Group A Streptococcal meningitis in children: a short case series and systematic review.

BACKGROUND: Group A streptococcal(GAS) meningitis is a severe disease with a high case fatality rate. In the era of increasing GAS meningitis, our understanding about this disease is limited. PURPOSE: To gain a better understanding about GAS meningitis. METHODS: Five new cases with GAS meningitis were reported. GAS meningitis related literatures were searched for systematic review in PUBMED and EMBASE. Case reports and case series on paediatric cases were included. Information on demographics, risk factors, symptoms, treatments, outcomes, and emm types of GAS was summarized. RESULTS: Totally 263 cases were included. Among 100 individuals, 9.9% (8/81) had prior varicella, 11.1% (9/81) had anatomical factors, and 53.2% (42/79) had extracranial infections. Soft tissue infections were common among infants (10/29, 34.5%), while ear/sinus infections were more prevalent in children ≥ 3 years (21/42, 50.0%). The overall case fatality rate (CFR) was 16.2% (12/74). High risk of death was found in patients with shock or systemic complications, young children(< 3 years) and cases related to hematogenic spread. The predominate cause of death was shock(6/8). Among the 163 patients included in case series studies, ear/sinus infections ranged from 21.4 to 62.5%, while STSS/shock ranged from 12.5 to 35.7%, and the CFR ranged from 5.9 to 42.9%. CONCLUSIONS: A history of varicella, soft tissue infections, parameningeal infections and CSF leaks are important clinical clues to GAS in children with meningitis. Young children and hematogenic spread related cases need to be closely monitored for shock due to the high risk of death.

Proteomic analysis of hexahydro-ß-acids/hydroxypropyl-ß-cyclodextrin inhibit Listeria monocytogenes.

Food safety affected by food-borne pathogen has received increasing attention by researchers. Listeria monocytogenes (L. monocytogenes), widespread in the environment, could easily cause some diseases. The aim of this study was to investigate how L. monocytogenes ATCC 19,115 regulated and shaped its proteome in response to hexahydro-ß-acids (HBA) formed inclusion complex with hydroxypropyl-ß-cyclodextrin (HP-ß-CD), compared to untreated cells growing under optimal conditions. HP-ß-CD enhanced the solubility of HBA to 0.589 g/100 mL. The minimum inhibitory concentration (MIC) and the minimal bactericidal concentration (MBC) of HBA/HP-ß-CD to L. monocytogenes were 25 µg/mL and 100 µg/mL, respectively. Scanning electron microscope (SEM) images demonstrated that HBA could destroy the cell membrane of L. monocytogenes. The proteomic analysis revealed that 2882 proteins were initially identified, among which 153 and 201 proteins were differentially upregulated and downregulated respectively. Changes of L. monocytogenes proteome in response to treatments were mainly related to carbohydrate metabolism, protein synthesis, ribosome composition proteins, cell wall composition proteins, and cell division anomalies process. This research is conducive to understanding the molecular mechanisms underlying the inhibiting effects of HBA/HP-ß-CD against L. monocytogenes, providing novel insights for further development of HBA/HP-ß-CD antimicrobial agents. KEY POINTS: • MIC and MBC of HBA/HP-ß-CD to L. monocytogenes were 25 µg/mL and 100 µg/mL. • HBA/HP-ß-CD cause significant changes in bacterial proteome. • The process of ribosome composition and carbohydrate metabolism was inhibited.

Cordyceps acid alleviates lung cancer in nude mice.

The aim of this study is to examine the effect of cordyceps acid (CA) on lung cancer in mice. A lung cancer animal model was established by inoculating lung cancer cells under the armpit of nude mice. The mental state, body weight, and tumor growth of nude mice were recorded in detail. The levels of Nrf-2/HO-1/NLRP3/NF-κB pathway and apoptosis in tumor tissues of nude mice were detected by the Western blot analysis and immunohistochemical methods. Our results show that CA inhibited lung cancer by regulating the Nrf-2/HO-1/NLRP3/NF-κB signal. In summary, CA has an obvious tumor inhibiting effect on lung cancer via regulation of the Nrf-2/HO-1/NLRP3/NF-κB signal.

Metal/metalloid levels in hair of Shenzhen residents and the associated influencing factors.

