The first report of Apiotrichum mycotoxinivorans isolation from human cerebrospinal fluid.

Fungal infections due to Apiotrichum mycotoxinivorans are clinically rare. Here, we report a case of invasive blood and cerebrospinal fluid infection by Apiotrichum mycotoxinivorans in a girl with B-cell acute lymphoblastic leukemia. This is the first report of the isolation of Apiotrichum mycotoxinivorans from human cerebrospinal fluid. MRI features of meningitis caused by this fungus are presented. Three small isoquinoline alkaloids inhibited the growth of this rare fungus in vitro, providing a starting point for the application of natural products to treat this highly fatal fungal infection. Our case presentation confirms Apiotrichum mycotoxinivorans as a potential emerging pathogen in patients with hematological malignancy undergoing chemotherapy.

Operando Spectroscopic Analysis of Axial Oxygen-Coordinated Single-Sn-Atom Sites for Electrochemical CO2 Reduction.

Sn-based materials have been demonstrated as promising catalysts for the selective electrochemical CO2 reduction reaction (CO2RR). However, the detailed structures of catalytic intermediates and the key surface species remain to be identified. In this work, a series of single-Sn-atom catalysts with well-defined structures is developed as model systems to explore their electrochemical reactivity toward CO2RR. The selectivity and activity of CO2 reduction to formic acid on Sn-single-atom sites are shown to be correlated with Sn(IV)-N4 moieties axially coordinated with oxygen (O-Sn-N4), reaching an optimal HCOOH Faradaic efficiency of 89.4% with a partial current density (jHCOOH) of 74.8 mA·cm-2 at -1.0 V vs reversible hydrogen electrode (RHE). Employing a combination of operando X-ray absorption spectroscopy, attenuated total reflectance surface-enhanced infrared absorption spectroscopy, Raman spectroscopy, and 119Sn Mössbauer spectroscopy, surface-bound bidentate tin carbonate species are captured during CO2RR. Moreover, the electronic and coordination structures of the single-Sn-atom species under reaction conditions are determined. Density functional theory (DFT) calculations further support the preferred formation of Sn-O-CO2 species over the O-Sn-N4 sites, which effectively modulates the adsorption configuration of the reactive intermediates and lowers the energy barrier for the hydrogenation of *OCHO species, as compared to the preferred formation of *COOH species over the Sn-N4 sites, thereby greatly facilitating CO2-to-HCOOH conversion.

Unraveling the Electronic Structure and Dynamics of the Atomically Dispersed Iron Sites in Electrochemical CO2 Reduction.

Single-atom catalysts with a well-defined metal center open unique opportunities for exploring the catalytically active site and reaction mechanism of chemical reactions. However, understanding of the electronic and structural dynamics of single-atom catalytic centers under reaction conditions is still limited due to the challenge of combining operando techniques that are sensitive to such sites and model single-atom systems. Herein, supported by state-of-the-art operando techniques, we provide an in-depth study of the dynamic structural and electronic evolution during the electrochemical CO2 reduction reaction (CO2RR) of a model catalyst comprising iron only as a high-spin (HS) Fe(III)N4 center in its resting state. Operando 57Fe Mössbauer and X-ray absorption spectroscopies clearly evidence the change from a HS Fe(III)N4 to a HS Fe(II)N4 center with decreasing potential, CO2- or Ar-saturation of the electrolyte, leading to different adsorbates and stability of the HS Fe(II)N4 center. With operando Raman spectroscopy and cyclic voltammetry, we identify that the phthalocyanine (Pc) ligand coordinating the iron cation center undergoes a redox process from Fe(II)Pc to Fe(II)Pc-. Altogether, the HS Fe(II)Pc- species is identified as the catalytic intermediate for CO2RR. Furthermore, theoretical calculations reveal that the electroreduction of the Pc ligand modifies the d-band center of the in situ generated HS Fe(II)Pc- species, resulting in an optimal binding strength to CO2 and thus boosting the catalytic performance of CO2RR. This work provides both experimental and theoretical evidence toward the electronic structural and dynamics of reactive sites in single-Fe-atom materials and shall guide the design of novel efficient catalysts for CO2RR.

Operando Mössbauer Spectroscopic Tracking the Metastable State of Atomically Dispersed Tin in Copper Oxide for Selective CO2 Electroreduction.

