Molecular Glues: The Adhesive Connecting Targeted Protein Degradation to the Clinic.

Targeted protein degradation is a rapidly exploding drug discovery strategy that uses small molecules to recruit disease-causing proteins for rapid destruction mainly via the ubiquitin-proteasome pathway. It shows great potential for treating diseases such as cancer and infectious, inflammatory, and neurodegenerative diseases, especially for those with "undruggable" pathogenic protein targets. With the recent rise of the "molecular glue" type of protein degraders, which tighten and simplify the connection of an E3 ligase with a disease-causing protein for ubiquitination and subsequent degradation, new therapies for unmet medical needs are being designed and developed. Here we use data from the CAS Content Collection and the publication landscape of recent research on targeted protein degraders to provide insights into these molecules, with a special focus on molecular glues. We also outline the advantages of the molecular glues and summarize the advances in drug discovery practices for molecular glue degraders. We further provide a thorough review of drug candidates in targeted protein degradation through E3 ligase recruitment. Finally, we highlight the progression of molecular glues in drug discovery pipelines and their targeted diseases. Overall, our paper provides a comprehensive reference to support the future development of molecular glues in medicine.

Iruplinalkib (WX­0593), a novel ALK/ROS1 inhibitor, overcomes crizotinib resistance in preclinical models for non-small cell lung cancer.

Despite remarkable initial responses of anaplastic lymphoma kinase (ALK) inhibitors in ALK-positive non-small cell lung cancer (NSCLC) patients, cancers eventually develop resistance within one to two years. This study aimed to compare the properties of iruplinalkib (WX­0593) with other ALK inhibitors and report the comprehensive characterization of iruplinalkib against the crizotinib resistance. The inhibitory effect of iruplinalkib on kinase activity was detected. A kinase screen was performed to evaluate the selectivity of iruplinalkib. The effect of iruplinalkib on related signal transduction pathways of ALK and c-ros oncogene 1 (ROS1) kinases was examined. The cellular and in vivo activities of ALK inhibitors were compared in engineered cancer-derived cell lines and in mice xenograft models, respectively. Human hepatocytes derived from three donors were used for evaluating hepatic enzyme inducing activity. HEK293 cell lines expressing transportors were used to invesigated the drug interaction potential mediated by several transporters. The results showed iruplinalkib potently inhibited the tyrosine autophosphorylation of wild-type ALK, ALKL1196M, ALKC1156Y and epidermal growth factor receptor (EGFR)L858R/T790M. The inhibitory effects of iruplinalkib in patient-derived xenograft and cell line-derived xenograft models were observed. Moreover, iruplinalkib showed robust antitumor effects in BALB/c nude mice xenograft models with ALK-/ROS1-positive tumors implanted subcutaneously, and the tumor suppressive effects in crizotinib-resistant model was significantly better than that of brigatinib. Iruplinalkib did not induce CYP1A2, CYP2B6 and CYP3A4 at therapeutic concentration, and was also a strong inhibitor of MATE1 and MATE2K transporters, as well as P-gp and BCRP. In conclusion, iruplinalkib, a highly active and selective ALK/ROS1 inhibitor, exhibited strong antitumor effects in vitro and in crizotinib-resistant models.

Observation of the bound states in the continuum supported by mode coupling in a terahertz metasurface.

Metasurface supporting bound states in the continuum (BIC) provides a unique approach for the realization of intense near-field enhancement and high quality factor (Q-factor) resonance, which promote the advancement of various applications. Here we experimentally demonstrate a Friedrich-Wintgen BIC based on the mode coupling in the terahertz metasurface, which produces BIC by the coupling of the LC mode and dipole mode resonances. The transition from ideal BIC to quasi-BIC is caused by the mismatch of the coupling, and the mode decay rate during this process is analyzed by temporal coupled mode theory. The Q-factor and the electric field enhancement of the quasi-BIC resonance are significantly increased, which provides enormous potential in sensing, nonlinear optics, and topological optics.

Four New Sb-based Orthophosphates: Cation Regulation to Investigate Diversified Structural Architecture.

