR4 and TLR9 mRNA, inhibition of p38 kinase prevented the up-regulation of TLR2 and TLR4 mRNA expression but enhanced the up-regulation of TLR9 expression. These results demonstrated that TLR2, TLR4 and TLR9 gene expression was differently regulated by LPS in mouse immature DC. Up-regulation of TLR2, TLR4 and TLR9 expression by LPS might promote the overall responses of DC to bacteria and help to explain the synergy between LPS and other bacterial products in the induction of cytokine production.