Allosteric Activator-Regulated CRISPR/Cas12a System Enables Biosensing and Imaging of Intracellular Endogenous and Exogenous Targets.

Sensors designed based on the trans-cleavage activity of CRISPR/Cas12a systems have opened up a new era in the field of biosensing. The current design of CRISPR/Cas12-based sensors in the "on-off-on" mode mainly focuses on programming the activator strand (AS) to indirectly switch the trans-cleavage activity of Cas12a in response to target information. However, this design usually requires the help of additional auxiliary probes to keep the activator strand in an initially "blocked" state. The length design and dosage of the auxiliary probe need to be strictly optimized to ensure the lowest background and the best signal-to-noise ratio. This will inevitably increase the experiment complexity. To solve this problem, we propose using AS after the "RESET" effect to directly regulate the Cas12a enzymatic activity. Initially, the activator strand was rationally designed to be embedded in a hairpin structure to deprive its ability to activate the CRISPR/Cas12a system. When the target is present, target-mediated strand displacement causes the conformation change in the AS, the hairpin structure is opened, and the CRISPR/Cas12a system is reactivated; the switchable structure of AS can be used to regulate the degree of activation of Cas12a according to the target concentration. Due to the advantages of low background and stability, the CRISPR/Cas12a-based strategy can not only image endogenous biomarkers (miR-21) in living cells but also enable long-term and accurate imaging analysis of the process of exogenous virus invasion of cells. Release and replication of virus genome in host cells are indispensable hallmark events of cell infection by virus; sensitive monitoring of them is of great significance to revealing virus infection mechanism and defending against viral diseases.

Multifunctional DNA Nanoflower Applied for High Specific Photodynamic Cancer Therapy In Vivo.

Photodynamic therapy (PDT) is a newly emerged strategy for disease treatment. One challenge of the application of PDT drugs is the side-effect caused by the non-specificity of the photosensitive molecules. Most of the photosensitizers may invade not only the pathogenic cells but also the normal cells. In recent, people tried to use special cargoes to deliver the drugs into target cells. DNA nanoflowers (NFs) are a kind of newly-emerged nanomaterial which constructed through DNA rolling cycle amplification (RCA) reaction. It is reported that the DNA NFs were suitable materials which have been widely applied as nanocargos for drug delivery in cancer chemotherapeutic treatment. In this paper, we have introduced a new multifunctional DNA NF which could be prepared through an one-pot RCA reaction. This proposed DNA NF contained a versatile AS1411 G-quadruplex moiety, which plays key roles not only for specific recognition of cancer cells but also for near-infrared ray based photodynamic therapy when conjugating with a special porphyrin molecule. We demonstrated that the DNA NF showed good selectivity toward cancer cells, leading to highly efficient photo-induced cytotoxicity. Moreover, the in vivo experiment results suggested this DNA NF is a promising nanomaterial for clinical PDT.

MiR-125b-1-3p-mediated UQCRB inhibition facilitates mitochondrial metabolism disorders in a rat cellular senescencemodel.

BACKGROUD: Cellular senescence is closely related to human aging and multiple aging-related diseases, and impaired mitochondrial energy metabolism is an important mechanism of cellular senescence. Notably, microRNA-125b-1-3p (miR-125b-1-3p) is a microRNA (miR, miRNA) that may be associated with mitochondrial energy metabolism. Ubiquinol-cytochrome c reductase binding protein (UQCRB) gene, predicted by bioinformatics tools to be targeted by miR-125b-1-3p, could serve as a novel diagnostic indicator and therapeutic target for cellular senescence-associated diseases, as well as a new idea for delaying aging. METHODS: First, the dual-luciferase reporter gene assay was used to identify UQCRB as a target gene of miR-125b-1-3p. Next, miRNA interference technology was conducted to verify that miR-125b-1-3p could negatively regulate the expression of UQCRB. Subsequently, the influence of miR-125b-1-3p on mitochondrial energy metabolism function was explored by observing the internal substances and ultrastructure of mitochondria. Further, an in vitro model of cellular senescence was established in rat renal tubular epithelial cells, which was characterized by detecting senescence-related proteins p16 and p21 and beta-galactosidase (ß-gal) activity. Finally, the mitochondrial energy metabolism function of hydrogen peroxide (H2O2)-incubated cells was explored. RESULTS: The experimental results revealed that miR-125b-1-3p affected the mitochondrial energy metabolism function by inhibiting the target gene UQCRB. Meanwhile, the level of mitochondrial energy metabolism function in H2O2-incubated senescent cells was lower than that in normal cells. CONCLUSION: In this study, we identified the target gene, UQCRB, of miR-125b-1-3p, and demonstrated its role in the pathway of mitochondrial energy metabolism, as well as its possible effect on cellular senescence through this pathway. The ameliorative effects on cellular senescence can be further explored in subsequent studies to provide additional options for delaying aging or treating aging-related diseases.

