Genome-Wide Association Analysis and Genetic Parameters for Egg Production Traits in Peking Ducks.

Egg production traits are crucial in the poultry industry, including age at first egg (AFE), egg number (EN) at different stages, and laying rate (LR). Ducks exhibit higher egg production capacity than other poultry species, but the genetic mechanisms are still poorly understood. In this study, we collected egg-laying data of 618 Peking ducks from 22 to 66 weeks of age and genotyped them by whole-genome resequencing. Genetic parameters were calculated based on SNPs, and a genome-wide association study (GWAS) was performed for these traits. The SNP-based heritability of egg production traits ranged from 0.09 to 0.54. The GWAS identified nine significant SNP loci associated with AFE and egg number from 22 to 66 weeks. These loci showed that the corresponding alleles were positively correlated with a decrease in the traits. Moreover, three potential candidate genes (ENSAPLG00020011445, ENSAPLG00020012564, TMEM260) were identified. Functional enrichment analyses suggest that specific immune responses may have a critical impact on egg production capacity by influencing ovarian function and oocyte maturation processes. In conclusion, this study deepens the understanding of egg-laying genetics in Peking duck and provides a sound theoretical basis for future genetic improvement and genomic selection strategies in poultry.

EEG Emotion Recognition Network Based on Attention and Spatiotemporal Convolution.

Human emotions are complex psychological and physiological responses to external stimuli. Correctly identifying and providing feedback on emotions is an important goal in human-computer interaction research. Compared to facial expressions, speech, or other physiological signals, using electroencephalogram (EEG) signals for the task of emotion recognition has advantages in terms of authenticity, objectivity, and high reliability; thus, it is attracting increasing attention from researchers. However, the current methods have significant room for improvement in terms of the combination of information exchange between different brain regions and time-frequency feature extraction. Therefore, this paper proposes an EEG emotion recognition network, namely, self-organized graph pesudo-3D convolution (SOGPCN), based on attention and spatiotemporal convolution. Unlike previous methods that directly construct graph structures for brain channels, the proposed SOGPCN method considers that the spatial relationships between electrodes in each frequency band differ. First, a self-organizing map is constructed for each channel in each frequency band to obtain the 10 most relevant channels to the current channel, and graph convolution is employed to capture the spatial relationships between all channels in the self-organizing map constructed for each channel in each frequency band. Then, pseudo-three-dimensional convolution combined with partial dot product attention is implemented to extract the temporal features of the EEG sequence. Finally, LSTM is employed to learn the contextual information between adjacent time-series data. Subject-dependent and subject-independent experiments are conducted on the SEED dataset to evaluate the performance of the proposed SOGPCN method, which achieves recognition accuracies of 95.26% and 94.22%, respectively, indicating that the proposed method outperforms several baseline methods.

Optimal CXCR5 Expression during Tfh Maturation Involves the Bhlhe40-Pou2af1 Axis.

The pair of transcription factors Bcl6-Blimp1 is well-known for follicular T helper (Tfh) cell fate determination, however, the mechanism(s) for Bcl6-independent regulation of CXCR5 during Tfh migration into germinal center (GC) is still unclear. In this study, we uncovered another pair of transcription factors, Bhlhe40-Pou2af1, that regulates CXCR5 expression. Pou2af1 was specifically expressed in Tfh cells whereas Bhlhe40 expression was found high in non-Tfh cells. Pou2af1 promoted Tfh formation and migration into GC by upregulating CXCR5 but not Bcl6, while Bhlhe40 repressed this process by inhibiting Pou2af1 expression. RNA-Seq analysis of antigen-specific Tfh cells generated in vivo confirmed the role of Bhlhe40-Pou2af1 axis in regulating optimal CXCR5 expression. Thus, the regulation of CXCR5 expression and migration of Tfh cells into GC involves a transcriptional regulatory circuit consisting of Bhlhe40 and Pou2af1, which operates independent of the Bcl6-Blimp1 circuit that determines the Tfh cell fate.

Visible-Light-Induced Hydrodifluoromethylation of Unactivated Alkenes with Difluoroacetic Anhydride.

We herein described a practical and efficient protocol for hydrodifluoromethylation of unactivated alkenes using readily available difluoroacetic anhydride as a difluoromethyl source by merging photocatalysis and N-hydroxyphthalimide activation. This method features a wide substrate scope and excellent compatibility with various functional groups, as demonstrated by more than 50 examples, including bioactive molecules and pharmaceutical derivatives. Mechanism investigation indicated that N-hydroxyphthalimide may also serve as the hydrogen atom donor.

