Search Results (42)

This study investigates the anti-inflammatory effects of the marine diterpene glycosides pseudopterosin A-D (PsA-D) in mitigating nickel sulfate (NiSO₄)-induced skin sensitization. In dermal dendritic cell (DDC) surrogates, PsA-D pre-treatment significantly reduced NiSO₄-induced upregulation of key activation surface markers, cluster of differentiation (CD)54 (~1.2-fold), and CD86 (~1.6-fold). Additionally, PsA-D inhibited the NiSO₄-induced activation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway by suppressing inhibitor of kappa B alpha (IκBα) degradation. Furthermore, PsA-D suppressed inflammatory responses by inhibiting the NiSO₄-induced secretion of pro-inflammatory cytokines, including interleukin (IL)-8 (~6.8-fold), IL-6 (~2.2-fold), and IL-1β (~5.3-fold). In a full-thickness human skin model incorporating DDC surrogates, topical application of PsA-D effectively attenuated NiSO₄-induced mRNA expression of IL-8 (~2.1-fold), IL-6 (~2.6-fold), and IL-1β (~2.2-fold), along with the key inflammatory mediators cyclooxygenase-2 (COX-2) (~3.5-fold) and NOD-like receptor family pyrin domain-containing 3 (NLRP3) (~2.1-fold). Overall, PsA-D demonstrated comparable efficacy to dexamethasone, a benchmark corticosteroid, providing a promising therapeutic alternative to corticosteroids for the treatment of skin sensitization and allergic contact dermatitis. However, to maximize PsA-D’s therapeutic potential, future studies on optimizing the bioavailability and formulation of PsA-D are required. Full article

Background: The testosterone-to-PSA (T/PSA) ratio has been proposed as a novel biomarker to enhance the diagnostic specificity of prostate-specific antigen (PSA) in prostate cancer (PCa) detection. The objective of this study was to evaluate the diagnostic performance of the T/PSA ratio in distinguishing PCa from benign conditions in men undergoing prostate biopsy. Materials and Methods: Eighty men who underwent systematic and targeted transrectal prostate biopsy were retrospectively studied. Clinical variables included serum PSA, testosterone, prostate volume, PSA density (PSAD), and the T/PSA ratio. Diagnostic accuracy was assessed using Receiver Operating Characteristic (ROC) curve analysis. Optimal cutoffs were determined using Youden’s index. Results: PCa was diagnosed in 53 patients (66.3%). Median T/PSA was significantly lower in PCa versus non-PCa patients (0.46 vs. 0.86; p < 0.01). T/PSA showed good diagnostic performance (AUC = 0.75) with an optimal cutoff of 0.81 (sensitivity: 59.3%, specificity: 86.8%). In patients with PSA ≤10 ng/mL, T/PSA retained strong discriminatory ability (AUC = 0.76), with sensitivity and specificity of 82.4% and 72.7%, respectively. Among all parameters, PSAD showed the highest diagnostic accuracy (AUC = 0.813). T/PSA was not significantly associated with Gleason score (p = 0.48). Conclusions: The T/PSA ratio is a clinically accessible and cost-effective biomarker that may improve PCa risk stratification and reduce unnecessary biopsies, particularly in patients with borderline PSA levels. Although it does not correlate with tumor aggressiveness, its combination with PSAD could enhance diagnostic accuracy in routine clinical practice. Full article

