Developmental toxicity of the neonicotinoid pesticide clothianidin to the larvae of the crustacean Decapoda, Penaeus vannamei.

The developmental toxicity effects of neonicotinoid pesticides such as clothianidin have not been fully explored in agricultural applications. This is particularly noteworthy because such pesticides significantly impact the survival rates of invertebrates, with arthropod larvae being particularly vulnerable. This study aimed to address this research gap by specifically investigating the toxicological effects of clothianidin on the developmental stages of the larvae of the economically important aquaculture species Penaeus vannamei. In these experiments, shrimp eggs were exposed to seawater containing different concentrations of clothianidin beginning at N1, and each phase was observed and analyzed to determine its toxic impact on larval development. These results revealed that clothianidin induces an increase in deformity rates and triggers abnormal cell apoptosis. It also significantly reduced survival rates and markedly decreased body length and heart rate in the later stages of larval development (P3). Transcriptomic analysis revealed disruptions in larval DNA integrity, protein synthesis, and signal transduction caused by clothianidin. To survive prolonged exposure, larvae may attempt to maintain their viability by repairing cell structures and enhancing signal transduction mechanisms. This study offers the first empirical evidence of the toxicity of clothianidin to arthropod larvae, underscoring the impact of environmental pollution on aquatic health.

Next-generation neonicotinoid: The impact of cycloxaprid on the crustacean decapod Penaeus vannamei.

Cycloxaprid, a new neonicotinoid pesticide, poses ecological risks, particularly in aquatic environments, due to its unique action and environmental dispersal. This study investigated the ecotoxicological effects of various concentrations of cycloxaprid on Penaeus vannamei over 28 days. High cycloxaprid levels significantly altered shrimp physiology, as shown by changes in the hepatosomatic index and fattening. Indicators of oxidative stress, such as increased serum hemocyanin, respiratory burst, and nitric oxide, as well as decreased phenol oxidase activity, were observed. Additionally, elevated activities of lactate dehydrogenase, succinate dehydrogenase, and isocitrate dehydrogenase indicated disrupted energy metabolism in the hepatopancreas. Notably, analyses of the nervous system revealed marked disturbances in neural signaling, as evidenced by elevated acetylcholine, octopamine, and acetylcholinesterase levels. Transcriptomic analysis highlighted significant effects on gene expression and metabolic processes in the hepatopancreas and nervous system. This study demonstrated that cycloxaprid disrupts neural signaling and oxidative balance in P. vannamei, potentially affecting its growth, and provides key insights into its biochemical and transcriptomic toxicity in aquatic systems.

Dinotefuran exposure alters biochemical, metabolomic, gut microbiome, and growth responses in decapoda pacific white shrimp Penaeus vannamei.

Dinotefuran, a neonicotinoid insecticide, may impact nontarget organisms such as Decapoda P. vannamei shrimp with nervous systems similar to insects. Exposing shrimp to low dinotefuran concentrations (6, 60, and 600 µg/L) for 21 days affected growth, hepatosomatic index, and survival. Biomarkers erythromycin-N-demethylase, alanine aminotransferase, and catalase increased in all exposed groups, while glutathione S-transferase is the opposite; aminopyrin-N-demethylase, malondialdehyde, and aspartate aminotransferase increased at 60 and 600 µg/L. Concentration-dependent effects on gut microbiota altered the abundance of bacterial groups, increased potentially pathogenic and oxidative stress-resistant phenotypes, and decreased biofilm formation. Gram-positive/negative microbiota changed significantly. Metabolite differences between the exposed and control groups were identified using mass spectrometry and KEGG pathway enrichment. N-acetylcystathionine showed potential as a reliable dinotefuran metabolic marker. Weighted correlation network analysis (WGCNA) results indicated high connectivity of cruecdysone in the metabolite network and significant enrichment at 600 µg/L dinotefuran. The WGCNA results revealed a highly significant negative correlation between two key metabolites, caldine and indican, and the gut microbiota within co-expression modules. Overall, the risk of dinotefuran exposure to non-target organisms in aquatic environments still requires further attention.