Metastable state is the most active catalyst state that dictates the overall catalytic performance and rules of catalytic behaviors; however, identification and stabilization of the metastable state of catalyst are still highly challenging due to the continuous evolution of catalytic sites during the reaction process. In this work, operando 119Sn Mössbauer measurements and theoretical simulations were performed to track and identify the metastable state of single-atom Sn in copper oxide (Sn1-CuO) for highly selective CO2 electroreduction to CO. A maximum CO Faradaic efficiency of around 98% at -0.8 V (vs. RHE) over Sn1-CuO was achieved at an optimized Sn loading of 5.25 wt. %. Operando Mössbauer spectroscopy clearly identified the dynamic evolution of atomically dispersed Sn4+ sites in the CuO matrix that enabled the in situ transformation of Sn4+-O4-Cu2+ to a metastable state Sn4+-O3-Cu+ under CO2RR conditions. In combination with quasi in situ X-ray photoelectron spectroscopy, operando Raman and attenuated total reflectance surface enhanced infrared absorption spectroscopies, the promoted desorption of *CO over the Sn4+-O3 stabilized adjacent Cu+ site was evidenced. In addition, density functional theory calculations further verified that the in situ construction of Sn4+-O3-Cu+ as the true catalytic site altered the reaction path via modifying the adsorption configuration of the *COOH intermediate, which effectively reduced the reaction free energy required for the hydrogenation of CO2 and the desorption of the *CO, thereby greatly facilitating the CO2-to-CO conversion. This work provides a fundamental insight into the role of single Sn atoms on in situ tuning the electronic structure of Cu-based catalysts, which may pave the way for the development of efficient catalysts for high-selectivity CO2 electroreduction.

Three-Dimensional Hierarchical Seaweed-Derived Carbonaceous Network with Designed g-C3N4 Nanosheets: Preparation and Mechanism Insight for 4-Nitrophenol Photoreduction.

The development of g-C3N4-based photocatalysts with abundant active sites is of great significance for photocatalytic reactions. Herein, a smart and robust strategy was presented to fabricate three-dimensional (3D) g-C3N4 nanosheet-coated alginate-based hierarchical porous carbon (g-C3N4@HPC), including coating melamine on calcium alginate (CA) hydrogel beads, freeze-drying hydrogel beads as well as pyrolysis at high temperatures. The resulting photocatalyst possessed a significantly high surface area and a large amount of interconnected macropores compared with porous carbon without the melamine coating. The unique structural features could effectively inhibit the curling and agglomeration of g-C3N4 nanosheets, provide abundant photocatalytic active sites, and promote mass diffusion. Therefore, the g-C3N4@HPC composite exhibited remarkable photocatalytic activity and outstanding stability toward the photoreduction of 4-nitrophenol (4-NP) to 4-aminophenol (4-AP) by NaBH4 under natural sunlight and simulated visible-light irradiation (λ > 420 nm) using a 300 W xenon lamp. Moreover, the mechanism toward the photocatalytic reaction was extensively studied by quenching experiments and electron spin resonance (ESR) experiments. The results showed that active hydrogen species were able to be achieved by following a dual-channel pathway in the NaBH4 system, which included photocatalytic reduction of H+ ions and photocatalytic oxidation of BH4- ions. This work not only opens up a new way to design efficient photocatalysts for various reactions but also provides a reference for an in-depth study of the photoreduction mechanism.

Plasma Concentrations of Trace Elements Selenium and Cobalt During and After Coronary Artery Bypass Grafting Surgery.

Trace elements selenium (Se) and cobalt (Co) are essential in the human body, and a correlation between Se and cardiac surgery has been suggested. We investigated the plasma concentrations of Se and Co during and after coronary artery bypass grafting (CABG) surgery under cardiopulmonary bypass (CPB). From December 2019 to January 2020, preoperative plasma samples from isolated first-time CABG patients (n=20; 10 males, 10 females) were prospectively collected post-anesthesia and before CPB (T1), 45 min after CPB started (T2), 90 min after CPB started (T3), and postoperative days 1 (T4), and day 4 (T5). The plasma concentrations of Se and Co were measured. The Se concentration was significantly decreased at T2 (105.24±4.08 vs. 68.56±2.42 µg/L, p<0.001) and T3 (105.24±4.08 vs. 80.41±3.40 µg/L, p<0.001). The Co concentration was significantly decreased at T4 (0.35±0.19 vs. 0.26±0.13 µg/L, p<0.01) and T5 (0.35±0.19 vs. 0.23±0.11 µg/L, p<0.001). Five patients developed atrial fibrillation (AF); there was no other operative mortality or major morbidity. This is the first report of alterations of plasma Se and Co concentrations during and after CABG surgery. Our results may indicate that Se supplementation before or during CABG and Co supplementation after CABG may become necessary for patients undergoing CABG.

