Ethyl acetate as an acetyl source and solvent for acetylation of alcohols by KOH.

A KOH mediated mild, efficient, convenient and gram-scalable protocol for the acetylation of alcohols with EtOAc as acetyl source and solvent. Various types of alcohols were successfully transformed into according acetylated products. Good to excellent yields were offered by primary alcohols and low to moderate yields were offered by secondary alcohols.

In vitro pharmacokinetics/pharmacodynamics of FL058 (a novel beta-lactamase inhibitor) combined with meropenem against carbapenemase-producing Enterobacterales.

Objective: FL058 is a novel beta-lactamase inhibitor with a broad spectrum of activity and a favorable safety profile. The objective of this study was to evaluate pharmacokinetic/pharmacodynamic (PK/PD) relationships for the combination of FL058 and meropenem in an in vitro infection model. Methods: By simulating human concentration-time profiles in the in vitro model, meropenem combined with FL058 when administered 1 g/0.5 g, 1 g/1 g, 2 g/1 g, and 2 g/2 g q8h by 3-h infusion achieved approximately 2- and 4-log10 kill to KPC/OXA-producing Klebsiella pneumoniae and Escherichia coli; the combination therapy could not inhibit NDM-producing K. pneumoniae but could maintain NDM-producing E. coli around a baseline. Results: The PK/PD indexes that best described the bacterial killing from baseline in log10 CFU/mL at 24 h were the percent time of free drug above the minimal inhibitory concentration (MIC) (%fT > MIC, MIC with FL058 at 4 mg/L) for meropenem and the percent time of free drug above 1 mg/L (%fT > 1 mg/L) for FL058. The targets for achieving a static effect and the 1- and 2-log10 kill were 74, 83, and 99 for %fT > MIC of meropenem and 40, 48, and 64 for %fT > 1 mg/L of FL058, respectively. The PK/PD index of %fT > 1 mg/L can provide a basis for evaluating clinical dosing regimens for FL058 combined with meropenem. Conclusion: FL058 combined with meropenem might be a potential treatment for KPC- and/or OXA-48-producing Enterobacterales infection.

Coupling-Based Multiple Bound States in the Continuum and Grating-Assisted Permittivity Retrieval in the Terahertz Metasurface.

The terahertz (THz) metasurfaces that support bound states in the continuum (BICs) provide a promising platform for various applications due to their high Q-factor resonance. In this study, we experimentally demonstrate multiple BICs with different resonance symmetries in the THz metasurface based on mode coupling. The proposed metasurface is composed of 2 × 2 split ring resonators (SRRs) metamolecules. The SRRs of two different gap angles in the metamolecule lattice provide intrinsic resonance with different frequencies, and the coupling between them exhibits high transmission quasi-BIC resonance, which can be tuned by varying the gap angle. The arrangement of SRRs in the 2 × 2 metamolecule lattice determines the types of coupling that govern the resonance symmetry of quasi-BIC. More interestingly, the multiple quasi-BICs enabled by different couplings can be simultaneously achieved in a metasurface. Apart from tuning the gap angles, the permittivity in the vicinity of SRRs also changes the resonance frequency. Consequently, quasi-BIC can be artificially formed by deliberately constructing the permittivity difference of the dielectric environment on the SRRs. In view of this, we introduce the scheme of permittivity retrieval for the dispersive analyte, assisted by the fixed-permittivity gratings. In addition, we experimentally demonstrate the metasurface in combination with the microfluidic chip for the sensing of the glucose solution concentration. Our findings offer a possible strategy for the existing manufactured metasurface to achieve quasi-BIC resonance and provide a promising candidate for approaching the spectral analysis of the biochemical.

A novel method for colposcopic shunting in HPV-positive women: Quantitative detection of HPV E7 oncoprotein.

