Constructing Nano-Interlayer Inhibiting Interfacial Degradation toward High-Voltage PEO-Based All-Solid-State Lithium Batteries.

The interfacial instability between PEO-based solid electrolyte (SPE) and high-voltage cathode materials inhibits the longevity of high-energy-density all-solid-state polymer lithium metal batteries (ASSPLBs). Herein, for the first time it is demonstrated, that contact loss caused by gas generation from interfacial side reactions between the high-voltage cathode and solid polymer electrolyte (SPE) can also arise in ASSPLBs. To alleviate the interfacial side reactions, a LiNb0.6Ti0.5O3 (LNTO) layer is well coated on LiNi0.83Co0.07Mn0.1O2 (NCM83), denoted as (CNCM83). The LNTO layer with low electronic conductivity reduces the decomposition drive force of SPE. Furthermore, Ti and Nb in the LNTO layer spontaneously migrate inside the NCM83 surface to form a strong Ti/Nb─O bond, stalling oxygen evolution in high-voltage cathodes. The interfacial degradation phenomena, including SPE decomposition, detrimental phase transition and intragranular cracks of NCM83, and void formation between cathode and SPE, are effectively mitigated by the LNTO layer. Therefore, the growth rate of interfacial resistance (RCEI) decreases from 37.6 Ω h-0.5 for bare NCM83 to 2.4 Ω h-0.5 for CNCM83 at 4.2 V. Moreover, 4.2 V PEO-based ASSPLBs achieve impressive cyclability with high capacity retention of 135 mAh g-1 (75%) even after 300 cycles at 0.5 C.

Direct Fabrication of Sub-10 nm Nanopores in WO3 Nanosheets Using Single Swift Heavy Ions.

Extending the fabrication methodology of solid-state nanopores in a wide range of materials is significant in the fields of single molecule detection, nanofluidic devices, and nanofiltration membranes. Here, we demonstrate a new method to directly fabricate size- and density-controllable sub-10 nm nanopores in WO3 nanosheets using single swift heavy ions (SHIs) without any chemical etching process. By selecting ions of different electronic energy losses (Se), nanopores with sizes from 1.8 to 7.4 nm can be created in WO3 nanosheets. The creation efficiency of nanopores achieves ∼100% for Se > 20 keV/nm, and there exists a critical thickness below which nanopores can be created. Combined with molecular dynamics simulations, we propose that the viscosity and surface tension of the transient molten phase caused by SHIs are the key factors for the formation of nanopores. This method paves a way to fabricate solid-state nanopores in materials with a low viscosity and surface tension.

A GATA-type transcription factor SreA affects manganese susceptibility by regulating the expression of iron uptake-related genes.

SreA has been identified as a GATA-type transcription factor that represses iron uptake to avoid iron excess during iron sufficiency. However, knowledge about whether SreA also affects the homeostasis of other divalent metal ions is limited. In this study, by screening Aspergillus fumigatus transcription factor deletion mutant libraries, we demonstrate that the sreA deletion mutant shows the greatest tolerance to MnCl2 among the tested divalent metal ions. Fe and Mn stimuli are able to enhance the expression of SreA with the different time-dependent manner, while the expression of SreA contributes to Mn2+ tolerance. Lack of SreA results in abnormally increased expression of a series of siderophore biosynthesis genes and iron transport-related genes, especially under MnCl2 treatment. Further mechanistic exploration indicated that lack of SreA exacerbates abnormal iron uptake, and iron excess inhibits cellular Mn content; thus, deletion of sreA results in Mn tolerance. Thus, findings in this study have demonstrated a new unexplored function for the transcription factor SreA in regulation of the Mn2+ tolerance.

Molecular Characterization and the Essential Biological Function of the Metal Chaperone Protein MtmA in Aspergillus fumigatus.

