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Abstract Objective To compare the outcomes of patients undergoing Retroperitoneal laparoscopic Radical nephrectomy (RLRN) and Transperitoneal laparoscopic Radical nephrectomy (TLRN). Methods A total of 120 patients with localized renal cell carcinoma were randomized into either RLRN or TLRN group. Mainly by comparing the patient perioperative related data, surgical specimen integrity, pathological results and tumor results. Results Each group comprised 60 patients. The two group were equivalent in terms of perioperative and pathological outcomes. The mean integrity score was significantly lower in the RLRN group than TLRN group. With a median follow-up of 36.4 months after the operation, Kaplan–Meier survival analysis showed no significant difference between RLRN and TLRN in overall survival (89.8% vs. 88.5%; P = 0.898), recurrence-free survival (77.9% vs. 87.7%; P = 0.180), and cancer-specific survival (91.4% vs. 98.3%; P = 0.153). In clinical T2 subgroup, the recurrence rate and recurrence-free survival in the RLRN group was significantly worse than that in the TLRN group (43.2% vs. 76.7%, P = 0.046). Univariate and multivariate COX regression analysis showed that RLRN (HR: 3.35; 95%CI: 1.12–10.03; P = 0.030), male (HR: 4.01; 95%CI: 1.07–14.99; P = 0.039) and tumor size (HR: 1.23; 95%CI: 1.01–1.51; P = 0.042) were independent risk factor for recurrence-free survival. Conclusions Our study showed that although RLRN versus TLRN had roughly similar efficacy, TLRN outperformed RLRN in terms of surgical specimen integrity. TLRN was also significantly better than RLRN in controlling tumor recurrence for clinical T2 and above cases. Trial registration Chinese Clinical Trial Registry ( https://www.chictr.org.cn/showproj.html?proj=24400 ), identifier: ChiCTR1800014431, date: 13/01/2018.

Although significant progress has been made in the geological theory and exploration and development of shale gas in China, the research on the geological particularity and enrichment regularity associated with shale gas accumulation remains weak. With this in mind, we analyzed the shale gas accumulation patterns in China. The findings show that: (1) A variety of organic-rich shales were deposited in the continental margin-type marine and transitional environments during the Pre-Mesozoic period and the basin-type terrestrial environment during the Mesozoic and Cenozoic eras. (2) The basins dominated by Mesozoic and Cenozoic terrestrial sediments superimpose on the Pre-Mesozoic continental margin-type marine–or transitional-facies sediments. The former developed the terrestrial shales with large thickness, high organic matter abundance, new age, and low thermal maturity; meanwhile, the deep parts of the basins are favorable for shale gas enrichment. However, the latter preserves the shale with old age, high thermal maturity, and undergoing multiphase tectonic movements; and the tectonically stable regions are favorable for shale gas enrichment. (3) The aulacogens mainly formed in the Meso-Neoproterozoic, Sinian-Ordovician, and Devon-Triassic periods are favorable for marine organic-rich shale deposition; moreover, this type of shale and other types including transitional facies shales with favorable reservoir-forming assemblages, coal-measure shales in small and medium-sized basins, and low-medium mature shales affected by magma intrusion, have jointly constituted the various shale gas accumulation patterns in China. (4) Based on the drilling discoveries in China, shale gas accumulation patterns can be categorized into two types: tectonic-controlled and stratigraphic-controlled. The former is mainly related to structural features, whereas the latter is mainly related to the variation of lithology and strata. (5) Shale development and gas content are mainly affected and controlled by geological factors including sedimentation, diagenesis, and later tectonic movements. Favorable sedimentary environments, appropriate thermal maturity, good sealing capacity of caprock, and excellent structural preservation are the necessary conditions for shale gas enrichment.

