Analysis of mild and severe neonatal enterovirus infections in a Chinese neonatal tertiary center: a retrospective case-control study.

PURPOSE: To compare the clinical characteristics, virus serotype, and outcome in cases of mild and severe enteroviral infection at a tertiary neonatal intensive care unit in China. METHODS: A retrospective analysis of cases hospitalized between June and August 2019. Samples (stool or throat swabs) were examined using reverse transcription polymerase chain reaction. Positive cases were divided into two groups: mild infection and severe infection. RESULTS: A total of 149 cases were assigned to one of two groups: mild infection (n = 104) and severe infection (n = 45). There were no significant differences between the groups in terms of sex, gestational age, birth weight, mode of delivery, and onset within 7 days. Clinical symptoms in both groups mostly resembled sepsis (fever, rash, poor feeding, and lethargy); however, there were significant variations in concomitant symptoms such as hepatitis, thrombocytopenia, encephalitis, coagulopathy, and myocarditis. Severe cases were more likely to have abnormal complete blood counts, biochemical parameters, and cerebrospinal fluid markers. The predominant serotypes implicated in neonatal enterovirus infections were echoviruses and Coxsackievirus B. Invasive ventilation, intravenous immunoglobulin, vasoactive medications, and blood product transfusions were often required, with high mortality rates among severe cases. CONCLUSION: We found significant differences between mild and severe cases of neonatal enterovirus infection with respect to complications, laboratory findings, and enterovirus serotypes. It is crucial to exercise caution when newborns exhibit symptoms of sepsis, during an enterovirus outbreak. Anemia, thrombocytopenia, abnormal liver function, and coagulation dysfunction should be monitored closely as they could indicate the presence of a severe enteroviral infection.

Newly discovered variants in unexplained neonatal encephalopathy.

BACKGROUND: The genetic background of neonatal encephalopathy (NE) is complicated and early diagnosis is beneficial to optimizing therapeutic strategy for patients. METHODS: NE Patients with unclear etiology received regular clinical tests including ammonia test, metabolic screening test, amplitude-integrated electroencephalographic (aEEG) monitoring, brain Magnetic Resonance Imaging (MRI) scanning, and genetic test. The protein structure change was predicted using Dynamut2 and RoseTTAFold. RESULTS: 15 out of a total of 113 NE Patients were detected with newly reported pathogenic variants. In this sub-cohort, (1) seizure was the primary initial symptoms; (2) four patients had abnormal metabolic screening results, and two of them were also diagnosed with excessive blood ammonia concentration; (3) the brain MRI results were irregular in three infants and the brain waves were of moderate-severe abnormality in about a half of the patients. The novel pathogenic variants discovered in this study belonged to 12 genes, and seven of them were predicted to introduce a premature translation termination. In-silicon predictions showed that four variants were destructive to the protein structure of KCNQ2. CONCLUSION: Our study expands the mutation spectrum of genes associated with NE and introduces new evidence for molecular diagnosis in this newborn illness.

Production of recombinant HPV11/16 E6/E7-MBP-His6 fusion proteins and their potential to induce cytokine secretion by immune cells in peripheral blood.

Human papillomavirus (HPV) infection poses a significant threat to public health worldwide. Targeting the function of HPV E6 and E7 proteins and activating the host immune response against these proteins represent promising therapeutic strategies for combating HPV-related diseases. Consequently, the efficient production of soluble, high-purity E6 and E7 proteins is crucial for function and host immune response studies. In this context, we selected the pMCSG19 protein expression vector for Escherichia coli to produce soluble MBP-His6 tagged HPV11/16 E6/E7 proteins, achieving relatively high purity and yield. Notably, these proteins exhibited low toxicity to peripheral blood mononuclear cells (PBMCs) and did not compromise their viability. Additionally, the recombinant proteins were capable of inducing the secretion of multiple cytokines by immune cells in peripheral blood, indicating their potential to elicit immune responses. In conclusion, our study offers a novel approach for the production of HPV11/16 E6/E7 fusion proteins with relatively high purity and yield. The fusing HPV11/16 E6/E7 proteins to MBP-His6 tag may serve as a valuable method for large-scale protein production in future research endeavors.