An analysis of the efficacy of botulinum neurotoxin type a in treating cervical dystonia.

BACKGROUND: The first-line treatment for cervical dystonia (CD) consists of repeated intramuscular injections of botulinum toxin (BoNT). However, the efficacy in some patients may be unsatisfactory and they may discontinue treatment. OBJECTIVE: To examine the factors associated with the maximum rate of remission in patients with CD after initial botulinum neurotoxin type A (or botulinum toxin type A abbreviated as BTX-A or BoNT-A) treatment. METHODS: Patients with CD who received BoNT-A injections were evaluated using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and the Tsui scale, with follow-up endpoints lasting until the start of the second injection. Patients who did not receive a second injection of BoNT-A were followed up for at least 5 months. The maximum remission rates were determined using the lowest Tsui and TWSTRS total scores during the follow-up period. We obtained basic information about these patients such as age, gender, duration of disease, presence of additional disease, types of torticollis, presence of anxiety, depression, tremors, single-photon emission computed tomography (SPECT) findings, injected dose, and so on from their medical records. RESULTS: A total of 70 patients with CD participated in this study, with males comprising 35.7% (25 individuals) with an average age of 45 ± 14 years old. The duration of disease was an independent risk factor for determining whether a complete remission has been attained using the Tsui scale (odds ratio [OR] = 0.978, 95% confidence interval [CI]: 0.959-0.997, P= 0.026). The optimal cut-off point for predicting patients who were unable to achieve complete remission based on duration of disease was 7.5 months (AUG = 0.711). Patients with CD with additional disease had greater difficulty achieving complete remission than those with CD alone based on TWSTRS assessments (P= 0.049). During the study, approximately 17% of all participants reported experiencing adverse reactions that lasted between 1 to 3 weeks before disappearing. CONCLUSION: BoNT is an effective and safe method for treating CD. The maximum remission rates of patients after their first injections are influenced by the duration of their disease. Thus, treatment using BoNT injections must be administered as soon as possible.

Active DHEA uptake in the prostate gland correlates with aggressive prostate cancer.

Strategies for patient stratification and early intervention are required to improve clinical benefits for patients with prostate cancer. Here, we found that active DHEA utilization in the prostate gland correlated with tumor aggressiveness at early disease stages, and 3ßHSD1 inhibitors were promising for early intervention. [3H]-labeled DHEA consumption was traced in fresh prostatic biopsies ex vivo. Active DHEA utilization was more frequently found in patients with metastatic disease or therapy-resistant disease. Genetic and transcriptomic features associated with the potency of prostatic DHEA utilization were analyzed to generate clinically accessible approaches for patient stratification. UBE3D, by regulating 3ßHSD1 homeostasis, was discovered to be a regulator of patient metabolic heterogeneity. Equilin suppressed DHEA utilization and inhibited tumor growth as a potent 3ßHSD1 antagonist, providing a promising strategy for the early treatment of aggressive prostate cancer. Overall, our findings indicate that patients with active prostatic DHEA utilization might benefit from 3ßHSD1 inhibitors as early intervention.

Diagnostic value of clinical deep tendon reflexes in diabetic peripheral neuropathy.

Introduction: The aim of the present study was to evaluate the diagnostic efficacy of different tendon reflexes in detecting diabetic peripheral neuropathy (DPN). Material and methods: According to the changes in tendon reflexes, all patients with diabetes were divided into three strata: impaired Achilles reflex only, impaired lower extremity reflexes, and impaired lower and upper extremity reflexes. Taking nerve conduction studies (NCS) as the gold standard, the sensitivity, specificity, and predictive ability of the tendon reflexes of these three strata, as well as the Toronto clinical scoring system (TCSS) and Michigan Neuropathy Screening Instrument (MNSI), were calculated. Then, the electrophysiological characteristics of diabetic patients with different tendon reflexes were analysed. Results: Among the 240 patients studied, 92 (38.3%) presented evidence of neuropathy, which was confirmed by abnormal NCS, while 148 (61.7%) had normal NCS results. Taking NCS as the gold standard, stratum 1 yielded a sensitivity and specificity of 93.5% and 54.7%, respectively, while stratum 3 had higher specificity (96.6%) and lower sensitivity (34.8%) when compared to stratum 1. However, stratum 2 had the highest specificity (75.7%). Conclusions: The assessment of tendon reflexes can be proposed as a test for screening diabetic polyneuropathy.