DNA vaccines containing only antigenic components have limited efficacy and may fail to induce effective immune responses. Consequently, adjuvant molecules are often added to enhance immunogenicity. In this study, we generated a tumor vaccine using a plasmid encoding NMM (NY-ESO-1/MAGE-A3/MUC1) target antigens and immune-associated molecules. The products of the vaccine were analyzed in 293 T cells by western blotting, flow cytometry, and meso-scale discovery electrochemiluminescence. To assess the immunogenicity obtained, C57BL/6 mice were immunized using the DNA vaccine. The results revealed that following immunization, this DNA vaccine induced cellular immune responses in C57BL/6 mice, as evaluated by the release of IFN-γ, and we also detected increases in the percentages of nonspecific lymphocytes, as well as those of antigen-specific T cells. Furthermore, immunization with the pNMM vaccine was found to significantly inhibit tumor growth and prolonged the survival of mice with B16-NMM+-tumors. Our data revealed that pNMM DNA vaccines not only confer enhanced immunity against tumors but also provide a potentially novel approach for vaccine design. Moreover, our findings provide a basis for further studies on vaccine pharmacodynamics and pharmacology, and lay a solid foundation for clinical application.

Periodontitis is a pathological dental condition that damages the periodontal tissue and leads to tooth loss. Bone regeneration in periodontitis-related alveolar bone defects remains a challenge for periodontists and tissue engineers because of the complex periodontal microenvironment. The inflammatory microenvironment is associated with poor osteogenesis; therefore, the reduction of inflammation is essential for bone regeneration in periodontitis-related alveolar bone defects. Here, we developed a programmed core-shell nanofibers that allows the sequential and controlled release of tea polyphenols (TP) and AdipoRon (APR) to control inflammation and promote bone regeneration to repair periodontitis-related alveolar bone defects. Core-shell nanofibers with a sequentially controlled release function were synthesized using electrospinning. We investigated the therapeutic effects of the nanofibers in vitro and in a mouse periodontitis model. The results of the release profiles demonstrated that TP was released rapidly in the early stages and APR was continuously released thereafter. In vitro experiments showed that the programmed core-shell nanofibers reduced the levels of proinflammatory cytokines and increased osteogenic differentiation in an inflammatory microenvironment. In vivo experiments, the programmed core-shell nanofibers ameliorated periodontal tissue inflammation and improved alveolar bone regeneration. Our results indicated that the programmed core-shell nanofibers with a sequential-release function provides an ideal strategy for repairing periodontitis-related alveolar bone defects, and its application in the treatment of diseases with spatiotemporal specificity is promising.

China is highly dependent on foreign oil and gas, and the exploration and exploitation of shale gas is an important way to alleviate the energy and environmental pressure of China. Although a series of significant progress has been made in a short time, China is still at the crossroads of shale gas exploration direction. Therefore, this paper systematically reviews the particularity of shale gas geological conditions in China, and points out China's exploration direction of shale gas in different fields combined with the research achievements of shale gas accumulation mechanism. The following results were obtained. (1) China's shale gas exploration fields can be divided into three major parts, i.e., marine, continental and marine–continental transitional facies. The geological characteristics of shale gas in North China, Yangtze and Tarim plates are different. The interaction of multiple factors, including tectonic and sedimentary evolution, shale gas accumulation, late-stage transformation and etc., has led the complexity of the geological distribution and the diversity of exploration fields of shale gas in China. (2) The organic pores and fractures of marine shale are developed. The Ordovician Wufeng-Silurian Longmaxi Formation will still be the primary target of shale gas exploration in future. Meanwhile, the Cambrian Niutitang and Sinian Doushantuo Formation in the Yangtze region, the Devonian Luofu and Carboniferous Jiusi Formation in the Yunnan-Guizhou-Guangxi region, the Jixianian Hongshuizhuang and Mesoproterozoic Xiamaling Formation will be the targets of strategic breakthrough in shale gas exploration. (3) The structural deep and slope of middle-large basins and the sedimentation centers of small-middle basins are the main directions of continental shale gas exploration. Inter-laminar cracks and intergranular pores are well developed in continental shale. The coupling of various organic matter types and thermal evolution results in the symbiosis of shale oil and shale gas, which will become an important field for further exploration of continental shale gas. (4) The marine–continental transitional shale, which mainly formed in Late Carboniferous-Permian, is characterized by cyclic association with sandstone, mudstone, coal and carbonate. Diagenetic fractures are well developed in transitional shale. The favorable structural and diagenetic preservation are the two major factors for the enrichment of this type of shale gas. The flat-lagoon and delta sedimentary systems, middle-large superimposed and small-middle residual basins, and deep layers with quality caprock and good structural preservation are the favorable directions for shale gas exploration in transitional facies.