In the work, four new Sb-based phosphates, K4 (SbO2 )5 (PO4 )3 , Rb(SbO2 )2 PO4 , Rb3 (SbO2 )3 (PO4 )2 and Cs3 (SbO2 )3 (PO4 )2 (H2 O)1.32 , were successfully synthesized by a high-temperature melt method. Among them, Rb(SbO2 )2 PO4 and Rb3 (SbO2 )3 (PO4 )2 are the first reported examples of Rb-containing alkali metal Sb-based phosphates. They show three-dimensional (3D) frameworks composed of [Sb8 P4 O30 ]∞ layer for K4 (SbO2 )5 (PO4 )3 and [Sb6 P2 O20 ]∞ layer for Rb(SbO2 )2 PO4 , and 2D lamellar structure composed of [Sb3 P2 O10 ]∞ for Rb3 (SbO2 )3 (PO4 )2 and Cs3 (SbO2 )3 (PO4 )2 (H2 O)1.32 . A detailed structural comparison shows that the structure dimensions for them transfer from 1D to complex 3D framework with the increase of (Sb+P)/O ratio, which affects performances of the compounds. Optical property and energy band structure calculations were also carried out based on the density functional theory (DFT). The present study enriches the diversity of Sb-based phosphates and paves the way for further explore their optical properties in the future.

The effect of albumin and hemoglobin levels on the prognosis of early-stage cervical cancer: a prospective, single-center-based cohort study.

BACKGROUND: Serum albumin (ALB) and hemoglobin (HGB) are important serum biochemical indices of the nutritional status of patients and are associated with cancer development. We investigated the relationship between ALB and HGB levels and clinicopathologic characteristics of early-stage cervical cancer to determine the influence of ALB and HGB on the prognosis of early-stage cervical cancer. METHODS: The clinical data of 560 patients with International Federation of Gynaecology and Obstetrics (FIGO, 2009) stage IA1-IIA2 cervical cancer from January 2005 to December 2010 were retrospectively analyzed. The relationship between serum ALB and HGB levels and clinicopathological characteristics of patients were analyzed. The patients were followed-up for 12-138 months. The effects of ALB and HGB levels on the prognosis were analyzed by Cox regression, log-rank test, and the Kaplan-Meier method. RESULTS: The rate of patients with pelvic lymph node metastasis (PLNM), tumor diameter ≥ 4 cm, lymphovascular space invasion (LVSI), and deep stromal invasion was significantly higher in the anemia and hypoalbuminemia group than in the normal group (P < 0.05). The progression-free survival (PFS) and overall survival (OS) of patients in the hypoalbuminemia group and anemia group were significantly lower than that of the normal group (P < 0.05). FIGO stage, tumor diameter, PLNM, depth of stromal invasion, LVSI, the levels of ALB and HGB were risk factors for the prognosis of cervical cancer patients (P < 0.05). CONCLUSION: Patients with hypoproteinemia and anemia in early-stage cervical cancer are more likely to have higher tumor stage, larger tumor size, PLNM, LVSI, and deep stromal invasion. In addition, patients with hypoproteinemia and anemia have a poorer prognosis than those without the condition. Therefore, it is of great significance to detect the ALB and HGB levels of patients and improve the nutritional status of patients in a timely manner for better prognosis of cervical cancer.

Impacts of eosinophil percentage on prognosis acute type A aortic dissection patients.

BACKGROUND: Eosinophils are pro-inflammatory cells involved in thrombosis and have been proposed as a prognosis marker in acute ischemic stroke and ST-elevation myocardial Infarction. Here, we sought to clarify the prognostic value of eosinophil percentage (EOS%) in patients with acute type A aortic dissection (AAAD). METHODS: We examined 183 consecutive AAAD patients. Based on the optimum cut-off value of EOS% determined by X-tile software, patients were classified into the low EOS% (EOS% ≤ 0.1) and high EOS% groups (EOS% > 0.1). We performed multivariate regression analysis and Kaplan-Meier (KM) survival curves to assess the association between EOS% and mortality. Eosinophil accumulation in aortic dissection intraluminal thrombus was confirmed using hematoxylin-eosin (H&E) staining. An external cohort from Medical Information Mart for Intensive Care IV was performed to validate the results. RESULTS: Relative to surviving patients, those who died during hospitalization had significantly lower EOS% (p = 0.001) but significantly higher WBC (p = 0.002) and neutrophil (p = 0.001) counts. Multivariate regression analysis identified EOS% as an independent predictor of in-hospital and 1-year mortality. KM curves revealed that 1-year cumulative mortality was significantly higher in the low EOS% group, although it was mainly attributed to the higher 30-day mortality. H&E staining revealed massive infiltration of eosinophils in all 20 thrombus specimens. The external validation confirmed that relative to survivors, patients with in-hospital mortality (p = 0.010) had significantly lower EOS%. Moreover, multivariate regression analyses identified that decreased EOS% was independently significantly associated with in-hospital mortality. CONCLUSIONS: Low EOS% is significantly related to increased mortality rates in AAAD patients.

