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Copper can be toxic at very high intracellular concentrations and can inhibit prostate cancer (PCa) progression. Recently, a study reported the mechanism of cuproptosis and the potentially associated genes. However, the function of these cuproptosis-related genes in PCa remains unknown. Based on the RNA sequence and clinical data from public databases, we analyzed the clinical value of cuproptosis-related genes in PCa. DLD, DLAT, PDHA1, and CDKN2A were expressed differently between normal and PCa tissues. The FDX1, LIAS, DLAT, GLS, and CDKN2A genes can affect PCa progression, while PDHA1 and CDKN2A influence the patients’ disease-free survival (DFS) status. The expression of LIAS, LIPT1, DLAT, and PDHB did not alter upon the incidence of PCa in Chinese patients. A constructed regression model showed that FDX1, PDHA1, MTF1, and CDKN2A can be risk factors leading to PCa in both Western and Chinese patients with PCa. The lasso regression model reflected that these genes can affect the patients’ DFS status. Additionally, the cuproptosis-related genes were associated with immune cell infiltration. We also verified the high expression of PDHA1 and CDKN2A, in clinical samples. In conclusion, we identified a novel cuproptosis-related gene signature for predicting the development of PCa.

Gastric carcinoma (GC) ranks the fifth most common cancer worldwide, with high incidence and mortality rates. Numerous microRNAs (miRNAs), including miR-654-5p, have been implicated in the pathophysiological processes of tumorigenesis. Nevertheless, the mechanism of miR-654-5p in GC is unclear.

Ubiquitin-conjugating enzyme E2T (UBE2T) functions as an E2 ubiquitin-conjugating enzyme in the ubiquitin-proteasome degradation system and mediates cellular processes, such as cell cycle, proliferation, and differentiation. UBE2T has been considered to be an oncogene in a variety of tumors. However, the oncogenic role of UBE2T in cervical cancer remains unclear. In this study, our results first showed that the expression of UBE2T was higher in both of cervical cancer tissues and cells than that in the normal tissues and cells. Knockdown of UBE2T reduced cervical cancer cell viability and suppressed the proliferation, invasion, and migration. However, overexpression of UBE2T contributed to cervical cancer cell growth and metastasis. Moreover, UBE2T overexpression cervical cancer cells demonstrated enhanced self-renewal capacity with upregulation of SOX2, Oct-4, and Nanog protein. Silencing of UBE2T downregulated protein expression of SOX2, Oct-4, and Nanog in cervical cancer cells reduced self-renewal capacity. Furthermore, ectopic UBE2T expression promoted protein expression of glucose-regulated protein 78 (GRP78) and focal adhesion kinase (FAK) phosphorylation in cervical cancer cells. The knockdown of UBE2T reduced protein expression of GRP78 and FAK phosphorylation. Collectively, UBE2T promoted cervical cancer stem cell traits and exerted an oncogenic role through activation of the GRP78/FAK pathway.

We present the design, fabrication, and characterization of suspended arrays of small volume, high quality factor (Q) silicon nitride photonic crystal nanobeam (PCNB) cavities with lateral nanorod fin structures. By controlling the alignment position of the fins with respect to the air holes, the resonance wavelength and Q-factor of the PCNB cavities can be tuned to realize the desired performance. Measured tunable range of 2 × 104 and 10 nm is achieved for Q-factor and resonance wavelength, respectively, with the highest Q-factor measured at 2.5 × 104. Incorporating such nanorod fins into the nanobeam cavity is demonstrated to provide improved mechanical support, thermal transport, and channels of lateral carrier injection for the suspended PCNB. The proposed PCNB cavities with lateral fins are advantageous for energy efficient, ultra-compact lasers, modulators, filters, and sensors.

We report here an optically pumped deep UV edge emitting laser with AlGaN multiple quantum wells (MQWs) active region grown on AlN substrate by low pressure organometallic vapor phase epitaxy (LP-OMVPE) in a high-temperature reactor. The 21 period Al0.53Ga0.47N/Al0.7Ga0.3N MQWs laser structure was optically pumped using 193 nm deep UV excimer laser source. A laser peak was achieved from the cleaved facets at 280.3 nm with linewidth of 0.08 nm at room temperature with threshold power density of 320 kW/cm2. The emission is completely TE polarized and the side mode suppression ratio (SMSR) is measured to be around 14 dB at 450 kW/cm2.

The integrated navigation system is used to estimate the position, velocity, and attitude of a vehicle with the output of inertial sensors. This paper concentrates on the problem of the INS/GPS integrated navigation system design and simulation. The structure of the INS/GPS integrated navigation system is made up of four parts: 1) GPS receiver, 2) Inertial Navigation System, 3) Extended Kalman filter, and 4) Integrated navigation scheme. Afterwards, we illustrate how to simulate the integrated navigation system with the extended Kalman filter by measuring position, velocity and attitude. Particularly, the extended Kalman filter can estimate states of the nonlinear system in the noisy environment. In extended Kalman filter, the estimation of the state vector and the error covariance matrix are computed by steps: 1) time update and 2) measurement update. Finally, the simulation process is implemented by Matlab, and simulation results prove that the error rate of statement measuring is lower when applying the extended Kalman filter in the INS/GPS integrated navigation system.