Qualitative and quantitative analysis of chemical components in Qianggan capsule by UHPLC-Q-TOF-MS/MS and LC-sMRM.

Qianggan capsule (QGC) is a complex preparation composed of 16 traditional Chinese medicines (TCM) that can clear heat and dampness, fortify the spleen and blood, typify qi and relieve depression. However, the chemical composition of QGC remains incompletely understood, despite its clinical use in treating chronic hepatitis and liver injury. The objective of this study was to explore the quality markers of QGC through qualitative and quantitative analysis of its chemical components. First, the chemical composition of QGC was qualitatively analyzed using UHPLC-Q-TOF-MS/MS. Subsequently, the LC-sMRM method was developed and optimized to accurately quantify various chemical components of 10 batches of QGC. Finally, the variations in chemical components between batches were analyzed via multivariate statistical analysis. UHPLC-Q-TOF-MS/MS analysis revealed 167 chemical constituents in QGC, comprised of 48 flavonoids, 32 terpenoids, 18 phenolic acids, 9 coumarins, 9 phenylpropanoids, and 51 nucleosides, sugars, amino acids, anthraquinones, and other compounds. The LC-sMRM method was established for the quantitative analysis of 42 chemical components in 10 batches of QGC. The ultrasonic-assisted extraction parameters were optimized using RSM. Compared with conventional MRM, sMRM demonstrated superior sensitivity and precision. PCA and OPLS-DA identified eight chemical components with content differences among batches. This study established the chemical composition of QGC, offering useful guidance for assessing its quality.

Metabolic activation and cytochrome P450 inhibition of piperlonguminine mediated by CYP3A4.

Piperlonguminine (PLG) is a major alkaloid found in Piper longum fruits. It has been shown to possess a variety of biological activities, including anti-tumor, anti-hyperlipidemic, anti-renal fibrosis and anti-inflammatory properties. Previous studies have reported that PLG inhibits various CYP450 enzymes. The main objective of this study was to identify reactive metabolites of PLG in vitro and assess its ability to inhibit CYP450. In rat and human liver microsomal incubation systems exposed to PLG, two oxidized metabolites (M1 and M2) were detected. Additionally, in microsomes where N-acetylcysteine was used as a trapping agent, N-acetylcysteine conjugates (M3, M4, M5 and M6) of four isomeric O-quinone-derived reactive metabolites were found. The formation of metabolites was dependent on NADPH. Inhibition and recombinant CYP450 enzyme incubation experiments showed that CYP3A4 was the primary enzyme responsible for the metabolic activation of PLG. This study characterized the O-dealkylated metabolite (M1) through chemical synthesis. The IC50 shift assay showed time-dependent inhibition of CYP3A4, 2C9, 2E1, 2C8 and 2D6 by PLG. This research contributes to the understanding of PLG-induced enzyme inhibition and bioactivation.

Copper Sulfate Combined with Photodynamic Therapy Enhances Antifungal Effect by Downregulating AIF1.

Candida albicans is a clinically significant opportunistic fungus that is generally treated with antifungal drugs such as itraconazole and fluconazole. However, the recent emergence of fungal resistance has made treatment increasingly difficult. Therefore, novel antifungal treatment methods are urgently required. Hexanol ethosome photodynamic therapy (HE-PDT) is a method that uses photosensitizers (PS), such as hexanol ethosome, to exert antifungal effects, and can be used to treat resistant fungal strains. However, due to the high dose of PS required for antifungal treatment, excess photosensitizers may remain. Furthermore, once exposed to light, normal tissues or cells are damaged after photodynamic therapy, which limits the clinical application of HE-PDT. Therefore, improving the efficacy without increasing the dose is the key to this treatment. In this study, the antifungal effect of copper sulfate combined with HE-PDT was investigated, and its mechanism was explored. The results suggested that exogenous copper sulfate significantly increased the antifungal effect of HE-PDT by enhancing the rate of C. albicans inhibition, increasing reactive oxygen species (ROS) accumulation, increasing the rate of apoptosis, and altering the mitochondrial membrane potential (MMP) and ATP concentration, which is related to the downregulation of apoptosis-inducing factor (AIF1) expression. In conclusion, copper sulfate combined with photodynamic therapy significantly inhibited the activity of C. albicans by inducing apoptosis. The combined approach reported herein provides new insights for future antifungal therapy.