Association of Ang-2, vWF, and EVLWI with risk of mortality in sepsis patients with concomitant ARDS: A retrospective study.

BACKGROUND/PURPOSE: This study aimed to determine the potential effects of angiopoietin-2 (Ang-2), von Willebrand factor (vWF), and extravascular lung water index (EVLWI) on the risk of mortality in sepsis patients with concomitant acute respiratory distress syndrome (ARDS). METHODS: This retrospective study recruited 41 sepsis patients with concomitant ARDS from January 2015 to June 2018. Data of Ang-2 and vWF levels, EVLWI, and sequential organ failure assessment scores were collected at 0, 24, and 48 h after admission to the hospital. RESULTS: The length of intensive care unit stay (P = 0.041) and Acute Physiology and Chronic Health Evaluation-2 (APACHE II) score (P = 0.003) were associated with the risk of mortality. Furthermore, increased Ang-2 levels and EVLWI at 24 h and 48 h were associated with an increased risk of mortality. Moreover, the APACHE II score at hospital admission significantly predicted the risk of mortality (area under the curve [AUC], 0.834; 95% confidence interval [CI], 0.665-0.983). Finally, the models containing a combination of Ang-2 level and EVLWI at 24 h (AUC, 0.908; 95% CI, 0.774-0.996) and Ang-2 level and EVLWI at 48 h (AUC, 0.981; 95% CI, 0.817-1.000) had high diagnostic values for predicting risk of mortality. CONCLUSION: The study findings indicate that Ang-2 levels and EVLWI at 24 h and 48 h after admission are significantly associated with the risk of mortality.

Transmission dynamics of COVID-19 in Wuhan, China: effects of lockdown and medical resources.

Due to the strong infectivity of COVID-19, it spread all over the world in about three months and thus has been studied from different aspects including its source of infection, pathological characteristics, diagnostic technology and treatment. Yet, the influences of control strategies on the transmission dynamics of COVID-19 are far from being well understood. In order to reveal the mechanisms of disease spread, we present dynamical models to show the propagation of COVID-19 in Wuhan. Based on mathematical analysis and data analysis, we systematically explore the effects of lockdown and medical resources on the COVID-19 transmission in Wuhan. It is found that the later lockdown is adopted by Wuhan, the fewer people will be infected in Wuhan, and nevertheless it will have an impact on other cities in China and even the world. Moreover, the richer the medical resources, the higher the peak of new infection, but the smaller the final scale. These findings well indicate that the control measures taken by the Chinese government are correct and timely.

Antibiotic Resistance Profiles of Haemophilus influenzae Isolates from Children in 2016: A Multicenter Study in China.

BACKGROUND AND OBJECTIVE: Haemophilus influenzae (HI) is a common cause of community-acquired pneumonia in children. In many countries, HI strains are increasingly resistant to ampicillin and other commonly prescribed antibiotics, posing a challenge for effective clinical treatment. This study was undertaken to determine the antibiotic resistance profiles of HI isolates from Chinese children and to provide guidelines for clinical treatment. METHODS: Our Infectious Disease Surveillance of Pediatrics (ISPED) collaboration group includes six children's hospitals in different regions of China. The same protocols and guidelines were used by all collaborators for the culture and identification of HI. The Kirby-Bauer method was used to test antibiotic susceptibility, and a cefinase disc was used to detect ß-lactamase activity. RESULTS: We isolated 2073 HI strains in 2016: 83.9% from the respiratory tract, 11.1% from vaginal secretions, and 0.5% from blood. Patients with respiratory isolates were significantly younger than nonrespiratory patients (P < 0.001). Of all 2073 strains, 50.3% were positive for ß-lactamase and 58.1% were resistant to ampicillin; 9.3% were ß-lactamase-negative and ampicillin-resistant. The resistance rates of the HI isolates to trimethoprim-sulfamethoxazole, azithromycin, cefuroxime, ampicillin-sulbactam, cefotaxime, and meropenem were 71.1%, 32.0%, 31.2%, 17.6%, 5.9%, and 0.2%, respectively. CONCLUSIONS: More than half of the HI strains isolated from Chinese children were resistant to ampicillin, primarily due to the production of ß-lactamase. Cefotaxime and other third-generation cephalosporins could be the first choice for the treatment of ampicillin-resistant HI infections.

