Search Results (4,862)

Normogonadotropic azoospermia (NOAN) represents a diagnostic and therapeutic challenge in male infertility, affecting men with normal gonadotropin levels but absent sperm in the ejaculate. Emerging evidence has identified 17-hydroxyprogesterone (17OHP) as a potential biomarker for detecting reduced intratesticular testosterone (ITT) levels, and the presence of round spermatids in ejaculate as an indicator of residual spermatogenic activity. This report synthesizes current evidence on a proposed hypothesis-generating diagnostic framework that utilizes these markers to guide hormonal treatment strategies. Specifically, patients with elevated 17OHP levels (>1.18 ng/mL) and detectable round spermatids may benefit from combined human chorionic gonadotropin (hCG) and follicle-stimulating hormone (FSH) therapy at doses lower than those used for hypogonadotropic hypogonadism. However, this cutoff has not been prospectively validated in NOAN-specific cohorts, and the evidence supporting this approach remains preliminary, derived from small heterogeneous cohorts. Alternative therapeutic strategies, including FSH monotherapy and non-hormonal pharmacological treatments, are also discussed. This framework requires rigorous prospective validation before clinical implementation. Full article

Qinghai Lake, the largest endorheic saline lake in China, has undergone a pronounced hydrological regime shift from a multi-decadal decline to a rapid post-2004 recovery, reflecting strong hydroclimatic non-stationarity in the northeastern Tibetan Plateau (TP). This paper supplements the current water level and lake area status of Qinghai Lake to provide basic background for future prediction. Reliable forecasting of such climate sensitive lake systems remains difficult because conventional statistical models often fail to capture non-linear fluctuations, whereas standalone deep learning models may overlook long-term deterministic evolution. To address this challenge, we developed a serial decomposition GeoAI framework that integrates autoregressive integrated moving average (ARIMA), one-dimensional convolutional neural networks (1D-CNNs), and long short-term memory (LSTM) networks for non-stationary water level forecasting. Using annual water level observations from 1960 to 2025, the ARIMA component was first used to extract the low-frequency deterministic trend, after which the CNN-LSTM module reconstructed the nonlinear residual variability. The model was trained on the 1960–2012 period and validated over 2013–2025, which represents the most dynamic expansion stage of Qinghai Lake. The hybrid framework outperformed the benchmark models, achieving a Root Mean Square Error (RMSE) of 0.2033 m, Mean Absolute Error (MAE) of 0.1727 m, and Mean Squared Error (MSE) of 0.0413 m² during validation. The decomposition strategy effectively reduced phase lag and amplitude attenuation, improving both predictive accuracy and process interpretability. Multi-step forecasting for 2026–2056 suggests that Qinghai Lake will continue to rise, reaching approximately 3204.08 m by 2056, although the growth rate is projected to slow as negative hydrological feedback strengthen. By explicitly separating deterministic climate scale signals from nonlinear short-term variability, the proposed framework provides a robust and transferable geoinformation based tool for forecasting water level dynamics and supporting adaptive management in climate sensitive, data scarce lake basins. Full article

The sweet potato weevil, Cylas formicarius (Fabricius) (Coleoptera: Brentidae), is one of the most destructive pests of sweet potato [Ipomoea batatas (L.) Lam.] crops worldwide. Current management of the sweet potato weevil relies heavily on conventional pesticides, raising concerns about pesticide residues, environmental impacts, and the development of pesticide resistance. This study evaluated the effects of seven essential oils (EOs): eucalyptus (Eucalyptus globulus), garlic (Allium sativum), marigold (Calendula officinalis), mustard seed (Sinapis alba), peppermint (Mentha piperita), rosemary (Rosmarinus officinalis), and thyme (Thymus gobicus) against different life stages of C. formicarius under laboratory conditions. Feeding activity, oviposition, larval mortality, pupal mortality, and adult survival were evaluated using EO concentrations of 1%, 5%, and 10%, with acetone and distilled water as control treatments. Each treatment consisted of six replicates, with 10 insects per replicate. Statistical analyses were performed using logistic regression models with a binomial distribution. Significant effects of oil type and concentration were observed as lethal to weevil larval and pupal stages. Similarly, the feeding and oviposition were significantly impacted (p < 0.0001). Peppermint oil exhibited the highest efficacy, causing complete or near-complete mortality of second- and third-instar larvae and pupae at 10%. This also substantially reduced adult survival, feeding activity, and oviposition. Rosemary, thyme, and eucalyptus, at higher concentrations. Most oils almost completely suppressed oviposition. These findings demonstrate that plant-derived essential oils (EOs) exhibit significant insecticidal activity against Cylas formicarius, indicating their promise as sustainable tools for integrated pest management programs in sweet potato production systems. Full article