Modeling of gas emission in coal mine excavation workface: a new insight into the prediction model.

Coalbed methane (CBM) is a clean energy source, but its utilization is inefficient due to the complexity and low accuracy of its emission prediction model. In this research, we constructed a mathematical model of gas emission from the excavation workface, and combined the experimental results to propose a new model for accurate and concise prediction. The new model was validated in the field workface and compared with the traditional prediction model. Moreover, the sensitivity of gas emission parameters and the participation ratio of gas emission sources were analyzed. The study results show that the new model has higher calculation accuracy than the old model prediction, with an average error reduction of 4.693%. In the excavation workface, the coal fall gas emission conforms to the negative power function equation, and the coal wall gas emission conforms to the negative exponential function equation. In the early stage of excavation, the proportion of coal fall gas emission is higher than that of coal wall gas emission, and the peak proportion reaches 58.5%. In the later stage, the proportion of coal fall gas emission gradually decreases to below 30%. The order of the sensitivity of gas emission parameters is coal wall gas initial velocity > coal fall gas decay coefficient > coal fall gas initial velocity > coal wall gas decay coefficient. The new model is successfully applied in engineering, which helps to improve the efficiency of coal mine gas disaster control and utilization.

Flexible solar cells based on foldable silicon wafers with blunted edges.

Flexible solar cells have a lot of market potential for application in photovoltaics integrated into buildings and wearable electronics because they are lightweight, shockproof and self-powered. Silicon solar cells have been successfully used in large power plants. However, despite the efforts made for more than 50 years, there has been no notable progress in the development of flexible silicon solar cells because of their rigidity1-4. Here we provide a strategy for fabricating large-scale, foldable silicon wafers and manufacturing flexible solar cells. A textured crystalline silicon wafer always starts to crack at the sharp channels between surface pyramids in the marginal region of the wafer. This fact enabled us to improve the flexibility of silicon wafers by blunting the pyramidal structure in the marginal regions. This edge-blunting technique enables commercial production of large-scale (>240 cm2), high-efficiency (>24%) silicon solar cells that can be rolled similarly to a sheet of paper. The cells retain 100% of their power conversion efficiency after 1,000 side-to-side bending cycles. After being assembled into large (>10,000 cm2) flexible modules, these cells retain 99.62% of their power after thermal cycling between -70 °C and 85 °C for 120 h. Furthermore, they retain 96.03% of their power after 20 min of exposure to air flow when attached to a soft gasbag, which models wind blowing during a violent storm.

Minocycline induces tolerance to dendritic cell production probably by targeting the SOCS1/ TLR4/NF-κB signaling pathway.