129 Shenzhen residents' hair samples were collected and the metal/metalloid concentrations of Hg, As, Pb, Cd, Cr, Cu, Mn, Zn, Fe and Ni were detected. Meanwhile, the relationships between metal/metalloid contents in human hair and gender, age, seafood diet habit, smoking habit, as well as the housing type (dwelling environment) were analyzed. Results showed that the average content of Hg, As, Pb, Cd, Cr, Cu, Mn, Zn, Fe and Ni in human hair of Shenzhen residents was 0.76 ± 0.96, 0.10 ± 0.04, 5.25 ± 4.88, 0.25 ± 0.33, 0.60 ± 0.31, 13.84 ± 3.67, 2.82 ± 2.01, 196.90 ± 145.01, 12.20 ± 5.10 and 0.34 ± 0.32 µg/g, respectively. Compared with other regions at home and abroad, most metal/metalloids in Shenzhen residents were at a moderate level, and the highly toxic elements (i.e. Pb, Cd, As and Hg) didn't exceed the upper limit of normal values in China. Statistical analysis showed that the young male people contained significantly higher (p < 0.05) level of Pb (in age group of 20-30 years old) and Fe (in age group of 20-40 years old) in hair than the female people. Smokers had significantly (p < 0.05) higher level of Cd (0.35 µg/g) but lower level of Zn (101.24 µg/g) than non-smokers (Cd: 0.17 µg/g; Zn: 252.63 µg/g). Hg and Pb contents in hair of Shenzhen people were positively related with the frequencies of seafood consumption and the age, respectively. Moreover, residents lived in private buildings (well decorated house) accumulated significantly higher (p < 0.05) levels of Pb, Cr, Fe and Ni as compared with those lived in public rental house and village house (no decoration or simple decoration), suggesting that decoration material was also an important way for human exposure to heavy metals.

Graphite-Templated Amyloid Nanostructures Formed by a Potential Pentapeptide Inhibitor for Alzheimer's Disease: A Combined Study of Real-Time Atomic Force Microscopy and Molecular Dynamics Simulations.

Self-assembly of peptides is closely related to many diseases, including Alzheimer's, Parkinson's, and prion diseases. Understanding the basic mechanism of this assembly is essential for designing ultimate cure and preventive measures. Template-assisted self-assembly (TASA) of peptides on inorganic substrates can provide fundamental understanding of substrate-dependent peptides assemble, including the role of hydrophobic interface on the peptide fibrillization. Here, we have studied the self-assembly process of a potential pentapeptide inhibitor on the surface of highly oriented pyrolytic graphite (HOPG) using real time atomic force microscopy (RT-AFM) as well as molecular dynamics (MD) simulation. Experimental and simulation results show nanofilament formation consisting of ß-sheet structures and epitaxial growth on HOPG. Height analysis of the nanofilaments and MD simulation indicate that the peptides adopt a lying down configuration of double-layered antiparallel ß-sheets for its epitaxial growth, and the number of nanofilament layers is concentration-dependent. These findings provide new perspective for the mechanism of peptide-based fibrillization in amyloid diseases as well as for designing well-ordered micrometrical and nanometrical structures.

Study on physisorption between G-actin and amphiphilic polymer-coated gold nanoparticles.

Physisorptions occurs everywhere and constantly in living organisms and between nanomaterials and biomolecules. In this study, one of the most important proteins, G-actin, was selected to investigate its bio-nano physisorption with a model nanoparticle coated with a amphiphilic polymer. Using a photoluminescence quenching method, both the binding constant and the Hill constant were determined as 1.79 × 107  M-1 and 0.84, respectively. Thermodynamic calculations proved that such a physisorption was a spontaneous procedure. The physisorption-mediated protein-nanoparticle conjugates were robust enough to resist gel electrophoresis, and protein conformation was kept intact, as revealed using circular dichroism. This conjugate might be a promising candidate for nanofabrication or could play a significant role in actin-related bioactivities.

Prognostic significance of migrasomes in neuroblastoma through machine learning and multi-omics.