The detoxification system of reactive oxygen species (ROS) plays critical roles in the survival and virulence of fungal pathogens in infected hosts, while superoxide dismutase (SOD) is the primary ROS scavenger. In the model yeast Saccharomyces cerevisiae, the metal chaperone protein Mtm1 is required for mitochondrial Sod2 activation and responses to oxidative stress. However, the function of the S. cerevisiae Mtm1 homolog in the human fungal pathogen Aspergillus fumigatus has not yet been clarified. In this study, we found that mitochondria-localized MtmA in A. fumigatus, a putative homolog of yeast Mtm1, not only has a similar function to Mtm1 in responding to oxidative stress resistance by affecting SodB (MnSOD) activity but is also essential for hyphal growth such that repressed expression of MtmA results in severe growth defects in A. fumigatus. In addition, the chelation of Zn2+ can obviously rescue growth defects caused by repression of MtmA, suggesting that MtmA may be involved in hyphal growth by affecting cellular Zn2+ detoxification. Moreover, MtmA contains four Mito-carr domains, whereas only the first Mito-carr domain is required for the function of MtmA. Therefore, the findings in this study suggest that MtmA in A. fumigatus has an important and unique function that is different from that in yeast. IMPORTANCE Knowledge of the key factors required for the viability of pathogenic fungi can help to explore new antifungal drugs. Here, we demonstrate that MtmA is involved in responding to oxidative stress by activating mitochondrial SodB activity. MtmA, especially for the first Mito-carr domain, is essential for colony growth by regulating cellular Zn2+ equilibrium and responses to oxidative stress in A. fumigatus. This is the first report of the vital and unique role of the MtmA protein in pathogenic fungi, indicating that it might be a potential antifungal drug target.

The C2H2 Transcription Factor SltA Contributes to Azole Resistance by Coregulating the Expression of the Drug Target Erg11A and the Drug Efflux Pump Mdr1 in Aspergillus fumigatus.

The emergence of azole-resistant fungal pathogens has posed a great threat to public health worldwide. Although the molecular mechanism of azole resistance has been extensively investigated, the potential regulators of azole resistance remain largely unexplored. In this study, we identified a new function of the fungal specific C2H2 zinc finger transcription factor SltA (involved in the salt tolerance pathway) in the regulation of azole resistance of the human fungal pathogen Aspergillus fumigatus A lack of SltA results in an itraconazole hypersusceptibility phenotype. Transcriptional profiling combined with LacZ reporter analysis and electrophoretic mobility shift assays (EMSA) demonstrated that SltA is involved in its own transcriptional regulation and also regulates the expression of genes related to ergosterol biosynthesis (erg11A, erg13A, and erg24A) and drug efflux pumps (mdr1, mfsC, and abcE) by directly binding to the conserved 5'-AGGCA-3' motif in their promoter regions, and this binding is dependent on the conserved cysteine and histidine within the C2H2 DNA binding domain of SltA. Moreover, overexpression of erg11A or mdr1 rescues sltA deletion defects under itraconazole conditions, suggesting that erg11A and mdr1 are related to sltA-mediated itraconazole resistance. Most importantly, deletion of SltA in laboratory-derived and clinical azole-resistant isolates significantly attenuates drug resistance. Collectively, we have identified a new function of the transcription factor SltA in regulating azole resistance by coordinately mediating the key azole target Erg11A and the drug efflux pump Mdr1, and targeting SltA may provide a potential strategy for intervention of clinical azole-resistant isolates to improve the efficiency of currently approved antifungal drugs.

The Copper Chaperone CcsA, Coupled with Superoxide Dismutase SodA, Mediates the Oxidative Stress Response in Aspergillus fumigatus.

Superoxide dismutases (SODs) are important metalloenzymes that protect fungal pathogens against the toxic effects of reactive oxygen species (ROS) generated by host defense mechanisms during the infection process. The activation of Cu/Zn-SOD1 is found to be dependent on copper chaperone for SOD1 (Ccs1). However, the role of the Ccs1 ortholog in the human pathogen Aspergillus fumigatus and how these SODs coordinate to mediate oxidative stress response remain elusive. Here, we demonstrated that A. fumigatus CcsA, a Saccharomyces cerevisiae Ccs1 ortholog, is required for cells in response to oxidative response and the activation of Sod1. Deletion of ccsA resulted in increased ROS accumulation and enhanced sensitivity to oxidative stress due to the loss of SodA activity. Molecular characterization of CcsA revealed that the conserved CXC motif is required not only for the physical interaction with SodA but also for the oxidative stress adaption. Notably, addition of Mn2+ or overexpression of cytoplasmic Mn-SodC could rescue the defects of the ccsA or sodA deletion mutant, indicating the important role of Mn2+ and Mn-SodC in ROS detoxification; however, deletion of the CcsA-SodA complex could not affect A. fumigatus virulence. Collectively, our findings demonstrate that CcsA functions as a Cu/Zn-Sod1 chaperone that participates in the adaptation to oxidative stress in A. fumigatus and provide a better understanding of the CcsA-SodA complex-mediated oxidative stress response in filamentous fungi. IMPORTANCE Reactive oxygen species (ROS) produced by phagocytes have been reported to participate in the killing of fungal pathogens. Superoxide dismutases (SODs) are considered to be the first line of defense against superoxide anions. Characterizing the regulatory mechanisms of SOD activation is important for understanding how fungi adapt to oxidative stress in hosts. Our findings demonstrated that CcsA functions as a SodA chaperone in A. fumigatus and that the conserved CXC motif within CcsA is required for its interaction with SodA and the CcsA-SodA-mediated oxidative response. These data may provide new insights into how fungal pathogens adapt to oxidative stress via the CcsA-SodA complex.