[Clinical characteristics and drug sensitivity in children with invasive pneumococcal disease: a multicenter study].

OBJECTIVE: To study the clinical characteristics, drug sensitivity of isolated strains, and risk factors of drug resistance in children with invasive pneumococcal disease (IPD). METHODS: The clinical characteristics and drug sensitivity of the isolated strains of 246 hospitalized children with IPD in nine grade A tertiary children's hospitals from January 2016 to June 2018 were analyzed. RESULTS: Of the 246 children with IPD, there were 122 males and 124 females. Their ages ranged from 1 day to 14 years, and among them, 68 (27.6%) patients were less than 1 year old, 54 (22.0%) patients were 1 to 2 years old, 97 (39.4%) patients were 2 to 5 years old, and 27 (11.0%) patients were 5 to 14 years old. Pneumonia with sepsis was the most common infection type (58.5%, 144/246), followed by bloodstream infection without focus (19.9%, 49/246) and meningitis (15.0%, 37/246). Forty-nine (19.9%) patients had underlying diseases, and 160 (65.0%) had various risk factors for drug resistance. The isolated Streptococcus pneumoniae strains were 100% sensitive to vancomycin, linezolid, moxifloxacin, and levofloxacin, 90% sensitive to ertapenem, ofloxacin, and ceftriaxone, but had a low sensitivity to erythromycin (4.2%), clindamycin (7.9%), and tetracycline (6.3%). CONCLUSIONS: IPD is more common in children under 5 years old, especially in those under 2 years old. Some children with IPD have underlying diseases, and most of the patients have various risk factors for drug resistance. Pneumonia with sepsis is the most common infection type. The isolated Streptococcus pneumoniae strains are highly sensitive to vancomycin, linezolid, moxifloxacin, levofloxacin, ertapenem, and ceftriaxone in children with IPD.

Epidemiology of Carbapenem-Resistant Enterobacteriaceae Infections: Report from the China CRE Network.

Carbapenem-resistant Enterobacteriaceae (CRE) infection is highly endemic in China, but estimates of the infection burden are lacking. We established the incidence of CRE infection from a multicenter study that covered 25 tertiary hospitals in 14 provinces. CRE cases defined as carbapenem-nonsusceptible Citrobacter freundii, Escherichia coli, Enterobacter cloacae, or Klebsiella pneumoniae infections during January to December 2015 were collected and reviewed from medical records. Antimicrobial susceptibility testing and carbapenemase gene identification were performed. Among 664 CRE cases, most were caused by K. pneumoniae (73.9%), followed by E. coli (16.6%) and E. cloacae (7.1%). The overall CRE infection incidence per 10,000 discharges was 4.0 and differed significantly by region, with the highest in Jiangsu (14.97) and the lowest in Qinghai (0.34). Underlying comorbidities were found in 83.8% of patients; the median patient age was 62 years (range, 45 to 74 years), and 450 (67.8%) patients were male. Lower respiratory tract infections (65.4%) were the most common, followed by urinary tract infection (16.6%), intra-abdominal infection (7.7%), and bacteremia (7.7%). The overall hospital mortality rate was 33.5%. All isolates showed nonsusceptibility to carbapenems and cephalosporins. The susceptibility rate of polymyxin B was >90%. Tigecycline demonstrated a higher susceptibility rate against E. coli than against K. pneumoniae (90.9% versus 40.2%). Of 155 clinical isolates analyzed, 89% produced carbapenemases, with a majority of isolates producing KPC (50%) or NDM (33.5%)-type beta-lactamases among K. pneumoniae and E. coli The incidence of CRE infection in China was 4.0 per 10,000 discharges. The patient-based disease burden in tertiary hospitals in China is severe, suggesting an urgent need to enhance infection control.

Alpha7 nicotinic acetylcholine receptor is required for blood-brain barrier injury-related CNS disorders caused by Cryptococcus neoformans and HIV-1 associated comorbidity factors.

