Theoretical calculations and experimental verification of carbon dioxide reduction electrocatalyzed by metalloporphyrin.

Metal-functionalized porphyrin-like graphene structures are promising electrocatalysts for carbon dioxide reduction reaction (CO2RR) as their metal centers can modulate activity. Yet, the role of metal center of metalloporphyrins (MTPPs) in CO2 reaction activity is still lacking deep understanding. Here, CO2RR mechanism on MTPPs with five different metal centers (M = Fe, Co, Cu, Zn and Ni) are examined by first-principles calculations. The *COOH formation is the rate determined step on the five MTPP structures, and the CoTPP exhibits the best CO2RR activity while ZnTPP and NiTPP are the worst, which is also verified by our experiment. The CO2RR activity is controlled by adsorption states of intermediates (*CO, *COOH), i.e., chemisorption (e.g., on CoTPP) and physisorption (on ZnTPP and NiTPP) of intermediates will lead to good and poor activity, respectively. The deeper the d-band center of the porphyrin ring complexed metal atom, the weaker bonding of MTPP with CO and COOH. Theoretical calculations and experimental results indicate that MTPPs with Co and Fe centers lead to a reduction in the energy barriers for the two uphill reaction steps in the electrocatalytic CO2 reduction process, thereby enhancing CO2 reduction electrocatalytic activity. Faradaic efficiency of CO is correlated with the reaction energy barrier of the first proton-coupled electron reduction process, displaying a strong linear correlation. This work provides a fundamental understanding of MTPPs used as electrocatalysts for CO2RR.

In vitro and in vivo synergistic effects of hydroxychloroquine and itraconazole on Cryptococcus neoformans.

Cryptococcus neoformans is an opportunistic fungal pathogen that can cause life-threatening invasive fungal infections. As its prevalence and drug resistance continue to rise, cryptococcosis requires new treatment options. Tapping into the potential antifungal effects of traditional drugs or combination therapy has become one of the options. This study was the first to examine the interaction of hydroxychloroquine (HCQ) and itraconazole (ITR) on Cryptococcus neoformans in vitro and in vivo. Our results showed that HCQ alone and in combination with ITR exhibited antifungal activity against C. neoformans planktonic cells. When HCQ was combined with ITR, the minimal inhibitory concentration (MIC) value of HCQ decreased to 32 µg/mL, and the MIC value of ITR decreased from 0.25 µg/mL to 0.06-0.25 µg/mL. The time-killing curve showed that the combined application of HCQ and ITR significantly shortened the killing time, dynamically defining the antifungal activity. The minimum biofilm clearance concentration (MBEC) of HCQ was only 32 µg/mL, which was significantly lower than the MIC of HCQ for planktonic cells. When combined with ITR, the MBEC of ITR decreased from 128 µg/mL to 2-1 µg/mL, and the MBEC of HCQ decreased from 32 µg/mL to 4 µg/mL, indicating a synergistic antifungal biofilm effect. In comparison to ITR alone, the combination of HCQ and ITR treatment increased the survival of C. neoformans-infected Galleria mellonella larvae and decreased the fungal burden of infected larvae. Mechanistic investigations revealed that HCQ might damage C. neoformans cell membranes, impact the structure of fungal cells, cause extracellular material leakage, and have a potent affinity for attaching to the C. neoformans genomic DNA. In conclusion, HCQ has potential clinical application in the treatment of cryptococcosis.

Human Disseminated Protothecosis: The Skin is the "Window"?

Human disseminated protothecosis is a rare infection caused by members of the genus Prototheca, an achlorophyllic algae always associated with debilitated hosts. The presence of non-budding cells and large, spherical cells (sporangia) with endosporulation (morula) in histology is proof of Prototheca infection. Regrettably, due to the lack of specificity of clinical features and low awareness among clinicians, protothecosis is always underestimated and misdiagnosed. The available data on a species-specific analysis of this infection are limited. In this review, we summarize the etiological, epidemiological, and clinical aspects of disseminated protothecosis. The potential pathogenicity and clinical differences between P. zopfii and P. wickerhamii were observed. Additionally, the skin not only became the main invasion site but also the most involved organ by the pathogen. With the increasing numbers of immunocompromised individuals throughout the world, the incidence of disseminated infection caused by Prototheca is bound to increase, and disseminated protothecosis that accompanies skin symptoms should be taken into account by clinicians.

The epidemic of the multiresistant dermatophyte Trichophyton indotineae has reached China.