This study explores migrasomes' role in neuroblastoma, a common malignant tumor in children, and their potential impact on tumor formation. We analyzed neuroblastoma RNA-seq datasets from public databases, including GSE62564, GSE181559, target, and fwr144. Through data normalization and unsupervised classification using migrasome-specific molecular markers, Differentially Expressed Genes were identified, followed by functional enrichment analysis. Our novel migrasome-associated machine learning model, MigScore, was developed using ten algorithms and 101 combinations, validated on two single-cell datasets. This enabled immune infiltration assessment and drug compatibility prediction, highlighting the utility of MS275, a histone deacetylase inhibitor. Results showed a significant inverse relationship between MigScore and favorable clinical outcomes, elucidating the link between migrasome pathways and tumor immunogenicity. These findings suggest that migrasomes are crucial in neuroblastoma prognosis, leading to the possibility of personalized treatment strategies and improved outcomes.

The plasticity of neuropeptide Y-Y1 receptor system on Tac2 neurons contributes to mechanical hyperknesis during chronic itch.

Rationale: In the physiological states, the act of scratching protects the person from harmful substances, while in certain pathological conditions, the patient suffers from chronic itch, both physically and mentally. Chronic itch sufferers are more sensitive to mechanical stimuli, and mechanical hyperknesis relief is essential for chronic itch treatment. While neuropeptide Y-Y1 receptor (NPY-Y1R) system is known to play a crucial role in modulating mechanical itch in physiological conditions, it is elusive how they are altered during chronic itch. We hypothesize that the negative regulatory effect of Y1Rs on Tac2 neurons, the key neurons that transmit mechanical itch, declines during chronic itch. Methods: We combined transgenic mice, chemogenetic manipulation, immunofluorescence, rabies virus circuit tracing, and electrophysiology to investigate the plasticity of Y1Rs on Tac2 neurons during chronic itch. Results: We found that Tac2 neurons receive direct input from Npy neurons and that inhibition of Npy neurons induces activation of Tac2 neurons. Moreover, the expression of Y1Rs on Tac2 neurons is reduced, and the regulatory effect is also reduced during chronic itch. Conclusion: Our study clarifies the plasticity of Y1Rs on Tac2 neurons during chronic itch and further elucidates the mechanism by which NPY-Y1R system is responsible for modulating mechanical itch. We highlight Y1Rs as a promising therapeutic target for mechanical hyperknesis during chronic itch.

Hairpin DNA-Based Nanomaterials for Tumor Targeting and Synergistic Therapy.

Background: While nanoplatform-based cancer theranostics have been researched and investigated for many years, enhancing antitumor efficacy and reducing toxic side effects is still an essential problem. Methods: We exploited nanoparticle coordination between ferric (Fe2+) ions and telomerase-targeting hairpin DNA structures to encapsulate doxorubicin (DOX) and fabricated Fe2+-DNA@DOX nanoparticles (BDDF NPs). This work studied the NIR fluorescence imaging and pharmacokinetic studies targeting the ability and biodistribution of BDDF NPs. In vitro and vivo studies investigated the nano formula's toxicity, imaging, and synergistic therapeutic effects. Results: The enhanced permeability and retention (EPR) effect and tumor targeting resulted in prolonged blood circulation times and high tumor accumulation. Significantly, BDDF NPs could reduce DOX-mediated cardiac toxicity by improving the antioxidation ability of cardiomyocytes based on the different telomerase activities and iron dependency in normal and tumor cells. The synergistic treatment efficacy is enhanced through Fe2+-mediated ferroptosis and the ß-catenin/p53 pathway and improved the tumor inhibition rate. Conclusion: Harpin DNA-based nanoplatforms demonstrated prolonged blood circulation, tumor drug accumulation via telomerase-targeting, and synergistic therapy to improve antitumor drug efficacy. Our work sheds new light on nanomaterials for future synergistic chemotherapy.

Multidimensional Analgesia of Acupuncture by Increasing Expression of MD2 in Central Nervous System.