BackgroundCardiovascular disease (CVD) poses a tremendous threat to global health, giving rise to exceedingly high morbidity and mortality among patients. A migraine is a common neurological disorder characterized by recurrent attacks of severe headache, while its cardiovascular burden remains unclear. Therefore, this study aims to investigate whether migraine is associated with CVD.MethodsThe cross-sectional data of 5,692 subjects aged 20 or above was obtained from the National Health and Nutrition Examination Survey (NHANES) 1999–2004. To determine whether migraine is associated with CVD, weighted logistic regression models were used. In a subsequent subgroup analysis, several confounding factors were also explored to investigate the association between migraine and CVD.ResultsIn total, 5,692 subjects were enrolled in this study, with the prevalence of CVD being 13.3%. Participants with CVD tended to be older, male, non-Hispanic whites, more educated, former smokers, and alcohol drinkers, and had a higher waist circumference, less physical activity, a higher level of triglyceride and creatinine as well as a lower level of high-density lipoprotein cholesterol (HDL-C) and estimated glomerular filtration rate (eGFR) (all P < 0.05). Considering all potential confounders, migraine was associated with a higher risk of CVD [odds ratios (ORs) 2.77; 95% confidence intervals (CIs): 1.56–4.90]. Subgroup analysis showed a higher risk of CVD in females, those older than 60 years, with a lower body mass index (BMI) level (≤ 30 kg/m2), a higher level of eGFR (> 90 mL/min/1.73 m2), hypertension and hyperlipidemia and without diabetes.ConclusionIn summary, our study revealed a positive association between migraine with CVD in a nationally representative US adult population. Our findings highlighted that migraine should be considered an important risk factor for CVD.

BackgroundDiabetes is a critical contributor to the pathogenesis of cardiovascular diseases. Klotho is an anti−aging protein with cardiovascular-renal protective effects. However, the relationship between serum Klotho levels and diabetes remains poorly understood.ObjectivesThis study aimed to investigate the relationship between serum Klotho levels and diabetes in US adults.MethodsWe analyzed the cross-sectional data obtained from 13751 subjects aged 40-79 years in the National Health and Nutrition Examination Survey (NHANES) (2007–2016). Serum Klotho concentration was measured using an enzyme-linked immunosorbent assay (ELISA) and categorized into four quartiles (Q1-Q4). Multivariate logistic regression and restricted cubic spline (RCS) regression were conducted to explore the association between serum Klotho levels and the prevalence of diabetes.ResultsAs compared with quartile 1, serum Klotho levels in quartiles 2-4 yielded odds ratios (OR) (95% CI) of diabetes of 0.96 (0.80–1.15), 0.98 (0.82–1.18), and 1.25 (1.04–1.50), respectively, after covariate adjustment (P for trend = 0.018). The results implied an increased risk of diabetes. The RCS plot showed a U-shaped relationship linking serum Klotho levels with diabetes (P for nonlinearity = 0.003).ConclusionsIn summary, a nonlinear and positive association was found between serum Klotho levels and the prevalence of diabetes. Further study is needed to verify the causality of this association and elucidate the underlying mechanisms.