The mechanisms underlying leaf variegation in the ornamental Ilex × ‘Solar Flare’ remain poorly understood. To investigate this phenomenon, we conducted a comprehensive characterization of its variegated leaves. Compared to green sectors, yellow sectors exhibited severe chloroplast structural abnormalities, including swollen chloroplasts, damaged thylakoid membranes, and reduced chloroplast numbers. These yellow sectors also showed significantly lower chlorophyll and carotenoid levels, along with a depletion of key chlorophyll precursors—protoporphyrin IX (Proto IX), magnesium protoporphyrin IX (Mg-Proto IX), and protochlorophyllide (Pchlide). Photosynthetic efficiency was significantly impaired. Comparative transcriptome analysis identified 3510 differentially expressed genes (DEGs) between yellow and green sectors. Key disruptions in chlorophyll biosynthesis included upregulated CHLD expression and downregulated CHLH and CHLG expression, leading to impaired chlorophyll synthesis. Additionally, chlorophyll degradation was accelerated by PAO upregulation. Defective chloroplast development in yellow sectors was associated with the downregulation of GLK1, GLK2, and thylakoid membrane-related genes (PsbC, PsbO, PsbR, PsaD, and PsaH). These molecular alterations likely drive the variegated phenotype of I. × ‘Solar Flare’. These observations advance our understanding of the genetic and physiological mechanisms regulating leaf variegation in this cultivar. Full article

Prostate Imaging Reporting and Data System version 2.1 (PI-RADS) category 3 lesions are a challenge in the clinical workflow. A better detection of the infrequently occurring clinically significant prostate cancer (csPCa) in PI-RADS 3 lesions is an important objective. The purpose of this study was to evaluate if feature maps calculated from T2-weighted (T2w) 3 Tesla (3T) MRI can help detect csPCa in PI-RADS category 3 lesions. In-house biparametric 3T prostate MRI examinations acquired between January 2019 and June 2023 because of elevated prostate-specific antigen (PSA) levels were retrospectively screened. Inclusion criteria were a PI-RADS 3 lesion and available results of an ultrasound-guided targeted and systematic biopsy. Exclusion criteria were a simultaneous PI-RADS category 4 or 5 lesion and hip replacement. Target lesions with the International Society of Urological Pathology (ISUP) grade group 1 were rated clinically insignificant PCa (ciPCa) and ≥2 csPCa. This resulted in 52 patients being included in the final analysis, of whom 11 (21.1%), 8 (15.4%), and 33 (63.5%) patients had csPCa, ciPCa, and no PCa, respectively, with the latter two groups being combined as non-csPCa. Eight of the csPCas were located in the peripheral zone (PZ) and three in the transition zone (TZ). In the non-csPCa group, 29 were located in the PZ and 12 in the TZ. Target lesions were marked with volumes of interest (VOIs) on axial T2w images. Axial T2w images were then converted to 93 feature maps. VOIs were copied into the maps, and feature quantity was retrieved directly. Features were tested for significant differences with the Mann–Whitney U-test. Univariate models for single feature performance and bivariate models implementing PSA density (PSAD) were calculated. Ten map-derived features differed significantly between the csPCa and non-csPCa groups (AUCs: 0.70–0.84). The diagnostic performance for TZ lesions (AUC: 0.83–1.00) was superior to PZ lesions (AUC: 0.74–0.85). In the bivariate models, performance in the PZ improved with AUCs >0.90 throughout. Parametric feature maps alone and as bivariate models with PSAD can (?) noninvasively identify csPCa in PI-RADS 3 lesions and could serve as a quantitative tool reducing ambiguity in PI-RADS 3 lesions. Full article

Background: MRI fusion prostate biopsy has improved the detection of clinically significant prostate cancer (CSC). Continued refinements in predicting the pre-biopsy probability of CSC are essential for optimal patient counseling. We investigated potential factors related to improved cancer detection rates (CDR) of CSC in patients with PI-RADS ≥ 3 lesions. Methods: The pathology of 980 index lesions in 980 patients sampled by transrectal mpMRI-targeted prostate biopsy across four medical centers between 2017–2020 was reviewed. PI-RADS lesion distribution included 291 PI-RADS-5, 374 PI-RADS-4, and 315 PI-RADS-3. We compared CDR of index PI-RADS ≥ 3 lesions based on location (TZ) vs. (PZ), PSA density (PSAD), and history of prior negative conventional transrectal ultrasound-guided biopsy (TRUS). Results: Mean age, PSA, prostate volume, and level of prior negative TRUS biopsy were 66 years (43–90), 7.82 ng/dL (5.6–11.2), 54 cm³ (12–173), and 456/980 (46.5%), respectively. Higher PSAD, no prior history of negative TRUS biopsy, and PZ lesions were associated with higher CDR. Stratified CDR highlighted significant variance across subgroups. CDR for a PI-RADS-5 score, PZ lesion with PSAD ≥ 0.15, and prior negative biopsy was 77%. Conversely, the CDR rate for a PI-RADS-4 score, TZ lesion with PSAD < 0.15, and prior negative biopsy was significantly lower at 14%. Conclusions: For index PI-RADS ≥ 3 lesions, CDR varied significantly based on location, prior history of negative TRUS biopsy, and PSAD. Such considerations are critical when counseling on the merits and potential yield of prostate needle biopsy. Full article