OBJECTIVE: To investigate changes of myeloid differentiation factor 2 (MD2) in inflammation-induced pain and acupuncture-mediated analgesia. METHODS: Mice were randomly divided into three groups by a random number table method: saline group (n=16), complete Freund's adjuvant (CFA) group (n=24) and CFA+electroacupuncture (EA) group (n=26). Inflammation-induced pain was modelled by injecting CFA to the plantar surface of the hind paw of mice and EA was applied to bilateral Zusanli (ST 36) to alleviate pain. Only mice in the CFA+EA group received EA treatment (30 min/d for 2 weeks) 24 h after modelling. Mice in the saline and CFA groups received sham EA. von-Frey test and Hargreaves test were used to assess the pain threshold. Brain and spinal tissues were collected for immunofluorescence staining or Western blotting to quantify changes of MD2 expression. RESULTS: CFA successfully induced plantar pain and EA significantly alleviated pain 3 days after modelling (P<0.01). Compared with the CFA group, the number of MD2+/c-fos+ neurons was significantly increased in the dorsal horn of the spinal cord 7 and 14 days after EA, especially in laminae I - IIo (P<0.01). The proportion of double positive cells to the number of c-fos positive cells and the mean fluorescence intensity of MD2 neurons were also significantly increased in laminae I - IIo (P<0.01). Western blotting showed that the level of MD2 was significantly decreased by EA only in the hippocampus on day 7 and 14 (both P<0.01) and no significant changes were observed in the cortex, thalamus, cerebellum, or the brainstem (P<0.05). Fluorescence staining showed significant decrease in the level of MD2 in periagueductal gray (PAG) and locus coeruleus (LC) after CFA injection on day 7 (P<0.01 for PAG, P<0.05 for LC) and EA significantly reversed this decrease (P<0.01 for PAG, P<0.05 for LC). CONCLUSION: The unique changes of MD2 suggest that EA may exert the analgesic effect through modulating neuronal activities of the superficial laminae of the spinal cord and certain regions of the brain.

Sirt3 regulates NLRP3 and participates in the effects of plantainoside D on acute lung injury sepsis.

Sepsis, a common critical disease, has high morbidity and mortality. Acute lung injury (ALI) is one of the important complications of sepsis, its effective treatment measures remain scarce. The purpose of the present study was to search for the biomarker and effective treatment measures. Lipopolysaccharide (LPS) was used to establish sepsis induced ALI model in vivo and in vitro. Proteomics, immunoprecipitation, molecular docking techniques, and Sirt3 knockout (KO) mice and silence MLE-12 cells were used to search for biomarker and treatment measures for sepsis ALI. 38 differentially expressed proteins were found in the lung tissues of sepsis ALI mice, among which Sirt3 changed most. Further study found that Sirt3 could inhibit NLRP3 activation. Sirt3 KO or silence significantly aggravated sepsis induced ALI and MLE-12 cell injury. Plantainoside D (PD), an effective component of Plantago asiatica L., significantly improved sepsis induced ALI by regulation of Sirt3/NLRP3 pathway. In conclusion, Sirt3 may be the important molecular targets for sepsis ALI. PD could protect sepsis ALI via Sirt3/NLRP3 signal pathway. The findings provide a new treatment target for sepsis ALI and a potential treatment measure.

Natural products: protective effects against ischemia-induced retinal injury.

Ischemic retinal damage, a common condition associated with retinal vascular occlusion, glaucoma, diabetic retinopathy, and other eye diseases, threatens the vision of millions of people worldwide. It triggers excessive inflammation, oxidative stress, apoptosis, and vascular dysfunction, leading to the loss and death of retinal ganglion cells. Unfortunately, minority drugs are available for treating retinal ischemic injury diseases, and their safety are limited. Therefore, there is an urgent need to develop more effective treatments for ischemic retinal damage. Natural compounds have been reported to have antioxidant, anti-inflammatory, and antiapoptotic properties that can be used to treat ischemic retinal damage. In addition, many natural compounds have been shown to exhibit biological functions and pharmacological properties relevant to the treatment of cellular and tissue damage. This article reviews the neuroprotective mechanisms of natural compounds involve treating ischemic retinal injury. These natural compounds may serve as treatments for ischemia-induced retinal diseases.

Pyroptosis-Related Gene Signature Predicts the Prognosis and Immune Infiltration in Neuroblastoma.

Neuroblastoma is the most common pediatric extracranial solid tumor. The 5-year survival rate for high-risk neuroblastoma is less than 50%, despite multimodal treatment. Pyroptosis, an inflammatory type of programmed cell death, manifested pro-tumor and anti-tumor roles in the adult tumor. Thus, we aimed to elucidate the function of pyroptosis in neuroblastoma. We classified neuroblastoma patients into two clusters based on the pyroptosis gene expression. We found high pyroptosis neuroblastoma manifested favorable overall survival and more anti-tumor immune cell infiltration. Based on the results of a stepwise Cox regression analysis, we built a four-gene predictive model including NLRP3, CASP3, IL18, and GSDMB. The model showed excellent predictive performance in internal and external validation. Our findings highlight that high pyroptosis positively correlated with neuroblastoma outcomes and immune landscape, which may pave the way for further studies on inducing pyroptosis therapy in high-risk neuroblastoma treatment.