The objective of the study was to evaluate the clinical application potential of quantitatively detecting human papillomavirus (HPV) E7 oncoprotein in HPV-positive women, with the goal of detecting potential high-grade cervical squamous intraepithelial lesions (HSIL) and cervical cancer improving the accuracy of colposcopic shunting in these patients.HPV-positive women (N = 611) were selected for quantitatively detecting HPV E7 protein levels by magnetic particle-based chemiluminescence immunoassay before colposcopy. Receiver operating characteristic (ROC) curve analysis was performed (n = 400) to determine diagnostic detection thresholds for HPV E7 oncoprotein. ThinPrep cytology test (TCT) and Aptima HPV E6/E7 mRNA analysis were also performed (n = 211). The diagnostic performance of these three diagnostic methods in detecting HSIL and cervical cancer was compared with the gold standard of pathological diagnosis. The area under the ROC curve was 0.724. The diagnostic detection threshold of HPV E7 oncoprotein was ≥10.88 ng/mL. The sensitivity (SEN), specificity (SPE), positive predictive value (PPV), negative predictive value (NPV), and Youden index of HPV E7 oncoprotein for the identification of HSIL and cervical cancer were 78.7 %, 77.9 %, 72.2 %, 83.3 %, and 56.6 %, respectively, which were higher than those of TCT and HPV E6/E7 mRNA.The results indicate that quantitative detection of HPV E7 oncoprotein can effectively shunt HPV-positive women and reduce unnecessary colposcopy and biopsy. It can detect potential HSIL and cervical cancer in a timely manner and prevent high-risk patients from missing diagnosis.

Antiaging Strategies and Remedies: A Landscape of Research Progress and Promise.

Aging is typified by a gradual loss of physiological fitness and accumulation of cellular damage, leading to deteriorated functions and enhanced vulnerability to diseases. Antiaging research has a long history throughout civilization, with many efforts put forth to understand and prevent the effects of aging. Multiple strategies aiming to promote healthy aging and extend the lifespan have been developed including lifestyle adjustments, medical treatments, and social programs. A multitude of antiaging medicines and remedies have also been explored. Here, we use data from the CAS Content Collection to analyze the publication landscape of recent research related to antiaging strategies and treatments. We review the recent advances and delineate trends in research headway of antiaging knowledge and practice across time, geography, and development pipelines. We further assess the state-of-the-art antiaging approaches and explore their correlations with age-related diseases. The landscape of antiaging drugs has been outlined and explored. Well-recognized and novel, currently evaluated antiaging agents have also been summarized. Finally, we review clinical applications of antiaging products with their development pipelines. The objective of this review is to summarize current knowledge on preventive strategies and treatment remedies in the field of aging, to outline challenges and evaluate growth opportunities, in order to further efforts to solve the problems that remain.

Aging Hallmarks and Progression and Age-Related Diseases: A Landscape View of Research Advancement.

Aging is a dynamic, time-dependent process that is characterized by a gradual accumulation of cell damage. Continual functional decline in the intrinsic ability of living organisms to accurately regulate homeostasis leads to increased susceptibility and vulnerability to diseases. Many efforts have been put forth to understand and prevent the effects of aging. Thus, the major cellular and molecular hallmarks of aging have been identified, and their relationships to age-related diseases and malfunctions have been explored. Here, we use data from the CAS Content Collection to analyze the publication landscape of recent aging-related research. We review the advances in knowledge and delineate trends in research advancements on aging factors and attributes across time and geography. We also review the current concepts related to the major aging hallmarks on the molecular, cellular, and organismic level, age-associated diseases, with attention to brain aging and brain health, as well as the major biochemical processes associated with aging. Major age-related diseases have been outlined, and their correlations with the major aging features and attributes are explored. We hope this review will be helpful for apprehending the current knowledge in the field of aging mechanisms and progression, in an effort to further solve the remaining challenges and fulfill its potential.

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.

HPV16 E7 oncoprotein test as a triage strategy for HPV16-positive women in cervical cancer screening: long-term follow-up outcome.