The OxrA Protein of Aspergillus fumigatus Is Required for the Oxidative Stress Response and Fungal Pathogenesis.

An efficient reactive oxygen species (ROS) detoxification system is vital for the survival of the pathogenic fungus Aspergillus fumigatus within the host high-ROS environment of the host. Therefore, identifying and targeting factors essential for oxidative stress response is one approach to developing novel treatments for fungal infections. The oxidation resistance 1 (Oxr1) protein is essential for protection against oxidative stress in mammals, but its functions in pathogenic fungi remain unknown. The present study aimed to characterize the role of an Oxr1 homolog in A. fumigatus. The results indicated that the OxrA protein plays an important role in oxidative stress resistance by regulating the catalase function in A. fumigatus, and overexpression of catalase can rescue the phenotype associated with OxrA deficiency. Importantly, the deficiency of oxrA decreased the virulence of A. fumigatus and altered the host immune response. Using the Aspergillus-induced lung infection model, we demonstrated that the ΔoxrA mutant strain induced less tissue damage along with decreased levels of lactate dehydrogenase (LDH) and albumin release. Additionally, the ΔoxrA mutant caused inflammation at a lower degree, along with a markedly reduced influx of neutrophils to the lungs and a decreased secretion of cytokine usually associated with recruitment of neutrophils in mice. These results characterize the role of OxrA in A. fumigatus as a core regulator of oxidative stress resistance and fungal pathogenesis. IMPORTANCE Knowledge of ROS detoxification in fungal pathogens is useful in the design of new antifungal drugs and could aid in the study of oxidative stress resistance mechanisms. In this study, we demonstrate that OxrA protein localizes to the mitochondria and functions to protect against oxidative damage. We demonstrate that OxrA contributes to oxidative stress resistance by regulating catalase function, and overexpression of catalase (CatA or CatB) can rescue the phenotype that is associated with OxrA deficiency. Remarkably, a loss of OxrA attenuated the fungal virulence in a mouse model of invasive pulmonary aspergillosis and altered the host immune response. Therefore, our finding indicates that inhibition of OxrA might be an effective approach for alleviating A. fumigatus infection. The present study is, to the best of our knowledge, a pioneer in reporting the vital role of Oxr1 protein in pathogenic fungi.

A sphingolipid synthesis-related protein OrmA in Aspergillus fumigatus is responsible for azole susceptibility and virulence.

Previous studies identified that the budding yeast Saccharomyces cerevisiae have two sphingolipid synthesis-related proteins, Orm1p and Orm2p, that negatively regulate the activities of SPT, which is a key rate-limiting enzyme in sphingolipid synthesis. However, little is known about whether sphingolipids in the cell membrane, which are closely related to ergosterols, could affect the efficacy of azole drugs, which target to the ergosterol biosynthesis. In this study, through genome-wide homologue search analysis, we found that the Aspergillus fumigatus genome only contains one Orm homologue, referred to as OrmA for which the protein expression could be induced by azole antifungals in a dose-dependent manner. Deletion of ormA caused hypersensitivity to azoles, and adding the sphingolipid synthesis inhibitor myriocin rescued the azole susceptibility induced by lack of ormA. In contrast, overexpression of OrmA resulted in azole resistance, indicating that OrmA is a positive azole-response regulator. Further mechanism analysis verified that OrmA is related to drug susceptibility by affecting endoplasmic reticulum stress responses in an unfolded protein response pathway-HacA-dependent manner. Lack of ormA led to an abnormal profile of sphingolipid ceramide components accompanied by hypersensitivity to low temperatures. Furthermore, deletion of OrmA significantly reduced virulence in an immunosuppressed mouse model. The findings in this study collectively suggest that the sphingolipid metabolism pathway in A. fumigatus plays a critical role in azole susceptibility and fungal virulence.