Medical Image Fusion Based on Local Saliency Energy and Multi-scale Fractal Dimension.

BACKGROUND: At present, there are some problems in multimodal medical image fusion, such as texture detail loss, leading to edge contour blurring and image energy loss, leading to contrast reduction. OBJECTIVE: To solve these problems and obtain higher-quality fusion images, this study proposes an image fusion method based on local saliency energy and multi-scale fractal dimension. METHODS: First, by using a non-subsampled contourlet transform, the medical image was divided into 4 layers of high-pass subbands and 1 layer of low-pass subband. Second, in order to fuse the high-pass subbands of layers 2 to 4, the fusion rules based on a multi-scale morphological gradient and an activity measure were used as external stimuli in pulse coupled neural network. Third, a fusion rule based on the improved multi-scale fractal dimension and new local saliency energy was proposed, respectively, for the low-pass subband and the 1st closest to the low-pass subband. Layerhigh pass sub-bands were fused. Lastly, the fused image was created by performing the inverse non-subsampled contourlet transform on the fused sub-bands. RESULTS: On three multimodal medical image datasets, the proposed method was compared with 7 other fusion methods using 5 common objective evaluation metrics. CONCLUSION: Experiments showed that this method can protect the contrast and edge of fusion image well and has strong competitiveness in both subjective and objective evaluation.

Zfp281 and Zfp148 control CD4+ T cell thymic development and TH2 functions.

How CD4+ lineage gene expression is initiated in differentiating thymocytes remains poorly understood. Here, we show that the paralog transcription factors Zfp281 and Zfp148 control both this process and cytokine expression by T helper cell type 2 (TH2) effector cells. Genetic, single-cell, and spatial transcriptomic analyses showed that these factors promote the intrathymic CD4+ T cell differentiation of class II major histocompatibility complex (MHC II)-restricted thymocytes, including expression of the CD4+ lineage-committing factor Thpok. In peripheral T cells, Zfp281 and Zfp148 promoted chromatin opening at and expression of TH2 cytokine genes but not of the TH2 lineage-determining transcription factor Gata3. We found that Zfp281 interacts with Gata3 and is recruited to Gata3 genomic binding sites at loci encoding Thpok and TH2 cytokines. Thus, Zfp148 and Zfp281 collaborate with Gata3 to promote CD4+ T cell development and TH2 cell responses.

Safety of high-carbohydrate fluid diet 2 h versus overnight fasting before non-emergency endoscopic retrograde cholangiopancreatography: A single-blind, multicenter, randomized controlled trial.

BACKGROUND: Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients' recovery. METHODS: This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group (n = 665) and fasting group (n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. RESULTS: The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t = 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26-0.71, P <0.001) and 0.76 (95% CI: 0.57-0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05-0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39-0.95, P = 0.028) in the multivariable models. CONCLUSION: Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery. TRAIL REGISTRATION: ClinicalTrials.gov, No. NCT03075280.

GATA3 induces the pathogenicity of Th17 cells via regulating GM-CSF expression.

T-bet-expressing Th17 (T-bet+RORγt+) cells are associated with the induction of pathology during experimental autoimmune encephalomyelitis (EAE) and the encephalitic nature of these Th17 cells can be explained by their ability to produce GM-CSF. However, the upstream regulatory mechanisms that control Csf2 (gene encoding GM-CSF) expression are still unclear. In this study, we found that Th17 cells dynamically expressed GATA3, the master transcription factor for Th2 cell differentiation, during their differentiation both in vitro and in vivo. Early deletion of Gata3 in three complimentary conditional knockout models by Cre-ERT2, hCd2 Cre and Tbx21 Cre, respectively, limited the pathogenicity of Th17 cells during EAE, which was correlated with a defect in generating pathogenic T-bet-expressing Th17 cells. These results indicate that early GATA3-dependent gene regulation is critically required to generate a de novo encephalitogenic Th17 response. Furthermore, a late deletion of Gata3 via Cre-ERT2 in the adoptive transfer EAE model resulted in a cell intrinsic failure to induce EAE symptoms which was correlated with a substantial reduction in GM-CSF production without affecting the generation and/or maintenance of T-bet-expressing Th17 cells. RNA-Seq analysis of Gata3-sufficient and Gata3-deficient CNS-infiltrating CD4+ effector T cells from mixed congenic co-transfer recipient mice revealed an important, cell-intrinsic, function of GATA3 in regulating the expression of Egr2, Bhlhe40, and Csf2. Thus, our data highlights a novel role for GATA3 in promoting and maintaining the pathogenicity of T-bet-expressing Th17 cells in EAE, via putative regulation of Egr2, Bhlhe40, and GM-CSF expression.