The valorization of winemaking by-products is a sustainable strategy consistent with circular bioeconomy principles and current public health priorities. This study aimed to evaluate residual oenological yeast sediment from local Moldovan grape varieties, Viorica and Fetească Regală, as a multifunctional ingredient and partial fat replacer in muffins. Sunflower oil was replaced with wine lees (WL) at 20%, 35%, and 50%, and the obtained products were analyzed in terms of physicochemical, nutritional, microbiological, colorimetric, and sensory characteristics. WL incorporation reduced the caloric value by up to 10% and decreased lipid content, while contributing to higher protein and dietary fiber levels. Moisture values remained within acceptable limits, whereas titratable acidity increased with the substitution level (p < 0.05). Muffin density showed a slight increase, and water absorption capacity improved markedly, reaching 269%, mainly due to the fiber-rich composition of WL. Color analysis indicated reduced lightness and increased redness, associated with yeast pigments and thermal reactions during baking. Microbiological results showed lower total viable counts with increasing WL addition; however, the 50% substitution level exceeded the permissible limits for yeasts and molds. Sensory evaluation indicated that the muffin with 20% WL was the most acceptable sample. Overall, WL may be considered a promising sustainable ingredient for developing reduced-fat muffins with improved nutritional value. Full article

Series–series (S–S) compensated wireless power-transfer (WPT) systems are increasingly deployed where connector-free and reliable energy delivery is required, but practical monitoring becomes ambiguous when receiver-resonance drift and magnetic-coupling variation produce similar transmitter-side impedance changes. This paper addresses that ambiguity by separating the two effects without receiver-side sensing. During a low-power diagnostic interval, the receiver terminal is briefly placed in open and short states, and only the fundamental phasors of the inverter output voltage and primary current are processed together with the known compensation capacitances. After the open-state measurement identifies the primary self-impedance, the short-state residual is mapped to an affine D–${\omega }^2$ line; its zero crossing gives the receiver resonant frequency and secondary self-inductance, while its slope gives the mutual inductance and coupling coefficient. The routine is implementable as a start-up or periodic diagnostic function in WPT hardware that already measures the primary voltage and current and can impose the required receiver terminal states; it requires no receiver-side measurement, auxiliary sensing coil, short-loop resistance measurement, or iterative zero-phase search. In simulation, the coupling-coefficient error remained below $0.014\%$ under receiver-inductance tolerance and mutual-inductance variation. In a prototype, the short-state data followed the predicted linear relation with $R^2=0.9979$, and the extracted coupling coefficient agreed with the reference within about $5\%$. The identified receiver resonance was also used to guide operating-frequency adjustment in a practical power-transfer test. Full article

Vericiguat is currently indicated for patients with heart failure with reduced ejection fraction (HFrEF) following recent clinical worsening, based on evidence demonstrating a reduction in cardiovascular death or heart failure hospitalization in a high-risk population. While this positioning is clinically justified, it may underestimate the broader pathophysiological context in which soluble guanylate cyclase (sGC) stimulation may be relevant, particularly in phases of persistent biological activation following apparent clinical stabilization. In routine practice, acute coronary syndromes (ACS), acute heart failure (AHF), and chronic HFrEF are approached as distinct clinical entities. However, these conditions often represent sequential manifestations of a continuous disease trajectory driven by persistent endothelial dysfunction, impaired nitric oxide–sGC–cyclic guanosine monophosphate (NO–sGC–cGMP) signaling, and residual vascular risk. In this perspective, we revisit the mechanistic and clinical rationale for vericiguat and propose a reframing of its therapeutic role. Its greatest utility may lie in patients with recently worsening HFrEF who remain biologically vulnerable after stabilization. Extension of this concept to post-ACS populations remains hypothesis-generating and is not supported by direct clinical evidence. This “post-stabilization vulnerable state” represents a clinically recognizable yet insufficiently targeted phase, characterized by ongoing biological activation despite apparent clinical improvement. Adopting a continuum-based view of cardiovascular disease may improve alignment between pathophysiology and treatment, refine patient selection, and inform future trial design focused on this early post-event window. Importantly, this perspective is hypothesis-generating and reflects an effort to align emerging mechanistic insights with clinical trajectory, rather than to extend current indications beyond the available evidence base. Full article