Damage resistance protein (Dap) contributes to azole resistance in a sterol-regulatory-element-binding protein SrbA-dependent way.

The targeting of stress-response regulators has emerged as a powerful strategy to enhance azole drug efficacy and to abrogate azole drug resistance. Previously, we reported that a damage resistance protein (Dap) family, composed of DapA, DapB, and DapC, could respond to azole stress stimuli in Aspergillus fumigatus, although the exact response mechanisms remain unknown. In this study, RNA-seq analysis found that a total of 180 genes are induced by azole in a dapA-dependent manner. These genes are involved in oxidation-reduction, metabolic processes, and transmembrane transport. Following azole stress stimuli, DapA and DapC consistently show a stable endoplasmic reticulum (ER)-localization pattern. In comparison, the sterol-regulatory element-binding protein SrbA is capable of nuclear translocation from the ER after azole-stress stimuli, suggesting that SrbA, but not Daps, can directly sense azole stress. Moreover, we found that SrbA is required for the normal expression of DapA and DapC but not of DapB. In addition, in the absence of SrbA, the enhanced expression of DapA induced by azole-itraconazole is blocked, indicating that SrbA is required for the DapA response to azole stress. Double mutants together with overexpression experiments suggest that DapA might act downstream of SrbA to respond to azole stress stimuli. Compared with the ΔsrbA strain, no additional increase in sensitivity was observed in the double mutants ΔsrbAΔdapB and ΔsrbAΔdapC, indicating that DapA might be of central importance in the response to azole drugs. Thus, our findings demonstrate that Dap proteins indirectly sense azole stress and link the function of the azole stress-regulator SrbA with the role of Daps in azole susceptibility.

A putative mitochondrial calcium uniporter in A. fumigatus contributes to mitochondrial Ca(2+) homeostasis and stress responses.

Ca(2+) uptake into mitochondria plays a central role in cell physiology by stimulating ATP production, shaping cytosolic Ca(2+) transients and regulating cell survival or death. Although this system has been studied extensively in mammalian cells, the physiological implications of Ca(2+) uptake into mitochondria in fungal cells are still unknown. In this study, a bi-directional best-hit BLASTP search revealed that the genome of Aspergillus fumigatus encodes a homolog of a putative mitochondrial Ca(2+) uniporter (MCU) and a mitochondrial carrier protein AGC1/MICU1 homolog. Both putative homologs are mitochondrially localized and required for the response to azole and oxidative stress such that the loss of either McuA or AgcA results in reduced susceptibility to azole and oxidative stress, suggesting a role in environmental stress adaptation. Overexpressing mcuA restores the azole-resistance phenotype of the ΔagcA strain to wild-type levels, but not vice versa, indicating McuA plays a dominant role during these stress responses. Using a mitochondrially targeted version of the calcium-sensitive photoprotein aequorin, we found that only mcuA deletion leads to dysfunctional [Ca(2+)]mt and [Ca(2+)]c homeostasis, suggesting that McuA, but not AgcA, contributes to Ca(2+) uptake into mitochondria. Further point-mutation experiments combined with extracellular Ca(2+) chelator treatment verified that two predicted Ca(2+)-binding sites in McuA are required for Ca(2+) uptake into mitochondria and stress responses through the regulation of [Ca(2+)]c homeostasis.

The regulatory roles of microRNA-146b-5p and its target platelet-derived growth factor receptor α (PDGFRA) in erythropoiesis and megakaryocytopoiesis.