Effect of alkali pretreatment time on kitchen waste anaerobic digestion performance enhanced by alkali pretreatment combined with bentonite: performance enhancement, microbial community structure, and functional gene analysis.

Kitchen waste was mainly composed of carbohydrates, lipids, and proteins. Anaerobic digestion (AD) of kitchen waste usually occurred acidification and further deteriorated. In our previous study, alkali pretreatment combined with bentonite (AP/Be) treatment was proved to enhance high solid AD of kitchen waste. However, effects of AP time on AP/Be were not yet studied. This study investigated the effects of AP time on AP/Be treatment on enhancing high solid AD. The results showed that compared with the control group, the cumulative methane production rate could be increased by 3.30 times (149.7 mL CH4/g VS) and the volatile solids (VS) reduction rate increased by 63.36%. Microbial community analysis showed that the relative abundance of Methanosarcina and Methanosaeta were increased from 6.49 and 7.83% to 47.14 and 16.39% respectively. Predictive functional analysis showed that AP/Be treatment increased the abundance of energy production and conversion, coenzyme transport, and metabolism. This study revealed the potential mechanism of AP/Be enhanced kitchen waste AD performance and AP/Be was a potential strategy to strengthen AD.

Evaluation of HPV infection helps to direct ALA-PDT of condyloma acuminata.

BACKGROUND AND OBJECTIVES: Aminolaevulinic acid-mediated photodynamic therapy (ALA-PDT) is increasingly applied for the treatment of condyloma acuminata (CA). However, the determinants for the sessions and end points of ALA-PDT treatment remains unclear. Here, we recorded HPV screening, evaluated the frequency and efficacy of ALA-PDT in different types of CA, in order to individualize ALA-PDT treatment to CA. METHODS: A total of 227 CA patients with HPV infection and visible warts were recruited. Prior to PDT, visible lesions were removed by radio frequency or microwave. HPV DNA detection were performed before each PDT treatment and at follow-up. Treatment was ended after two consecutive negative HPV DNA detection. RESULTS: Of the 227 patients, 119 patients received ALA-PDT and 116 patients completed all treatments. We found that CA patients with multiple-site infection, intra-luminal infection or multiple-type of HPV infection required more sessions of ALA-PDT. The recurrence rate was 8.62% (10/116). Viral load was significantly lower after six PDT treatments compared to viral load after three PDT treatments. Gender, HPV subtypes and warts location had no significant effect on the recurrence rate. CONCLUSION: Comprehensive evaluation of HPV infection state helps to individualize ALA-PDT treatment scheme for CA patients and predict the therapeutic efficacy.

The plant protection preparation GZM improves crop immunity, yield, and quality.

Lauryl alcohol, a natural compound found in plants and other organisms, is widely used to make surfactants, food, and pharmaceuticals. GZM, a plant protection preparation with lauryl alcohol as its major component is thought to establish a physical barrier on the plant surface, but its physiological functions are unknown. Here, we show that GZM improves the performance of peanut (Arachis hypogaea) plants in both the laboratory and the field. We demonstrate that the treatment with GZM or lauryl alcohol raises the contents of several specific lysophospholipids and induces the biosynthesis of phenylpropanoids, flavonoids, and wax in various plant species. In the field, GZM improves crop immunity, yield, and quality. In addition, GZM and lauryl alcohol can inhibit the growth of some pathogenic fungi. Our findings provide insights into the physiological and biological effects of GZM treatment on plants and show that GZM and lauryl alcohol are promising preparations in agricultural production.

Selective degradation of organic micropollutants by activation of peroxymonosulfate by Se@NC: Role of Se doping and nonradical pathway mechanism.