Acute myeloid leukemia (AML) is a genetically and clinically heterogeneous hematologic malignancy in which intensive induction chemotherapy remains the standard therapeutic platform for medically fit adults. In recent years, however, the frontline treatment paradigm has progressively evolved from a purely cytotoxic approach toward a biologically informed strategy. This shift has been driven by the identification of recurrent molecular alterations—particularly FLT3 and IDH1/2 mutations—as well as renewed interest in antibody-based therapies and the growing recognition that relapse, resistance, and measurable residual disease (MRD) are shaped by clonal architecture rather than blast burden alone. This review examines the development of targeted therapies combined with intensive chemotherapy in AML. We discuss the biological rationale for combination approaches and summarize the key clinical studies that have defined current practice, including trials evaluating FLT3 inhibitors, gemtuzumab ozogamicin, IDH inhibitors, and venetoclax-based strategies. We also address the role of targeted therapy across different treatment phases, including induction, consolidation, and post-remission settings, and analyze emerging data regarding MRD-guided treatment strategies, mechanisms of resistance, and integration with allogeneic hematopoietic stem cell transplantation. The integration of targeted agents with intensive chemotherapy is reshaping frontline AML therapy and represents a critical step toward precision medicine. While genotype-directed strategies—such as FLT3 inhibition—have already demonstrated survival benefit, optimal patient selection, treatment sequencing, and duration remain areas of active investigation. Future progress will likely depend on MRD-driven treatment adaptation, improved understanding of clonal evolution, and the development of rational multi-agent combinations capable of achieving deeper and more durable remissions. Full article

By synthesizing BiSbO₄ material with a molar ratio of Bi₂O₃ to Sb₂O₃ of 0.6:1 and calcining it at 700 °C, a relatively pure compound was obtained. Additionally, the effects of varying BiSbO₄ content on the microstructure and electrical properties of ZnO varistor ceramics were investigated. Results indicate that as BiSbO₄ content increased from 0% to 3%, the voltage gradient of the varistor rose with increasing BiSbO₄ content while leakage current gradually decreased. The nonlinear coefficient continued to rise, while the residual voltage ratio first decreased then increased. At a BiSbO₄ content of 2%, outstanding electrical properties were achieved: voltage gradient (E_1mA) = 346 V·mm⁻¹, leakage current J_L = 0.14 μA·cm⁻², nonlinear coefficient α = 32, and residual voltage ratio K = 1.73. Furthermore, after undergoing a 100 kA surge, the U_1mA value remained at 93.5% of its initial value, demonstrating outstanding surge stability. This provides a new approach for fabricating high-gradient, high-stability varistors. Full article

Resistance spot welding was performed to join 2 mm thick TA2 titanium plate and Q235 steel plate using an Nb-Ni bi-interlayer. The microstructure of the interfacial zone was observed and analyzed, and the tensile shear load of the joint was evaluated. The joints obtained display double-nugget-type and penetration-type joints. For the double-nugget-type joint, Ni₆Nb₇ and Ni₃Nb layers have been formed in the region between the residual Nb layer and the steel, while for the penetration-type joint, a mixed nugget composed of Ti-Fe intermetallic compounds was formed at the center zone of the weld. As the welding current increased or welding time extended, the tensile shear load of the joint exhibited a trend of initially increasing and subsequently decreasing. When a bi-interlayer consisting of 0.05 mm-Nb and 0.04 mm-Ni is utilized, the tensile shear load of the joint reached the maximum value of approximately 8.7 kN under the condition of 11 kA welding current, 300 ms welding time, and 3 kN electrode pressure. The results indicate that the Nb layer can effectively impede the cross-interface diffusion of Ti atoms and Ni-Nb intermetallic compound layers are formed in the interface region in the case that the interlayer thickness and the welding parameters are well-matched when resistance spot welding of Ti/steel is performed with a bi-interlayer of Nb-Ni. Full article

Glyphosate (Gly) is currently the most commonly used broad-spectrum herbicide in the world. The extensive residues of Gly and its major metabolite aminomethylphosphonic acid (AMPA) in food and the environment make it inevitable for humans to consume them. Although Gly has been shown to disturb the homeostasis of gut microbiome by inhibiting the shikimic acid pathway of microorganisms, the potential health effects [such as the occurrence of antibiotic resistance genes (ARGs)] remain unclear. Furthermore, as antibiotics that also act on the intestinal microbiota, their extensive residues inevitably lead to co-exposure with Gly. For these reasons, this study used zebrafish as experimental organisms to explore the effects of Gly/AMPA and oxytetracycline (OTC) exposure alone or in combination on ARGs in the intestine. Our results indicate that Gly exposure, rather than AMPA exposure, led to a 1.67-fold increase in the relative abundance of ARGs in the zebrafish intestine. Combined exposure to Gly and OTC led to a 2.30-fold increase in the relative abundance of ARGs in the zebrafish intestine, indicating a synergistic effect, whereas the additive effect of AMPA and OTC was negligible. In conclusion, the health risk of antibiotic resistance caused by Gly through the gut microbiota is a neglected hot topic. Further studies are needed to clarify Gly-induced functional drug resistance and to assess the human relevance of these findings using more appropriate model organisms. Full article