The adequacy and efficacy of simple and hybrid machine learning and Computational Intelligence algorithms were evaluated for the classification of potential prostate cancer patients in two distinct categories, the high- and the low-risk group for PCa. The evaluation is based on randomly generated surrogate data for the biomarker PSA, considering that reported epidemiological data indicated that PSA values follow a lognormal distribution. In addition, four more biomarkers were considered, namely, PSAD (PSA density), PSAV (PSA velocity), PSA ratio, and Digital Rectal Exam evaluation (DRE), as well as patient age. Seven simple classification algorithms, namely, Decision Trees, Random Forests, Support Vector Machines, K-Nearest Neighbors, Logistic Regression, Naïve Bayes, and Artificial Neural Networks, were evaluated in terms of classification accuracy. In addition, three hybrid algorithms were developed and introduced in the present work, where Genetic Algorithms were utilized as a metaheuristic searching technique in order to optimize the training set, in terms of minimizing its size, to give optimal classification accuracy for the simple algorithms including K-Nearest Neighbors, a K-means clustering algorithm, and a genetic clustering algorithm. Results indicated that prostate cancer cases can be classified with high accuracy, even by the use of small training sets, with sizes that could be even smaller than 30% of the dataset. Numerous computer experiments indicated that the proposed training set minimization does not cause overfitting of the hybrid algorithms. Finally, an easy-to-use Graphical User Interface (GUI) was implemented, incorporating all the evaluated algorithms and the decision-making procedure. Full article

Convolutional neural network-based detection models have been extensively applied in industrial production for monitoring the use of safety protection equipment, ensuring worker safety. This paper addresses scenarios in electrical operations where the safety protection requirements are more comprehensive and stringent. This paper proposes an improved detection model, ML-YOLOv8n-Light, based on YOLOv8n, targeting issues of low detection efficiency and large model size that make deployment challenging in current safety protection equipment-wearing detection models for electrical operations. Our model confronts the disparity in safety protection equipment sizes with a novel, lightweight multi-scale grouped convolution (MSGC) scheme integrated into the architecture. A lightweight adaptive weight downsampling (LAWD) mechanism is also fashioned to replace the traditional downsampling methods, optimizing resource consumption without sacrificing performance. Additionally, to enhance the detection fidelity of smaller items, such as insulated gloves, we added feature-rich shallow maps and a dedicated detection head for such objects. To enhance the detection efficiency of YOLOv8n, inspired by part convolution, we improved the spatial pyramid pooling fast (SPPF) and the detection heads. The experiments conducted on the custom dataset power safe attire dataset (PSAD) showed that compared to the original model, mAP50 increased by 2.1%, mAP50-95 by 3.1%, with a 29% reduction in parameters, an 18% reduction in computations, and a 23% compression of the model size. There are fewer detection omissions at long distances and under occlusion, fewer false positives, and computing resources are allocated more efficiently. Full article