BACKGROUND: Cryptococcal meningitis is the most common fungal infection of the central nervous system (CNS) in HIV/AIDS. HIV-1 virotoxins (e.g., gp41) are able to induce disorders of the blood-brain barrier (BBB), which mainly consists of BMEC. Our recent study suggests that α7 nAChR is an essential regulator of inflammation, which contributes to regulation of NF-κB signaling, neuroinflammation and BBB disorders caused by microbial (e.g., HIV-1 gp120) and non-microbial [e.g., methamphetamine (METH)] factors. However, the underlying mechanisms for multiple comorbidities are unclear. METHODS: In this report, an aggravating role of α7 nAChR in host defense against CNS disorders caused by these comorbidities was demonstrated by chemical [inhibitor: methyllycaconitine (MLA)] and genetic (α7(-/-) mice) blockages of α7 nAChR. RESULTS: As shown in our in vivo studies, BBB injury was significantly reduced in α7(-/-) mice infected with C. neoformans. Stimulation by the gp41 ectodomain peptide (gp41-I90) and METH was abolished in the α7(-/-) animals. C. neoformans and gp41-I90 could activate NF-κB. Gp41-I90- and METH-induced monocyte transmigration and senescence were significantly inhibited by MLA and CAPE (caffeic acid phenethyl ester, an NF-κB inhibitor). CONCLUSIONS: Collectively, our data suggest that α7 nAChR plays a detrimental role in the host defense against C. neoformans- and HIV-1 associated comorbidity factors-induced BBB injury and CNS disorders.

Mutational and structural characteristics of four novel heterozygous C-propeptide mutations in the proα1(I) collagen gene in Chinese osteogenesis imperfecta patients.

OBJECTIVE: Osteogenesis imperfecta (OI) with C-propeptide mutations in proα1(I) collagen gene are rarely reported. We report four novel C-propeptide mutations in COL1A1 gene from Chinese OI patients. METHODS: Clinical characteristics and radiographic findings were described for four OI patients with C-propeptide mutations in proα1(I) collagen gene. Mutations were identified by traditional DNA sequencing based on PCR. The locations of mutations were mapped, and in silico prediction was conducted to analyse their effects on protein structure. Histology studies of skin, bone and muscle tissues were performed. RESULTS: All four C-propeptide heterozygous mutations identified were in the COL1A1 gene. Heterozygous mutation of c.4021C>T (p.Q1341X) disrupted the chain recognition sequences and was found in patients with type IV OI. Mutations of c.3893C>A (p.T1298N) and c.3897C>A (p.C1299X) impeded the formation of disulphide bonds and were associated with type IV OI phenotype. Missense mutation of c.3835A>C (p.N1279H) disrupted Ca(2+) binding and led to a severe type III OI phenotype. In silico programs predicted damaging effects for the patients with type III OI and the creation of an exonic splicing enhancer hexamer sequence for the type IV patients. Expansion of the bone marrow cavity and disorganization of osteocyte alignment was evident in bone specimens; and muscle atrophy and enlargement of intramuscular connective tissue were found in muscle specimens. CONCLUSIONS: Four novel C-propeptide mutations in proα1(I) collagen gene were identified in Chinese OI patients, and their clinical severity ranged from moderate type IV to severe type III. In silico prediction of the mutation effect and histological characteristics of tissue specimens was in accordance with the OI phenotypes.

A novel deletion mutation and structural abnormality in the Bruton's tyrosine kinase gene identified in a Chinese patient with X-linked agammaglobulinemia.

BACKGROUND: X-linked agammaglobulinemia (XLA) is a heritable primary immune deficiency disorder caused by mutation of Bruton's tyrosine kinase (BTK) gene. The main clinical characteristics of XLA are recurrent respiratory tract infections and profoundly low serum immunoglobulin levels and B cells. METHODS: The clinical characteristics of a five-year-old Chinese boy with XLA were described. Mutations of BTK genes were identified by traditional DNA sequencing based on PCR. A three-dimensional model of the truncated BTK protein was constructed. RESULTS: Molecular analysis showed a point deletion of an adenine nucleotide at position 1427 (p.Tyr476Ser), which would cause a frameshift and premature termination at codon 484. Three-dimensional analysis showed that the truncated protein had lost the functional region for both ATP and substrate binding such that tyrosine kinase activity would be affected. CONCLUSIONS: The study identified a novel BTK mutation of one Chinese XLA patient. The truncated BTK model identified the loss of a functional domain.