Covalent organic framework with sulfonic acid functional groups for visible light-driven CO2 reduction.

In this study, a covalent organic framework (TpPa-SO3H) photocatalyst with sulfonic acid function groups was synthesized using a solvothermal method. The morphologies and structural properties of the as-prepared composites were characterized by X-ray diffraction, infrared spectroscopy, ultraviolet-visible diffuse reflectance spectroscopy, X-ray photoelectron spectroscopy, N2 adsorption-desorption measurements, and field emission scanning electron microscopy. An electrochemical workstation was used to test the photoelectric performance of the materials. The results show that TpPa-SO3H has -SO3H functional groups and high photocatalytic performance for CO2 reduction. After 4 h of visible-light irradiation, the amount of CO produced is 416.61 µmol g-1. In addition, the TpPa-SO3H photocatalyst exhibited chemical stability and reusability. After two testing cycles under visible light irradiation, the amount of CO produced decreased slightly to 415.23 and 409.15 µmol g-1. The XRD spectra of TpPa-SO3H were consistent before and after the cycles. Therefore, TpPa-SO3H exhibited good photocatalytic activity. This is because the introduction of -SO3H narrows the bandgap of TpPa-SO3H, which enhances the visible light response range and greatly promotes the separation of photogenerated electrons.

Characteristics of Zusanli Dorsal Root Ganglion Neurons in Rats and Their Receptor Mechanisms in Response to Adenosine.

Neural systems play important roles in the functions of acupuncture. But the unclear structure and mechanism of acupoints hinder acupuncture standardization and cause the acupuncture effects to be varying or even paradoxical. It has been broadly assumed that the efficacy of acupuncture depends on the biological signals triggered at acupoints and passed up along neural systems. However, as the first station to transmit such signals, the characters of the dorsal root ganglia (DRG) neurons innervating acupoints are still not well elucidated. We adopted Zusanli (ST36) as a representative acupoint and found most DRG neurons innervating ST36 acupoint are middle-size neurons with a single spike firing pattern. This suggests that proprioceptive neurons take on greater possibility than small size nociceptive neurons do to mediate the acupuncture signals. Moreover, we found that adenosine injected into ST36 acupoints could dose- and acupoint-dependently mimic the analgesic effect of acupuncture. However, adenosine could not elicit action potentials in the acutely isolated ST36 DRG neurons, but it inhibited ID currents and increased the areas of overshoots. Further, we found that 4 types of adenosine receptors were all expressed by ST36 DRG neurons, and A1, A2b, and A3 receptors were the principal reactors to adenosine. PERSPECTIVE: This study provides the major characteristics of ST36 DRG neurons, which will help to analyze the neural pathway of acupuncture signals. At the same time, these findings could provide a new possible therapy for pain relief, such as injecting adenosine or corresponding agonists into acupoints.

Lateral Habenula and Its Potential Roles in Pain and Related Behaviors.

The lateral habenula (LHb) is a tiny structure that acts as a hub, relaying signals from the limbic forebrain structures and basal ganglia to the brainstem modulatory area. Facilitated by updated knowledge and more precise manipulation of circuits, the progress in figuring out the neural circuits and functions of the LHb has increased dramatically over the past decade. Importantly, LHb is found to play an integrative role and has profound effects on a variety of behaviors associated with pain, including depression-like and anxiety-like behaviors, antireward or aversion, aggression, defensive behavior, and substance use disorder. Thus, LHb is a potential target for improving pain management and related disorders. In this review, we focused on the functions, related circuits, and neurotransmissions of the LHb in pain processing and related behaviors. A comprehensive understanding of the relationship between the LHb and pain will help to find new pain treatments.

Engineering a Synthetic Pathway for Tyrosol Synthesis in Escherichia coli.