In this study,a method is proposed to identify structural damages by the change of structural generalized flexibility. By adding known masses to the physical structure,measuring the lower modes of the mass-modified structure,and then using these new data as well as the original test information,structural damages can be detected using the generalized flexibility perturbation technique. The effectiveness of the proposed method is illustrated using simulated data on a plane truss structure. The results show that the proposed method can identify structural damages accurately only using the first modal parameters. The presented scheme may be useful for damage identification of large-scale structures.

The corpus cavernosum is the most important structure for penile erection, and its dysfunction causes many physiological and psychological problems. However, its cellular heterogeneity and signalling networks at the molecular level are poorly understood because of limited access to samples. Here, we profile 64,993 human cavernosal single-cell transcriptomes from three males with normal erection and five organic erectile dysfunction patients. Cell communication analysis reveals that cavernosal fibroblasts are central to the paracrine signalling network and regulate microenvironmental homeostasis. Combining with immunohistochemical staining, we reveal the cellular heterogeneity and describe a detailed spatial distribution map for each fibroblast, smooth muscle and endothelial subcluster in the corpus cavernosum. Furthermore, comparative analysis and related functional experiments identify candidate regulatory signalling pathways in the pathological process. Our study provides an insight into the human corpus cavernosum microenvironment and a reference for potential erectile dysfunction therapies.

Abstract Background Metabolic Syndrome (MetS) is a high risk factor for Cardiovascular Diseases (CVD). We estimated to investigate how MetS prevalence by glucose homeostasis varies across different age and gender groups. Methods We studied 9257 Chinese subjects over the age of 15 years in two cross-sectional surveys in 2006. With oral glucose tolerance test (OGTT) test, 2341 subjects were normal glucose tolerance (NGT), and 5448 were diagnosed as having type 2 diabetes (T2D). All other 1468 subjects were considered to be impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) subjects. Diabetes was diagnosis by WHO99 criteria. We used modified NCEP-III criteria for the diagnosis of MetS. Results The prevalences of MetS in the male NGT, IFG/IGT and T2D groups were 25.9% (404/1559), 65.6% (769/1172), and 73.5% (2483/3376), respectively. The prevalences of MetS in the female NGT, IFG/IGT and T2D groups were 13.4% (105/782), 51.0% (151/296), and 75.4% (1563/2072), respectively. The prevalence of MetS in the male IFG/IGT group gradually decreased from 73.26% to 41.08% in subjects over the age of 30 years. The prevalence of MetS in the female IFG/IGT group gradually increased from 30% to 75% with aging. Conclusions The prevalence of MetS in subjects with different glucose tolerances in China was high and gradually increased with impaired glucose homeostasis both in males and females.

Abstract Introduction The use of methadone as an analgesic is on the increase, but it is widely recognized that the goal of predictable and reproducible dosing is confounded by considerable variability in methadone pharmacokinetics, and unpredictable side effects that include sedation, respiratory depression and cardiac arrhythmias. The mechanisms underlying these unpredictable effects are frequently unclear. Here, to the best of our knowledge we present the first report of an association between accidental methadone overexposure and increased plasma protein binding, a new potential mechanism for drug interactions with methadone. Case presentation We describe here the cases of two patients who experienced markedly different responses to the same dose of methadone during co-administration of letrozole. Both patients were post-menopausal Caucasian women who were among healthy volunteers participating in a clinical trial. Under the trial protocol both patients received 6 mg of intravenous methadone before and then after taking letrozole for seven days. One woman (aged 59) experienced symptoms consistent with opiate overexposure after the second dose of methadone that were reversed by naloxone, while the other (aged 49) did not. To understand the etiology of this event, we measured methadone pharmacokinetics in both patients. In our affected patient only, a fourfold to eightfold increase in methadone plasma concentrations after letrozole treatment was observed. Detailed pharmacokinetic analysis indicated no change in metabolism or renal elimination in our patient, but the percentage of unbound methadone in the plasma decreased 3.7-fold. As a result, the volume of distribution of methadone decreased approximately fourfold. The increased plasma binding in our affected patient was consistent with observed increases in plasma protein concentrations. Conclusions The marked increase in the total plasma methadone concentration observed in our patient, and the enhanced pharmacodynamic effect, appear primarily due to a reduced volume of distribution. The extent of plasma methadone binding may help to explain the unpredictability of its pharmacokinetics. Changes in volume of distribution due to plasma binding may represent important causes of clinically meaningful drug interactions.