Biological pretreatment with white rot fungi for preparing hierarchical porous carbon from Banlangen residues with high performance for supercapacitors and dye adsorption.

White rot fungi possess superior infiltrability and biodegradability on lignocellulosic substrates, allowing them to form tailored microstructures which are conducive to efficient carbonization and chemical activation. The present research employed white rot fungus pretreatment as a viable approach for preparing porous carbon from Banlangen residues. The resultant F-A-BLGR-PC prepared by pretreating Banlangen residues with white rot fungi followed by carbonization and activation has a hierarchical porous structure with a high specific surface area of 898 m2 g-1, which is 43.4% greater than that of the unprocessed sample (R-BLGR-PC). When used as an electrode for supercapacitors, the F-A-BLGR-PC demonstrated a high specific capacitance of 308 F g-1 at 0.5 A g-1 in 6 M KOH electrolyte in three-electrode configuration. Moreover, the F-A-BLGR-PC based symmetric supercapacitor device achieved a superb cyclic stability with no obvious capacitance decay after 20,000 cycles at 5 A g-1 in 1 M Na2SO4 electrolyte. Additionally, the F-A-BLGR-PC sample was found to be an ideal adsorbent for removing methyl orange (MO) from water, exhibiting an adsorption ability of 173.4 mg g-1 and a maximum removal rate of 86.6%. This study offers a promising method for the preparation of a porous carbon with a high specific surface area in a biological way using white rot fungi pretreatment, and the derived carbon can not only be applied in energy storage but also in environmental remediation, catalysis, and so on.

Synergetic Photodynamic-Photothermal-Chemotherapy Dual Targeting Nanoplatform Effective Against Breast Cancer in-Mice Model.

Introduction: Combined multimodal therapy for breast cancer is a promising therapeutic approach to increase treatment efficacy and reduce systemic toxicity. The present study aimed to develop a novel multifunctional drug release nanoplatform based on RGD-conjugated hyaluronic acid (HA)-functionalized copper sulfide (CuS) for activatable dual-targeted synergetic therapy against cancer. Methods: The pH and NIR-responsive dual-targeting nanoplatform CuS:Ce6@HA:DOX@RGD was prepared, characterized, and evaluated for its stability and photodynamic and photothermal properties. The loading and release of the drug were measured at different pH values with or without laser radiation using the dialysis method. The cellular uptake of the platform specifically by the tumor cells treated with different formulations was investigated through fluorescence imaging. The in vitro and in vivo biosafety levels were assessed systematically. Finally, the antitumor efficiencies against breast cancer were assessed via in vitro and in vivo experiments. Results: The spheroid CuS:Ce6@HA:DOX@RGD exhibited remarkable stability and monodispersity in solution. The photosensitive CuS and Ce6 could simultaneously absorb the near-infrared light efficiently to convert NIR light to fatal heat and to generate reactive oxygen species. The CuS:Ce6@HA:DOX@RGD dissociated under an acid environment, causing the release of DOX into the tumor to accelerate upon laser irradiation. The CuS:Ce6@HA:DOX@RGD exhibited target-specific and strong binding ability via a synergic CD44/αvß3 receptor-mediated bimodal targeting, which led to improved therapeutic efficacy. The tumor growth was effectively inhibited using synergetic photodynamic/photothermal/chemo therapy. No evident systemic toxicity was noted during treatment. Conclusion: The newly prepared CuS:Ce6@HA:DOX@RGD has great potential as an activatable theranostic nanoplatform for efficient dual-targeted synergistic therapy against breast cancer.

Next-Generation Rapid and Ultrasensitive Lateral Flow Immunoassay for Detection of SARS-CoV-2 Variants.