Smart classroom learning environment preferences of higher education teachers and students in China: An ecological perspective.

By evaluating learners' perceived preferences for the learning environment, we can understand the important characteristics and better improve the learning environment, ultimately to provide great potential for the optimization of teaching practice. Seeing that the current research pays less attention to teachers' and students' preferences for the space environment simultaneously, based on the survey of 1937 undergraduates and 107 teachers from a university in central China, this study aims to explore their preferences for smart learning environment. Based on the ecological theory and research results of the existing learning environment, this paper constructed an ecological model and a conceptual model of learning space preferences. An empirical study was conducted to explore the impact of sociodemographic variables on personal spatial preference. The results showed that teachers and students had a positive attitude towards the smart learning environment, and gender, age, grade, subject category and other variables had limited impact on spatial preference.

Hybrid Domain Consistency Constraints-Based Deep Neural Network for Facial Expression Recognition.

Facial expression recognition (FER) has received increasing attention. However, multiple factors (e.g., uneven illumination, facial deflection, occlusion, and subjectivity of annotations in image datasets) probably reduce the performance of traditional FER methods. Thus, we propose a novel Hybrid Domain Consistency Network (HDCNet) based on a feature constraint method that combines both spatial domain consistency and channel domain consistency. Specifically, first, the proposed HDCNet mines the potential attention consistency feature expression (different from manual features, e.g., HOG and SIFT) as effective supervision information by comparing the original sample image with the augmented facial expression image. Second, HDCNet extracts facial expression-related features in the spatial and channel domains, and then it constrains the consistent expression of features through the mixed domain consistency loss function. In addition, the loss function based on the attention-consistency constraints does not require additional labels. Third, the network weights are learned to optimize the classification network through the loss function of the mixed domain consistency constraints. Finally, experiments conducted on the public RAF-DB and AffectNet benchmark datasets verify that the proposed HDCNet improved classification accuracy by 0.3-3.84% compared to the existing methods.

Using "Age and Total-PSA" as the Main Indicators: The Results of Taizhou Integrated Prostate Screening (No 2).

The aim of the study was to analyze population-based prostate cancer (PCa) screening and the incidence of PCa among males ≥50 years of age residing in the Luqiao district of Taizhou, China. From October to December 2020, male residents ≥50 years of age were screened for serum total prostate-specific antigen (total-PSA). If t-PSA re-test levels persisted above 4 µg/L, subjects underwent further noninvasive examinations, including digital rectal examination or multiparameter magnetic resonance imaging (mpMRI) of the prostate. Subjects underwent prostate biopsy of pathological tissue based on t-PSA and mpMRI results. A total of 3524 (49.1%) residents participated in this PCa screening study. In total, 285 (8.1%) subjects exhibited t-PSA levels ≥4.0 µg/L and 112 (3.2%) underwent noninvasive examinations. Forty-two (1.2%) residents underwent prostate biopsy, of which 16 (0.45%) were diagnosed with PCa. Of those diagnosed with PCa, three (19%) had localized PCa (cT1-cT2N0M0), six (37%) had locally advanced PCa (cT3a- cT4N0-1M0), and seven (44%) had advanced metastatic PCa (M1). Unfortunately, 3477 (48.5%) residents did not participate in the study, mainly due to lack of awareness of PCa based on feedback from local health centers. Age and t-PSA were used as primary screening indicators and, when further combined with mpMRI and prostate biopsy, confirmed the diagnosis of PCa among participating residents. Although this was a relatively economical and convenient screening method, education and knowledge should be further enhanced to increase the participation rate in PCa screening programs.

Emotion Classification from Multi-Band Electroencephalogram Data Using Dynamic Simplifying Graph Convolutional Network and Channel Style Recalibration Module.