OBJECTIVE: Dendritic cells (DCs) are professional antigen-presenting cells that play a key role in maintaining peripheral immune tolerance. The use of tolerogenic DCs (tolDCs), i.e., semi-mature DCs that express co-stimulatory molecules but not pro-inflammatory cytokines, has been proposed. However, the mechanism of tolDCs induced by minocycline is still unclear. Our previous bioinformatics analyses based on multiple databases suggested that the suppressor of cytokine signaling 1/Toll-like receptor 4/NF-κB (SOCS1/TLR4/NF-κB) signal pathway was associated with DCs maturation. Thus, we studied whether minocycline could induce DC tolerance through this pathway. METHODS: A search for potential targets was carried out through public databases, and pathway analysis was performed on these potential targets to obtain pathways relevant to the experiment. Flow cytometry was used to detect the expression of DC surface markers CD11c, CD86, and CD80, and major histocompatibility complex II. The secretion of interleukin (IL)-12p70, tumor necrosis factor alpha (TNF- α), and IL-10 in the DC supernatant was detected by enzyme-linked immunoassay. The ability of three groups (Ctrl-DCs, Mino-DCs, and LPS-DCs) of DCs to stimulate allogeneic CD4+ T cells was analyzed using a mixed lymphocyte reaction assay. Western blotting was used to detect the expression of TLR4, NF-κB-p65, NF-κB-p-p65, IκB-α, and SOCS1 proteins. RESULTS: The hub gene plays a vital role in biological processes; in related pathways, the regulation of other genes is often affected by it. The SOCS1/TLR4/NF-κB signaling pathway was further validated by searching for potential targets through public databases to obtain relevant pathways. The minocycline-induced tolDCs showed characteristics of semi-mature DCs. Moreover, the IL-12p70 and TNF-α levels in the minocycline-stimulated DC group (Mino-DC group) were lower than those in the lipopolysaccharide (LPS)-DC group, and the IL-10 levels were higher in the Mino-DC group than in the LPS-DC and control DC groups. In addition, the Mino-DC group had decreased protein expression levels of TLR4 and NF-κB-p65 and upregulated protein levels of NF-κB-p-p65, IκB-α, and SOCS1 compared with the other groups. CONCLUSION: The results of this study indicate that minocycline could improve the tolerance of DCs probably by blocking the SOCS1/TLR4/NF-κB signaling pathway.

Prospective role of 3ßHSD1 in prostate cancer precision medicine.

BACKGROUND: Prostate cancer is addicted to androgens. The steroidogenic enzyme 3ß-hydroxysteroid dehydrogenase 1 (3ßHSD1) recognizes pregnenolone, dehydroepiandrosterone (DHEA), and steroidal medicine abiraterone as substrates to accelerate disease progression. METHODS: References for this review were identified through searches of PubMed with the search terms "prostate cancer", "HSD3B1", and "3bHSD1" from 1990 until June, 2022. RESULTS: Genotype of 3ßHSD1 has been reported to correlate with tumor aggressiveness of advanced prostate cancer in multiple clinical scenarios. The ethnic differences and limitations of using 3ßHSD1 genotype as a prognostic biomarker have been discussed here. The activity of 3ßHSD1 increases in patients treated with abiraterone and enzalutamide, giving rise to treatment resistance. Further elucidation of 3ßHSD1 regulatory mechanisms will shed light on more approaches for disease intervention. We also review the recent advance on 3ßHSD1 inhibitors and targeting 3ßHSD1 for prostate cancer management. Novel 3ßHSD1 inhibitors will be needed to provide additional options for prostate cancer management. CONCLUSION: 3ßHSD1 is both a predictive biomarker and a promising therapeutic target for prostate cancer.

Novel missense variant in the TMEM151A gene causing paroxysmal kinesigenic dyskinesia: a case report with literature review.

BACKGROUND: Paroxysmal kinesigenic dyskinesia (PKD) is a rare movement disorder with high clinical and genetic heterogeneity. Proline-rich transmembrane protein 2 (PRRT2) was identified as the first causative gene for PKD in 2011. Recently, heterozygous variants in transmembrane protein 151A (TMEM151A) were identified as another pathogenic cause of PKD. CASE DESCRIPTION: A 16-year-old man diagnosed with PKD exhibited hemidystonia triggered by sudden voluntary movements. His mother also had similar symptoms since the age of 20. Whole-exome sequencing revealed a likely pathogenic missense variant (c.892 T > C) in the TMEM151A gene. At the same time, we reviewed the literature focusing on the molecular characteristics and the clinical phenotypes in patients with TMEM151A variants, especially within the same family. CONCLUSION: This case further validated the pathogenic role of TMEM151A variants in PKD. The findings of interfamilial and intrafamilial variability in the phenotypes expanded our understanding of TMEM151A-related PKD.