Background: Colposcopy is recommended once human papillomavirus (HPV)16/18 infection is detected. However, not all HPV16/18-positive women will necessarily develop cervical lesions. Therefore, this study aimed to investigate the application of quantitative HPV16 E7 oncoprotein detection as a cervical cancer screening method for more efficient screening while minimizing unnecessary colposcopy. Methods: E7 oncoprotein (HPV16) was quantitatively detected in cervical exfoliated cells of HPV16-positive women. The levels of HPV16 E7 oncoprotein in different degrees of cervical lesions were compared, and the optimal cut-off value for identifying HSIL+ was determined by receiver operating characteristic (ROC) curve analysis. With a pathological diagnosis as the gold standard, the sensitivity (SEN), specificity (SPE), positive predictive value (PPV), negative predictive value (NPV), and Kappa value were calculated to verify the diagnostic value of the method. Women diagnosed with low-grade squamous intraepithelial lesions (LSIL) and normal women were followed up for 5 years to evaluate the predictive value of HPV16 E7 protein for disease progression/persistent infection. Results: The expression level of HPV16 E7 oncoprotein was positively correlated with the degree of the cervical lesion (r = 0.589, P < 0.01). The area under the ROC curve (AUC) was 0.817 (confidence interval: 0.729-0.904). The cut-off value of E7 oncoprotein for identifying HSIL+ was 8.68 ng/ml. The SEN, SPE, PPV, NPV, and Kappa values of HPV16 E7 oncoprotein for the identification of HSIL+ were 87.1%,70.0%, 87.1%, 70.0%, and 0.571, respectively, which were higher than those of ThinPrep cytology test (TCT). The SEN, SPE, PPV, and NPV of HPV16 E7 oncoprotein in predicting disease progression/persistent infection were 93.75%, 91.30%, 88.24%, and 95.45%, respectively. Conclusion: The quantitative detection of HPV 16 E7 oncoprotein can not only accurately screen cervical lesions but also achieve efficient colposcopy referral. Additionally, HPV16 E7 oncoprotein can accurately predict the progression of cervical lesions and persistent HPV infection.

The early effects of sleeve gastrectomy on postprandial chylomicron triglycerides during the progression of type 2 diabetes.

BACKGROUND: It remains unclear whether early sleeve gastrectomy (SG) improves postprandial very-low-density lipoprotein (VLDL) as well as chylomicron triglycerides (TGs) in a weight-independent manner in patients with or without type 2 diabetes (DM). Herein we investigated the early effects of SG on postprandial VLDL and chylomicron kinetics. METHODS: A liquid meal test was performed before and after 1 week of SG. The plasma was collected for postprandial triglyceride-rich lipoprotein kinetics analyses, including VLDLs and chylomicrons, isolated by high-speed ultracentrifugation. Lipidomics and metabolomics were used to profile lipid and metabolite compositions of plasma and postprandial chylomicrons. De novo fatty acid synthesis in intestinal epithelial cells treated with chylomicron metabolites was examined using RT-PCR, immunoblotting, and free fatty acid measurement. RESULTS: We found that patients with DM had markedly higher VLDL TGs than patients without DM, and such an increase was still retained after SG. In contrast, SG significantly decreased postprandial chylomicron TGs, but surprisingly, the degree of the reduction in patients with DM was less prominent than in patients without DM, confirmed by untargeted lipidomics analysis. Moreover, 5 unique metabolites potentially linked to de novo fatty acid synthesis from the pathway analysis were discovered by further metabolomic analysis of postprandial chylomicrons from patients with DM who underwent SG and verified by In vitro intestinal epithelial cell culture experiments. CONCLUSIONS: SG in 1 week did not impact postprandial VLDL but decreased chylomicron TGs. Patients with DM keep higher postprandial chylomicron TG concentrations than patients without it after SG, potentially through some unique metabolites that increase intestinal fatty acid synthesis. These results implicate the timing for SG to reach lower intestinal fatty acid synthesis and postprandial chylomicron TG production is prior to the diagnosis of DM to potentially reduce cardiovascular risks.

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.

The relationship between dietary patterns derived from inflammation and cognitive impairment in patients undergoing hemodialysis.