Because of its ability to objectively reflect people's emotional states, electroencephalogram (EEG) has been attracting increasing research attention for emotion classification. The classification method based on spatial-domain analysis is one of the research hotspots. However, most previous studies ignored the complementarity of information between different frequency bands, and the information in a single frequency band is not fully mined, which increases the computational time and the difficulty of improving classification accuracy. To address the above problems, this study proposes an emotion classification method based on dynamic simplifying graph convolutional (SGC) networks and a style recalibration module (SRM) for channels, termed SGC-SRM, with multi-band EEG data as input. Specifically, first, the graph structure is constructed using the differential entropy characteristics of each sub-band and the internal relationship between different channels is dynamically learned through SGC networks. Second, a convolution layer based on the SRM is introduced to recalibrate channel features to extract more emotion-related features. Third, the extracted sub-band features are fused at the feature level and classified. In addition, to reduce the redundant information between EEG channels and the computational time, (1) we adopt only 12 channels that are suitable for emotion classification to optimize the recognition algorithm, which can save approximately 90.5% of the time cost compared with using all channels; (2) we adopt information in the θ, α, ß, and γ bands, consequently saving 23.3% of the time consumed compared with that in the full bands while maintaining almost the same level of classification accuracy. Finally, a subject-independent experiment is conducted on the public SEED dataset using the leave-one-subject-out cross-validation strategy. According to experimental results, SGC-SRM improves classification accuracy by 5.51-15.43% compared with existing methods.

Crosstalk between ILC2s and Th2 cells varies among mouse models.

Type 2 T helper (Th2) cells and group 2 innate lymphoid cells (ILC2s) provide protection against helminth infection and are involved in allergic responses. However, their relative importance and crosstalk during type 2 immune responses are still controversial. By generating and utilizing mouse strains that are deficient in either ILC2s or Th2 cells, we report that interleukin (IL)-33-mediated ILC2 activation promotes the Th2 cell response to papain; however, the Th2 cell response to ovalbumin (OVA)/alum immunization is thymic stromal lymphopoietin (TSLP) dependent but independent of ILC2s. During helminth infection, ILC2s and Th2 cells collaborate at different phases of the immune responses. Th2 cells, mainly through IL-4 production, induce the expression of IL-25, IL-33, and TSLP, among which IL-25 and IL-33 redundantly promote ILC2 expansion. Thus, while Th2 cell differentiation can occur independently of ILC2s, activation of ILC2s may promote Th2 responses, and Th2 cells can expand ILC2s by inducing type 2 alarmins.

A method for reducing thermal injury during the ureteroscopic holmium laser lithotripsy.

Objective: Many studies have demonstrated the heat effect from the holmium laser lithotripsy can cause persistent thermal injury to the ureter. The purpose of this study was to elucidate the use of a modified ureteral catheter with appropriate firing and irrigation to reduce the thermal injury to the "ureter" during the ureteroscopic holmium laser lithotripsy in vitro. Methods: An in vitro lithotripsy was performed using a modified catheter (5 Fr) as the entrance for the irrigation and the holmium laser fiber while using the remaining space in the ureteroscopic channel as an outlet. Different laser power settings (10 W, 20 W, and 30 W) with various firing times (3 s, 5 s, and 10 s) and rates of irrigation (15 mL/min, 20 mL/min, and 30 mL/min) were applied in the experiment. Temperature changes in the "ureter" were recorded with a thermometer during and after the lithotripsy. Results: During the lithotripsy, the local highest mean temperature was 60.3 °C and the lowest mean temperature was 26.7 °C. When the power was set to 10 w, the temperature was maintained below 43 °C regardless of laser firing time or irrigation flow. Regardless of the power or firing time selected, the temperature was below 43 °C at the rate of 30 mL/min. There was a significant difference in temperature decrease when continuous 3 s drainage after continuous firing (3 s, 5 s, or 10 s) compared to with not drainage (p<0.05) except for two conditions of 0.5 J×20 Hz, 30 mL/min, firing 5 s, and 1.0 J×10 Hz, 30 mL/min, firing 5 s. Conclusion: Our modified catheter with timely drainage reducing hot irrigation may significantly reduce the local thermal injury effect, especially along with the special interrupted-time firing setting during the simulated holmium laser procedure.