Ambient particulate air pollution, blood cell parameters, and effect modification by psychosocial stress: Findings from two studies in three major Chinese cities.

The associations between particulate matter (PM) exposure, psychosocial stress and blood cell parameters are bringing novel insights to characterize the early damage of multiple diseases. Based on two studies conducted in three Chinses cities using cross-sectional (Beijing, 425 participants) and panel study (Tianjin and Shanghai, 92 participants with 361 repeated measurements) designs, this study explored the associations between short-term exposure to ambient PM and blood cell parameters, and the effect modification by psychosocial stress. Increasing PM2.5 exposure was significantly associated with decreases in red blood cell (RBC) count and mean corpuscular hemoglobin concentration (MCHC), and increases in mean corpuscular volume (MCV), platelets count (PLT) and platelet hematocrit (PCT) in both studies. For instance, a 10 µg/m3 increment in PM2.5 concentration was associated with a 1.04% (95%CI: 0.16%, 1.92%) increase in PLT (4-d) and a 1.09% (95%CI: 0.31%, 1.87%) increase in PCT (4-d) in the cross-sectional study, and a 0.64% (95%CI: 0.06%, 1.22%) increase in PLT (1-d) and a 0.72% (95%CI: 0.33%, 1.11%) increase in PCT (1-d) in the panel study, respectively. In addition, stronger increases in MCV, PLT, and PCT associated with PM2.5 exposure were found in higher psychosocial stress group compared to lower psychosocial stress group (p for interaction <0.10), indicating that blood cell parameters of individuals with higher psychosocial stress might be more susceptible to the early damages of PM2.5 exposure.

Effectiveness and safety of path-based analgesic regimens designed by clinical pharmacists based on the type of biliary and pancreatic surgery.

WHAT IS KNOWN AND OBJECTIVE: As the incidence of postoperative pain in patients with biliary and pancreatic diseases has gradually increased, how to control postoperative pain has received increasing research attention. By reading pain management guidelines and multidisciplinary communication and cooperation, clinical pharmacists designed multi-mode analgesia regimens based on surgical types, in order to provide strong evidence for the effectiveness and safety of postoperative analgesia regimens and better serve patients. METHODS: Data from biliary or pancreatic surgery performed at Nanjing Drum Tower Hospital from 2019 to 2021 were collected. Take October 2020 as the time point to compare the outcomes before and after the implementation of the path-based postoperative analgesic regimens. The primary outcomes were NRS pain scores, sleep quality, and incidence of adverse reactions. Length of stay was a secondary outcome. RESULTS AND DISCUSSION: A total of 268 and 239 patients were enrolled in the study and control groups, respectively. Four path-based postoperative analgesic management regimens significantly reduced patients' static and dynamic NRS scores in the 24 h (p < 0.05). The patients' sleep quality were better than controls (p > 0.05). The incidence of adverse reactions and the length of stay in the study group were numerically lower than controls. Moderate analysis indicated that four analgesia regimens are more precise and better meet actual clinical needs. WHAT IS NEW AND CONCLUSION: Effective and safe postoperative pain management is particularly important for clinical purposes. Path-based postoperative analgesia regimens based on different types of surgery overcome the disadvantages of overly broad and generalized traditional guidelines, which play an important role in providing personalized and precise clinical services. Further, study findings provide evidence that four path-based analgesic regimens can reduce postoperative pain and reduce the length of hospital stay, which may provide a better direction for clinical postoperative pain management.

