All-Inorganic Halide Perovskites Boost High-Ranged Figure-of-Merit in Bi0.4Sb1.6Te3 for Thermoelectric Cooling and Low-Grade Heat Recovery.

The all-inorganic halide perovskite CsPbX3 (X = Cl, Br, or I) offers various advantages, such as tunable electronic structure and high carrier mobility. However, its potential application in thermoelectric materials remains underexplored. In this study, we propose a simple yet effective method to synthesize a CsPbX3/Bi0.4Sb1.6Te3 (BST) nanocomposite by sintering a uniformly mixed raw powder. The intrinsic excitation of the BST system is suppressed by exploiting the rich phase structure and tunable electrical transport properties of CsPbX3, and the thermoelectric properties were synergistically optimized. Notably, for CsPbI3, its phase-transition-induced dislocation arrays together with low group velocities drastically reduce thermal conductivity. As a result, the composite achieves an ultrahigh average figure-of-merit (ZT) of 1.4 from 298 to 523 K. The two-pair TE module demonstrates a superior conversion efficiency of 7.3%. This study expands the potential applications of inorganic halide perovskites, into thermoelectrics.

Photodynamic application in diagnostic procedures and treatment of non-melanoma skin cancers.

OPINION STATEMENT: Skin tumors commonly seen in dermatology are involved in all layers of the skin and appendages. While biopsy of affected skin remains an essential method to confirm diagnosis and to predicate tumor prognosis, it has its limitations. Recently, photodynamic diagnosis (PDD) has demonstrated high sensitivity in detecting affected skin and mucosal tissues, providing valuable guidance for precision surgery to resect skin and mucosal tumors. In this review, we summarized the literatures concerning the applications of PDD in diagnostic process and treatment of skin and mucosal conditions such as actinic keratoses (AK), basal cell carcinoma (BCC), squamous cell carcinoma (SCC), Bowen's disease (BD) and extramammary Paget's disease (EMPD). The findings suggest that PDD holds substantial promise for expanding clinical applications and deserves further research exploration.

Galleria mellonella in vitro model for chromoblastomycosis shows large differences in virulence between isolates.

BACKGROUND: Chromoblastomycosis is the World Health Organization (WHO)-recognized fungal implantation disease that eventually leads to severe mutilation. Cladophialophora carrionii (C. carrionii) is one of the agents. However, the pathogenesis of C. carrionii is not fully investigated yet. METHODS: We investigated the pathogenic potential of the fungus in a Galleria mellonella (G. mellonella) larvae infection model. Six strains of C. carrionii, and three of its environmental relative C. yegresii were tested. The G. mellonella model was also applied to determine antifungal efficacy of amphotericin B, itraconazole, voriconazole, posaconazole, and terbinafine. RESULTS: All strains were able to infect the larvae, but virulence potentials were strain-specific and showed no correlation with clinical background of the respective isolate. Survival of larvae also varied with infection dose, and with growth speed and melanization of the fungus. Posaconazole and voriconazole exhibited best activity against Cladophialophora, followed by itraconazole and terbinafine, while limited efficacy was seen for amphotericin B. CONCLUSION: Infection behavior deviates significantly between strains. In vitro antifungal susceptibility of tested strains only partly explained the limited treatment efficacy in vivo.

Effects of secukinumab and ixekizumab on major adverse cardiovascular events in patients with psoriasis: a meta-analysis of randomized controlled trials.

Introduction: The aims of this study is to analyze the risk of major adverse cardiovascular events (MACEs) in patients with psoriasis treated with secukinumab and ixekizumab. Methodology: We systematically identified randomized controlled trials (RCTs) that focused on the treatment of psoriasis with secukinumab and ixekizumab by conducting computerized searches of PubMed, Embase, and the Cochrane Library databases, spanning from their inception to October 31st, 2022. The search terms used included psoriasis, secukinumab, ixekizumab, and randomized controlled trial. Two independent evaluators conducted literature screening, data extraction, and assessed the quality of included studies based on predetermined inclusion and exclusion criteria. The gather data was subjected to meta-analysis using the statistical software RevMan 5.4. Results: A total of 20 articles, encompassing 23 randomized controlled trials involving 10,746 psoriasis patients were included in the analysis. During the double-blind treatment period, the meta-analysis results indicated the following: There was no significant difference in the incidence of MACEs between the secukinumab and placebo groups [RR = 0.61, 95% CI (0.26, 1.44), p = 0.26]. Similarly, there was no significant difference in the incidence of MACEs with ixekizumab compared to the placebo group [RR = 0.47, 95% CI (0.15, 1.47), p = 0.20]. Furthermore, no significant difference in the incidence of MACEs was observed between secukinumab 300 mg and secukinumab 150 mg treatment groups [RR = 1.00, 95% CI (0.23, 4.35), p = 1.00]. Likewise, there was no significant difference in the incidence of MACEs between the ixekizumab Q4W (every 4 weeks) and ixekizumab Q2W (every 2 weeks) administration groups [RR = 4.01, 95% CI (0.45, 35.89), p = 0.21]. Conclusion: The findings of this study suggest that neither secukinumab nor ixekizumab is significantly associated with the risk of MACEs in patients with psoriasis during double-blind treatment.Systematic review registration: Unique Identifier: CRD42022373756 https://www.crd.york.ac.uk/.