Kennedy's disease presented with mastication fatigue combined with positive titin antibody: a case report.

BACKGROUND: Spinal and bulbar muscular atrophy (SBMA) is an X-linked recessive hereditary neuromuscular disorder caused by the expanded trinucleotide repeat in the androgen receptors gene. The major clinical manifestations of SBMA consist of weakness in the bulbar and limb muscles, fasciculations, tremors, cramps, sensory impairment, and gynecomastia. However, atypical SBMA cases may lead to misdiagnosis. Muscular fatigue and decremental responses to repetitive nerve stimulation (RNS), despite being observed in some SBMA patients, are usually occurred in MG patients, and patient with the symptom of mastication fatigue was rarely reported. In addition, cardiological investigations have been performed in SBMA patients and several ECG alterations were identified. Here we report an SBMA patient presenting with a rare onset symptom of mastication fatigue, who has been detected with a positive titin antibody in the serum and showed a WPW pattern electrocardiogram. CASE PRESENTATION: The patient showed mildly progressive fatigue in the muscles of mastication over 3 years. Neurological examination showed facial muscle weakness and a wasting tongue with fasciculations, but the weakness, wasting, or fasciculations were not obvious in the limbs. 3-Hz RNS showed a decremental response in bilateral orbicularis oculi. The test of titin antibody was positive in the serum, and the electrocardiogram showed a WPW pattern ECG. Genetic analysis revealed an increased number (39 repeats) of tandem CAG repeats in the AR gene, which confirmed the diagnosis of SBMA. The fatigue symptom was significantly improved after oral pyridostigmine bromide treatment. CONCLUSION: This case calls for more attention to muscular fatigue as the onset symptoms of Kennedy's disease. ECG screening is of importance in SBMA patients and further studies are needed to investigate the titin antibody in SBMA patients as well as other neurogenic disorders.

Celastrol recruits UBE3A to recognize and degrade the DNA binding domain of steroid receptors.

Strategies to degrade steroid receptors and their alternative splicing isoforms are critical for disease management. Here we report that celastrol recruited the ubiquitin ligase UBE3A and degraded androgen receptor (AR), AR-v7, and glucocorticoid receptor (GR) to suppress prostate cancer development. UBE3A was not an optimal endogenous AR ubiquitin ligase in mice and patients, but celastrol promoted the interaction between UBE3A and AR. Multiple domains of AR, including the DNA binding domain (DBD), were implicated into the UBE3A-AR interaction. Sharing a conserved DBD, GR, AR-v7, and other steroid receptors were recognized and degraded by UBE3A after celastrol treatment. Thus, celastrol suppressed prostate cancer cell proliferation more potently than enzalutamide. Modifying the carboxyl group of celastrol improved its anti-tumor activity. Together, our findings revealed that celastrol might be a potential molecular glue to enhance the interaction between UBE3A and steroid receptors to degrade multiple steroid receptors and splicing isoforms in prostate cancer, paving a way for further drug optimization and disease treatment.

The clinical efficacy and limitations of dutasteride-regulated abiraterone metabolism in abiraterone-resistant patients: a prospective single-arm clinical trial in Chinese patients.