Association of DNA methylation in circulating CD4+T cells with short-term PM2.5 pollution waves: A quasi-experimental study of healthy young adults.

BACKGROUND: Fine particulate matter (PM2.5) is a modifiable environmental risk factor with established adverse effects on human health. However, associations between acute PM2.5 fluctuation and DNA methylation remain unknown. METHODS: A quasi-experimental study utilizing naturally occurring PM2.5 pollution waves (PPWs) was conducted on 32 healthy young adults. Repeated follow-up measurements were performed and participants served as their own controls before, during, and after PPWs. Exposure measurements including indoor and ambient PM2.5 levels, and equivalent personal PM2.5 exposure were further estimated based on the time-location information. DNA methylation profiles of circulating CD4+T cells were obtained using Illumina HumanMethylationEPIC BeadChip. Linear mixed-effect models were applied to estimate the associations between two scenarios (during-PPWs vs. pre-PPWs periods and during-PPWs vs. post-PPWs periods) and methylation level of each CpG site. We further validated their associations with the personal PM2.5 exposure, and GO and KEGG analyses and mediation analysis were conducted accordingly. RESULTS: Data from 26 participants were included in final analysis after quality control. Short-term high PM2.5 exposure was associated with DNA methylation changes of participants. Nine differently methylated CpG sites were not only significantly associated with PPWs periods but also with personal PM2.5 exposure in 24-h prior to the health examinations (p < 0.01). Gene ontology analysis found that five sites were associated with two pathways relating to membrane protein synthesis. PM2.5-related changes in CpG sites were mediated by sP-selectin, 8-isoPGF2α, EGF, GRO, IL-15, and IFN-α2, with mediated proportions ranging from 9.65% to 23.40%. CONCLUSIONS: This is the first quasi-experimental study showing that short-term high PM2.5 exposure could alter the DNA methylation of CD4+T cells, which provided valuable information for further exploring underlying biological mechanisms and epigenetic biomarkers for PM2.5-related acute health effects.

Circ_0067934 reduces JNK phosphorylation through a microRNA-545-3p/PPA1 axis to enhance tumorigenesis and cisplatin resistance in ovarian cancer.

BACKGROUND: Circular RNA 0067934 (circ_0067934) has been revealed as a cancer driver in multiple human malignancies, whereas its action in the pathogenesis of ovarian cancer (OC) remains unclear. This study focuses on the function of circ_0067934 in tumorigenesis and cisplatin (DDP) resistance in OC and the molecular mechanism. METHODS: Expression of circ_0067934 in OC tissues and cells was examined, and its correlation with the clinical characteristics of patients was analyzed. Candidate targets of circ_0067934 were predicted using bioinformatics systems. Binding relationships between circ_0067934 and microRNA (miR)-545-3p and between miR-545-3p and inorganic pyrophosphatase 1 (PPA1) were validated via luciferase assays. Gain- and loss-of functions of circ_0067934, miR-545-3p and PPA1 were performed to determine their functions in proliferation, invasion, apoptosis and DDP resistance of OC cells in vitro and in vivo. RESULTS: Circ_0067934 was overexpressed in OC samples and associated with advanced tumor staging and lymph node metastasis. Downregulation of circ_0067934 reduced DDP resistance of the DDP-resistant A2780/DDP cell line and reduced cell proliferation and invasion, but the malignant behaviors of OC cells were restored after further miR-545-3p downregulation. Circ_0067934 served as a sponge for miR-545-3p and diminished its suppressive effect on PPA1 translation. Artificial upregulation of PPA1 enhanced proliferation, invasion and DDP resistance of A2780/DDP cells, and it reduced phosphorylation of the pro-apoptotic JNK signaling. Similar results were found in vivo. CONCLUSION: This study suggests that circ_0067934 sequesters miR-545-3p and enhances PPA1 expression to promote tumorigenesis and DDP resistance in OC. This study may provide novel approaches in the management of OC.

Multi-band terahertz resonant absorption based on an all-dielectric grating metasurface for chlorpyrifos sensing.