The coronavirus disease 2019 (COVID-19) pandemic highlighted the need for rapid and accurate viral detection at the point-of-care testing (POCT). Compared with nucleic acid detection, lateral flow immunoassay (LFIA) is a rapid and flexible method for POCT detection. However, the sensitivity of LFIA limits its use for early identification of patients with COVID-19. Here, an innovative surface-enhanced Raman scattering (SERS)-LFIA platform based on two-dimensional black phosphorus decorated with Ag nanoparticles as important antigen-capturing and Raman-signal-amplification unit was developed for detection of SARS-CoV-2 variants within 5-20 min. The novel SERS-LFIA platform realized a limit of detection of 0.5 pg/mL and 100 copies/mL for N protein and SARS-CoV-2, demonstrating 1000 times more sensitivity than the commercial LFIA strips. It could reliably detect seven different SARS-CoV-2 variants with cycle threshold (Ct) < 38, with sensitivity and specificity of 97 and 100%, respectively, exhibiting the same sensitivity with q-PCR. Furthermore, the detection results for 48 SARS-CoV-2-positive nasopharyngeal swabs (Ct = 19.8-38.95) and 96 negative nasopharyngeal swabs proved the reliability of the strips in clinical application. The method also had good specificity in double-blind experiments involving several other coronaviruses, respiratory viruses, and respiratory medications. The results showed that the innovative SERS-LFIA platform is expected to be the next-generation antigen detection technology. The inexpensive amplification-free assay combines the advantages of rapid low-cost POCT and highly sensitive nucleic acid detection, and it is suitable for rapid detection of SARS-CoV-2 variants and other pathogens. Thus, it could replace existing antigens and nucleic acids to some extent.

Genetic diversity of norovirus associated with outbreaks in school children with acute gastroenteritis in Changzhou, China, 2018-2019.

Norovirus is one of the major causes of outbreaks and sporadic cases of acute gastroenteritis in school children. Obtaining local genotype diversity information regarding norovirus is important for developing and evaluating prevention strategies of the transmission of this virus in school children. Clinical specimens, obtained from the routine acute gastroenteritis surveillance network from 2018 to 2019, were primarily tested using commercial real-time PCR Kit. Samples with Ct value less than 25 were selected and used for complete genome sequencing and those with Ct value between 25 and 30 were selected and used for he partial VP1 and RdRp regions sequencing. Phylogenetic trees of the viral genome were constructed by using the neighbor-joining method with bootstrap analysis of 1000 replicates in MEGA 6.0. Epidemiological surveillance of acute intestinal infections (n = 384) showed high-level detection (73.18%) of human norovirus in school endemic acute gastroenteritis events in Changzhou, with obvious epidemic characteristics in autumn and winter. Through genotyping, it was found that 93.12% of norovirus were GII, including GII.2, GII.3, GII.4, GII.6, GII.7, and GII.17. By October 2019, two norovirus genotypes, GII.4[P31] and GII.17[P17], became the preponderant epidemic strains. Phylogenetic analysis of the new GII.17[P17] complete genomes showed close relationship with Miyagi strain identified in Japan in 2015, and GII.4[P31] showed close relationship with Jinan strain indentified in China in 2017. The study highlights the emerging role of GII.4[P31] and GII.17[P17] in causing endemic acute gastroenteritis outbreaks at school children, in Changzhou, China in 2019.

Genomic surveillance of coxsackievirus A10 reveals genetic features and recent appearance of genogroup D in Shanghai, China, 2016-2020.

Coxsackievirus A10 (CVA10) is one of the major causative agents of hand, foot and mouth disease (HFMD). To investigate the epidemiological characteristics as well as genetic features of CVA10 currently circulating in Shanghai, China, we collected a total of 9,952 sporadic HFMD cases from January 2016 to December 2020. In the past five years, CVA10 was the fourth prevalent causatives associated with HFMD in Shanghai and the overall positive rate was 2.78%. The annual distribution experienced significant fluctuations over the past five years. In addition to entire VP1 sequencing, complete genome sequencing and recombination analysis of CVA10 isolates in Shanghai were further performed. A total of 64 near complete genomes and 11 entire VP1 sequences in this study combined with reference sequences publicly available were integrated into phylogenetic analysis. The CVA10 sequences in this study mainly belonged to genogroup C and presented 91%-100% nucleotide identity with other Chinese isolates based on VP1 region. For the first time, our study reported the appearance of CVA10 genogroup D in Chinese mainland, which had led to large-scale outbreaks in Europe previously. The recombination analysis showed the recombination break point located between 5,100 nt and 6,700 nt, which suggesting intertypic recombination with CVA16 genogroup D. To conclusion, CVA10 genogroup C was the predominant genogroup in Shanghai during 2016-2020. CVA10 recombinant genogroup D was firstly reported in circulating in Chinese mainland. Continuous surveillance is needed to better understand the evolution relationships and transmission pathways of CVA10 to help to guide disease control and prevention.