The effect of physical fitness exercise on relieving psychological anxiety of college students / El efecto del ejercicio físico en el alivio de la ansiedad psicológica de los estudiantes universitarios

The study aims to determine whether engaging in physical activity reduces college students' psychological anxiety. With the assistance of college physical education teachers, this study uses random cluster sampling, literary analysis, and mathematical statistics. Measurement data are expressed by mean and standard deviation while counting data are expressed by frequency and percentage. It has been determined that the detection rates for inactivity among college students were 56.5%, anxiety was discovered at 22.2%, and depression was identified at 34.9%. The general state of exercise, anxiety, and sadness among college students is not encouraging, with depression and inactivity being more pronounced. Higher levels of physical activity can lead to lower sadness and anxiety scores and higher levels of mental wellness. The study has shown that kids who experience low anxiety may learn well, and anxiety can be managed by physical exercise and fitness. In this regard, the study has stressed that parents and college administration play a crucial role in encouraging college students to maintain the physical fitness required for their mental health and advance their academic careers. Psychological anxiety has been the subject of numerous studies, but this study has improved the model of psychological novelty with physical activity and physical fitness. This is a unique literary contribution.(AU)

Design and Implementation of Taizhou Integrated Prostate Screening.

A community-based prostate cancer screening program was conducted to assess the morbidity and associated factors for prostate cancer among the subpopulation of men aged ≥50 years in Taizhou, China. Taizhou Integrated Prostate Screening (TIPS) is a large, observational, population-based study of prostate cancer screening data based on serum prostate-specific antigen (PSA) concentrations. A pilot census of all male residents aged 50 years or older was conducted in Luqiao District, one of the field sites of the TIPS cohort in the city of Taizhou, Zhejiang. The interviewer-administered questionnaire evaluated demographic characteristics and environmental exposure factors. A total of 1,806 out of 3,516 participants completed the questionnaire. The overall prevalence of PSA ≥4 ng/mL was 11.5%, and included participants at low risk (9.2%), moderate risk (1.7%), and high risk (0.6%). Participants aged 60-69, 70-79, and ≥80 years had a 2.7-fold, 4.2-fold, and 6.5-fold higher risk of elevated PSA, respectively, in comparison with those aged 50 to 59 years (p < .001). Eighteen patients were diagnosed with prostate cancer, of whom 11 (61.1%) underwent radical surgery. This community-based PSA screening program indicated the results for early detection of prostate cancer among men aged ≥50 years. Early screening and appropriate clinical therapy for the management of prostate cancer are essential in this subpopulation.

Hexyl-Aminolevulinate Ethosomes: a Novel Antibiofilm Agent Targeting Zinc Homeostasis in Candida albicans.

Substantial drug resistance afforded by Candida albicans biofilms results in ineffective treatment with conventional drugs and persistent infection. Our previous study showed that hexyl-aminolevulinate ethosomes (HAL-ES) act against C. albicans biofilms and weaken their drug resistance and pathogenicity; however, the mechanism involved remains unclear. Here, we systematically evaluated the effects and mechanisms of HAL-ES on biofilm formation and drug resistance. We found that, in addition to mediating antifungal photodynamic therapy, HAL-ES inhibited the early, developmental, and mature stages of biofilm formation compared with fluconazole, HAL, or ES. Notably, adhesion and hyphal formation were significantly inhibited by postdrug effects even after brief exposure (2 h) to HAL-ES. Its therapeutic effect in vivo also has been demonstrated in cutaneous candidiasis. RNA sequencing and quantitative PCR showed that HAL-ES inhibited ribosome biogenesis by disrupting zinc homeostasis in C. albicans, thereby reducing the translation process during protein synthesis. Furthermore, HAL-ES downregulated the expression of multidrug resistance genes and increased fluconazole susceptibility in C. albicans. Our findings provide a novel and efficient method for the treatment of biofilm resistance in C. albicans infection as well as a basis for the application of HAL-ES. We also describe a new strategy for the treatment of biofilm-related infections via zinc restriction. IMPORTANCE Candida albicans is the most prevalent fungal species of the human microbiota. The medical impact of C. albicans on its human host depends on its ability to form biofilms. The intrinsic resistance conferred by biofilms to conventional antifungal drugs makes biofilm-based infections a significant clinical challenge. In this study, we demonstrate the attenuating effect of HAL-ES on C. albicans biofilm formation and drug resistance. Furthermore, we propose that HAL-ES inhibits protein translation by disrupting zinc homeostasis in C. albicans. This study not only provides a novel and effective therapeutic strategy against C. albicans biofilm but also proposes a new strategy to resolve C. albicans biofilm infection by disrupting zinc homeostasis.