In this study, Se@NC-x decorated with Se was successfully prepared via two-step calcination with zeolitic imidazole framework (ZIF) as a precursor. Mechanistic studies show that PMS would be adsorbed onto the surface of Se@NC-900 to form an active complex (Se@NC-900/PMS*), and the active Se@NC-900/PMS* could oxidize phenol by the rapid decomposition of PMS. Specifically, electrons are extracted by Se@NC-900/PMS* and then transferred to the surface of Se@NC-900, which can trigger the degradation of phenol. Notably, it is found that the local charge redistribution caused by the doping of Se can activate the catalytic potential of the intrinsically inert carbon skeleton through density flooding theory (DFT) calculations. The XLogP, ΔE, VIP, and ELUMO (Se@NC/PMS)-HOMO (pollutants) and degradation rate constants of different micropollutants were correlated well linearly. This indicates that the Se@NC-900/PMS system has a great selectivity for the degradation of pollutants. Overall, these findings not only illustrate the role of Se in tuning the electronic structure of Se@NC-x to enhance the activation of PMS, but also bridge the gap in our knowledge about the physicochemical properties and degradation performance of Se@NC catalysts.

Dual Sensitization Anti-Resistant Nanoparticles for Treating Refractory Breast Cancers via Apoptosis-Inducing.

Purpose: Current chemotherapy fails to offer a desirable efficacy in clinical treatment against breast cancer due to the extensive multi-drug resistance. In this study, we developed dual sensitization anti-resistant nanoparticles to treat refractory breast cancer, aiming to benefit from photodynamic therapy and chemotherapy. Methods: Hyaluronic acid (HA) derivative and photosensitizer chlorin e6 (Ce6) derivative were synthesized and confirmed by mass spectrometry. These derivatives and the chemotherapy agent paclitaxel were incorporated into nanoparticles by an emulsion-solvent evaporation method. The prepared nanoparticles were characterized by dynamic laser scattering, atomic force microscopy, and high performance liquid chromatography (HPLC). The efficacy and mechanisms of the nanoparticles, both in vitro and in vivo, were investigated by flow cytometry, confocal/fluorescence microscopy, and a high-content screening system. Results: The prepared dual sensitization anti-resistant nanoparticles were round with a diameter of ~ 100 nm, exhibiting high encapsulation efficiency for the anticancer agent paclitaxel. The nanoparticles demonstrated a robust inhibitory effect against drug-resistant breast cancer cells by enhanced uptake, synergistic effect of photodynamic therapy and chemotherapy, and apoptosis-inducing via multiple pathways. In vivo efficacy, biocompatibility and safety were further confirmed acceptable in tumor-bearing mice. Conclusion: The prepared dual sensitization anti-resistant nanoparticles were promising to treat refractory breast cancer with a controllable treatment site and minimal side effects.

Facile fabrication of solar-heating and Joule-heating hyperelastic MXene-modified sponge for fast all-weather clean-up of viscous crude oil spill.

Developing rational sorbent for viscous crude oil clean-up is still a daunting challenge, which requires rapid oil-uptake capability and scalable fabrication process. Herein, a heatable hydrophobic sponge sorbent (H-MXene/PVA/MS) with excellent light/Joule-heating performances was fabricated by a simple and feasible top-down approach. MXene nanosheets firmly coated on the substrate skeleton gave the sorbent outstanding ability to convert solar/electricity into heat rapidly due to the localized surface plasmon resonance (LSPR) effect and ultrahigh metallic conductivity. The surface temperature of H-MXene/PVA/MS could reach about 80 â„ƒ under 1.0 sun irradiation within 30 s and 125 â„ƒ under a low applying voltage of 6 V within 25 s. The rapid and sufficient heat generation on the sorbent would effectively warm the surrounding oil and accelerate its absorption. The oil absorption rate under 1.0 sun irradiation (1 kW/m2) improved about 41.5 times compared to the unheated sorbent. Moreover, the sorbent showed practical application potential in harsh environments due to its high coating firmness, durability, elasticity, and suitability for large-scale production and operations. Thus, the easily-prepared H-MXene/PVA/MS sorbent, which mainly focuses on solar-heating, supplemented by Joule-heating, provides an efficient and energy-efficient strategy for addressing large-scale viscous oil spill clean-up.

Exploring the mechanism of a novel recirculating aquaculture system based on water quality parameters and bacterial communities.