ObjectiveTurn-amplitude clouds were widely used in automatic electromyography (EMG) interference pattern analysis. Earlier works employed the intercept ± 2SD (standard deviation) of the linear regression equation as the upper and lower boundaries of the clouds. The goal of this study was to employ the linear regression method and percentile method to calculate the reference value of turn-amplitude clouds, identify the determining criteria in accordance with the receiver operator characteristic curve (ROC), and analyze the sensitivity and specificity of the linear regression cloud, percentile cloud, and quantitative assessment of the motor unit potential (QMUP).MethodsFirst, we explore what factors affect the number of turns per second and the mean amplitude. Then, their logarithms were taken for the normal test. All muscle data were used to calculate the reference values of percentile clouds. However, the reference values of the linear regression clouds were obtained for the muscles with a bivariate normal distribution, homogeneous variances and a linear correlation. We calculated the prediction interval with the standard errors of the intercept and slope of the linear regression equation, which can determine the upper and lower boundaries of the linear regression clouds. Furthermore, we obtained ROCs of these clouds, which were used as the determining criteria to determine the optimum cut-off values. Finally, our study analyzed the sensitivity and specificity of the linear regression cloud, percentile cloud, and QMUP.ResultsWe here presented the reference values and ROCs of the linear regression clouds and percentile clouds. We suggest the determining criteria be based on ROCs. The areas under the curve (AUC) of both clouds are larger than 0.8, revealing that they have significant diagnostic value. Our results display that the specificities of the linear regression clouds, percentile clouds, and QMUP are almost identical to each other, whereas the sensitivity of percentile cloud is higher than those of QMUP and linear regression clouds.ConclusionAccording to ROCs, the researchers determine the determining criteria of the linear regression clouds and percentile clouds. Our findings suggest that the percentile clouds possess a wide application range and significant diagnostic value, therefore it may be the optimum for automatic EMG interference pattern analysis.

The development of carbon fiber-reinforced polymers (CFRPs) with high electromagnetic interference (EMI) shielding effectiveness is highly desirable for engineering applications. Nevertheless, poor interfacial adhesion between carbon fibers (CFs) and polymer matrix remains a serious issue. Herein, a mechanically enhanced CF/epoxy composite with highly efficient EMI shielding was fabricated through in-situ polymerization of polyaniline (PANI) nanolayer. The PANI nanolayer improved the interfacial adhesion in the composites via the entanglement of molecular chains, π–π stacking, and chemical bonding et al. The resulting CF/PANI/epoxy composite exhibited an interlaminar shear strength of 72.8 MPa, which was a 24% improvement over 58.5 MPa for the virgin CF/epoxy composite. Moreover, an excellent EMI shielding effectiveness of 54.8 dB was achieved, which was 58% higher than that of the virgin CF/epoxy composite. This could be attributed to the significant enhancement in conduction loss, interfacial polarization loss, and multiple reflections with the help of PANI nanolayer. This study provides a novel strategy for the development of high-performance CFRPs for efficient EMI shielding.

Defect engineering and heteroatom doping can significantly enhance the activity of zinc-aluminum layered double hydroxides (ZnAl-LDHs) in photocatalytic CO2 reduction to fuel. However, the in-depth understanding of the associated intrinsic mechanisms is limited. Herein, we systematically investigated Zn vacancies (VZn), oxygen vacancies (VO), and Cu doping on the geometry and electronic structure of ZnAl-LDH using density functional theory (DFT). We also revealed the related reaction mechanism. The results reveal the concerted roles of VO, VZn, and doped-Cu facilitate the formation of the unsaturated metal complexes (Znδ+-VO and Cuδ+-VO). They can localize the charge density distribution, function as new active centers, and form the intermediate band. Simultaneously, the intermediate band of functionalized ZnAl-LDHs narrows the band gap and lowers the band edge location. Therefore, it can broaden the absorption range of light and improve the selectivity of CO. Additionally, the unsaturated metal complex lowers the Gibbs free energy barrier for effective CO2 activation by bringing the d-band center level closer to the Fermi level. The work provided guidance for developing LDH photocatalysts with high activity and selectivity.

Chinese tongue sole (Cynoglossus semilaevis) is an important marine flatfish which is widely cultured in coastal areas in China. Infectious bacterial diseases such as Edwardsiella tarda imposed serious threats to this species. A potential strategy to prevent this disease is to select resistance strains. The aim of the present work was to estimate the genetic variation of disease resistance to E. tarda and to evaluate the genetic correlations between resistance traits and growth traits. Three types of models were fitted by using different trait definitions (binary, continuous and categorical). After a 9-day challenge test, the overall survival was 75.4% (ranging from 6.4% to 100% in families), and at test day 6, the overall survival was 50.7%. We set test day 6 and 9 as cut-off point times respectively. The heritabilities of survival traits were ranging from 0.10 to 0.36. Considerably higher heritability values were obtained at day 6 than at day 9, regardless of which model or trait definition used (except Trait 2 in LIN). The genetic correlations between disease resistance traits and growth traits (i.e. body weight and total length) were low and not significant from zero (−0.12–0.24). There is a substantial re-ranking of families when defined resistance as categorical and continuous traits compared to binary trait. These results confirm the existence of genetic variation for resistance against E. tarda and weak genetic correlations indicate that joint genetic improvement of E. tarda resistance and growth is scarcely available.