Tracking emergence and outbreak of Klebsiella pneumoniae co-producing NDM-1 and KPC-2 after sulfamethoxazole-trimethoprim treatment: Insights from genetic analysis.

The co-production of KPC and NDM carbapenemases in carbapenem-resistant Klebsiella pneumoniae (CRKP) complicates clinical treatment and increases mortality rates. The emergence of KPC-NDM CRKP is believed to result from the acquisition of an NDM plasmid by KPC CRKP, especially under the selective pressure of ceftazidime-avibactam (CZA). In this study, a CRKP-producing KPC-2 (JNP990) was isolated from a patient at a tertiary hospital in Shandong Province, China. Following sulfamethoxazole-trimethoprim (SXT) treatment, the isolate evolved into a strain that co-produces KPC and NDM (JNP989), accompanied by resistance to SXT (minimum inhibitory concentration >2/38 µg/mL) and CZA (dd ≤14 mm). Whole-genome sequencing and S1 nuclease pulsed-field gel electrophoresis revealed that JNP989 acquired an IncC plasmid (NDM plasmid) spanning 197 kb carrying sul1 and blaNDM-1 genes. The NDM plasmid could be transferred successfully into Escherichia coli J53 at a conjugation frequency of (8.70±2.47) × 10-4. The IncFⅡ/IncR plasmid carrying the blaKPC-2 gene in JNP990 could only be transferred in the presence of the NDM plasmid at a conjugation frequency of (1.93±0.41) × 10-5. Five CRKP strains with the same resistance pattern as JNP989, belonging to the same clone as JNP989, with sequence type 11 were isolated from other patients in the same hospital. Two strains lost resistance to CZA due to the loss of the blaNDM-1-carrying fragment mediated by insertion sequence 26. Plasmid stability testing indicated that the IncC plasmid was more stable than the blaNDM-1 genes in the hosts. This study describes the evolution of KPC-NDM CRKP and its spread in hospitalized patients following antibiotic treatment, highlighting the severity of the spread of resistance.

Epidemiology and antifungal susceptibility of fungal infections from 2018 to 2021 in Shandong, eastern China: A report from the SPARSS program.

PURPOSE: We analyzed the pathogenic fungal epidemiology and antifungal susceptibility from 2018 to 2021 in Shandong Province, China, to provide the basis for empiric antifungal therapy. METHODS: Fungal isolates were collected from 54 hospitals in Shandong province from 2018 to 2021 through the Shandong Province Pediatric bacterial & fungal Antimicrobial Resistance Surveillance System (SPARSS), WHONET v5.6 and SPSS software v20.0 were used for statistical analysis. RESULTS: A total of 15,348 strains of fungi were collected, with Candida accounting for 78.25 %, followed by Aspergillus at 15.45 %, and other species at 6.27 %. Candida albicans was the predominant Candida species, but more than half of the Candida isolates were non-albicans species, with C. tropicalis being the most dominant (22.74 %), followed by C. glabrata (17.50 %) and C. parapsilosis (11.02 %). The composition of fungi varied significantly among different age groups. Children had a higher proportion of C. albicans (47.30 %) compared to non-children (32.06 %). The non-wild-type phenotype rate of Candida for Amphotericin B was less than 3 %, while Cryptococcus neoformans was 16.67 %. In addition, less than 6 % of C. albicans and C. parapsilosis were resistant to fluconazole and voriconazole, and 96.30 % of C. glabrata were SDD to fluconazole. We also found that 80.56 % of C. glabrata and 83.70 % of C. krusei were voriconazole WT/susceptibility phenotype. However, the susceptibility rates of C. tropicalis to fluconazole/voriconazole decreased from 70.40 %/46.40 % in 2018 to 62.30 %/35.20 % in 2021. The comprehensive susceptibility rate to fluconazole of C. albicans, C. tropicalis, C. parapsilosis and C. glabrata isolated from the blood has decreased from 69.36 % to 56.62 %. CONCLUSIONS: The study reveals that the composition and antifungal susceptibility of pathogenic fungi in Shandong Province differ from other regions. Moreover, the resistance to azoles is more severe, especially in C. tropicalis. These findings indicate the need for region-specific antifungal treatment strategies to combat fungal infections effectively.

Vacancy Defects Inductive Effect of Asymmetrically Coordinated Single-Atom Fe─N3 S1 Active Sites for Robust Electrocatalytic Oxygen Reduction with High Turnover Frequency and Mass Activity.