Virulence capacity of different Aspergillus species from invasive pulmonary aspergillosis.

Introduction: The opportunistic filamentous fungus Aspergillus causes invasive pulmonary aspergillosis (IPA) that often turns into a fatal infection in immunocompromised hosts. However, the virulence capacity of different Aspergillus species and host inflammation induced by different species in IPA are not well understood. Methods: In the present study, host inflammation, antimicrobial susceptibilities and virulence were compared among clinical Aspergillus strains isolated from IPA patients. Results: A total of 46 strains were isolated from 45 patients with the invasive infection, of which 35 patients were diagnosed as IPA. Aspergillus flavus was the dominant etiological agent appearing in 25 cases (54.3%). We found that the CRP level and leukocyte counts (elevated neutrophilic granulocytes and monocytes, and reduced lymphocytes) were significantly different in IPA patients when compared with healthy individuals (P < 0.05). Antifungal susceptibilities of these Aspergillus isolates from IPA showed that 91%, 31%, 14%, and 14% were resistant to Fluconazole, Micafungin, Amphotericin B and Terbinafine, respectively. The survival rate of larvae infected by A. flavus was lower than larvae infected by A. niger or A. fumigatus (P < 0.05). Discussion: Aspergillus flavus was the dominant clinical etiological agent. Given the prevalence of A. flavus in our local clinical settings, we may face greater challenges when treating IPA patients.

Inducible nitric oxide synthase-expressing myeloid-derived suppressor cells regulated by interleukin 35 contribute to the pathogenesis of psoriasis.

Although psoriasis is classified as a T cell-mediated inflammatory disease, the contribution of myeloid cells to the pathogenesis of psoriasis is not fully understood. In the present study, we demonstrated that the expression of the anti-inflammatory cytokine interleukin-35 (IL-35) was significantly increased in patients with psoriasis with a marked increase in the number of myeloid-derived suppressor cells (MDSCs). Similar results were obtained in an imiquimod-induced psoriasis mouse model. IL-35 reduced the total number of MDSCs and their subtypes in the spleens and psoriatic skin lesions, ameliorating psoriasis. IL-35 also reduced the expression of inducible nitric oxide synthase in MDSCs, although it had no significant effect on interleukin-10 expression. Adoptive transfer of MDSCs from imiquimod-challenged mice aggravated the disease and weakened the effect of IL-35 in the recipient mice. In addition, mice transferred with MDSCs isolated from inducible nitric oxide synthase knockout mice had milder disease than those with wild-type MDSCs. Furthermore, wild-type MDSCs reversed the effects of IL-35, while MDSCs isolated from inducible nitric oxide synthase knockout mice did not affect IL-35 treatment. In summary, IL-35 may play a critical role in the regulation of iNOS-expressing MDSCs in the pathogenesis of psoriasis, highlighting IL-35 as a novel therapeutic strategy for patients with chronic psoriasis or other cutaneous inflammatory diseases.

Surgery plus photodynamic therapy for a diabetic patient with cutaneous infectious granuloma caused by Curvularia lunata.

Curvularia lunata (C. lunata) can be easily found in environment and plants and rarely causes human infections. Antifungal agents have been the primary approach to treat such infections; however, adverse hepatotoxic reactions may require discontinuation of the long-term use of antifungal agents in patients with pre-existing liver diseases. New therapeutic approaches are thus needed to cope with these circumstances. Here, we report a 66-year-old diabetic female patient, suffering from a rapidly growing lesion on the nose for 2 months. The patient was diagnosed with cutaneous fungal infection caused by C. lunata, which was based on mycological study and ITS sequencing. The lesion was completely disappeared after a combination of surgery and 3 times of photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) at 9- day intervals. The patient did not receive any antifungal agents during the treatment. There was no recurrence at 6-month fellow-up. In the following in vitro study, C. Lunata growth was significantly inhibited by ALA-PDT treatment. Therapeutic success in this patent suggests that the ALA-PDT method could be a promising treatment for cutaneous fungal infection caused by C. Lunata and others.

Correlation Between Drug Resistance and Virulence of Candida Isolates from Patients with Candidiasis.