Uncovering the Nexus between Urban Heat Islands and Material Stocks of Built Environment in 335 Chinese Cities.

China's unprecedented rapid urbanization has dramatically reshaped the urban built environment, disrupting the thermal balance of cities. This disruption causes the urban heat island (UHI) effect, adversely affecting urban sustainability and public health. Although studies have highlighted the remarkable impacts of the built environment on UHIs, the specific effects of its various structures and components remain unclear. In this study, a multidimensional remote sensing data set was used to quantify the atmospheric UHIs across 335 Chinese cities from 1980 to 2020. In conjunction with stocks of three end-use sectors and three material groups, the impacts of gridded material stocks on UHI variations were analyzed. The findings reveal that building stocks exert a predominant influence in 48% of cities. Additionally, the extensive use of metal and inorganic materials has increased thermal stress in 220 cities, leading to an average UHI increase of 0.54 °C. The effect of organic materials, primarily arising from mobile heat sources, is continuously increasing. Overall, this study elucidates the effect of the functional structure and material composition of urban landscapes on UHIs, highlighting the complexities associated with the influence of the built environment on the urban heat load.

Epidemiologic features and therapeutic strategies of kerion: A nationwide multicentre study.

BACKGROUND: Kerion is a severe type of tinea capitis that is difficult to treat and remains a public health problem. OBJECTIVES: To evaluate the epidemiologic features and efficacy of different treatment schemes from real-world experience. METHODS: From 2019 to 2021, 316 patients diagnosed with kerion at 32 tertiary Chinese hospitals were enrolled. We analysed the data of each patient, including clinical characteristics, causative pathogens, treatments and outcomes. RESULTS: Preschool children were predominantly affected and were more likely to have zoophilic infection. The most common pathogen in China was Microsporum canis. Atopic dermatitis (AD), animal contact, endothrix infection and geophilic pathogens were linked with kerion occurrence. In terms of treatment, itraconazole was the most applied antifungal agent and reduced the time to mycological cure. A total of 22.5% of patients received systemic glucocorticoids simultaneously, which reduced the time to complete symptom relief. Furthermore, glucocorticoids combined with itraconazole had better treatment efficacy, with a higher rate and shorter time to achieving mycological cure. CONCLUSIONS: Kerion often affects preschoolers and leads to serious sequelae, with AD, animal contact, and endothrix infection as potential risk factors. Glucocorticoids, especially those combined with itraconazole, had better treatment efficacy.

Metagenomic Next-Generation Sequencing Contributes to the Early Diagnosis of Mixed Infections in Central Nervous System.

Central nervous system (CNS) infections represent a challenge due to the complexities associated with their diagnosis and treatment, resulting in a high incidence rate and mortality. Here, we presented a case of CNS mixed infection involving Candida and human cytomegalovirus (HCMV), successfully diagnosed through macrogenomic next-generation sequencing (mNGS) in China. A comprehensive review and discussion of previously reported cases were also provided. Our study emphasizes the critical role of early pathogen identification facilitated by mNGS, underscoring its significance. Notably, the integration of mNGS with traditional methods significantly enhances the diagnostic accuracy of CNS infections. This integrated approach has the potential to provide valuable insights for clinical practice, facilitating early diagnosis, allowing for treatment adjustments, and ultimately, improving the prognosis for patients with CNS infections.

NLRP3 inflammasome activation contributes to fungal clearance and lung injury during Talaromyces marneffei infection.