Emerging evidence has shown that microRNAs have key roles in regulating various normal physiological processes, whereas their deregulated expression is correlated with various diseases. The miR-146 family includes miR-146a and miR-146b, with a distinct expression spectrum in different hematopoietic cells. Recent work indicated that miR-146a has a close relationship with inflammation and autoimmune diseases. miR-146-deficient mice have developed some abnormal hematopoietic phenotypes, suggesting the potential functions of miR-146 in hematopoietic development. In this study, we found that miR-146b was consistently up-regulated in both K562 and CD34(+) hematopoietic stem/progenitor cells (HSPCs) undergoing either erythroid or megakaryocytic differentiation. Remarkably, erythroid and megakaryocytic maturation of K562 cells was induced by excess miR-146b but inhibited by decreased miR-146b levels. More importantly, an mRNA encoding receptor tyrosine kinase, namely platelet-derived growth factor receptor α (PDGFRA), was identified and validated as a direct target of miR-146b in hematopoietic cells. Gain-of-function and loss-of-function assays showed that PDGFRA functioned as a negative regulator in erythroid and megakaryocytic differentiation. miR-146b could ultimately affect the expression of the GATA-1 gene, which is regulated by HEY1 (Hairy/enhancer-of-split related with YRPW motif protein 1), a transcriptional repressor, via inhibition of the PDGFRA/JNK/JUN/HEY1 pathway. Lentivirus-mediated gene transfer also demonstrated that the overexpression of miR-146b promoted erythropoiesis and megakaryocytopoiesis of HSPCs via its regulation on the PDGFRA gene and effects on GATA-1 expression. Moreover, we confirmed that the binding of GATA-1 to the miR-146b promoter and induction of miR-146b during hematopoietic maturation were dependent on GATA-1. Therefore, miR-146b, PDGFRA, and GATA-1 formed a regulatory circuit to promote erythroid and megakaryocytic differentiation.

Low temperature route synthesis of SiC-Al2O3 hetero-structural nanofibers.

SiC-Al2O3 hetero-structural nanofibers have been synthesized by the chemical solution approach at 200 ° C. The diameters of nanofibers are in the range of 60-100 nm while the lengths are from tens of micrometers to hundreds of micrometers. The microstructural analysis shows that the fibers possess a like-epitaxial relationship between (104) of hexagonal Al2O3 and (111) of cubic SiC. Additionally, the optical investigation of the nanofibers suggests there are some defects in the low annealing temperature synthesized SiC-Al2O3 nanofibers.

Covalent Organic Framework-Coated Polyimide Ion-Track-Etched Separator with High Thermal Stability for Developing Lithium-Ion Batteries with Long Lifespans.

Separators play a crucial role in inhibiting thermal runaway in lithium-ion batteries (LIBs). In this study, the doctor blade coating method and heavy-ion track etching technology were used to prepare a polyimide-based covalent organic framework (PI_COF) separator with excellent thermal stability and a long cycle life. Specifically, COF300 was simply coated on the surface of a polyimide-based track-etched membrane (PI_TEM) with straight through holes, which provided a rigid framework and high-temperature stability at 300 °C. These features were conducive to inhibiting thermal runaway, while porous COF300 with large holes increased the wettability of the electrolyte, facilitating lithium-ion migration and suppression of lithium dendrite growth; consequently, LIBs with an excellent cycling performance and a high rate capacity were obtained. The cell with the PI_COF separator delivered a high capacity of 90.0 mA h g-1 after 1000 cycles. The PI_COF separator with high thermal stability exhibited a long cycle life in LIBs. These features are beneficial for improving the safety characteristics of LIBs as well as for accelerating the practical application process of the PI_COF separator.

Schottky barrier reduction on optoelectronic responses in heavy ion irradiated WSe2 memtransistors.

Two-dimensional transition metal dichalcogenide-based memtransistors provide simulation, sensing, and storage capabilities for applications in a remotely operated aerospace environment. Swift heavy ion (SHI) irradiation technology is a common method to simulate the influences of radiation ions on electronic devices in space environments. Here, SHI irradiation technology under different conditions was utilized to produce complex defects in WSe2-based memtransistors. Low-resistance state to low-resistance state (LRS-LRS) switching behaviors under light illumination were achieved and photocurrent responses with different spike trains were observed in SHI-irradiated memtransistors, which facilitated the design of devices with enriched analog functions. Reduction of the Schottky barrier height due to the introduced defects at the metal/WSe2 interface was confirmed to be the major factor responsible for the observed behaviors. 1T phase and concentric circle-type vacancies were also created in the SHI-irradiated 2H-WSe2 channel besides the amorphous structure; these complex defects could seriously affect the transport properties of the devices. We believe that this work serves as a foundation for aerospace radiation applications of all-in-one devices. It also opens a new application field of heavy ion irradiation technology for the development of multiterminal memtransistor-based optoelectronic artificial synapses for neuromorphic computing.

Posterior paramedian approach combined with a novel inverted V-shaped surgical access for intraspinal schwannomas: a retrospective case series study.