Mitigating carbon emissions intensity (CEI) and promoting carbon neutrality at the city level are essential for addressing the challenges of global climate change and advancing sustainable development. This study examines the influence of producer services agglomeration diversification (PSAD) on CEI using an unbalanced panel dataset including 252 Chinese prefectural-level cities from 2005 to 2018 for empirical analyses. We find that improving PSAD in a city can significantly mitigate CEI. Stronger PSAD accelerates a city’s industrial structure transformation from secondary- to tertiary-dominated in addition to boosting green development capabilities, both of which are confirmed to have concrete carbon emissions reduction effects. Furthermore, PSAD only significantly alleviates CEI in non-eastern cities in China, and the benefits of carbon emissions reduction are stronger after 2010. Our policy insights highlight land utilization in shaping the intracity layouts of producer services agglomerations (PSAs) and stress regional-level measures. Recognizing regional differences and integrating PSAs allocation with broader institutional measures can amplify PSAD’s benefits. Full article

Oocystis borgei, a microalgae species employed for regulating the quality of aquaculture water, demonstrates the capacity to adsorb noxious substances, curtail the growth of detrimental bacteria, and outcompete blooming cyanobacteria. It can be concentrated by natural sedimentation and stored at room temperature, making it costless and simple to transport and use. To study the mechanism of adaptation to room temperature preservation, O. borgei was concentrated (1.19 × 10⁷−1.21 × 10⁷ cell/mL) and stored for 50 days at low (5 °C, LT), normal (25 °C, NT), and high (35 °C, HT) temperatures, respectively. Polysaccharide content, lipid content, cell survival, and resuscitation were evaluated. RNA-Seq was also used to examine how concentrated O. borgei responded to temperature. During storage, there was an increase in polysaccharide content and a decrease in lipid content, with both being significantly upregulated in the LT and HT groups. Survival and cell density were highest in the NT group. The RNA-Seq analysis revealed extensive differences in transcript levels. ATP synthesis was inhibited in the LT group due to the reduced expression of PsaD, PsaE, PsaF, PsaK, and PsaL. Under HT, the formation of reactive oxygen species (ROS) was facilitated by low levels of redox-related genes (nirA) and high levels of oxidative genes (gdhA, glna, and glts). The findings suggest that storing concentrated O. borgei at room temperature is optimal for microalgae preservation, enhancing theoretical research in this field. Our study provides further theoretical and practical support for the development of O. borgei as a live ecological preparation for aquaculture microalgae ecology management. Full article

The aim of this study was to demonstrate the correlation between ADC values and the ADC/PSAD ratio for potentially malignant prostate lesions classified into ISUP grades and to determine threshold values to differentiate benign lesions (noPCa), clinically insignificant (nsPCa) and clinically significant prostate cancer (csPCa). We enrolled a total of 403 patients with 468 prostate lesions, of which 46 patients with 50 lesions were excluded for different reasons. Therefore, 357 patients with a total of 418 prostate lesions remained for the final evaluation. For all lesions, ADC values were measured; they demonstrated a negative correlation with ISUP grades (p < 0.001), with a significant difference between csPCa and a combined group of nsPCa and noPCa (ns-noPCa, p < 0.001). The same was true for the ADC/PSAD ratio, but only the ADC/PSAD ratio proved to be a significant discriminator between nsPCa and noPCa (p = 0.0051). Using the calculated threshold values, up to 31.6% of biopsies could have been avoided. Furthermore, the ADC/PSAD ratio, with the ability to distinguish between nsPCa and noPCa, offers possible active surveillance without prior biopsy. Full article