In order to improve the service life of AerMet100 steel in complex environment, the structure and properties of AerMet100 steel coating film fabricated by micro-arc oxidation were investigated, and the differences between hot-dip micro-arc oxidation (HMAO) and in situ micro-arc oxidation (IMAO) coating films prepared by two different preparation methods were also clarified. The findings reveal that the IMAO film was mainly composed of Al2O3 and FeAl2O4 phases. The bonding strength between the film and the substrate was higher, and the structure of the film was compact. The ceramic film can effectively reduce the impact stress overload and improve the impact resistance of the substrate. The wear rate of IMAO film was 43% lower than that of HMAO film and the ceramic film had the characteristics of capacitance, which can significantly improve the corrosion performance of the substrate, but the defects of the film on the surface had a great effect on the corrosion resistance.

Dysregulation of the cell cycle underlies many human genetic diseases and cancers, yet numerous organisms, including microbes, also manipulate the cell cycle to generate both morphologic and genetic diversity as a natural mechanism to enhance their chances for survival. The eukaryotic pathogen Cryptococcus neoformans

With the development of the green food industry, land conflicts are gradually escalating, and the coordinated development of competitiveness level and land use efficiency is crucial to the green food industry. The competitiveness level of China’s green food industry at the provincial level between 2011 and 2020 was measured by constructing an index system using the entropy method and VlseCriterion Optimisation and Compromise Resolution (VIKOR) method, and then the land use efficiency was evaluated using the super efficiency Slacks-based Measurement (SBM) model, and the coupling coordination degree was analyzed using the coupling coordination model based on the results of both measurements. The results showed that the competitiveness level of the green food industry was “high in the west and low in the east”; most provinces and cities were with the middle competitiveness level. Land use efficiency generally showed a trend of rising and then falling and leveling off, and the average value of the three regions was ranked as eastern (1.13) > western (0.84) > middle (0.63). The mean value (0.82) of the overall coupling coordination in China floated at the boundary of high-quality coordination, and all three regions showed a trend of rising and then falling and leveling off, and the number of provinces and cities in high-quality coordination in China was shifting from the north to the south during 2011–2020. This study can provide theoretical support for the coordinated development between industrial development and land use, and provide feasible suggestions for the intensive and efficient use of resources.

Abstract The transmittance, conductivity, and flexibility are the crucial properties for the development of next-generation flexible electrodes. Achieving a good trade-off between transmittance and conductivity of flexible electrodes has been a challenge because the two properties are inversely proportional. Herein, we reveal a good trade-off between transmittance and conductivity of gold nanomesh (AuNM) can be achieved through appropriately increasing the AuNM thickness no more than 40 nm, the mean free path of electrons in Au metal. The further flexibility investigation indicates that the AuNM electrodes with mesh structure show higher tolerance than the Au bulk film, and the AuNM electrodes with smaller inter-aperture wire width can accommodate more tensile strains than a counterpart with bigger inter-aperture wire width. The simulated results based on finite element analysis (FEA) show good agreement with experimental results, which indicates the fabrication method of versatile nanosphere lithography (NSL) is reliable. These results established a promising approach toward next-generation large-scale flexible transparent AuNM electrodes for flexible electronics.