Perfect metasurface absorbers play a significant role in imaging, detecting, and manipulating terahertz radiation. We utilize all-dielectric gratings to demonstrate tunable multi-band absorption in the terahertz region. Simulation reveals quad-band and tri-band absorption from 0.2 to 2.5 THz for different grating depths. Coupled-mode theory can explain the absorption phenomenon. The absorption amplitude can be precisely controlled by changing the pump beam fluence. Furthermore, the resonant frequency is sensitive to the medium's refractive index, suggesting the absorber may be of great potential in the sensor detection field. The experimental results exhibit a high detectivity of pesticides.

Necessity for subsequent surgery in women of child-bearing age with positive margins after conization.

BACKGROUND: 20-25% of women with high-grade cervical intraepithelial neoplasias (HSIL) have residual lesions after conization. The state of the margin is generally considered to be a risk factor for recurrence or persistent lesions. Predictors of positive margins and residual lesions need to be identified. A design for postoperative management and avoidance of overtreatment needs to be provided, especially for women of child-bearing age. METHODS: This study was a retrospective analysis of 1309 women of child-bearing age with HSIL, who underwent cold knife conization (CKC). Age, gravidity, parity, human papillomavirus (HPV) species, cytology, transformation zone type, results of endocervical curettage (ECC), quadrant involvement, glandular involvement, and Cervical Intraepithelial Neoplasia (CIN) grade were analyzed. Among those with positive margins, 245 patients underwent secondary surgery within three months, including CKC, a loop electrosurgical excision procedure, and total hysterectomy. Risk factors for positive margins and residual lesions were assessed. RESULTS: There was no significant difference in age, gravidity, parity, glandular involvement, and CIN grade between the two groups (P > 0.3). There was a significant difference in HPV species, cytology, ECC results, and quadrant involvement (P < 0.002). Multivariate analysis showed a major cytology abnormality, high-risk HPV infection, type III transformation zone, positive ECC result, and multiple quadrant involvement were independent risk factors for positive margins and residual lesions (P < 0.02). Age > 35 years was also a risk factor for residual lesions (P < 0.03). CONCLUSION: High-risk women should be treated appropriately considering fertility. Patients with positive margins should be managed uniquely. Surgery for women without fertility may be appropriate. Close follow-up is necessary for women who have fertility requirements or are unwilling to undergo subsequent surgery if they have no risk factors, especially women < 35 years.

The role of serum ß-trophin and endostatin in patients with polycystic ovary syndrome: Are they correlated?

BACKGROUND: It's necessary to investigate the serum ß-trophin and endostatin (ES) level and its influencing factors in patients with newly diagnosed polycystic ovary syndrome (PCOS). METHODS: Newly diagnosed PCOS patients treated in our hospital were selected, and healthy women who took physical examination during the same period as healthy controls. We detected and compared the related serum indicators between two groups, Pearson correlation were conducted to identify the factors associated with ß-trophin and ES, and the influencing factors of ß-trophin and ES were analyzed by logistic regression. RESULTS: A total of 62 PCOS patients and 65 healthy controls were included. The BMI, WHI, LH, FSH, TT, FAI, FBG, FINS, HOMA-IR, TC, TG, LDL, ES in PCOS patients were significantly higher than that of healthy controls, while the SHBG and HDL in PCOS patients were significantly lower than that of healthy controls (all p < 0.05). ß-trophin was closely associated with BMI (r = 0.427), WHR (r = 0.504), FBG (r = 0.385), TG (r = 0.405) and LDL (r = 0.302, all p < 0.05), and ES was closely associated with BMI (r = 0.358), WHR (r = 0.421), FBG (r = 0.343), TC (r = 0.319), TG (r = 0.404, all p < 0.05). TG, BMI, WHR and FBG were the main factors affecting the serum ß-trophin levels (all p < 0.05). FBG, TC and BMI were the main factors affecting the serum ES levels (all p < 0.05). The TG, ß-trophin, ES level in PCOS patients with insulin resistance (IR) were significantly higher than that of those without IR (all p < 0.05). CONCLUSION: Increased ß-trophin is closely associated with increased ES in patients with PCOS, which may be the useful indicators for the management of PCOS.

Effect of Laser Parameters on Optical Stealth Transmission System Performance.