Purpose: This article aims to provide a theoretical basis for new or adjuvant strategies to facilitate the early diagnosis and treatment of candidiasis and to determine if drug-resistant Candida would affect virulence. Patients and Methods: Our strains were collected from patients diagnosed with candidiasis in our hospital. The strains were identified by MALDI-TOF system and ITS sequencing. Antifungal sensitivity testing in vitro was performed to evaluate susceptibility of these isolates to current widely used antifungal drugs. The Galleria mellonella larvae model infected by Candida spp. was used to compare the virulence of drug-resistant and susceptible Candida spp. Results: A total of 206 Candida strains were collected from clinical specimens. Candida albicans was the most common species among them, and was predominantly isolated from male patients aged over 40 years in ICU environments suffering from pulmonary and/or cerebral conditions. The accuracy rate of MALDI TOF-MS identification was 92.72% when compared with ITS sequencing as the standard method. Most Candida species, except for C. tropicalis which showed high resistance to micafungin, showed high susceptibilities to voriconazole, itraconazole, amphotericin B and micafungin but were highly resistant to terbinafine. For each specific Candida species, the G. mellonella larvae model revealed that the virulence of drug-resistant Candida isolates did not markedly differ from that of the drug-susceptible isolates, however, the virulence was dose-dependent on inoculated fungal cells in this model. Conclusion: The possibility of Candida infection should not be neglected in patients at critical care hospital settings and C. albicans is the most common causative agent. MALDI-TOF MS has the advantages of rapidity and high accuracy, and should be a preferred method for identification of Candida spp. in a clinical laboratory. Voriconazole, itraconazole, amphotericin B and micafungin can still be recommended as the first line antifungals to treat candidiasis.

Distinct host immune responses in recurrent vulvovaginal candidiasis and vulvovaginal candidiasis.

Recurrent vulvovaginal candidiasis (RVVC) and vulvovaginal candidiasis (RVVC) are one of the most common gynecological infections, primarily caused by Candida species. Although risk factors of RVVC and VVC have been identified in many studies, antifungal immunological mechanisms are still not fully understood. We performed a 1-year prospective study in a local hospital to monitor 98 patients clinically diagnosed with gynecological Candida infection. The results showed that 20.41% (20/98) are with RVVC, and 79.59% (78/98) patients have VVC. C. albicans accounts for 90% and 96.1% of all strains isolated collected from RVVC and VVC patients, respectively. Antifungal susceptibility testing showed no significant difference in Candida species between RVVC and VVC patients. However, the serum levels of IFN-γ, TNF-α, and IL-17F in the RVVC group were significantly lower than those of the VVC group, while IL-4, IL-6, and IL-10 were higher in the RVVC patients than VVC patients. IL-17A and IL-2 levels were comparable between the two groups. Taken together, our results suggest that the host-immune responses, especially Th1/2 immunity, may play important roles in prognosis of RVVC and VVC.

Photodynamic therapy, a promising treatment approach for cutaneous infectious granulomas.

Cutaneous infectious granulomas are mainly caused by fungi and bacteria. Antibiotics are the primary therapeutic choices for these diseases, but drug-resistant pathogens have become increasingly prevalent. Thus, there is a need to explore novel approaches to treat cutaneous infectious granulomas. Photodynamic therapy (PDT) is widely used as a treatment for various kinds of skin diseases, and evidence has been accumulating that PDT is also effective for the treatment of cutaneous infectious granulomas. In this narrative review, we sought to summarize the recent literature concerning the applications and mechanisms of PDT in the treatment of cutaneous infectious granulomas. Clinical and basic research has demonstrated that PDT is an effective approach in treating fungal infections such as sporotrichosis and chromoblastomycosis. In addition, PDT is also used to treat atypical mycobacterial infections such as Mycobacterium marinum. PDT can significantly shorten the duration of antibiotics treatment, resulting in diminishment of adverse effects. The potential mechanisms of PDT are to kill the pathogens directly or elicit modulatory effects on the immune microenvironments. We conclude that PDT is a promising therapeutic choice for the treatment of cutaneous infectious granulomas.

5-aminolevulinic acid-photodynamic therapy ameliorates cutaneous granuloma by killing drug-resistant Mycobacterium marinum.