Improvement in living standards has led to the development and utilization of forest green foods. The study seeks to examine the foundation and potential of forest green food industry in Yunnan Province. By constructing the industrial competitive advantage model, this paper measured and analyzed the competitiveness of forest green food industry in Yunnan Province from 2016 to 2020 by using fuzzy evaluation method and AHP. The conclusions were as follows: (1) The competitiveness of forest green food industry in Yunnan Province was at a medium level with competitiveness index of 83.98. (2) The competitive advantage of forest green food industry in Yunnan Province mainly depended on key factors such as natural endowment and education level. The area is however not having comparative advantage in general factors and important factors. Therefore, there is the need to put in place measures to realise the full potential of forest green food industry in the area by providing players in the sector with requisite skills.

Knowledge, attitude and willingness of ethnic minorities in China towards cadaver donation programs were assessed. Questionnaire and interviews were conducted to investigate Yi, Bai, Hani, Dai and Han ethnicities. Educational level and per capita income of ethnic minorities were lesser than those of Han ethnicity (p

Abstract The acoustic emission signal of laser plasma shock wave, which comes into being when femtosecond laser ablates pure Cu, Fe, and Al target material, has been detected by using the fiber Fabry-Perot (F-P) acoustic emission sensing probe. The spectrum characters of the acoustic emission signals for three kinds of materials have been analyzed and studied by using Fourier transform. The results show that the frequencies of the acoustic emission signals detected from the three kinds of materials are different. Meanwhile, the frequencies are almost identical for the same materials under different ablation energies and detection ranges. Certainly, the amplitudes of the spectral character of the three materials show a fixed pattern. The experimental results and methods suggest a potential application of the plasma shock wave on-line measurement based on the femtosecond laser ablating target by using the fiber F-P acoustic emission sensor probe.

A common problem existing in wound dressing is to integrate the properties of against water erosion while maintaining a high water-uptake capacity. To tackle this issue, we imbedded one layer of hydrogel nanofibrous mat into two hydrophobic nanofibrous mats, thereafter, the sandwich structural membrane (SSM) was obtained. Particularly, SSM is composed of three individual nanofibrous layers which were fabricated through sequential electrospinning technology, including two polyurethane/antibacterial agent layers, and one middle gelatin/rutin layer. The obtained SSM is characterized in terms of morphology, component, mechanical, and functional performance. In addition to the satisfactory antibacterial activity against Staphylococcus aureus and Escherichia coli, and antioxidant property upon scavenging DPPH free radicals, the obtained SSM also shows a desirable thermally regulated water vapor transmission rate. More importantly, such SSM can be mechanically stable and keep its intact morphology without appearance damage while showing a high water-absorption ratio. Therefore, the prepared sandwich structural membrane with hydrogel nanofibrous mat as inner layer can be expected as a novel wound dressing.

The precast segmental bridge has the advantages of fast construction speed, good economic performance, and small impact on the surrounding environment. In order to study the role of the temporary pre-stressing system in the cantilever assembly process of the precast segment box girder bridge, ABAQUS was used to simulate the assembly process of the standard section of a viaduct. Studying the compressive stress and relative sliding of the joint section under the action of the self-weight and temporary pre-stress, the reasonable number and spatial arrangement of the tension pedestal are determined. The research results show that too few roof pedestals will cause the large area decompression state and too much will cause the construction period to be longer. When the roof symmetrical pedestal is located on the inner side of the web, it will obviously increase the area of the zero-compression stress at the end of the top slab. When the distance between the pedestal and the center of the web is 0.12L, the full section meets the minimum consolidation pressure requirement of the glued joint. The reasonable number of tension pedestals and their spatial arrangement will provide specific guidance and reference to assembling construction of actual precast segment box girder in the future.

We investigate the coherent perfect absorption laser points (CPA-LPs) in anti-parity−time-symmetric photonic crystals. CPA-LPs, which correspond to the poles of reflection and transmission, can be found in the parameter space composed of gain−loss factor and angular frequency. Discrete exceptional points (EPs) split as the gain−loss factor increases. The CPA-LPs sandwiched between the EPs are proved to be defective modes. The localization of light field and the bulk effect of gain/loss in materials induce a sharp change in phase of the reflection coefficient near the CPA-LPs. Consequently, a large spatial Goos−Hänchen shift, which is proportional to the slope of phase, can be achieved around the CPA-LPs. The study may find great applications in highly sensitive sensors.