Evaluation of Biological Pretreatment of Wormwood Rod Reies with White Rot Fungi for Preparation of Porous Carbon.

In this work, the wormwood rod residues are pretreated with white rot fungi as the precursor to preparing porous carbon following a simple carbonization and activation process (denoted herein as FWRA sample). The FWRA sample possesses abundant hierarchical pores structure with high specific surface area (1165.7 m2 g-1) and large pore volume (1.02 cm3 g-1). As an electrode for supercapacitors, the FWRA sample offers a high specific capacitance of 443.2 F g-1 at 0.5 A g-1 and superb rate ability holding a specific capacitance of 270 F g-1 at 100 A g-1 in 6 M KOH electrolyte. The corresponding symmetrical capacitor has a superb cyclic stability with a low specific capacitance decay rate of 0.4% after 20,000 cycles at 5 A g-1 in 1 M Na2SO4 electrolyte. Moreover, measurements revealed that when used as adsorbent, the FWRA sample is ideal for removing methyl orange (MO) from water, exhibiting a superior adsorption ability of 260.8 mg g-1. Therefore, this study is expected to provide a simple and environmentally friendly technique for the generation of value-added and functional porous carbon materials from Chinese medicinal herbal residues, thus offering promising candidates for broad application areas.

Re-utilization of Chinese medicinal herbal residue: waste wormwood rod-derived porous carbon as a low-cost adsorbent for methyl orange removal.

A cost-effective approach was applied to prepare porous carbon samples by the simple carbonization of wormwood rod followed by salt activator (NaCl) activation. The effect of preparation parameters on the characteristics of the wormwood rod-based porous carbons (WWRs) were studied. The properties of these samples were investigated by SEM, BET surface area, X-ray diffraction, FT-IR spectra and X-ray photoelectron spectrometer. The prepared WWRs were applied as new adsorbent materials to remove methyl orange (MO). The experimental results indicated that WWR-800 activated at 800 °C possesses the best adsorption performance. Several factors that affected the adsorption property of the system such as the solution pH, dosing of adsorbent, initial dye concentration and ionic strength were examined. In addition, the thermodynamic parameters and kinetic parameters of MO with WWR-800 were studied. The results indicated that the adsorption of MO on WWR-800 was an endothermic process and non-spontaneous under standard conditions. The maximum equilibrium adsorption capacity of MO on WWR-800 was 454.55 mg/g. After five adsorption/desorption cycles, the adsorption capacity of MO on WWR-800 remained at 94%, which indicated that wormwood rod-based porous carbon possessed good reusability.

Influenza A Virus (H1N1) Infection Induces Glycolysis to Facilitate Viral Replication.

Viruses depend on host cellular metabolism to provide the energy and biosynthetic building blocks required for their replication. In this study, we observed that influenza A virus (H1N1), a single-stranded, negative-sense RNA virus with an eight-segmented genome, enhanced glycolysis both in mouse lung tissues and in human lung epithelial (A549) cells. In detail, the expression of hexokinase 2 (HK2), the first enzyme in glycolysis, was upregulated in H1N1-infected A549 cells, and the expression of pyruvate kinase M2 (PKM2) and pyruvate dehydrogenase kinase 3 (PDK3) was upregulated in H1N1-infected mouse lung tissues. Pharmacologically inhibiting the glycolytic pathway or targeting hypoxia-inducible factor 1 (HIF-1), the central transcriptional factor critical for glycolysis, significantly reduced H1N1 replication, revealing a requirement for glycolysis during H1N1 infection. In addition, pharmacologically enhancing the glycolytic pathway further promoted H1N1 replication. Furthermore, the change of H1N1 replication upon glycolysis inhibition or enhancement was independent of interferon signaling. Taken together, these findings suggest that influenza A virus induces the glycolytic pathway and thus facilitates efficient viral replication. This study raises the possibility that metabolic inhibitors, such as those that target glycolysis, could be used to treat influenza A virus infection in the future.