Combining systematic biopsy (SB) with targeted biopsy (TB) in the case of a positive result from multiparametric magnetic resonance imaging (mpMRI) is a matter of debate. The Prostate Imaging Reporting and Data System (PIRADS) score of 5 indicates the highest probability of clinically significant prostate cancer (csPC) detection in TB. Potentially, omitting SB in the case of PIRADS 5 may have a marginal impact on the csPC detection rate. The aim of this study was to determine whether SB can be avoided in the case of PIRADS 5 and to identify potential factors allowing for performing TB only. This cohort study involved n = 225 patients with PIRADS 5 on mpMRI (PIRADS 2.0/2.1) who underwent transperineal or transrectal combined biopsy (CB). CsPC was diagnosed in 51.6% (n = 116/225) of cases. TB and SB resulted in the detection of csPC in 48% (n = 108/225) and 20.4% (n = 46/225) of cases, respectively (TB vs. SB, p < 0.001). When the TB was positive, SB detected csPC in n = 38 of the cases (38/108 = 35%). SB added to TB significantly improved csPC detection in 6.9% of cases in absolute terms (n = 8/116) (TB vs. CB, p = 0.008). The multivariate regression model proved that the significant predictors of csPC detection via SB were the densities of the prostate-specific antigen—PSAD > 0.17 ng/mL² (OR = 4.038, 95%CI: 1.568–10.398); primary biopsy setting (OR = 2.818, 95%CI: 1.334–5.952); and abnormal digital rectal examination (DRE) (OR = 2.746, 95%CI: 1.328–5.678). In a primary biopsy setting (n = 103), SB detected 10% (n = 6/60) of the additional cases of csPC (p = 0.031), while in a repeat biopsy setting (n = 122), SB detected 3.5% (n = 2/56) of the additional cases of csPC (p = 0.5). In the case of PSAD > 0.17 ng/mL² (n = 151), SB detected 7.4% (n = 7/95) of additional cases of csPC (p = 0.016), while in the case of PSAD < 0.17 ng/mL² (n = 74), SB detected 4.8% (n = 1/21) of the additional cases of csPC (p = 1.0). The omission of SB had an impact on the csPC diagnosis rate in patients with PIRADS 5 score lesions. Patients who have already undergone prostate biopsy and those with low PSAD are at a lower risk of missing csPC when SB is avoided. However, performing TB only may result in missing other csPC foci located outside the index lesion, which can alter treatment decisions. Full article

This study aimed to develop a noninvasive Machine Learning (ML) model to identify clinically significant prostate cancer (csPCa) according to Gleason Score (GS) based on biparametric MRI (bpMRI) radiomic features and clinical information. Methods: This retrospective study included 86 adult Hispanic men (60 ± 8.2 years, median prostate-specific antigen density (PSA-D) 0.15 ng/mL²) with PCa who underwent prebiopsy 3T MRI followed by targeted MRI–ultrasound fusion and systematic biopsy. Two observers performed 2D segmentation of lesions in T2WI/ADC images. We classified csPCa (GS ≥ 7) vs. non-csPCa (GS = 6). Univariate statistical tests were performed for different parameters, including prostate volume (PV), PSA-D, PI-RADS, and radiomic features. Multivariate models were built using the automatic feature selection algorithm Recursive Feature Elimination (RFE) and different classifiers. A stratified split separated the train/test (80%) and validation (20%) sets. Results: Radiomic features derived from T2WI/ADC are associated with GS in patients with PCa. The best model found was multivariate, including image (T2WI/ADC) and clinical (PV and PSA-D) information. The validation area under the curve (AUC) was 0.80 for differentiating csPCa from non-csPCa, exhibiting better performance than PI-RADS (AUC: 0.71) and PSA-D (AUC: 0.78). Conclusion: Our multivariate ML model outperforms PI-RADS v2.1 and established clinical indicators like PSA-D in classifying csPCa accurately. This underscores MRI-derived radiomics’ (T2WI/ADC) potential as a robust biomarker for assessing PCa aggressiveness in Hispanic patients. Full article