The performance of an optical stealth transmission system based on gain-switched laser depends largely on the laser parameters. Modulation frequency, bias current, and modulation current are considered to study the covertness and bit error rate performance of the optical stealth transmission system. According to optical stealth carrier generation with time spreading and all-optical encoding, the stealth signals are derived. A complementary encoding scheme is adopted in the system simulation. The simulation results show that the temporal and spectral characteristics of the generated stealth signal can be changed by adjusting the bias current, modulation current, and modulation frequency. However, there is a trade-off between bit error rate performance and covertness of the stealth channel. Under the premise of error-free transmission, the bias current and modulation frequency should be reduced and the modulation current should be improved to optimize the covertness of the stealth channel.

Follow-up program for blood donors with unconfirmed screening results reveals a high false-positive rate in Dalian, China.

BACKGROUND: Chinese blood donors with unconfirmed serological and/or molecular screening results are deferred permanently. This study investigated the implementation and performance of a follow-up program aiming to improve the notification and management of deferred donors in Dalian, China. STUDY DESIGN AND METHODS: From January 2013 to February 2018, 411,216 donations were tested for HBsAg, anti-HCV, anti-HIV/HIV antigen, and antibodies to Treponema pallidum. HBV, HCV, and HIV nucleic acid testing (NAT) was performed in mini-pools of six or in individual donations (IDs). Reactive donations were evaluated further with alternative serological assays and ID-NAT re-testing. A follow-up procedure was developed to evaluate a subset of deferred donors that were either potential NAT yield cases, serology non-reactive and NAT non-repeated reactive (NRR), or serology NRR irrespective of NAT result. RESULTS: Serological and molecular routine, plus supplemental testing, identified HBV, HCV, HIV, and TP in 503 (0.12%), 392 (0.09%), 156 (0.04%), and 2041 (0.49%) donations, respectively. Overall, 683 of 4156 (16.4%) eligible donors and 205 donors deferred prior 2013 participated in the program. They included 664 serology NRR and 224 NAT yield cases, and 58.8% repeat donors. All markers combined, follow-up documented false reactivity, primary acute infections, and OBI in 61.9% (550/888), 3.3% (29/888), and 12.8% (114/888) of these donors, respectively. Isolated anti-HBc or anti-HBs reactivity was observed in 22% of cases. CONCLUSION: Follow-up testing refined infection status in 78.0% (693/888) of deferred donors with unconfirmed screening results. This high false-positive rate encouraged to reevaluate the current screening strategies and to consider donor reentry.

Anaerophilus nitritogenes gen. nov., sp. nov., isolated from salt lake sediment in Xinjiang Province, China.

An obligately anaerobic, nitrate-reducing bacterial strain (MJB2T) was isolated from sediments of saline in Xinjiang province of China. Cells were Gram-stain-positive rods and motile by means of flagella and formed endospores. The novel strain MJB2T was able to grow at 15-37 °C (optimum 28-30 °C), pH 5.8-9.4 (optimum 7.8) and with 1.0-7.0% NaCl (optimum 5.0-6.0%, w/v). Sulfate, sulfite, thiosulfate, elemental sulfur, nitrite and Fe(III) were not used as terminal electron acceptors. Oxidase and catalase reactions were positive. H2S was producted from L-cystine. Complex substrates such as beef extract, peptone and yeast extract can be used as sole energy sources. The DNA G+C content was 29.4 mol%. The major cellular fatty acids (> 10%) were C14:0, C16:1 cis 7 and C16:1 cis 9. The main polar lipids consisted of phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine, three unidentified amino lipids, one unidentified amino glycolipid, two unidentified glycolipid, one unidentified aminophospholipid and two unidentified lipids. No respiratory quinones were detected. According to phylogenetic analysis based on 16S rRNA gene sequences, strain MJB2T was affiliated to the family Clostridiaceae (order Clostridiales) with highest 16S rRNA gene sequence similarity of 95.3% to Crassaminicella profunda Ra1766HT. Strain MJB2T exhibited 74.9% ANI values to C. profunda Ra1766HT. In silico DNA-DNA relatedness value between strain MJB2T and C. profunda Ra1766HT was 19.5%. The distinct biochemical, chemotaxonomic and phylogenetic differences from the previously described taxa supported that strain MJB2T represents a novel species of a new genus, for which the name Anaerophilus nitritogenes gen. nov., sp. nov. is proposed. The type strain is MJB2T (=KCTC 15800T=MCCC 1K03631T).