Introduction: Dietary patterns were shown to be closely related to inflammation, which was independently associated with cognitive impairment (CI) in patients undergoing hemodialysis (HD). However, it remains unclear the influence of dietary patterns derived from inflammation on CI in this population. This study aimed to examine the association between dietary patterns derived from C-reactive protein (CRP) and interleukin-6 (IL-6) and CI in patients undergoing HD. Methods: Dietary intake was obtained from the simplified quantitative food frequency questionnaire. Reduced rank regression (RRR) was used to extract two dietary patterns, with IL-6 and CRP as response variables. Cognitive function was examined by the Montreal Cognitive Assessment (Beijing version). Venous blood was drawn for measuring IL-6 and CRP levels. Multivariable logistic regression was used to investigate the association between dietary patterns and CI. Results: Dietary pattern derived from IL-6 was not significantly associated with CI. The third quartile of dietary pattern, which used CRP as the response variable, significantly contributed to the increased risk of CI (AOR 8.62, 95% CI 1.47-50.67) after controlling age, sex, education level, marital status, and residential pattern (p-for-trend = 0.028). After considering hypertension and diabetes, physical activity level, anxiety and depression, smoking and drinking status, social support, energy intake, and the dietary pattern derived from IL-6 (p-for-trend = 0.026), the relationship between the dietary pattern derived from CRP and CI remained significant (AOR 14.54, 95% CI 1.40-151.13). Conclusion: Dietary pattern associated with high CRP level, including high intake of rice, liquor, fruit, tea and coffee and low intake of dark vegetables and juice, contributed to the increased risk of CI. The association between the consumption of seafood, sweet beverages, and alcohol and CI is yet to be established. However, they may be dietary contributing factors to inflammation in patients undergoing HD.

The typical polypoid adenomyoma is a special form of endometrial polyp: a case-controlled study with a large sample size.

PURPOSE: To investigate clinicopathological differences between typical endometrial polypoid adenomyomas (TPAs) and endometrial polyps (EPs) and to determine the risk factors and recurrence of TPA and further clarify the pathogenesis and treatment of TPA. METHODS: We reviewed the medical records of 488 women with TPA and 500 women with EP. Then, we analyzed the clinical features and manifestations, ultrasonic manifestations, hysteroscopic morphology, and pathological results. In addition, 360 cases of TPA and 367 cases of EP were followed up for 22-77 months and the risk factors TPA recurrence were assessed. RESULTS: We detected significant differences in age, menopausal status, body mass index (BMI), the number of pregnancies, and parity between the two groups (P < 0.05). Hysteroscopy revealed that the incidence of polyps > 3 cm in diameter and multiple polyps in the TPA group was significantly higher than that in the EP group (P < 0.01). In addition, the rate of recurrence in the TPA group was significantly higher than that in the EP group (P < 0.05). Over three pregnancies, menopause, curettage, and the application of polyp clamps were all identified as independent risk factors for the recurrence of TPA (P < 0.05). CONCLUSION: In addition to high estrogen levels, endometrial injury was identified as the main contributor to TPA pathogenesis. Hysteroscopic electrotomy was identified as the preferential treatment for TPA to avoid recurrence, especially in women with risk factors. Increasing the depth of ablation may prevent the recurrence of TPA more efficiently.

Saikosaponin B2 ameliorates depression-induced microglia activation by inhibiting ferroptosis-mediated neuroinflammation and ER stress.

ETHNOPHARMACOLOGICAL RELEVANCE: Saikosaponins B2 (SSB2) is one of the main active components isolated from Radix Bupleuri (Bupleurum chinense DC.), a herb widely used of traditional Chinese medicine. It has been used for the treatment of depression for more than two thousand years. However, the molecular mechanisms remain to be determined. AIM OF THE STUDY: In this study, we evaluated the anti-inflammatory effect and elucidated underlying molecular mechanisms of SSB2 in LPS-induced primary microglia and CUMS-induced mice model of depression. METHOD: The effects of SSB2 treatment were investigated both in vitro and in vivo. The chronic unpredictable mild stimulation (CUMS) procedure was applied to establish the animal model of depression. Behavioural tests were used to evaluate the depressive-like behaviors in CUMS-exposed mice, including sucrose preference test, open field test, tail suspension test, and forced swimming test. The GPX4 gene of microglia was silenced using shRNA, and inflammatory cytokines were determined by Western Blot and immunofluorescence analysis. Endoplasmic reticulum stress and ferroptosis-related markers were detected by qPCR, flow cytometry and confocal microscopy. RESULT: SSB2 reversed depressive-like behaviours in CUMS-exposed mice and relieved central neuroinflammation and ameliorated hippocampal neural damage. SSB2 alleviated LPS-induced activation of microglia through the TLR4/NF-κB pathway. LPS-induced ferroptosis, with increased levels of ROS, intracellular Fe2+, mitochondrial membrane potential, lipid peroxidation, GSH, SLC7A11, FTH, GPX4 and Nrf2, and decreased transcription levels of ACSL4 and TFR1, was attenuated with SSB2 treatment in primary microglia cells. GPX4 knockdown activated ferroptosis, induced endoplasmic reticulum (ER) stress, and abrogated the protective effects of SSB2. Further, SSB2 attenuated ER stress, balanced calcium homeostasis, reduced lipid peroxidation and intracellular Fe2+ content by regulating the level of intracellular Ca2+. CONCLUSIONS: Our study suggested that SSB2 treatment can inhibit ferroptosis, maintain calcium homeostasis, relieve endoplasmic reticulum stress and attenuate central neuroinflammation. SSB2 exhibited anti-ferroptosis and anti-neuroinflammatory effects through the TLR4/NF-κB pathway in a GPX4-dependent manner.