As the incidence of prostate cancer (PCa) has increased, screening based on prostate-specific antigen (PSA) has become controversial due to the low specificity of PSA. Therefore, we investigated the diagnostic performance of prostate health index (PHI) density (PHID) for the detection of PCa and clinically significant PCa (csPCa) compared to PSA, PSA density (PSAD), and PHI as a triaging test. We retrospectively reviewed 306 men who underwent prostate biopsy for PSA levels of 2.5 to 10 ng/mL between January 2020 and April 2023. Of all cohorts, 86 (28.1%) and 48 (15.7%) men were diagnosed with PCa and csPCa, respectively. In ROC analysis, the highest AUC was identified for PHID (0.812), followed by PHI (0.791), PSAD (0.650), and PSA (0.571) for PCa. A similar trend was observed for csPCa: PHID (AUC 0.826), PHI (AUC 0.796), PSAD (AUC 0.671), and PSA (0.552). When the biopsy was restricted to men with a PHID ≥ 0.56, 26.5% of unnecessary biopsies could be avoided; however, 9.3% of PCa cases and one csPCa case (2.1%) remained undiagnosed. At approximately 90% sensitivity for csPCa, at the given cut-off values of PHI ≥ 36.4, and PHID ≥ 0.91, 48.7% and 49.3% of unnecessary biopsies could be avoided. In conclusion, PHID had a small advantage over PHI, about 3.6%, for the reduction in unnecessary biopsies for PCa. The PHID and PHI showed almost the same diagnostic performance for csPCa detection. PHID can be used as a triaging test in a clinical setting to pre-select the risk of PCa and csPCa. Full article

Prostate cancer (PCa) is the second most frequently diagnosed cancer in men. Despite the significant progress in cancer diagnosis and treatment over the last few years, the approach to disease detection and therapy still does not include histopathological biomarkers. The dissemination of PCa is strictly related to the creation of a premetastatic niche, which can be detected by altered levels of specific biomarkers. To date, the risk factors for biochemical recurrence include lymph node status, prostate-specific antigen (PSA), PSA density (PSAD), body mass index (BMI), pathological Gleason score, seminal vesicle invasion, extraprostatic extension, and intraductal carcinoma. In the future, biomarkers might represent another prognostic factor, as discussed in many studies. In this review, we focus on histopathological biomarkers (particularly CD169 macrophages, neuropilin-1, cofilin-1, interleukin-17, signal transducer and activator of transcription protein 3 (STAT3), LIM domain kinase 1 (LIMK1), CD15, AMACR, prostate-specific membrane antigen (PSMA), Appl1, Sortilin, Syndecan-1, and p63) and their potential application in decision making regarding the prognosis and treatment of PCa patients. We refer to studies that found a correlation between the levels of biomarkers and tumor characteristics as well as clinical outcomes. We also hypothesize about the potential use of histopathological markers as a target for novel immunotherapeutic drugs or targeted radionuclide therapy, which may be used as adjuvant therapy in the future. Full article

Microalgae biotechnology has the potential to produce high quality bioproducts in a sustainable manner. Here, Chlamydomonas reinhardtii has shown great potential as a host for biotechnological exploitation. However, low expression of nuclear transgenes is still a problem and needs to be optimized. In many model organisms, viral promoters are used to drive transgene expression at high levels. However, no viruses are known to infect Chlamydomonas, and known viral promoters are not functional. Recently, two different lineages of giant viruses were identified in the genomes of Chlamydomonas reinhardtii field isolates. In this work, we tested six potentially strong promoters from these viral genomes for their ability to drive transgene expression in Chlamydomonas. We used ble, NanoLUC, and mCherry as reporter genes, and three native benchmark promoters as controls. None of the viral promoters drove expression of any reporter gene beyond background. During our study, we found that mCherry variants are produced by alternative in-frame translational start sites in Chlamydomonas. We show that this problem can be overcome by mutating the responsible methionine codons to codons for leucine and by using the 5′-UTR of βTUB2 instead of the 5′-UTRs of PSAD or RBCS2. Apparently, the βTUB2 5′-UTR promotes the use of the first start codon. This could be mediated by the formation of a stem-loop between sequences of the βTUB2 5′-UTR and sequences downstream of the first AUG in the mCherry reporter, potentially increasing the dwell time of the scanning 40S subunit on the first AUG and thus decreasing the probability of leaky scanning. Full article