Tyrosol is an aromatic compound with great value that is widely used in the food and pharmaceutical industry. In this study, we reported a synthetic pathway for converting p-coumaric acid (p-CA) into tyrosol in Escherichia coli. We found that the enzyme cascade comprising ferulic acid decarboxylase (FDC1) from Saccharomyces cerevisiae, styrene monooxygenase (SMO), styrene oxide isomerase (SOI) from Pseudomonas putida, and phenylacetaldehyde reductase (PAR) from Solanum lycopersicum could efficiently synthesize tyrosol from p-CA with a conversion rate over 90%. To further expand the range of substrates, we also introduced tyrosine ammonia-lyase (TAL) from Flavobacterium johnsoniae to connect the synthetic pathway with the endogenous l-tyrosine metabolism. We found that tyrosol could be efficiently produced from glycerol, reaching 545.51 mg/L tyrosol in a tyrosine-overproducing strain under shake flasks. In summary, we have established alternative routes for tyrosol synthesis from p-CA (a potential lignin-derived biomass), glucose, and glycerol.

Shared nociceptive dorsal root ganglion neurons participating in acupoint sensitization.

When the body is under pathological stress (injury or disease), the status of associated acupoints changes, including decreased pain threshold. Such changes in acupoint from a "silent" to an "active" state are considered "acupoint sensitization," which has become an important indicator of acupoint selection. However, the mechanism of acupoint sensitization remains unclear. In this study, by retrograde tracing, morphological, chemogenetic, and behavioral methods, we found there are some dorsal root ganglion (DRG) neurons innervating the ST36 acupoint and ipsilateral hind paw (IHP) plantar simultaneously. Inhibition of these shared neurons induced analgesia in the complete Freund's adjuvant (CFA) pain model and obstruction of nociceptive sensation in normal mice, and elevated the mechanical pain threshold (MPT) of ST36 acupoint in the CFA model. Excitation of shared neurons induced pain and declined the MPT of ST36 acupoint. Furthermore, most of the shared DRG neurons express TRPV1, a marker of nociceptive neurons. These results indicate that the shared nociceptive DRG neurons participate in ST36 acupoint sensitization in CFA-induced chronic pain. This raised a neural mechanism of acupoint sensitization at the level of primary sensory transmission.

The Impact of Regional Culture on the Psychological Characteristics, Startup Behaviors and Regional Economy of Modern Chinese Business Gangs.

Business gang refers to the enterprise cluster formed by geographical relationship, which has always been the focus of research on entrepreneurship and regional economic development. The research of new institutional economics shows that culture, as an informal system, will change the social psychology, thinking mode and behavior of economic individuals, and provide a good environment for the growth of start-ups, thus affecting economic activities and economic development. Taking the five modern business gangs in China as the research subject, this paper uses the comparative method to analyze the regional cultural differences of the five modern business gangs, as well as the differences of the entrepreneurs' psychological characteristics and startup behaviors. Through the analysis of the economic data of the provinces where the modern business gangs are located, this paper summarizes the differences of economic development in different regions. It is concluded that regional culture has a significant impact on the development of modern business gangs and regional economy. It is necessary to give full play to the advantages of regional culture and promote the high-quality development of modern business gangs and regional economy.

Functional polysaccharide-based film prepared from chitosan and ß-acids: Structural, physicochemical, and bioactive properties.

ß-Acids are natural antibacterial and antioxidant ingredients, obtained from supercritical CO2 hop extract. In this study, ß-acids/chitosan complex films were prepared using the casting method. Complex films were characterized using scanning electron microscopy (SEM), atomic force microscope (AFM), Fourier transform infrared spectroscopy (FTIR), and X-ray diffraction analysis (XRD). Structure analysis revealed that ß-acids can be successfully combined with the chitosan matrix. Mechanical tests demonstrated that the tensile strength of the films showed a significant upward trend (1.9 MPa to 9.6 MPa) with increase in ß-acids content (0.1%-0.3%). Interestingly, the chitosan-based films showed excellent UV barrier capability below 400 nm. The release of ß-acids from the film followed Fickian diffusion (n < 0.45). In addition, the complex films inhibited the growth of five food-borne pathogens (Escherichia coli, Staphylococcus aureus, Bacillus subtilis, Salmonella enteritidis and Listeria monocytogenes). This study highlights the promising nature of composite film as a desirable alternative for active packaging.