The increased levels of IL-1ß and IL-18 cytokines have been associated with the severity of sepsis and outcomes of patients infected with Talaromyces marneffei. Previous studies have suggested that NLRP3 plays an important role in caspase-1 activated secretion of IL-1ß and IL-18 in fungal-infected macrophages. In the present study, the role of the NLRP3 inflammasome in talaromycosis is investigated in an in vitro assay and in vivo with a mice systemic infection model. We found that the NLRP3 inflammasome pathway in infected mice is activated along with increased production of IL-1ß. Such an activation of the NLRP3 inflammasome is also observed in either mice or human macrophages challenged with T. marneffei conidia. Our results indicate that IL-1ß release by infected macrophages is NLRP3 inflammasome-dependent and NLRP3 contributes to death of mice at the early stage of pulmonary infection. Moreover, a greater number of MPO-positive cells are found in the lungs of infected Nlrp3-/- mice and WT mice with reduced LDH levels, especially at the last stage of infection. Therefore, we conclude that the NLRP3 Inflammasome activation is important for fungal clearance, neutrophil recruitment and lung injury during T. marneffei Infection.

Autophagy benefits the in vitro and in vivo clearance of Talaromyces marneffei.

Talaromycosis, namely Talaromyces marneffei infection, is increasing gradually and has a high mortality rate even under antifungal therapy. Although autophagy acts differently on different pathogens, it is a promising therapeutic strategy. However, information on autophagy in macrophages and animals upon infection by T. marneffei is still limited. Therefore, several models were employed here to investigate the role of autophagy in host defense against T. marneffei, including RAW264.7 macrophages as in vitro models, different types of Caenorhabditis elegans and BALB/c mice as in vivo models. We applied the clinical T. marneffei isolate SUMS0152 in this study. T. marneffei-infected macrophages exhibit increased formation of autophagosomes. Further, macrophage autophagy promoted by rapamycin or Earle's balanced salt solution (EBSS) inhibited the viability of intracellular T. marneffei. In vivo, compared with uninfected Caenorhabditis elegans, the wild-type nematodes upregulated the expression of the autophagy-related gene lgg-1 and atg-18, and nematodes carrying GFP reporter were induced to form autophagosomes (GFP::LGG-1) after T. marneffei infection. Furthermore, the knockdown of lgg-1 significantly reduced the survival rate of T. marneffei-infected nematodes. Likewise, the autophagy activator rapamycin reduced the fungal burden and suppressed lung inflammation in a mouse model of infection. In conclusion, autophagy is essential for host defense against T. marneffei in vitro and in vivo. Therefore, autophagy may be an attractive target for developing new therapeutics to treat talaromycosis.

The relationship between the preference of mating type (MAT) and source in the opportunistic pathogen Talaromyces marneffei.

Genome-wide comparisons have shown Talaromyces marneffei possessed a stable mating type locus in its meiosis genes. But the function of the mating type locus in T. marneffei is not clear. The potential sex recombination might lead to problems in clinical, such as the evolution of increased resistance to antifungal drugs and virulence. To determine the mating type in a sample of 107 T. marneffei isolates and to explore the possible relationship between fungus virulence and mating type or source. We used PCR analysis to determine the distribution of mating type genes and also analyzed the relationship between mating type and isolated sources (including HIV-positive patients, HIV-negative patients, bamboo rats, and the environment). Further, the Drosophila melanogaster model of infection was used to compare the differences of virulence in mating type and sources. Our results showed the entire sample population of T. marneffei with an overabundance of MAT1-2 alleles, but with a higher ratio of MAT1-1 in the isolates from HIV-negative patients. However, no significant differences in the survival of the D. melanogaster infected neither with MAT1-1 (6.5 days) nor MAT1-2 (4 days) isolates. Similar results were also observed in virulence analysis tested with different sources of isolates. So, we found that all isolates bore single mating type idiomorphs and unequal distribution. The distribution of the MAT genes seems related to different sources. And the virulence differences are independent of mating type genotype and source.

Our work shows the entire sample population of 107 Talaromyces marneffei isolates with an overabundance of MAT1-2 alleles, but with a higher ratio of MAT1-1 in the isolates from HIV-negative patients. And fungus virulence is independent of mating type genotype and source in the Drosophila melanogaster model.

Epidemiological characteristics and spatiotemporal analysis of mumps at township level in Wuhan, China, 2005-2019.