The Tobit-Unscented-Kalman-Filter-Based Attitude Estimation Algorithm Using the Star Sensor and Inertial Gyro Combination.

For the orbit operation of spacecraft, due to environmental factors, a star sensor installed on the spacecraft must have data censoring, which greatly reduces the attitude determination ability of the traditional combined-attitude-determination algorithm. To address this problem, this paper proposes an algorithm for high-precision attitude estimation based on a Tobit unscented Kalman filter. This is on the basis of establishing the nonlinear state equation of the integrated star sensor and gyroscope navigation system. The measurement update process of the unscented Kalman filter is improved. The Tobit model is used to describe the gyroscope drift when the star sensor fails. The latent measurement values are calculated using the probability statistics, and the measurement error covariance expression is derived. The proposed design is verified via computer simulations. When the star sensor fails for 15 min, the accuracy of the Tobit unscented Kalman filter based on the Tobit model is improved by approximately 90% compared to the unscented Kalman filter. Based on the results, the proposed filter can effectively estimate the error caused by the gyro drift, and the method is effective and feasible, provided there is theoretical support for the engineering practice.

Conversion of 5-hydroxymethylfurfural to furan-2,5-dicarboxylic acid by a simple and metal-free catalytic system.

A simple and metal-free catalytic system composed of NaOtBu/DMF and an O2 balloon efficiently converted 5-hydroxymethylfurfural (5-HMF) to furan-2,5-dicarboxylic acid with an 80.85% yield. 5-HMF analogues and various types of alcohols were also transformed to their corresponding acids in satisfactory to excellent yield by this catalytic system.

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.

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.

Clinical Significance of Lymphatic Infiltration Detected by Immunohistochemical Double Staining in Patients with Endometrial Cancer.

Background: The presence of lymph-vascular space invasion is a powerful predictor of lymph node metastasis. However, most studies do not distinguish lymph vessel invasion (LVI) and blood vessel invasion (BVI). The aim of this study was to distinguish the role of LVI and BVI in lymphatic metastasis and recurrence in patients with endometrial cancer. Methods: We examined 171 patients with endometrial cancer. Immunohistochemical double staining was used to distinguish lymphatic invasion and vascular invasion. First, the relationship between lymphatic/vascular invasion and clinicopathological features and lymphatic metastasis was studied. Then, the expression of D2-40/LVI and CD31/BVI in patients with recurrence was analyzed. Results: Pathological grading (G3) and D2-40/LVI were independent high-risk factors for lymph node metastasis of endometrial cancer. The area under the receiver operating characteristic curve values for predicting lymphatic metastasis using pathological grading (G3) or D2-40/LVI alone were .642 and .680, respectively, and the area under the curve value for the combined detection of pathological grading (G3) and D2-40/LVI was .726, which was greater than the values obtained for the abovementioned independent variables. Among the 15 recurrent patients, 5 (33.3%) were D2-40/LVI positive, 2 (13.3%) were CD31/BVI positive, and 8 (53.3%) were both D2-40/LVI and CD31/BVI positive. Conclusion: D2-40/LVI combined with G3 can effectively predict lymph node metastasis of endometrial carcinoma.

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.