The development of facile, efficient synthesis method to construct low-cost and high-performance single-atom catalysts (SACs) for oxygen reduction reaction (ORR) is extremely important, yet still challenging. Herein, an atomically dispersed N, S co-doped carbon with abundant vacancy defects (NSC-vd) anchored Fe single atoms (SAs) is reported and a vacancy defects inductive effect is proposed for promoting electrocatalytic ORR. The optimized catalyst featured of stable Fe─N3 S1 active sites exhibits excellent ORR activity with high turnover frequency and mass activity. In situ Raman, attenuated total reflectance surface enhanced infrared absorption spectroscopy reveal the Fe─N3 S1 active sites exhibit different kinetic mechanisms in acidic and alkaline solutions. Operando X-ray absorption spectra reveal the ORR activity of Fe SAs/NSC-vd catalyst in different electrolyte is closely related to the coordination structure. Theoretical calculation reveals the upshifted d band center of Fe─N3 S1 active sites facilitates the adsorption of O2 and accelerates the kinetics process of *OH reduction. The abundant vacancy defects around the Fe─N3 S1 active sites balance the OOH* formation and *OH reduction, thus synergetically promoting the electrocatalytic ORR process.

Epidemiology of human respiratory viruses in children with acute respiratory tract infections in Jinan, China.

The viral etiologies of UTRIs and LTRIs in children in Jinan city were investigated between July 2009 and June 2010. Nasal and throat swabs were collected from 397 children with URTIs and bronchoalveolar lavage fluid specimens were collected from 323 children with LRTIs. RT-PCR/PCR was used to examine all samples for IFV, PIV, RSV, RV, hMPV, HBoV, CoV, ADV, RSV, and EV. Viral pathogens were detected in 47.10% of URTI samples and 66.57% samples, and the incidence of viral coinfection was 5.29% and 21.05%, respectively. IFV was the most common virus in URTIs, with a detection rate of 19.40%, followed by PIV (10.83%), RV (10.58%), and EV (6.30%). For LRTIs, PIV and RV were both detected in 27% of samples, followed by RSV (9.91%), HBoV (8.36%), IFV (5.57%), and hMPV (5.57%). RSV and HBoV were more prevalent in the youngest children of no more than six months. Meanwhile, RV, PIV, and RSV were the most frequent viruses combined with bacterial pathogens in LRTIs. In conclusion, the spectrum of respiratory virus infections in URTIs and LRTIs differed in terms of the most common pathogens, seasonal distribution, and coinfection rate.

High specificity of metagenomic next-generation sequencing using protected bronchial brushing sample in diagnosing pneumonia in children.

Background: Lower respiratory tract infections are the leading cause of morbidity and mortality in children worldwide. Timely and accurate pathogen detection is crucial for proper clinical diagnosis and therapeutic strategies. The low detection efficiency of conventional methods and low specificity using respiratory samples seriously hindered the accurate detection of pathogens. Methods: In this study, we retrospectively enrolled 1,032 children to evaluate the performance of metagenomics next-generation sequencing (mNGS) using bronchoalveolar lavage fluid (BALF) sample and protected bronchial brushing (BB) sample in diagnosing pneumonia in children. In addition, conventional tests (CTs) were also performed. Results: The specificity of BB mNGS [67.3% (95% CI 58.6%-75.9%)] was significantly higher than that of BALF mNGS [38.5% (95% CI 12.0%-64.9%)]. The total coincidence rate of BB mNGS [77.6% (95% CI 74.8%-80.5%)] was slightly higher than that of BALF mNGS [76.5% (95% CI 68.8%-84.1%)] and CTs [38.5% (95% CI 35.2%-41.9%)]. During the epidemics of Mycoplasma pneumoniae, the detection rate of M. pneumoniae in the >6-year group (81.8%) was higher than that in the 3-6-year (78.9%) and <3-year groups (21.5%). The highest detection rates of bacteria, fungi, and viruses were found in the <3-year, >6-year, and 3-6-year groups, respectively. mNGS detection should be performed at the duration of 5-7 days after the start of continuous anti-microbial therapy or at the duration of 6-9 days from onset to mNGS test. Conclusions: This is the first report to evaluate the performance of BB mNGS in diagnosing pulmonary infections in children on a large scale. Based on our findings, extensive application of BB mNGS could be expected.