The resurgence and outbreaks of mumps occur frequently in many countries worldwide in recent years, even in countries with high vaccination coverage. In this study, a descriptive and spatiotemporal clustering analysis at the township level was conducted to explore the dynamic spatiotemporal aggregation and epidemiological characteristics of mumps in Wuhan. During 2005 and 2019, there were 40 685 cases reported in Wuhan, with an average annual morbidity of 28.11 per 100 000 populations. The morbidity showed a fluctuating tendency, and peaked in 2010 and 2018. Bimodal seasonality was found, with a large peak between May and July, and a mild peak from November to January in the following year. Male students aged 5-9-year-old were the main risk group of mumps infection. Significant global spatial auto-correlation was detected except in 2007, 2009 and 2015. The spatial and temporal scan statistics indicated that the hot-spots mainly located at the western and southern areas of Wuhan with variations almost every year. Our findings could assist the public health authorities to develop and improve targeted health strategies, and allocate health resources rationally.

Detection rates of abnormalities in over 10,000 amniotic fluid samples at a single laboratory.

BACKGROUND: A growing number of cytogenetic techniques have been used for prenatal diagnosis. This study aimed to demonstrate the usefulness of karyotyping, BACs-on-Beads (BoBs) assay and single nucleotide polymorphism (SNP) array in prenatal diagnosis during the second trimester based on our laboratory experience. METHODS: A total of 10,580 pregnant women with a variety of indications for amniocentesis were enrolled in this retrospective study between January 2015 and December 2020, of whom amniotic fluid samples were analysed in 10,320 women. The main technical indicators of participants in the three different technologies were summarized, and cases of chromosome abnormalities were further evaluated. RESULTS: The overall abnormality detection rate of karyotyping among all the amniotic fluid samples was 15.4%, and trisomy 21 was the most common abnormality (20.9%). The total abnormality detection rate of the BoBs assay was 5.6%, and the diagnosis rate of microdeletion/microduplication syndromes that were not identified by karyotyping was 0.2%. The detection results of the BoBs assay were 100.0% concordant with karyotyping analysis in common aneuploidies. Seventy (87.5%) cases of structural abnormalities were missed by BoBs assay. The total abnormality detection rate of the SNP array was 21.6%. The detection results of common aneuploidies were exactly the same between SNP array and karyotyping. Overall, 60.1% of structural abnormalities were missed by SNP array. The further detection rate of pathogenic significant copy number variations (CNVs) by SNP was 1.4%. CONCLUSIONS: Karyotyping analysis combined with BoBs assay or SNP array for prenatal diagnosis could provide quick and accurate results. Combined use of the technologies, especially with SNP array, improved the diagnostic yield and interpretation of the results, which contributes to genetic counselling. BoBs assay or SNP array could be a useful supplement to karyotyping.

Prevalence and Antifungal Susceptibility of Sporothrix species in Guangzhou, Southern China.

INTRODUCTION: Sporotrichosis is a subcutaneous and chronic infection caused by traumatic inoculation of pathogenic sporothrix species, usually infecting the skins and subcutaneous tissues of humans and animals. However, the lack of epidemiological data required further molecular identification to describe the distribution of this fungus in our region. In this study, forty-eight clinical sporothrix isolated from Sun Yat-Sen Memorial Hospital were classified, and the susceptibility of each strain to seven antifungal agents was determined. METHODS: Forty strains of S. globosa and eight strains of S. shenkshii were identified via colony morphology and PCR sequencing of calmodulin gene. RESULTS: Antifungal susceptibility tests of the mycelial phase in vitro showed terbinafine (TRB) and luliconazole (LULI) were the most effective, followed by itraconazole (ITZ) and amphotericin B (AMB). By contrast, voriconazole (VCZ), 5-flucytosine (5FC) and fluconazole (FCZ) have low efficacy with high MIC. CONCLUSION: Our results showed a predominantly S. globosa infection trend in southern China. Simultaneously, sporothrix is sensitive to TRB, LULI, ITZ and AMB whereas resistant to FCZ. This study firstly reports antifungal sensitivity test in vitro and epidemiological correlation analysis of sporothrix in southern China, and also the first time to find that sporothrix is sensitive to LULI.

Combination therapy with itraconazole and terbinafine for phaeohyphomycosis caused by Exophiala spinifera: A case report and literature review.