OBJECTIVE: To explore the efficacy and safety of the posterior paramedian approach combined with a novel inverted V-shaped surgical access for the treatment of intraspinal schwannomas. METHODS: This study retrospectively reviewed consecutive patients who underwent surgical resection of the intraspinal schwannomas via the inverted V-shaped approach at our center between January 2016 and May 2021. Changes between the preoperative and postoperative visual analog scale (VAS) scores and neurological function Japan Orthopaedic Association (JOA) scores were assessed. Secondary outcomes such as success rate of tumor resection, operation time, blood loss, spinal stability, and disruption degree of intervertebral joints. Postoperative complications were also investigated. RESULTS: Of these 36 consecutive patients, there were 6 cases in the cervical spine, 2 cases at the cervical-thoracic junction, 11 cases in the thoracic spine, 4 cases at the thoracic-lumbar junction and 13 cases in the lumbar spine. The average operation time was 99 min, and the average blood loss was 95.4 mL. The tumor removal rate was 100%. Postoperative CT re-examination showed that the spinous processes were intact in all cases, the facet joint surfaces were intact in 32 cases. At the time of last follow-up, the median JOA score was 25 (9-27), which was significantly improved compared to the preoperative median JOA score of 15 (10-22) (P < 0.01). The overall excellent and good rate were 88.9 %. The median VAS score at post-surgery was 0 (0-2), which was significantly improved compared to the preoperative median VAS score of 4 (2-8) (P < 0.01). As for complications, there were no cases of cerebrospinal fluid leakage or spinal instability. Three patients who had a postoperative fever finally recovered after lumbar cistern drainage. CONCLUSION: The inverted V-shaped surgical access via the posterior paramedian approach is an effective and safe method for the treatment of intraspinal schwannomas.

miR-29a and miR-142-3p downregulation and diagnostic implication in human acute myeloid leukemia.

Expression profiling of microRNAs (miRNAs) in most diseases might be popular and provide the possibility for diagnostic implication, but few studies have accurately quantified the expression level of dysregulated miRNAs in acute myeloid leukemia (AML). In this study, we analyzed the peripheral blood mononuclear cells (PBMCs) from 10 AML patients (subtypes M1 to M5) and six normal controls by miRNA microarray and identified several differentially expressed miRNAs. Among them miR-29a and miR-142-3p were selectively encountered in Northern blot analysis and their significantly decreased expression in AML was further confirmed. Quantitative real-time PCR in 52 primarily diagnosed AML patients and 100 normal controls not only verified the expression properties of these 2 miRNAs, but also established that the expression level of miR-142-3p and miR-29a in PBMCs could be used as novel diagnostic markers. A better diagnostic outcome was achieved by combining miR-29a and miR-142-3p with about 90% sensitivity, 100% specificity, and an area under the ROC curve (AUC) of 0.97. Our results provide insights into the involvement of miRNAs in leukemogenesis, and offer candidates for AML diagnosis and therapeutic strategy.

Fungal Zinc Homeostasis and Its Potential as an Antifungal Target: A Focus on the Human Pathogen Aspergillus fumigatus.

Aspergillus fumigatus is an opportunistic airborne fungus that causes severe invasive aspergillosis in immunocompromised patients. Zinc is an essential micronutrient for the growth of A. fumigatus and even for all microorganisms. An increasing number of studies have reported that fungal zinc acquisition ability plays a key role in fungal survival in hosts with an extremely zinc-limited microenvironment. The ability to fight scarcity and excess of zinc are tightly related to fungal virulence and may be used as new potential targets. Because the regulation of zinc homeostasis is important, a thorough understanding of the functional genes involved in the regulatory network for zinc homeostasis is required for fungal pathogens. The current mini-review summarized potential zinc homeostasis regulators in A. fumigatus and classified these regulators according to localization and function, which were identified or predicted based on A. fumigatus or deduced from homologs in model yeasts. Future perspectives for zinc homeostasis regulators as potential antifungal targets to treat invasive aspergillosis are also discussed.

The metal chaperone protein MtmA plays important roles in antifungal drug susceptibility in Aspergillus fumigatus.