To mitigate the serious environmental problems caused by aquaculture wastewater discharge, the development of improved aquaculture systems with more self-purification capacity and less environmental impact has become essential. A novel recirculating aquaculture system (RAS) with ecological ponds was introduced. However, the mechanism of how the ecological ponds decompose the nutrients from the residual feed and excrement of fish is still unclear. Therefore, we designed a seven-week field experiment to explore the dynamic of water quality and the shift of bacterial communities during the initial stage of the RAS ecosystem to maintain the stability of the system. According to the result, the dissolved oxygen concentration maintained at 5.63 to 10.22 mg·L-1 in aquaculture water, and electrical conductivity increased by 100% to over 800 µs·cm-1. High-throughput sequencing showed that the abundance and diversity of the bacterial communities in sediment samples were significantly higher than in water samples, and the Proteobacteria, Bacteroidetes, Cyanobacteria, and Actinobacteria were dominant phyla in all samples. The relative abundance of ammonia-oxidizing archaea, ammonia-oxidizing bacteria, and nitrite-oxidizing bacteria was lower than 0.10, but rising. Redundancy analysis suggested that TOC, EC, NO3-, and NO2- were the most important factors shaping the bacterial communities in aquaculture water. Our studies assessed the RAS with ecological ponds for the first time based on water quality parameters and bacterial communities, which indicates that decomposition capacity is insufficient but improved at the initial stage of the operation, and potential risks like eutrophication require attention.

Occurrence, source tracking and removal of antibiotics in recirculating aquaculture systems (RAS) in southern China.

The recirculating aquaculture system (RAS) has attracted much attention in China as a way to rapidly transform and upgrade aquaculture ponds to realize zero-emissions of pollutants in aquaculture tail water. Tail water purification ponds (TWPPs) play an important role in the treatment of aquaculture wastewater. However, until now, there have been few reports on the occurrence of antibiotics in RAS and the removal of antibiotics from the TWPPs of RAS. Therefore, this study focused on the occurrence of antibiotics in a typical ecological RAS. For comparison, the same measurements were simultaneously carried out in nearby open aquaculture ponds and rivers. The pollution level and spatial distribution of antibiotics in the RAS and the removal of antibiotics in the TWPPs were explored. The results showed that (1) eleven and twelve antibiotics were detected in water and sediment samples in the RAS, respectively, but no antibiotics were found in fish muscles and feed. Erythromycin (ERY), lincomycin (LIN), and ciprofloxacin (CFX) were the three main types of antibiotics found in water and sediment samples. (2) The TWPPs of the RAS can effectively remove antibiotics in aquaculture water. The antibiotic concentration in recirculating aquaculture ponds of the RAS was as high as 180 ng/L. After treatments in the TWPPs, the antibiotic concentration of aquaculture water decreased to 81.6 ng/L (3) The antibiotic concentrations in recirculating aquaculture ponds (25.2-180 ng/L) were lower than those in the nearby open aquaculture ponds (126-267.3 ng/L), and the concentration of antibiotics in the sediments of recirculating aquaculture ponds was up to 22.9 ng/g, while that in TWPPs was as high as 56.1 ng/g. In conclusion, the antibiotic residues in the RAS were low after antibiotics were banned in feed in China, and the removal of antibiotics in the TWPPs was more pronounced. Furthermore, cross-contamination was found between the RAS, surrounding open aquaculture ponds and the river, and the water supply of the RAS was likely to be the main contributor of antibiotics in the aquaculture environments. This study can help the government formulate discharge standards for antibiotics in aquaculture and also provide a reference for the transformation and upgrading of aquaculture ponds to achieve a zero-emission aquaculture mode.

Testing a Family Supportive End of Life Care Intervention in a Chinese Neonatal Intensive Care Unit: A Quasi-experimental Study With a Non-randomized Controlled Trial Design.