Exophiala spinifera is a rare dematiaceous fungus causing cutaneous, subcutaneous and disseminated phaeohyphomycosis (PHM). Standard antifungal therapy for PHM is still uncertain. Here, we report a case of a Chinese male with PHM caused by E. spinifera, who received significant clinical improvement after the treatment with oral itraconazole and terbinafine. With the aim of evaluating the antifungal therapy for PHM caused by E. spinifera, a detailed review was performed.

Epidemiology and Clinical Findings of Tinea Capitis: A 23-Year Retrospective, Single-Center Study in Guangzhou, China.

BACKGROUND: Tinea capitis (TC) is one of the most common public health concerns due to its high incidence in preadolescent children. The epidemiological and clinical characteristics of TC vary depending on geographical regions and have changed over the past decades. OBJECTIVES: This study aimed to identify epidemiological changes in recent decades, including the prevalence and clinical and mycological characteristics of TC in southern China. METHODS: We conducted a retrospective study at the Department of Dermatology of Sun Yat-sen Memorial Hospital, Sun Yat-sen University from June 1997 to August 2020. RESULTS: We retrospectively evaluated 401 TC patients. Of these, 157 patients (39.2%) were preschool children aged 3-7 years and the majority were males. However, the prevalence in children under 3 years old is on the rise (from 19.67% during 1997-2010 to 32.49% during 2011-2020). Grey patches were the most common clinical pattern and mostly occurred in children (71.3%), while the proportion of grey patches and black dots was almost the same in adults. Although Microsporum canis (76%) was the most common causative organism, the number of the T. mentagrophytes complex, as a zoophilic fungus, has increased more than that of the anthropophilic fungi T. violaceum in the recent decade. There was a significant difference in the portion of sex among different age groups, and the gender difference was more notable in the adult group, which showed that the TC prevalence in females was 9 times that in males. In males, M. canis and the T. mentagrophytes complex were the two most common causative fungi, while M. canis and T. violaceum were the two most common causative fungi in females. Additionally, approximately 61.7% of black dot TCs occurred in females. For treatment, oral antifungal therapeutics were widely used in most patients with different treatment durations, although without a significant difference in efficacy (P = 0.106). CONCLUSIONS: In the last decade, the prevalence of TC in children under 3 years old increased, and boys dramatically outnumbered girls. In adults, the TC prevalence in females is nine times that in males, and most TCs occurring in females are presented as black dots. Moreover, the zoophilic T. mentagrophytes complex has replaced T. violaceum and is now the second most prevalent organism, followed by M. canis of TC.

A temporospatial assessment of environmental quality in urbanizing Ethiopia.

Global environmental quality has been negatively affected by urbanization, particularly vulnerable in the Sub-Saharan Africa. Therefore, understanding the underlying mechanism and driving forces for the change of environmental quality with urbanization process is essential to improve the environmental sustainability. In this study, the compounded night light index (CNLI) and remote sensing ecological index (RSEI) were used respectively to evaluate the urbanization level and environmental quality in Ethiopia from 2010 to 2020. On this basis, a temporospatial assessment framework was proposed, followed by methods of coupling coordination degree, spatial autocorrelation, elasticity, and decomposition. The results showed that 63 out of 690 woredas experienced environmental deterioration. Socioeconomic effect, carbon intensity, and climate change were decomposed as drivers to environmental quality, with socioeconomic effects contributing >68% of environmental improvement, while carbon intensity and climate change were responsible for >51% and >58% of environmental deterioration from 2010 values. Continuous increase in impervious surfaces resulted in a six-fold increase in surface runoff, which raised the flooding risk in sub areas and rural landscapes. This demands reforms of climate strategies and proper livestock management.

The interactive effects of pre-pregnancy body mass index, thyroid function, and blood lipid levels on the risk of gestational diabetes mellitus: a crossover analysis.