Drug-resistant fungal infections are emerging as an important clinical problem. In general, antifungal resistance results from increased target expression or mutations within the target protein sequence. However, the molecular mechanisms of non-drug target mutations of antifungal resistance in fungal pathogens remain to be explored. Previous studies indicated that the metal chaperone protein Mtm1 is required for mitochondrial Sod2 activation and responses to oxidative stress in yeast and in the fungal pathogen Aspergillus fumigatus, but there is no report of MtmA-related antifungal resistance. In this study, we found that repressed expression of MtmA (only 10% expression) using a conditional promoter resulted in significantly enhanced itraconazole resistance, which was not the result of highly expressed drug targets Erg11A and Erg11B. Furthermore, we demonstrated that repressed expression of MtmA results in upregulation of a series of multidrug resistance-associated transport genes, which may cause multidrug resistance. Further mechanistic studies revealed that inhibition of MtmA expression led to abnormal activation of the calcium signaling system and prompted persistent nucleation of the calcium signaling transcription factor CrzA. Our findings suggest that the metal chaperone protein MtmA is able to negatively regulate fungal resistance via affecting calcium signaling pathway.

Nano-sulfur confined in a 3D carbon nanotube/graphene network as a free-standing cathode for high-performance Li-S batteries.

A free-standing nano-sulfur-based carbon nanotube/graphene (S/CNT/G) film with a conductive interlinked three-dimensional (3D) nanoarchitecture is fabricated via a facile solution-based method. This 3D multidimensional carbon-sulfur network combines three different nanoarchitectures, as follows: zero-dimensional sulfur nanoparticles, one-dimensional carbon nanotubes, and two-dimensional graphene. The CNTs with a one-dimensional structure act as a conductive matrix, and graphene with two-dimensional sheets is intercalated into the CNT scaffold to build a 3D structure, extending in an additional dimension to provide improved restriction for sulfur/polysulfides. Zero-dimensional sulfur nanoparticles are anchored uniformly on the interpenetrative 3D carbon framework to form a free-standing cathode. Moreover, this well-designed S/CNT/G film is flexible, highly conductive, binder free and current collector free. When directly used as a flexible cathode electrode, the synthesized S/CNT/G film delivers both excellent long-term cycling and high-rate performances. A high initial capacity of 948 mA h g-1 is obtained, and subsequently, a reversible discharge capacity of 593 mA h g-1 over 200 cycles is achieved at 0.5C. Even at a high rate of 3C, the S/CNT/G film with a 50 wt% sulfur content still exhibits a discharge capacity of 598 mA h g-1. These results demonstrate the great potential of the S/CNT/G nanocomposite as a flexible and binder-free cathode for high performance Li-S batteries.

Banana, pineapple, cassava and sugarcane residue biochars cannot mitigate ammonia volatilization from latosols in tropical farmland.

Ammonia (NH3) volatilization is a major pathway of soil nitrogen loss in tropical farmland, causing many environmental issues. Biochar can improve soil quality and affect soil NH3 volatilization. However, little is known about the effects of tropical crop residue biochar on soil NH3 volatilization in tropical farmland. Therefore, a laboratory incubation study was conducted using four kinds of tropical crop residue biochar (pineapple straw (stem and leaves), banana straw, cassava straw and sugarcane bagasse pyrolyzed at 500 °C) with five addition rates (0.5%, 1%, 2%, 4%, and 6%) to evaluate their impact on NH3 volatilization from tropical latosols. The results showed that NH3 volatilization peaked twice under biochar application, once at 1-5 days and again at 12-16 days. The cumulative NH3 volatilization (0.14-0.47 mg kg-1) of the 20 biochar treatments was higher than that of the control (0.12 mg kg-1). With the increase in the biochar addition rate, the soil pH, soil organic matter (SOM), urease activity, nitrate nitrogen content (NO3--N), nitrification rate and cumulative NH3 volatilization increased gradually, and the 6% biochar treatment resulted in the highest NH3 volatilization loss (0.19-0.47 mg kg-1). The type of biochar is also a main factor affecting soil NH3 volatilization. The cumulative NH3 volatilization was the highest under pineapple straw biochar, as it was 19-43% higher than when the other three biochars were applied. However, sugarcane bagasse biochar had the lowest cumulative NH3 volatilization due to its low quartz, sylvite and calcite contents, lack of -OH hydroxyl groups and high adsorbability. NH3 volatilization was positively correlated with the soil pH, SOM, urease activity, NO3--N and nitrification rate. In conclusion, four tropical crop residue biochars can increase NH3 volatilization in tropical latosols, so reducing NH3 volatilization needs to be further considered in tropical crop residue biochar applications.