Background/Objectives: Diabetes mellitus (DM) is a critical metabolic condition with escalated blood glucose levels caused by insulin resistance, restricted insulin production, and the activity of alpha-amylase and alpha-glucosidase enzymes. Methods: This current work focuses on the synthesis and evaluation of novel Pyrimidine-derived pyrazole-based thiadiazole derivatives to target DM by inhibiting α-amylase and α-glucosidase. Results: The findings exhibited that, except for three compounds, all other synthesized derivatives inhibited α-amylase and α-glucosidase enzymes with IC₅₀ values ranging from 5.17 μM to 29.84 μM on α-amylase and 7.60 μM to 31.62 μM on α-glucosidase, in comparison to the standard drug Acarbose (α-amylase IC₅₀ = 8.25 ± 0.80 μM; α-glucosidase IC₅₀ = 10.75 ± 1.10 μM). Analogs 8g, 8k, and 8b displayed superior or comparable inhibitory activity compared to the reference drug Acarbose. The inhibition potential of the derivatives can be attributed to their stable contacts with crucial amino acid residues of targeted enzymes, as shown through molecular docking analysis. Moreover, DFT-calculated HOMO–LUMO parameters and electrostatic potential (ESP) maps were used to gain complementary insight into the electronic characteristics, charge distribution, and potential interaction behavior of the synthesized derivatives, which supported the molecular docking observations. Conclusions: Experimental outcomes and in silico support display that these derivatives serve as potential leads for anti-diabetic drug development. These potent pyrimidine-derived pyrazole-based thiadiazole derivatives were comparable to an existing diabetic mellitus inhibitor, specifying potential for further therapeutic development and optimization against diabetic mellitus. Full article

Background/Objectives: Efficacy endpoint selection in adult primary central nervous system (CNS) tumor trials remains challenging because conventional solid tumor frameworks do not adequately capture the anatomical, radiographic, and biological complexity of brain tumors. In particular, postoperative irregular residual lesions, non-enhancing tumor components, and treatment-related imaging changes complicate the interpretation of objective response and progression. This narrative review examines the current landscape of endpoint selection in adult primary CNS tumor trials and discusses strategies for standardization in the Response Assessment in Neuro-Oncology (RANO) 2.0 era from integrated regulatory science and clinical perspectives. Methods: This study was conducted as a narrative review intended to provide a regulatory science-oriented synthesis of efficacy endpoint evaluation in adult primary CNS tumor trials. The literature search primarily utilized PubMed and ClinicalTrials.gov, supplemented by major consensus guidelines, pivotal clinical trials, and regulatory documents from the major regulatory authorities, including those in the United States, Europe, and Japan, published over the past two decades. Search terms included combinations of keywords such as “brain tumor,” “glioblastoma,” “meningioma,” “Phase I,” “Phase II,” “efficacy endpoint,” and “RANO”. In addition to the literature synthesis, this review incorporates findings from our previously published empirical analyses regarding endpoint selection in Phase II glioblastoma trials, Phase II meningioma trials, and Phase I brain tumor trials. Results: Response Evaluation Criteria in Solid Tumors-based response assessment remains fundamentally limited in neuro-oncology. Across recent early-phase trials, substantial heterogeneity persists in endpoint selection and in the operational definitions of objective response rate, progression-free survival, and progression. RANO 2.0 is intended to provide a more unified and implementation-oriented framework by refining baseline definition, progression confirmation, non-enhancing lesion interpretation, and the role of minor response, while improving compatibility with contemporary molecular classification and immunotherapy-era trial design. However, important implementation challenges remain, including potential reproducibility concerns in complex imaging assessments, operational complexity, imaging standardization, and the need for independent central review. Conclusions: Standardization of endpoint strategies in adult primary CNS tumor trials should move beyond simple adoption of conventional solid tumor metrics toward a disease-specific, harmonized framework integrating imaging, clinical context, tumor biology, and regulatory interpretability. This review provides a regulatory science-oriented synthesis linking response assessment criteria, early-phase adult primary CNS tumor trial endpoint trends, empirical analyses, and emerging endpoint frameworks. RANO 2.0 represents an important step toward this goal, but it should be regarded as an evolving framework that requires continued validation, international collaboration, and implementation-focused refinement. Full article