This study investigates the reflectance of the defective mode (DM) and the lateral shift of reflected beam in defective photonic crystals incorporated with single-layer graphene by the transfer matrix method (TMM). Graphene, treated as an equivalent dielectric with a thickness of 0.34 nm, was embedded in the center of a defect layer. The reflectance of the DM was greatly enhanced as the intraband transition of electrons was converted to an interband transition in graphene. The reflectance of the DM could be further enhanced by increasing the Bragg periodic number. Furthermore, a large lateral shift of the reflected beam could also be induced around the DM. This study may find great applications in highly sensitive sensors.

Hair follicle cycling can be divided into the following three stages: anagen, catagen, and telogen. The molecular signals that orchestrate the follicular transition between phases are still unknown. To better understand the detailed protein networks controlling this process, proteomics and bioinformatics analyses were performed to construct comparative protein profiles of mouse skin at specific time points (0, 8, and 20 days). Ninety-five differentially expressed protein spots were identified by MALDI-TOF/TOF as 44 proteins, which were found to change during hair follicle cycle transition. Proteomics analysis revealed that these changes in protein expression are involved in Ca2+-regulated biological processes, migration, and regulation of signal transduction, among other processes. Subsequently, three proteins were selected to validate the reliability of expression patterns using western blotting. Cluster analysis revealed three expression patterns, and each pattern correlated with specific cell processes that occur during the hair cycle. Furthermore, bioinformatics analysis indicated that the differentially expressed proteins impacted multiple biological networks, after which detailed functional analyses were performed. Taken together, the above data may provide insight into the three stages of mouse hair follicle morphogenesis and provide a solid basis for potential therapeutic molecular targets for this hair disease.

ABSTRACT Cryptococcus neoformans is a major life-threatening fungal pathogen. In response to the stress of the host environment, C. neoformans produces large polyploid titan cells. Titan cell production enhances the virulence of C. neoformans, yet whether the polyploid aspect of titan cells is specifically influential remains unknown. We show that titan cells were more likely to survive and produce offspring under multiple stress conditions than typical cells and that even their normally sized daughters maintained an advantage over typical cells in continued exposure to stress. Although polyploid titan cells generated haploid daughter cell progeny upon in vitro replication under nutrient-replete conditions, titan cells treated with the antifungal drug fluconazole produced fluconazole-resistant diploid and aneuploid daughter cells. Interestingly, a single titan mother cell was capable of generating multiple types of aneuploid daughter cells. The increased survival and genomic diversity of titan cell progeny promote rapid adaptation to new or high-stress conditions. IMPORTANCE The ability to adapt to stress is a key element for survival of pathogenic microbes in the host and thus plays an important role in pathogenesis. Here we investigated the predominantly haploid human fungal pathogen Cryptococcus neoformans, which is capable of ploidy and cell size increases during infection through production of titan cells. The enlarged polyploid titan cells are then able to rapidly undergo ploidy reduction to generate progeny with reduced ploidy and/or aneuploidy. Under stressful conditions, titan cell progeny have a growth and survival advantage over typical cell progeny. Understanding how titan cells enhance the rate of cryptococcal adaptation under stress conditions may assist in the development of novel drugs aimed at blocking ploidy transitions.

Morphological changes are a very common and effective strategy for pathogens to survive in the mammalian host. During interactions with their host, human pathogenic fungi undergo an array of morphological changes that are tightly associated with virulence. Candida albicans switches between yeast cells and hyphae during infection. Thermally dimorphic pathogens, such as Histoplasma capsulatum and Blastomyces species transform from hyphal growth to yeast cells in response to host stimuli. Coccidioides and Pneumocystis species produce spherules and cysts, respectively, which allow for the production of offspring in a protected environment. Finally, Cryptococcus species suppress hyphal growth and instead produce an array of yeast cells—from large polyploid titan cells to micro cells. While the morphology changes produced by human fungal pathogens are diverse, they all allow for the pathogens to evade, manipulate, and overcome host immune defenses to cause disease. In this review, we summarize the morphology changes in human fungal pathogens—focusing on morphological features, stimuli, and mechanisms of formation in the host.