BACKGROUND: Although 5-aminolevulinic acid photodynamic therapy (ALA-PDT) has been extensively used to treat various skin diseases, application for the treatment of cutaneous infection caused by Mycobacterium marinum (M. marinum), especially drug-resistant M. marinum, is unclear. OBJECTIVES: We evaluated the efficacy of ALA-PDT on M. marinum in a mouse infection model and tested its killing effect on M. marinum in vitro. We also investigated the clinical effect of ALA-PDT on cutaneous granuloma caused by drug-resistant M. marinum. MATERIALS AND METHODS: A total of 9 M. marinum strains isolated from patients were tested for anti-mycobacterial susceptibility. The effects of ALA-PDT on M. marinum in vitro and in mice model were investigated. Therapeutic efficacy was further assessed in two patients with cutaneous granuloma caused by drug- resistant M. marinum. RESULTS: We demonstrated that ALA-PDT directly killed M. marinum in vitro. The cutaneous lesions on mouse paws caused by M. marinum were fully recovered 4 weeks after the ALA-PDT treatment. ALA-PDT was also effective in two patients with cutaneous infection caused by drug-resistant M. marinum. The level of intracellular ROS in M. marinum treated with ALA-PDT was significantly higher than that of M. marinum alone. CONCLUSIONS: The results suggest that ALA-PDT is effective in treating M. marinum cutaneous infections by releasing more reactive oxygen species to kill M. marinum directly, and these effects are independent of systemic immune responses. The data highlights that ALA-PDT is a promising therapeutic choice for treatment of M. marinum cutaneous infections, especially drug-resistant M. marinum infections.

Presence of Malassezia Hyphae Is Correlated with Pathogenesis of Seborrheic Dermatitis.

Seborrheic dermatitis (SD) is a common, chronic, and relapsing skin disease. The roles of Malassezia spp. in the pathogenesis of SD are still not clear due to the lack of direct evidence for the existence of hyphae within affected skin tissues. We set out to elucidate if Malassezia mycelium contributes to the onset and development of SD and if Malassezia mycelium is correlated with the clinical severity of SD patients. We detected Malassezia hyphae in patients with SD using potassium hydroxide (KOH) and calcofluor white (CFW) staining. Fluorescent microscopy was performed for the analysis of fungal cell wall and morphological characteristics of Malassezia under CFW staining. Culture growth in modified Dixon agar was used for DNA extraction and sequencing, and Malassezia species were confirmed by a sequencing data BLAST search against the NCBI database. We demonstrated that Malassezia hyphae were positively correlated with the clinical severity of SD patients (P = 3.1738 × 10-11). All the patients responded well to antifungal treatment. There is no significant difference for species dominance across the variant groups. However, the exact molecular mechanisms of how Malassezia spp. affect SD need to be further explored. The results show that Malassezia spp. in the hyphal stage are restricted to SD patients compared with healthy controls, suggesting that the presence of Malassezia hyphae contributes to the pathogenesis of SD. The results highlight the importance of the antifungal therapy for the future treatment of SD patients. IMPORTANCE Our results support the proposal that the hyphal form of Malassezia could be one of the pathogenic factors that contribute to SD, which has been previously less well studied. This clinical observation paves the way for further investigations of the molecular mechanisms of Malassezia hyphal pathogenicity in SD.

Evaluation of Droplet Digital PCR Assay for the Diagnosis of Candidemia in Blood Samples.

Numerous studies have shown that droplet digital PCR (ddPCR) is a promising tool for the diagnosis of pathogens, especially in samples with low concentrations of pathogenic DNA. An early diagnosis of candidemia is critical for the effective treatment of patients. In this study, we evaluated the sensitivity and specificity of ddPCR assay for Candida DNA detection both in vitro by mixing fungal cells with human blood and in vivo by analyzing blood samples from infected mice and patients with suspected candidemia. The results showed that ddPCR assay could detect a minimum of 4.5 DNA copies per reaction in blood samples. ddPCR showed higher sensitivity and specificity for Candida DNA detection than traditional culture and quantitative PCR (qPCR) methods and also exhibited significantly better positive and negative predictive values than the culture and qPCR methods that were commonly used in clinical practice. Hence, our study demonstrates that ddPCR assay is a promising method for the timely diagnosis of candidemia and could be useful for monitoring the treatment of candidemia.

Rapid detection of fungi from blood samples of patients with candidemia using modified calcofluor white stain.

We reported a modified CFW assay for rapid detection of fungi in blood samples and evaluated its efficacy in vivo and in vitro. The positive rate, sensitivity, and negative predictive values of the modified CFW method were all significantly higher than those of traditional fungal culture and KOH methods.

Onychomycosis with greenish-black discolorations and recurrent onycholysis caused by Candida parapsilosis.

Candida parapsilosis (C. parapsilosis) has become a common pathogen, especially in immunocompromised hosts. Here, we present an immunocompetent adult with greenish-black discoloration of the right first finger nail in combination with recurrent onycholysis. C. parapsilosis was isolated from the right first finger nail and was confirmed by morphological characteristics as well as by DNA molecular analysis. Patient was successfully treated with oral itraconazole in a regimen of 5 cycles of 200 mg twice daily for one week, followed by an interruption of treatment for 3 weeks. To our knowledge, this is the first report of C. parapsilosis-induced onychomycosis with recurrent onycholysis.