Due to its high degree of natural resistance to terbinafine in vitro and its tendency to spread globally from the Indian subcontinent, the emerging dermatophyte Trichophyton indotineae has become a major concern in dermatology. Herein, we present the first report of T. indotineae from mainland China. The transmission of the fungus to Guizhou Province in central China and eventual host susceptibilities were investigated. We studied 31 strains of the T. mentagrophytes complex from outpatient clinics of our hospital collected during the past 5 years. The set comprised four ITS genotypes, two of which were T. mentagrophytes genotype VIII, now known as Trichophyton indotineae; the earliest isolation in the Guiyang area appeared to date back to 2018. The isolate was derived from an Indian patient, while local Chinese patients had no dermatophytosis caused by this genotype. Reports from around the world indicated that almost all of the globally reported T. indotineae cases originated from the Indian subcontinent and surrounding countries without transmission among native populations, suggesting deviating local conditions or racial differences in immunity against this fungus.

[Role of noninvasive mechanical ventilation in patients with severe avian influenza A (H7N9) complicated with acute respiratory distress syndrome].

OBJECTIVE: Human infection with avian influenza A (H7N9) is an acute contagious respiratory disease. Acute respiratory distress syndrome (ARDS) is a common complication in patients with severe avian influenza A (H7N9), for whom mechanical ventilation (MV) is an important supportive method. A patient, suffered from severe avian influenza A (H7N9) and complicated with ARDS, was admitted to the Second Affiliated Hospital of Guizhou Medical University in January 2017. With very intensive care for oxygenation, respiration and consciousness, and monitoring, she was successfully cured by comprehensive managements, among which noninvasive mechanical ventilation (NIV) was the major respiratory support method. The result demonstrate that, in patients with conscious state, satisfied expectoration ability and relatively good cooperation, and with close observation of oxygenation and respiratory rate, NIV may be accepted as an effective method for patient with ARDS caused by severe avian influenza A (H7N9).

Clinical characteristics from co-infection with avian influenza A H7N9 and Mycoplasma pneumoniae: a case report.

BACKGROUND: More and more cases of human infections with avian influenza A H7N9 have been reported since it was first mentioned in 2013 in China, but concurrence of influenza A H7N9 with Mycoplasma pneumoniae, however, has never been described. Here, we reported the case of a woman co-infected by influenza A H7N9 and Mycoplasma pneumoniae, whose treatment process was a little bit longer and a little bit complicated as well. CASE PRESENTATION: Our patient was an 80-year-old Chinese woman who presented with fever, cough, chest tightness, and shortness of breath. A computed tomography scan showed obvious infiltrations at lower parts of both lungs. Arterial blood gas analysis confirmed a severe respiratory failure (type I). Her sputum and throat swabs were checked for nucleic acid of influenza A and the result was positive for influenza A H7N9. She was diagnosed as having severe influenza A H7N9 and acute respiratory distress syndrome, and was admitted to an intensive care unit. She was given comprehensive treatment, including oseltamivir, methylprednisolone, immunoglobulin, gastric protection, and noninvasive mechanical ventilation. Her condition improved 4 days later. However, some symptoms exacerbated again 2 days later with ground-glass changes appearing in upper area of right lung and the titer of antibody to Mycoplasma pneumoniae rising from 1:80 to 1:640. She was reasonably considered to be infected with Mycoplasma pneumoniae as well, and azithromycin and moxifloxacin were added to her treatment. Oseltamivir was discontinued because of three consecutive negative results of nucleic acid for influenza A H7N9, but anti-Mycoplasma treatment was continued. Although her symptoms and abnormal changes on computed tomography scan slowly went away, she finally recovered from the mixed infection after a total of 33 days of management. CONCLUSION: In patients with confirmed influenza A H7N9 infection whose condition worsens again, especially with new infiltration or lung ground-glass infiltration, one should suspect infection by other pathogens such as Mycoplasma pneumoniae.

[A case of the severe human infection by avian influenza H7N9 was rescued successfully by the sepsis bundle].

OBJECTIVE: One confirmed diagnosis case of severe human infection by avian influenza H7N9 admitted to intensive care unit (ICU) of the Second Affiliated Hospital of Guizhou Medical University on January 12th, 2017 was reported. The patient was treated with the sepsis bundle, and recovered finally, including a series of comprehensive treatments, such as respiratory support, circulation support, antiviral, anti-inflammation, immunization enhancement, critical nursing, fluid management, nutritional support and treatment of complications. The critical patient was admitted on January 27th, and the treatment was successful. It has important significance to rescue the severe human infection from avian influenza H7N9 by the sepsis bundle.