BACKGROUND: Studies have demonstrated the associations between pre-pregnancy obesity, thyroid dysfunction, dyslipidemia, and increased risk of gestational diabetes mellitus (GDM) in pregnant women. This study was designed to investigate whether and to what extent, the interactions between these factors contribute to the risk of GDM. METHODS: A case-control study of 232 GDM cases and 696 controls was conducted among pregnant women from Hangzhou, China. Multiple logistic regression analysis was applied to identify independent risk factors of GDM. Crossover analysis was performed to assess the interactive effects of pre-pregnancy body mass index (pBMI), thyroid hormones, and blood lipid profiles on the risk of GDM. The indexes including attributable proportion (AP) to the interaction and the relative excess risk due to interaction (RERI) were calculated. RESULTS: Chinese pregnant women with pBMI > 23 kg/m2 (adjusted: OR = 4.162, p < 0.001), high triglyceride levels (> 2.30 mmol/L) (adjusted: OR = 1.735, p < 0.001), and the free triiodothyronine/free thyroxine (FT3/FT4) ratio ≥ 0.502 (OR = 4.162, p < 0.001) have significantly increased risk of GDM. Crossover analysis indicated that there were significant interactions between pre-pregnancy overweight/obesity and FT3/FT4 ≥ 0.502 (AP = 0.550, p < 0.001; RERI = 7.586, p = 0.009), high TG levels and FT3/FT4 ≥ 0.502 (AP = 0.348, 95%CI = 0.081-0.614, P = 0.010; RERI = 2.021, 95%CI = 0.064-3.978, p = 0.043) on the risk of GDM. CONCLUSION: The interactions between pBMI and FT3/FT4 ratio, TG level and FT3/FT4 ratio may have significant impacts on the risk of GDM in pregnant women. Such findings may help improve our understanding of the pathogenesis of GDM as well as develop comprehensive strategies for the management of GDM.

Deep learning-based diagnosis models for onychomycosis in dermoscopy.

BACKGROUND: Onychomycosis is a common disease. Emerging noninvasive, real-time techniques such as dermoscopy and deep convolutional neural networks have been proposed for the diagnosis of onychomycosis. However, deep learning application in dermoscopic images has not been reported. OBJECTIVES: To explore the establishment of deep learning-based diagnostic models for onychomycosis in dermoscopy to improve the diagnostic efficiency and accuracy. METHODS: We evaluated the dermoscopic patterns of onychomycosis diagnosed at Sun Yat-sen Memorial Hospital, Guangzhou, China, from May 2019 to February 2021 and included nail psoriasis and traumatic onychodystrophy as control groups. Based on the dermoscopic images and the characteristic dermoscopic patterns of onychomycosis, we gain the faster region-based convolutional neural networks to distinguish between nail disorder and normal nail, onychomycosis and non-mycological nail disorder (nail psoriasis and traumatic onychodystrophy). The diagnostic performance is compared between deep learning-based diagnosis models and dermatologists. RESULTS: All of 1,155 dermoscopic images were collected, including onychomycosis (603 images), nail psoriasis (221 images), traumatic onychodystrophy (104 images) and normal cases (227 images). Statistical analyses revealed subungual keratosis, distal irregular termination, longitudinal striae, jagged edge, and marble-like turbid area, and cone-shaped keratosis were of high specificity (>82%) for onychomycosis diagnosis. The deep learning-based diagnosis models (ensemble model) showed test accuracy /specificity/ sensitivity /Youden index of (95.7%/98.8%/82.1%/0.809) and (87.5%/93.0%/78.5%/0.715) for nail disorder and onychomycosis. The diagnostic performance for onychomycosis using ensemble model was superior to 54 dermatologists. CONCLUSIONS: Our study demonstrated that onychomycosis had distinctive dermoscopic patterns, compared with nail psoriasis and traumatic onychodystrophy. The deep learning-based diagnosis models showed a diagnostic accuracy of onychomycosis, superior to dermatologists.

[Interaction between Abnormal Prepregnancy Body Mass Index and Hyperlipidemia during Pregnancy on the Risk of Gestational Diabetes Mellitus].