Osteogenesis inducers promote distinct biological responses in aortic and mitral valve interstitial cells.

Both aortic and mitral valves calcify in pathological conditions; however, the prevalence of aortic valve calcification is high whereas mitral valve leaflet calcification is somewhat rare. Patterns of valvular calcification may differ due to valvular architecture, but little is known to that effect. In this study, we investigated the intrinsic osteogenic differentiation potential of aortic versus mitral valve interstitial cells provided minimal differentiation conditions. For the assessment of calcification at the cellular level, we used classic inducers of osteogenesis in stem cells: ß-glycerophosphate (ß-Gly), dexamethasone (Dex), and ascorbate (Asc). In addition to proteomic analyses, osteogenic markers and calcium precipitates were evaluated across treatments of aortic and mitral valve cells. The combination of ß-Gly, Asc, and Dex induced aortic valve interstitial cells to synthesize extracellular matrix, overexpress osteoblastic markers, and deposit calcium. However, no strong evidence showed the calcification of mitral valve interstitial cells. Mitral cells mainly responded to Asc and Dex by cell activation. These findings provide a deeper understanding of the physiological properties of aortic and mitral valves and tendencies for calcific changes within each valve type, contributing to the development of future therapeutics for heart valve diseases.

Multiband terahertz absorber and selective sensing performance.

Multiband terahertz absorbers are essential photonic components for responding to, manipulating, and modulating terahertz waves. In this work, improved electric split resonant ring arrays are used to demonstrate multiband terahertz wave absorption. The proposed design strategy is simple, practical, and significant. Experiments and simulations reveal perfect absorption at 0.918 THz and 1.575 THz for the transverse magnetic (TM) polarization and at 0.581, 1.294, and 1.556 THz for the transverse electric (TE) polarization. In addition, the weak resonant peaks that occurred in the experiments in both polarization states have been verified by the simulations. Furthermore, five concentration gradients of 2, 4-dichlorophenoxyacetic acid solutions and six concentration gradients of chlorpyrifos have been detected using the absorber. The lowest detectable concentration that could be monitored was 0.1 ppm. The absorption, intensity, and frequency shift values for the different solution concentrations at the resonant peaks were analyzed. The highest linear regression coefficients were 0.9862 and 0.9565 for the TE and TM polarizations, respectively. This multi-band absorber was demonstrated to be highly efficient in detecting pesticides for food safety applications.

Development of frequency-tunable multiple-band terahertz absorber based on control of polarization angles.

Controlling and tuning the spectral absorption response of metamaterial absorbers fabricated by arranging a set of resonators in a regular array is challenging. Polarization tunable multi-band terahertz resonant absorbers were developed using anisotropic microstructure arrays. The unit cell consisted of four pairs of H-shaped resonators of different sizes and a metallic ground plane separated by a dielectric layer. Discrete operating frequency shifts and dynamic amplitude tuning were observed by changing the polarization angle. The effect of the polarization angle on the absorption amplitude was evaluated. This work provides a concise approach to realize tunable absorption characteristics, which can be applied in sensors, detectors, and switches.

Synthesizing Depth Hand Images with GANs and Style Transfer for Hand Pose Estimation.

Hand pose estimation is a critical technology of computer vision and human-computer interaction. Deep-learning methods require a considerable amount of tagged data. Accordingly, numerous labeled training data are required. This paper aims to generate depth hand images. Given a ground-truth 3D hand pose, the developed method can generate depth hand images. To be specific, a ground truth can be 3D hand poses with the hand structure contained, while the synthesized image has an identical size to that of the training image and a similar visual appearance to the training set. The developed method, inspired by the progress in the generative adversarial network (GAN) and image-style transfer, helps model the latent statistical relationship between the ground-truth hand pose and the corresponding depth hand image. The images synthesized using the developed method are demonstrated to be feasible for enhancing performance. On public hand pose datasets (NYU, MSRA, ICVL), comprehensive experiments prove that the developed method outperforms the existing works.