A SARS-CoV-2 neutralizing antibody with extensive Spike binding coverage and modified for optimal therapeutic outcomes.

COVID-19 pandemic caused by SARS-CoV-2 constitutes a global public health crisis with enormous economic consequences. Monoclonal antibodies against SARS-CoV-2 can provide an important treatment option to fight COVID-19, especially for the most vulnerable populations. In this work, potent antibodies binding to SARS-CoV-2 Spike protein were identified from COVID-19 convalescent patients. Among them, P4A1 interacts directly with and covers majority of the Receptor Binding Motif of the Spike Receptor-Binding Domain, shown by high-resolution complex structure analysis. We further demonstrate the binding and neutralizing activities of P4A1 against wild type and mutant Spike proteins or pseudoviruses. P4A1 was subsequently engineered to reduce the potential risk for Antibody-Dependent Enhancement of infection and to extend its half-life. The engineered antibody exhibits an optimized pharmacokinetic and safety profile, and it results in complete viral clearance in a rhesus monkey model of COVID-19 following a single injection. These data suggest its potential against SARS-CoV-2 related diseases.

Neonatal hand, foot, and mouth disease due to coxsackievirus A6 in Shanghai.

BACKGROUND: Evidence of hand, foot, and mouth disease (HFMD) in neonates is limited. The aim of this study was to evaluate the clinical symptoms, pathogens, possible transmission routes, and prognosis of neonatal HFMD in Shanghai. METHODS: This was a case-control study based on the HFMD registry surveillance system. All neonates and infected family members were enrolled between 2016 and 2017 in Shanghai. Neonates with HFMD were followed for at least half a year. Detailed questionnaires, medical history, and physical examination were recorded. Routine blood examination, liver and renal function, immunophenotypes of peripheral blood lymphocytes (CD3, CD4, and CD8 T-cells; NK cells), immunoglobulin (Ig) M, IgG, and IgA, and cytokine interleukin (IL-1ß, IL-2R, IL-6, IL-8, IL-10, and TNF-α) levels were measured. All rectal swab specimens were collected and genotyped for enterovirus, and phylogenetic analysis based on the VP1 sequences of coxsackievirus A6 (CV-A6) was performed to investigate molecular and evolutionary characteristics. T-test or nonparametric test was used to evaluate the differences. Logistic analysis was applied to calculate the risk of clinical manifestations in the group of HFMD neonates and their paired siblings. RESULTS: There were 16 neonates among the 12,608 diagnosed patients with HFMD, accounting for 0.13%. All neonatal infections were transmitted by other members of the family, mainly the elder siblings, and were caused by CV-A6. CV-A6 was the emerging and predominant causative agent of HFMD in Shanghai. None of the neonates with HFMD experienced fever, onychomadesis, or severe complications. However, two elder sibling patients showed lethargy, and one developed hypoperfusion. In the elder siblings with HFMD, the proportion of white blood cells was generally higher than in neonates with HFMD. The immunologic function of the neonates with HFMD was basically normal. The levels of inflammatory markers were higher in both neonates and elder siblings with HFMD compared to age-matched controls. The clinical symptoms receded about 1 week after onset. None of the neonates had sequelae. CONCLUSIONS: In our study, CV-A6 infection in neonates was benign, but had the character of family clustering. Due to the two-child policy in China, elder siblings may be the main route of HFMD transmission.

The activation of antiviral RNA interference not only exists in neural progenitor cells but also in somatic cells in mammals.

The RNA interference (RNAi) pathway directs an important antiviral immunity mechanism in plants and invertebrates. Recently, we and others have demonstrated that the antiviral RNAi response is also conserved in mammals, at least to five distinct RNA viruses, including Zika virus (ZIKV). ZIKV may preferentially infect neuronal progenitor cells (NPCs) in the developing foetal brain. Ex vivo ZIKV infection induces RNAi-mediated antiviral response in human NPCs, but not in the more differentiated NPCs or somatic cells. However, litter is known about the in vivo property or function of the virus-derived small-interfering RNAs (vsiRNAs) targeting ZIKV. Here we report a surprising observation: different from ex vivo observations, viral small RNAs (vsRNAs) targeting ZIKV were produced in vivo upon infection in both central neuron system (CNS) and muscle tissues. In addition, our findings demonstrate the production of canonical vsiRNAs in murine CNS upon antiviral RNAi activation by Sindbis virus (SINV), suggesting the possibility of antiviral immune strategy applied by mammals in the CNS.