Objective To explore the interaction between abnormal prepregnancy body mass index(pBMI)and high blood lipid level during pregnancy on the risk of gestational diabetes mellitus(GDM). Methods A total of 235 patients with GDM and no blood lipid-related diseases before pregnancy were selected from Hangzhou Women's Hospital during March 2017 to July 2018 as the GDM group.At a ratio of 1∶3,a total of 705 individual age-matched pregnant women with normal glucose metabolism during prenatal examination from the same hospital were selected as the control group.The generalized multifactor dimension reduction(GMDR)method was employed to characterize the possible interaction between pBMI-blood lipid and GDM.The cross-validation consistency,equilibrium test accuracy,and P value were calculated to evaluate the interaction of each model. Results GMDR model analysis showed that the second-order model including pBMI and gestational blood lipid level had the best performance(P=0.001),with the cross-validation consistency of 10/10 and the equilibrium test accuracy of 64.48%,suggesting that there was a potential interaction between pBMI and gestational high blood lipid level.After adjustment of confounding factors,the model demonstrated that overweight/obesity patients with high triglyceride(TG) level had the highest risk of developing GDM(OR=14.349,95%CI=6.449-31.924,P<0.001).Stratified analysis showed that overweight/obesity patients under high TG level group had a higher risk of developing GDM than normal weight individuals(OR=2.243,95%CI=1.173-4.290,P=0.015). Conclusions Abnormal pBMI and high blood lipid level during pregnancy are the risk factors of GDM and have an interaction between each other.Overweight/obese pregnant women with high TG levels are more likely to develop GDM.

Oxygen Vacancy Engineering of Titania-Induced by Sr2+ Dopants for Visible-Light-Driven Hydrogen Evolution.

A Sr2+-doping strategy is developed to engineer rich oxygen vacancies in porous titania for boosting visible-light-driven photocatalytic activity. The incorporation of strontium, with a larger atom radius than titanium, leads to the release of a lattice oxygen atom in the titania, causing the generation of an oxygen vacancy. The optimal Sr2+-doped titania sample with rich oxygen vacancies achieves a photocatalytic hydrogen production rate as high as 1092 µmol h-1 g-1, which is 4 and 16 times higher than the unmodified titania with less oxygen vacancies and the bench-marked P25, respectively.

Combinatory Effect of ALA-PDT and Itraconazole Treatment for Trichosporon asahii.

BACKGROUND AND OBJECTIVES: Trichosporiosis is an opportunistic infection that includes superficial infections, white piedra, hypersensitivity pneumonitis, and invasive trichosporonosis. The effect of antifungal agents against these infections is largely weakened by drug resistance and biofilms-related virulence. Photodynamic therapy (PDT) is a new therapeutic approach developed not only to combat cancerous lesions but also to treat infectious diseases such as fungal infections. However, there are few studies on the antimicrobial mechanism of 5-aminolevulinic acid PDT (ALA-PDT) in treating Trichosporon. In this work, we explored the possibility of combining ALA-PDT with an antifungal agent to enhance the therapeutic efficacy of Trichosporon asahii (T. asahii) in a clinical setting and in vitro. STUDY DESIGN/MATERIALS AND METHODS: The biofilms of T. asahii were constructed by a 96-well plate-based method in vitro. The planktonic and adherent T. asahii were exposed to different concentrations of photosensitizers and different light doses. After PDT treatment, counting colony-forming units and tetrazolium (XTT) reduction assay were used to estimate the antifungal efficacy. The minimal inhibitory concentration of itraconazole before and after PDT treatment was determined by the broth dilution method, and XTT viability assay was used to detect and evaluate the synergistic potential of ALA-PDT and itraconazole combinations in inhibiting biofilms. Scanning electron microscopy (SEM) was performed to assess the disruption of biofilms. RESULTS: Using combination therapy, we have successfully treated a patient who had a T. asahii skin infection. Further in vitro studies showed that the antifungal effect of ALA-PDT on planktonic and adherent T. asahii was dependent on the concentration of ALA and light dosages used. We also found that the sensitivity of both planktonic and biofilm cells to itraconazole were increased after ALA-PDT. Synergistic effect were observed for biofilms in ALA-PDT and itraconazole-combined treatment. The disruption of biofilms was confirmed by SEM, suggesting that ALA-PDT effectively damaged the biofilms and the destruction was further enhanced by ALA-PDT combination of antifungal agents. CONCLUSIONS: In conclusion, these data suggest that ALA-PDT could be an alternative strategy for controlling infections caused by Trichosporon. The combination therapy of ALA-PDT with itraconazole could result in increased elimination of planktonic cells and biofilms compared with single therapy. All these findings indicate that it could be a promising treatment against trichosporonosis. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.