Background: The steroidal metabolism of abiraterone has been proposed to be involved in abiraterone resistance and limited approaches are available for abiraterone-resistant patients. Dutasteride regulates abiraterone metabolism in patients and might enhance the clinical efficacy of abiraterone. However, the function of dutasteride to overcome abiraterone resistance has not been investigated in clinic. Here we investigated the clinical efficacy and limitations of dutasteride in patients with abiraterone-resistant prostate cancer. Methods: Abiraterone-resistant patients with metastatic castration-resistant prostate cancer (mCRPC) were enrolled in this single-arm, open-label study, patients were treated with dutasteride (0.5 mg/day), abiraterone (1,000 mg/day), and prednisone (5 mg twice daily), prostate-specific antigen (PSA) was tested monthly. The primary objective was PSA response, and the secondary objectives were to assess symptom relief and safety. Kaplan-Meier analysis was used to assess the PSA progression free survival (PSA-PFS) of patients. Results: Twenty-two patients (median age: 75 years) were enrolled, and 19 patients completed the treatment. After a median treatment of 4.0 months, 7 (37%) patients showed a slight PSA reduction (-2% to -32%), and the median PSA-PFS was 2.0 months (1-7 months). No significant improvement was observed in Eastern Cooperative Oncology Group (ECOG) performance status. Bone pain was relieved in 6 patients after 1 month of treatment, but the improvement was not significant. No grade 3 or grade 4 adverse events were observed. Conclusions: The combination of dutasteride and abiraterone showed a mild effect in patients with abiraterone-resistant. The small sample size was the limitation of this study.

Terahertz meta-biosensor based on high-Q electrical resonance enhanced by the interference of toroidal dipole.

Electrical dipole resonances typically have low Q factor and broad resonant linewidth caused by strong free-space coupling with high radiative loss. Here, we present a strategy for enhancing the Q factor of the electrical resonance via the interference of a toroidal dipole. To validate such a strategy, a metasurface consisting of two resonators is designed that responsible to the electric and toroidal dipoles. According to constructive and destructive hybridizations of the two dipole modes, enhanced and decreased Q factors are found respectively for the two hybrid modes, compared to the one for the conventional electric dipole resonance. As a practical application of such high Q resonance, we further experimentally investigate the sensing performance of the metasurface biosensor by detecting the cell concentration of lung cancer cells (type A549). Moreover, through monitoring both resonance frequency and amplitude variation of the metasurface biosensor, the dielectric permittivity of the lung cancer cells is delicately estimated by the conjoint analysis of both simulated and measured results. Our proposed metasurface paves a promising way for the study of multipole interference in the field of nanophotonics and validates its effectiveness in biomedical sensing.

Incipient fault diagnosis for the cam-driven absolute gravimeter.

The vibration disturbance caused by incipient faults is an important factor affecting the measurement accuracy of the cam-driven absolute gravimeter. Based on the characteristics of the cam-driven absolute gravimeter, such as the small amplitude of the incipient faults, the inadequate representation of features for the faults, and hard-to-find in the noise, a novel method for incipient fault diagnosis of the cam-driven absolute gravimeter is put forward in this paper, which integrates the parameter-optimized Variational Mode Decomposition (VMD) with Light Gradient Boosting Machine (LightGBM). The sparrow search algorithm is used to optimize the VMD parameters. The parameter-optimized VMD algorithm is used to adaptively decompose the vibration signals of the gravimeter under different cases, and then an effective intrinsic mode function (IMF) is selected based on the Pearson correlation coefficient. Some high-frequency IMFs are subjected to adaptive noise reduction combined with low-frequency IMF reconstruction, and then the multi-scale permutation entropy with sensitive characteristics under different time scales is extracted as the fault feature vectors. The extracted multi-dimensional vector matrix is entered into the LightGBM classifier to realize the accurate diagnosis of the incipient faults for the cam-driven absolute gravimeter. The test results show that this method can effectively detect various incipient failures of the cam-driven absolute gravimeter, with an identification accuracy of 98.41%. With this method, the problem of low measurement accuracy for the cam-driven absolute gravimeter caused by the incipient faults is solved, and the rapid tracing and accurate positioning of these faults for the gravimeter are realized, promising a good prospect for engineering application.

Serum prolactin level as a predictive factor for abiraterone response in patients with metastatic castration-resistant prostate cancer.