Astragaloside IV attenuates IL-1ß secretion by enhancing autophagy in H1N1 infection.

Excessive secretion of inflammatory factors (cytokine storm) plays a significant role in H1N1-induced acute pneumonia, and autophagy acts as a cell-intrinsic mechanism to regulate inflammation. Astragaloside IV (AS-IV), originating from the astragalus root, possesses multiple pharmacological activities, such as anti-inflammation. However, the influences of AS-IV on H1N1-induced autophagy and inflammation have remained elusive. It has been reported that H1N1 infection leads to the accumulation of autophagosomes but obstructs autophagosomes incorporating into lysosomes, whereas the present study showed that AS-IV enhanced autophagy activation in H1N1 infection. Furthermore, we found that AS-IV promoted H1N1-triggered formation of autophagosomes and autolysosomes. Additionally, it was noted that AS-IV did not affect viral replication, mRNA level of interleukin-1 beta (IL-1ß) and pro-IL-1ß protein level, but significantly decreased secretion of IL-1ß, and chloroquine (CQ, as an inhibitor of autophagy) increased secretion of IL-1ß in H1N1 infection. In conclusion, AS-IV stimulates the formation of autophagosomes and the fusion of autophagosomes and lysosomes in H1N1 infection and may lead to decreased IL-1ß secretion.

Genome Analysis of A Novel Recombinant Human Adenovirus Type 1 in China.

Human adenovirus (HAdV) group C are the common etiologic in infants with severe acute respiratory infections (SARI). In the study, we report that a novel recombinant HAdV-C group strain (SH2016) was isolated from an infant with SARI in Shanghai in Feb. 4, 2016. The whole-genome sequence of SH2016 strain was generated and compared to other HAdV genomes publicly available. The strain SH2016 genome contains 35,946 nucleotides and coded 40 putative proteins, which was divided into 11 regions. RDP and phylogenetic analyses of the complete genome showed that the SH2016 strain was arranged into a novel subtype and might be recombined with HAdV-1 and HAdV-2. Our finding indicated that the frequent recombination among the HAdV-C group played an important role in driving force for polymorphism of human HAdV-C group prevalent in Shanghai, China. Further epidemiological surveillance of HAdV-C group is necessary to explore whether the novel HAdV-C group will maintain long-term stability. And the pathogenicity and clinical characteristics of the novel HAdV-C group member should be done more.

The coordinating role of the human norovirus minor capsid protein VP2 is essential to functional change and nuclear localization of the major capsid protein VP1.

Global outbreaks of norovirus (NOV) gastroenteritis are associated with the most prevalent genotype, GII.4. Mutations in the protruding domain 2 (P2 domain) of the norovirus major capsid protein (VP1) result in the emergence of various NOV variants, however, it is unclear whether the minor capsid protein (VP2) also affects the generation of VP1 variants. In this study, using a human 293T expression system, we investigated the interactions of VP1 and VP2 of three GII.4 strains, focusing on the changes in expression and cellular localization. We found that co-transfection with VP1 and VP2 leads to a significant increase in expression of both proteins compared to that in cells transfected with VP1 or VP2 alone. In contrast to VP1 expressed in the absence of VP2, which was dispersed throughout the cytosol, VP2 expressed in the absence of VP1 was found to be located in the nucleus. This could be attributed to a predicted specific nuclear localization signal found in this gene. When both proteins were expressed, VP1 was found together with VP2 in the nucleus. These results thus suggest that the VP2 of GII.4 NOVs affects the function and cellular location of VP1 and that, with the cooperation of VP2, VP1 could play a critical role in affecting cell functions by impairing the downstream transcriptional signaling and chromatin remodeling in the cell nuclei.

