Differential innate immune responses of human macrophages and bronchial epithelial cells against Talaromyces marneffei.

Talaromyces marneffei is a thermally dimorphic fungal pathogen endemic in Southeast Asia. As inhalation of airborne conidia is believed as the major infection route, airway epithelial cells followed by pulmonary macrophages are the first cell types which the fungus encounters inside the host. In this study, we established an in vitro infection model based on human peripheral blood-derived macrophages (hPBDMs) cultured with the supplementation of autologous plasma. Using this model, we determined the transcriptomic changes of hPBDMs in response to T. marneffei infection by quantitative real-time reverse-transcription polymerase chain reaction as well as high-throughput RNA sequencing. Results showed that T. marneffei infection could activate hPBDMs to the M1-like phenotype and trigger a potent induction of chemokine and pro-inflammatory cytokine production as well as the expression of other immunoregulatory genes. In contrast to hPBDMs, there was no detectable innate cytokine response against T. marneffei in human bronchial epithelial cells (hBECs). Using a green fluorescent protein-tagged T. marneffei strain and confocal microscopy, internalization of the fungus by hBECs was confirmed. Live cell imaging further demonstrated that the infected cells exhibited normal cellular physiology, especially that the process of cell division could be observed. Moreover, T. marneffei also survived better inside hBECs than hPBDMs. Our results illustrated a potential role of hBECs to serve as reservoir cells for T. marneffei to evade immunosurveillance by phagocytes, from which the fungus reactivates when the host immunity is weakened and causes infection. Such immunoevasion and reactivation may also help explain the long incubation period observed for talaromycosis, in particular the travel-related cases. IMPORTANCE Talaromyces marneffei is an important fungal pathogen especially in Southeast Asia. To understand the innate immune response to talaromycosis, a suitable infection model is needed. Here, we established an in vitro T. marneffei infection model using human peripheral blood-derived macrophages (hPBDMs). We then examined the transcriptomic changes of hPBDMs in response to T. marneffei infection with this model. We found that contact with T. marneffei could activate hPBDMs to the M1-like phenotype and induced mRNA expressions of five cytokines and eight immunoregulatory genes. Contrary to hPBDMs, such immunoresponse was not elicited in human bronchial epithelial cells (hBECs), despite normal physiology observed in infected cells. We also found that infected hBECs did not eliminate T. marneffei as efficiently as hPBDMs. Our observation suggested that hBECs may potentially serve as reservoir cells for T. marneffei to evade immunosurveillance. When the host immunity deteriorates later, then the fungus reactivates and causes infection.

A universal metasurface antenna to manipulate all fundamental characteristics of electromagnetic waves.

Metasurfaces have promising potential to revolutionize a variety of photonic and electronic device technologies. However, metasurfaces that can simultaneously and independently control all electromagnetics (EM) waves' properties, including amplitude, phase, frequency, polarization, and momentum, with high integrability and programmability, are challenging and have not been successfully attempted. Here, we propose and demonstrate a microwave universal metasurface antenna (UMA) capable of dynamically, simultaneously, independently, and precisely manipulating all the constitutive properties of EM waves in a software-defined manner. Our UMA further facilitates the spatial- and time-varying wave properties, leading to more complicated waveform generation, beamforming, and direct information manipulations. In particular, the UMA can directly generate the modulated waveforms carrying digital information that can fundamentally simplify the architecture of information transmitter systems. The proposed UMA with unparalleled EM wave and information manipulation capabilities will spark a surge of applications from next-generation wireless systems, cognitive sensing, and imaging to quantum optics and quantum information science.

A 6G meta-device for 3D varifocal.

The sixth-generation (6G) communication technology is being developed in full swing and is expected to be faster and better than the fifth generation. The precise information transfer directivity and the concentration of signal strength are the key topics of 6G technology. We report the synthetic phase design of rotary doublet Airy beam and triplet Gaussian beam varifocal meta-devices to fully control the terahertz beam's propagation direction and coverage area. The focusing spot can be delivered to arbitrary positions in a two-dimensional plane or a three-dimensional space. The highly concentrated signal can be delivered to a specific position, and the transmission direction can be adjusted freely to enable secure, flexible, and high-directivity 6G communication systems. This technology avoids the high costs associated with extensive use of active components. 6G communication systems, wireless power transfer, zoom imaging, and remote sensing will benefit from large-scale adoption of such a technology.