Background: Neonatal death often occurs in tertiary Neonatal Intensive Care Units (NICUs). In China, end-of-life-care (EOLC) does not always involve parents. Aim: The aim of this study is to evaluate a parent support intervention to integrate parents at the end of life of their infant in the NICU. Methods: A quasi-experimental study using a non-randomized clinical trial design was conducted between May 2020 and September 2021. Participants were infants in an EOLC pathway in the NICU and their parents. Parents were allocated into a family supportive EOLC intervention group or a standard EOLC group based on their wishes. The primary outcomes depression (Edinburgh Postnatal Depression Scale for mothers; Hamilton Depression rating scale for fathers) and Satisfaction with Care were measured 1 week after infants' death. Student t-test for continuous variables and the Chi-square test categorical variables were used in the statistical analysis. Results: In the study period, 62 infants died and 45 infants and 90 parents were enrolled; intervention group 20 infants, standard EOLC group 25 infants. The most common causes of death in both groups were congenital abnormalities (n = 20, 44%). Mean gestational age of infants between the family supportive EOLC group and standard EOLC group was 31.45 vs. 33.8 weeks (p = 0.234). Parents between both groups did not differ in terms of age, delivery of infant, and economic status. In the family support group, higher education levels were observed among mother (p = 0.026) and fathers (p = 0.020). Both mothers and fathers in the family supportive EOLC group had less depression compared to the standard EOLC groups; mothers (mean 6.90 vs. 7.56; p = 0.017) and fathers (mean 20.7 vs. 23.1; p < 0.001). Parents reported higher satisfaction in the family supportive EOLC group (mean 88.9 vs. 86.6; p < 0.001). Conclusions: Supporting parents in EOLC in Chinese NICUs might decreased their depression and increase satisfaction after the death of their infant. Future research needs to focus on long-term effects and expand on larger populations with different cultural backgrounds. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT05270915.

Mechanistic and structure investigation of the KOH activation ZIF-8 derived porous carbon as metal-free for unprecedented peroxymonosulfate activation degradation of bisphenol A.

The high-performance and free secondary pollution of the catalysts are the most critical issues in the peroxymonosulfate-based advanced oxidation processes (PMS-AOPs). In this research, the KOH was used to activate ZIF-8 derived carbon materials to synthesize the NC-KOH-x (x = 700, 800, 900 °C), which was an effective metal-free PMS activator. As-prepared NC-KOH-x showed significant improvement not only pore structure and BET surface area but also CO groups, and graphite N content, which were beneficial for the adsorptive and oxidative reaction. The NC-KOH-900 as an excellent metal-free carbon-catalyst exhibited considerable reactivity for bisphenol A (BPA) removal in broad pH ranges. Almost 100% of BPA was eliminated using 9 mg NC-KOH-900, 0.5 mM PMS within 60 min. Interestingly, It was found that the BPA removal efficiency by adding PMS after saturated adsorption of NC-KOH-x was better than that by adding NC-KOH-x and PMS simultaneously. Electronic paramagnetic resonance (EPR) and quenching experiments results demonstrated that the BPA degradation relied mainly on the nonradical (1O2) pathways and the defects (ID/IG), graphitic nitrogen, pyridinic nitrogen, and CO were verified as leading catalytic sites for BPA degradation via PMS activation. Finally, degradation pathways of BPA were proposed and the Toxicity Estimation Software Tool (T.E.S.T.) result implicated that the intermediates of BPA were environmentally friendly to the microorganism and recycled in the ecosystem. The outcomes of this study illustrated the NC-KOH-x owned many merits of state-of-the-art, eco-friendly, and high-performance for great potential practical application value.

Diagnosis and Surveillance of Neonatal Infections by Metagenomic Next-Generation Sequencing.

Microbial infections cause significant morbidity and mortality in neonates. Metagenomic next-generation sequencing is a hypothesis-free and culture-free test that enables broad identification of pathogens and antimicrobial resistance genes directly from clinical samples within 24 h. In this study, we used mNGS for etiological diagnosis and monitoring the efficacy of antibiotic treatment in a cohort of neonatal patients with severe infections. The median age was 19.5 (3-52) days, median gestational age was 37.96 (31-40+3) weeks, and the median birth weight was 3,261 (1,300-4,300) g. The types of infectious diseases included pneumonia, sepsis, and meningitis. mNGS reported microbial findings in all cases, which led to changes in antibiotic treatment. These included cases of Mycobacterium tuberculosis, Legionella pneumophila, and Bacillus cereus. Eight of ten infants recovered after antibiotic adjustment and showed normal development during follow-up. On the other hand, neurological retardation was seen in two infants with meningitis. mNGS enabled etiological diagnosis and guided antibiotic therapy when all conventional methods failed to discover the culprit. It has the potential to cut down the overall cost and burden of disease management in neonatal infections.