This paper presents a power-matched third-harmonic current analysis for a detuned series–series (S–S) compensated wireless power transfer (WPT) system operating across continuous conduction mode (CCM) and discontinuous conduction mode (DCM). In practical S–S WPT systems, the transmitter-side resonant frequency is often intentionally detuned from the switching frequency to satisfy the desired switching condition, which leaves a residual transmitter reactance and changes the harmonic current behavior. In addition, the rectifier conduction mode affects the receiver-side voltage waveform and its harmonic components. To analyze this behavior, the fundamental power-transfer path is modeled using the equivalent rectifier input resistance, whereas the harmonic path is formulated using the inverter and rectifier harmonic voltage sources coupled through the transmitter and receiver resonant tanks. Although the formulation is applicable to arbitrary odd harmonics, the third-harmonic current is selected as the main EMI-oriented comparison quantity because it is the dominant low-order harmonic in the considered operating range. Simulation and experimental results show that output power alone is not sufficient to determine the harmonic current level. When power-matched operating points exist across the CCM/DCM boundary, the CCM-side load point is generally more favorable, especially from the receiver-side third-harmonic viewpoint. When both power-matched points are in DCM, the load point closer to the CCM/DCM boundary is generally more favorable than the deeper DCM point. Full article

Zirconia-toughened alumina (ZTA) ceramics are promising for load-bearing biomedical applications because they combine the hardness, chemical stability, wear resistance, and biocompatibility of alumina with the transformation-toughening capability of zirconia. Grinding is indispensable for achieving dimensional accuracy and surface quality, yet it inevitably introduces surface and subsurface cracks, residual stresses, and a local tetragonal-to-monoclinic transformation of zirconia. These changes can degrade fracture toughness, increase reliability scatter, and reduce long-term service stability. Annealing is therefore often considered a post-grinding recovery strategy because it can relax residual stresses, blunt crack tips, and partially restore the zirconia phase state. However, the extent of recovery depends strongly on the initial damage state, ZTA microstructure, and thermal schedule. This review systematically summarizes the current understanding of grinding-induced damage and annealing-assisted recovery in ZTA ceramics, with particular emphasis on the coupled relationships among subsurface damage, residual-stress evolution, phase transformation, and fracture toughness. Particular attention is given to distinguishing direct ZTA-specific evidence from mechanistic interpretations inferred from related zirconia-containing ceramic systems, because datasets based exclusively on ZTA remain relatively limited. By integrating the existing evidence, this review proposes a coupled processing-damage-recovery framework and identifies the key knowledge gaps that must be addressed to achieve more reliable process optimization in advanced ZTA components. Full article

Zinc oxide (ZnO) varistors are a core component of surge arresters; their failure can directly affect the secure and reliable operation of power equipment. Therefore, this paper conducts an impulse degradation test on ZnO varistors, combining electrical and microstructural tests to systematically explore the intrinsic correlation mechanism between the electrical properties and microstructural characteristics. Test results show that this type of ZnO varistor is susceptible to side-glaze surface flashover under an impulse current with a waveform of 8/20 μs and an amplitude of 27 kA, and the discharge branches exhibit an extension from the negative electrode towards the positive electrode. Moreover, surface flashover causes the formation of local conductive channels in the side glaze layer, resulting in a significant drop in the direct-current (DC) reference voltage U_1mA. However, the residual voltage U_10kA increases slightly with an increase in the number of impulse groups, with a change in amplitude of less than 1.5%. Additionally, the microstructural testing reveals that the impulse currents cause the bismuth (Bi) element in ZnO grains to precipitate and form more Bi-rich phases at the grain boundaries. This results in an increase in the thickness of the grain boundary layer, which is negatively correlated with the U_1mA. Meanwhile, the grain morphology and size distribution of brand-new samples, samples with different degrees of degradation, and samples with side-glaze surface flashover damage are not significantly different. This is consistent with the fact that the change range of the residual voltage U_10kA during impulse degradation is very small. This test phenomenon indicates that the failure of this type of ZnO varistor to withstand an impulse current with a waveform of 8/20 μs and an amplitude of 27 kA is mainly due to changes in the volt-ampere properties of the small-current regions caused by ion migration within the grain boundary layer. This research provides an experimental basis and theoretical support for improving the impulse withstand capacity of ZnO varistors in their design. Full article