Demonstration of a terahertz multi-spectral 3×3 Mueller matrix polarimetry system for 2D and 3D imaging.

Mueller matrix polarimetry (MMP) has been demonstrated and recognized as an effective approach to attaining imaging enhancement as well as revealing polarization properties of an imaged sample. Generally, a minimum of 16 combinations of intensity-only measurements involving both linear and circular polarizations are required to completely and accurately determine the 4 × 4 Mueller matrix (MM) and comprehensively describe the polarization properties of the sample. However, broadband circular polarizations (CP) are rather difficult to obtain for design and fabrication limitations in the terahertz region, which poses a challenge to the acquisition of the 4 × 4 MM. In this circumstance, the 3 × 3 MM degradation using only linear polarizations (LP) is preferred and sufficient for characterization of non-depolarizing samples. In this paper, a multi-spectral 3 × 3 MMP system based on the THz time-domain spectroscopy (THz-TDS) is established from 0.1 to 1 THz. The system demonstrated is capable of fulfilling the accurate determination of the 3 × 3 MM. The Mueller matrix polar decomposition (MMPD), modified to be compatible with the MM degradation, is employed to explore the fine details and properties of the sample. By signal post-processing techniques, the MM elements in the time domain are retrieved, and the time dimension reflecting the depth information facilitates the 3D reconstruction of the sample. This work provides a prototype for 3D imaging of biological samples at higher frequencies in the future.

Hepatic phaeohyphomycosis due to a novel dematiaceous fungus, Pleurostoma hongkongense sp. nov., and importance of antifungal susceptibility testing.

Pleurostoma species are wood-inhabiting fungi and emerging opportunistic pathogens causing phaeohyphomycosis. In this study, we isolated a dematiaceous fungus, HKU44T, from the subhepatic abscess pus and drain fluids of a liver transplant recipient with post-transplant biliary and hepatico-jejunostomy bypass strictures. Histology of the abscess wall biopsy showed abundant fungal hyphae. The patient survived after a second liver transplant and antifungal therapy. On SDA, HKU44T grew initially as white powdery colonies which turned beige upon maturation. Hyphae were septate and hyaline. Phialides were monophialidic and laterally located, generally closely associated to a cluster of conidia which were usually reniform. Phylogenetic analyses showed that HKU44T is most closely related to, but distinct from, Pleurostoma ootheca and Pleurostoma repens. These suggested that HKU44T is a novel Pleurostoma species, for which the name Pleurostoma hongkongense sp. nov. is proposed. Antifungal susceptibility testing showed that Pleurostoma species possessed high MICs/MECs for fluconazole, 5-flucytosine and the echinocandins; whereas they exhibited a high strain-to-strain variability to the susceptibilities to the other triazoles. As for amphotericin B, ∼65% of the Pleurostoma strains had low MICs (≤1 µg/mL). DNA sequencing should be performed to accurately identify fungi with Pleurostoma/Phialophora-like morphologies, so is antifungal susceptibility testing for patients with Pleurostoma infections.

Antibiotics create a shift from mutualism to competition in human gut communities with a longer-lasting impact on fungi than bacteria.

BACKGROUND: Antibiotic treatment has a well-established detrimental effect on the gut bacterial composition, but effects on the fungal community are less clear. Bacteria in the lumen of the gastrointestinal tract may limit fungal colonization and invasion. Antibiotic drugs targeting bacteria are therefore seen as an important risk factor for fungal infections and induced allergies. However, antibiotic effects on gut bacterial-fungal interactions, including disruption and resilience of fungal community compositions, were not investigated in humans. We analysed stool samples collected from 14 healthy human participants over 3 months following a 6-day antibiotic administration. We integrated data from shotgun metagenomics, metatranscriptomics, metabolomics, and fungal ITS2 sequencing. RESULTS: While the bacterial community recovered mostly over 3 months post treatment, the fungal community was shifted from mutualism at baseline to competition. Half of the bacterial-fungal interactions present before drug intervention had disappeared 3 months later. During treatment, fungal abundances were associated with the expression of bacterial genes with functions for cell growth and repair. By extending the metagenomic species approach, we revealed bacterial strains inhibiting the opportunistic fungal pathogen Candida albicans. We demonstrated in vitro how C. albicans pathogenicity and host cell damage might be controlled naturally in the human gut by bacterial metabolites such as propionate or 5-dodecenoate. CONCLUSIONS: We demonstrated that antibacterial drugs have long-term influence on the human gut mycobiome. While bacterial communities recovered mostly 30-days post antibacterial treatment, the fungal community was shifted from mutualism towards competition. Video abstract.