Influenza A virus (H1N1) triggers a hypoxic response by stabilizing hypoxia-inducible factor-1α via inhibition of proteasome.

Virus reprogramming of host cellular function is a critical strategy for viral survival and replication. A better understanding of virus-host interaction may provide new potential avenues for the treatment of viral diseases. It has been reported that hypoxia-inducible factor-1 (HIF-1) pathway is activated by a range of pathogens via different mechanisms, but the impact of Influenza A virus on HIF-1 signaling is still unclear. In this study, we observed H1N1 infection stabilized HIF-1α under normoxic conditions. In detail, H1N1 did not increase HIF-1α mRNA transcription, nor impaired posttranslational prolyl hydroxylation or ubiquitination of HIF-1α, but inhibited the function of proteasome, resulting in HIF-1α accumulation. Furthermore, a decreased expression of factor inhibiting HIF-1 (FIH-1), which hydroxylates asparagine 803 within HIF-1α to repress HIF-1α activity, was seen after H1N1 infection. Taken together, these findings reveal a previously unrecognized mechanism of viral activation of the HIF-1 pathway, resembling a hypoxic response in normoxia.

Study of interaction between citrate-coated silver nanoparticles and gamma globulin using spectroscopic method.

Communicated by Ramaswamy H. Sarma.

Facile construction of a hyperbranched poly(acrylamide) bearing tetraphenylethene units: a novel fluorescence probe with a highly selective and sensitive response to Zn2.

Thermo-responsive hyperbranched copoly(bis(N,N-ethyl acrylamide)/(N,N-methylene bisacrylamide)) (HPEAM-MBA) was synthesized by using reversible addition-fragmentation chain-transfer polymerization (RAFT). Interestingly, the zinc ion (Zn2+) was found to have a crucial influence on the lowest critical solution temperature (LCST) of the thermo-responsive polymer. The tetraphenylethylene (TPE) unit was then introduced onto the backbone of the as-prepared thermo-responsive polymer, which endows a Zn2+-responsive "turn-off" effect on the fluorescence properties. The TPE-bearing polymer shows a highly specific response over other metal ions and the "turn-off" response can even be tracked as the concentration of Zn2+ reduces to 2 × 10-5 M. The decrement of fluorescence intensity was linearly dependent on the concentration of Zn2+ in the range of 4-18 µmol L-1. The flexible, versatile and feasible approach, as well as the excellent detection performance, may generate a new type of Zn2+ probe without the tedious synthesis of the moiety bearing Zn2+ recognition units.

Analysis of viral infection and biomarkers in patients with acute exacerbation of chronic obstructive pulmonary disease.

OBJECTIVE: To investigate viral infection in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in Shanghai, and to analyze the clinical characteristics and biomarkers in viral infection. METHODS: This study included all consecutive patients who were admitted for a diagnosis of AECOPD during June 2013 to May 2015. Thirty-one stable COPD patients and 31 healthy controls were also recruited. Oropharyngeal samples were assessed, PCR for respiratory viruses were performed. Patients were divided into AECOPD virus-positive (+) group and AECOPD virus-negative (-) group according to viral detection. Luminex was used to detect the concentrations of inflammatory cytokines in the serum. RESULTS: A total of 264 patients were included with a mean age of 75 ± 0.5 years. There were 72 patients (27.3%) identified with viral positive, of whom two patients were detected with double viral infections (FluA + FluB and RSVA + HRV, respectively). The rate of viral detection was associated with season, highest in winter. Comparisons of clinical characteristics showed no significant differences between AECOPD virus+ group and AECOPD virus- group. However, serum concentrations of interferon-inducible protein-10 (IP-10) and interferon-gamma (IFN-γ) in virus+ AECOPD patients were significantly higher than those in the virus- AECOPD, stable COPD and healthy control groups (P < .05). CONCLUSION: Viral infection was an important pathogen in AECOPD patients; the most common viruses included FluA, HRV and FluB. It was very difficult to diagnose the viral infection according to clinical characteristics. The increased of serum IP-10 and IFN-γ levels might be value to indicate viral infection in AECOPD.