Activation of peroxymonosulfate by ZIFs derived Fe/Cu encapsulated N-doped carbon for bisphenol A degradation: The role of N doping.

Bisphenol A (BPA) is a typical kind of endocrine disruption chemical, which has a negative effect on human health, and thus it is necessary to remove BPA from water. Herein, activation of peroxymonosulfate (PMS) by Fe, Cu-Coordinated ZIF-Derived Carbon Framework bifunctional catalyst (Fe/Cu@NC-x) fabricated via hydrothermal-calcination method for BPA removal. The physicochemical properties of Fe/Cu@NC-x were studied by X-ray diffraction, Transmission electron microscopy, Scanning electron microscopy, Raman Spectroscopy, Brunauer-Emmett Teller, and X-ray photoelectron spectroscopy. The effects of the Fe/Cu@NC-900 dosage and PMS concentration, initial pH, and co-existing anions on BPA degradation were evaluated. Under optimized factors (pH unadjusted, Fe/Cu@NC-900 = 0.2 g/L, and PMS = 0.75 g/L), the degradation efficiency of BPA can reach 98% after 30 min. In addition, the BPA degradation efficiency was different extents restrain by inorganic anions (SO42- > Cl- > HCO3- > NO3-). Furthermore, the free radicals (SO4-·, ·OH, and O2-·) and non-radical (1O2) contribute to rapid BPA degradation in Fe/Cu@NC-900/PMS system. This study presents a novel material with significant performance for the removal of organic pollutants.

Feasibility of micropollutants removal by solar-activated persulfate: Reactive oxygen species formation and influence on DBPs.

As a natural source of visible light and a type of renewable energy, solar energy is extensively used in the field of photochemistry. In this study, solar was employed to activate persulfate (PS) to degrade typical micropollutants. The removal kinetics of aspirin (ASA) and flunixin meglumine (FMME) in the solar/PS system were well fitted by pseudo-first-order models (R2 > 0.99). In the system containing 1.0 mM PS activated by solar irradiation at a fluence of 1.14 × 10-4 E·m-2·s-1, 72.6% and 97.5% of ASA and FMME were degraded, and the corresponding kinetic constants were 6.8-9.8 × 10-2 and 1.6-9.8 × 10-1 min-1, respectively. Qualitative and quantitative analyses of the reactive oxygen species (ROS) indicated that sulfate radical (SO4·-) played a major role in degradation, with the maximum contributions of 77.7% and 88.8% for the degradation of ASA and FMME, whereas the maximum contributions of hydroxyl radical (·OH) were only 11.6% and 6.5%, respectively. The contributions of singlet oxygen (1O2) were less than 15% at pH 5.5, but increased to 25.6% and 45.5% at pH 8.5, respectively. Solar/PS pre-oxidation increased disinfection byproducts (DBPs) (95.8% for trihalomethanes (THMs) and 47.9% for haloacetic acids (HAAs) at pH 7.0) after chlorination in deionized water, and an opposite trend was found in systems coexisting with natural organic matter (NOM). Residual PS after oxidation resulted in a high aquatic toxicity, with an inhibition rate of 18.70% to algae growth. Economic analysis showed that the electrical energy per order values of the system ranged from 23.5 to 86.5 kWh·m-3·order-1, indicating that the solar/PS system shows promise for practical applications.

High efficiency degradation of tetracycline by peroxymonosulfate activated with Fe/NC catalysts: Performance, intermediates, stability and mechanism.