All-optical diffractive neural networked terahertz hologram.

Holography has garnered an explosion of interest in tremendous applications, owing to its capability of storing amplitude and phase of light and reconstructing the full-wave information of targets. Spatial light modulators, metalenses, metasurfaces, and other devices have been explored to achieve holographic images. However, the required phase distributions for conventional holograms are generally calculated using the Gerchberg-Saxton algorithm, and the iteration is time-consuming without Fourier transform or other acceleration techniques. Few studies on designing holograms using artificial intelligence methods have been conducted. In this Letter, a three-dimensional (3D)-printed hologram for terahertz (THz) imaging based on a diffractive neural network (DNN) is proposed. Target imaging letters "THZ" with uniform field amplitude are assigned to a predefined imaging surface. Quantified phase profiles are primarily obtained by training the DNN with the target image and input field pattern. The entire training process takes only 60 s. Consequently, the hologram, that is, a two-dimensional array of dielectric posts with variational heights that store phase information, is fabricated using a 3D printer. The full-wave simulation and experimental results demonstrate the capability of the proposed hologram to achieve high-quality imaging in the THz regime. The proposed lens and design strategy may open new possibilities in display, optical-data storage, and optical encryption.

Diversity of phenotypically non-dermatophyte, non-Aspergillus filamentous fungi causing nail infections: importance of accurate identification and antifungal susceptibility testing.

Onychomycosis is most commonly caused by dermatophytes. In this study, we examined the spectrum of phenotypically non-dermatophyte and non-Aspergillus fungal isolates recovered over a 10-year period from nails of patients with onychomycosis in Hong Kong. A total of 24 non-duplicated isolates recovered from 24 patients were included. The median age of the patients was 51 years, and two-thirds of them were males. One-third and two-thirds had finger and toe nail infections respectively. Among these 24 nail isolates, 17 were confidently identified as 13 different known fungal species, using a polyphasic approach. These 13 species belonged to 11 genera and ≥9 families. For the remaining seven isolates, multilocus sequencing did not reveal their definite species identities. These seven potentially novel species belonged to four different known and three potentially novel genera of seven families. 33.3%, 41.7% and 95.8% of the 24 fungal isolates possessed minimum inhibitory concentrations of >1 µg/mL to terbinafine, itraconazole and fluconazole, respectively, the first line treatment of onychomycosis. A high diversity of moulds was associated with onychomycosis. A significant proportion of the isolates were potentially novel fungal species. To guide proper treatment, molecular identification and antifungal susceptibility testing should be performed for these uncommonly isolated fungal species.

Serodiagnosis of aspergillosis in falcons (Falco spp.) by an Afmp1p-based enzyme-linked immunosorbent assay.

Aspergillosis in falcons may be associated with high mortality and difficulties in clinical and laboratory diagnosis. We previously cloned an immunogenic protein, Afmp1p, in Aspergillus fumigatus and showed that anti-Afmp1p antibodies were present in human patients with A. fumigatus infections. In this study, we hypothesise that a similar Afmp1p-based enzyme-linked immunosorbent assay (ELISA) could be applied to serodiagnose falcon aspergillosis. A specific polyclonal antibody was first generated to detect falcon serum IgY. Horseradish peroxidase-conjugate of this antibody was then used to measure anti-Afmp1p antibodies in sera collected from falcons experimentally infected with A. fumigatus, and the performance of the Afmp1p-based ELISA was evaluated using sera from healthy falcons and falcons with documented A. fumigatus infections. All four experimentally infected falcons developed culture- and histology-proven invasive aspergillosis. Anti-Afmp1p antibodies were detected in their sera. For the Afmp1p-based ELISA, the mean ± SD OD450 nm using sera from 129 healthy falcons was 0.186 ± 0.073. Receiver operating characteristics curve analysis showed an absorbance cut-off value of 0.407. One negative serum gave an absorbance outside the normal range, giving a specificity of 99.2%. For the 12 sera from falcons with confirmed aspergillosis, nine gave absorbance values ≥ cut-off, giving a sensitivity of 75%. The Afmp1p-based ELISA is useful for serodiagnosis of falcons with aspergillosis.