BACKGROUND: To investigate the prognostic value and potential therapeutic target of the baseline serum hormones in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone. METHODS: This retrospective study was performed in patients with mCRPC receiving abiraterone acetate (AA) from July 2016 to September 2020. Patients who had serum hormone tests within 2 weeks before AA treatment were included. Univariate analysis and Cox regression were performed to evaluate the correlation of sex hormones with progression-free survival (PFS) and overall survival (OS). Prolactin (PRL) expression in the clinical specimens was evaluated by immunohistochemistry. Bone metastases were quantified by automated Bone Scan Index (aBSI). RESULTS: The study included 61 patients with a median follow-up of 19.0 months. Patients with lower baseline PRL levels (median) responded better to AA than those with higher baseline PRL levels as indicated by prostate-specific antigen (PSA) reduction (PSA90, 66.7% vs. 25.8%, p = 0.001), PFS (19.6 vs. 7.9 months), and OS (52.8 vs. 19.2 months). Cox regression adjusted for clinical factors also confirmed that baseline PRL level was an independent predictive factor for PFS (hazard ratio = 1.096, p = 0.007). Prostatic PRL expression increased as the disease progressed. PRL expression was also detected in biopsy samples from bone metastasis but not in normal bone tissue, and the serum PRL levels were positively correlated with aBSIs (r = 0.28, p = 0.037). CONCLUSIONS: Serum PRL levels are predictive of response to AA in patients with mCRPC. Serum PRL levels are positively correlated with the volume of metastatic bone disease.

Graphene-Based Optically Transparent Metasurface Capable of Dual-Polarized Modulation for Electromagnetic Stealth.

Microwave stealth technology with optical transparency is of great significance for solar-powered aircrafts (e.g., satellites or unmanned aerial vehicles) in increasingly complex electromagnetic environments. By coating them with optically transparent absorbing materials or devices, these large-sized solar panels could avoid detection by radar while maintaining highly efficient collection of solar energy. However, conventional microwave-absorbing materials/devices for solar panels suffer from bulky volume and fixed stealth performance that significantly hinders their practicality or multifunctionality. Particularly, dynamic modulation of microwave absorption for dual polarization remains a challenge. In this paper, we propose the design, fabrication, and characterization of an optically transparent and dynamically tunable microwave-absorbing metasurface that enables dual modulations (amplitude and frequency) independently for two orthogonal linearly polarized excitations. The tunability of the proposed metasurface is guaranteed by an elaborately designed anisotropic meta-atom composed of a patterned graphene structure whose electromagnetic responses for different polarizations can be dynamically and independently controlled via bias voltages. The dual tunability in such a graphene-based absorbing metasurface is experimentally measured, which agrees well with those numerical results. We further build an equivalent lumped circuit model to analyze the physical relation between the tunable sheet resistance of graphene and the polarization-independent modulations of the metasurface. Taking into account the advantages of optical transparency and flexibility, the proposed microwave-absorbing metasurface significantly enhances the multitasking stealth performance in complex scenarios and has the potential for advanced solar energy devices.

Management of prostate cancer by targeting 3ßHSD1 after enzalutamide and abiraterone treatment.

Novel strategies for prostate cancer therapy are required to overcome resistance to abiraterone and enzalutamide. Here, we show that increasing 3ßHSD1 after abiraterone and enzalutamide treatment is essential for drug resistance, and biochanin A (BCA), as an inhibitor of 3ßHSD1, overcomes drug resistance. 3ßHSD1 activity increases in cell lines, biopsy samples, and patients after long-term treatment with enzalutamide or abiraterone. Enhanced steroidogenesis, mediated by 3ßHSD1, is sufficient to impair enzalutamide function. In patients, accelerated abiraterone metabolism results in a decline of plasma abiraterone as disease progresses. BCA inhibits 3ßHSD1 and suppresses prostate cancer development alone or together with abiraterone and enzalutamide. Daidzein, a BCA analog of dietary origin, is associated with higher plasma abiraterone concentrations and prevented prostate-specific antigen (PSA) increases in abiraterone-resistant patients. Overall, our results show that 3ßHSD1 is a promising target to overcome drug resistance, and BCA suppresses disease progression as a 3ßHSD1 inhibitor even after abiraterone and enzalutamide resistance.