Carbon-based catalysts have the advantages of biological cleaning, eco-friendly and cost-effective in water treatment. While, nitrogen doped biochar promotes the development of non-radical peroxymonosulfate (PMS) activation in environmental remediation. Thus, three-dimensional sponge-like porous Fe and N co-doped biochar (Fe/CN-30) with high catalytic activity for PMS activation was synthesized. In a wide pH range (1-11), the Fe/CN-30 catalyst can efficiently degrade tetracycline (TC) with a small amount of PMS. The non-radical pathways are prominent in the TC decomposition process according to the quenching experiments, electron paramagnetic resonance (EPR) and gas chromatograph-mass spectrometer (GC-MS) analysis, in which the contribution of high-valent iron-oxo species (Fe(IV) = O) was dominant. X-ray photoelectron spectroscopy and reaction kinetic experiments confirmed that the coordination sites of Fe and N in the Fe/CN-30 are the reactive centers for TC degradation. Moreover, the successive addition of low concentration PMS into the system was confirmed to favor the PMS utilization, and the high selectivity of the Fe/CN-30 was confirmed by the analysis of pollutant structure. Furthermore, by-products of TC degradation in the Fe/CN-30/PMS system and the possible TC degradation pathways were proposed via liquid chromatography-mass spectrometry (LC-MS). Therefore, this study dedicates to providing new insights into the non-radical pathway-catalyzed AOPs.

Zinc Oxide Nanoparticles Prime a Protective Immune Response in Galleria mellonella to Defend Against Candida albicans.

Purpose: Zinc oxide nanoparticles (ZnO-NPs) have exerted antimicrobial properties. However, there is insufficient evaluation regarding the in vivo antifungal activity of ZnO-NPs. This study aimed to investigate the efficacy and mechanism of ZnO-NPs in controlling Candida albicans in the invertebrate Galleria mellonella. Methods: Galleria mellonella larvae were injected with different doses of ZnO-NPs to determine their in vivo toxicity. Non-toxic doses of ZnO-NPs were chosen for prophylactic injection in G. mellonella followed by C. albicans infection. Then the direct in vitro antifungal effect of ZnO-NPs against C. albicans was evaluated. In addition, the mode of action of ZnO-NPs was assessed in larvae through different assays: quantification of hemocyte density, morphology observation of hemocytes, characterization of hemocyte aggregation and phagocytosis, and measurement of hemolymph phenoloxidase (PO) activity. Results: Zinc oxide nanoparticles were non-toxic to the larvae at relatively low concentrations (≤20 mg/kg). ZnO-NP pretreatment significantly prolonged the survival of C. albicans-infected larvae and decreased the fungal dissemination and burden in the C. albicans-infected larvae. This observation was more related to the activation of host defense rather than their fungicidal capacities. Specifically, ZnO-NP treatment increased hemocyte density, promoted hemocyte aggregation, enhanced hemocyte phagocytosis, and activated PO activity in larvae. Conclusion: Prophylactic treatment with lower concentrations of ZnO-NPs protects G. mellonella from C. albicans infection. The innate immune response primed by ZnO-NPs may be part of the reason for the protective effects. This study provides new evidence of the capacity of ZnO-NPs in enhancing host immunity and predicts that ZnO-NPs will be attractive for further anti-infection applications.

[Application of continuous renal replacement therapy in the treatment of neonates with inherited metabolic diseases].

OBJECTIVE: To study the efficacy and safety of continuous renal replacement therapy (CRRT) in the treatment of neonates with inherited metabolic diseases and hyperammonemia. METHODS: A retrospective analysis was performed on the medical records of neonates with inherited metabolic diseases and hyperammonemia who were hospitalized and underwent CRRT in the Department of Neonatology, Hunan Children's Hospital, from September 2016 to March 2020, including general conditions, clinical indices, laboratory markers, and adverse reactions. RESULTS: A total of 11 neonates were enrolled, with 7 boys (64%) and 4 girls (36%). The neonates had a mean gestational age of (38.9±0.8) weeks, a mean body weight of (3 091±266) g on admission, and an age of (5.7±2.0) days at the time of CRRT. The main clinical manifestations were vomiting (100%), convulsions (100%), and coma (55%), and the main primary disease was urea cycle disorder (55%). The mean duration of CRRT was (44±14) hours, the medium duration of coma before CRRT was 2 hours, and the total duration of coma was 10 hours. The patients had a mean hospital stay of (18±10) days and a survival rate of 73%, and 2 survivors had epilepsy. After treatment, all patients had significant reductions in blood ammonia, lactic acid, and K+ concentration (P < 0.001) and a significant increase in pH (P < 0.001). The incidence rate of adverse reactions was 27%. CONCLUSIONS: CRRT is safe and effective in the treatment of neonates with inherited metabolic diseases and hyperammonemia.