Chiral Brønsted Base Activation of Donor-Acceptor Cyclopropanes toward Diastereo- and Enantioselective [3 + 2] Cycloaddition with Isatin-Derived Ketimines.

Organocatalyzed diastereo- and enantioselective [3 + 2] cycloaddition reactions of donor-acceptor (D-A) cyclopropanes with isatin-derived ketimines are presented. Different from well-developed Lewis acid activation protocols which promote the reactivity of D-A cyclopropanes through coordinating to the acceptor group, in this reaction, dicyanocyclopropylmethyl ketones can be activated through nucleophilic activation of the donor group by using dihydroquinine-derived squaramide as Brønsted base catalyst. The reaction affords functionalized spiro[oxindole-3,2'-pyrrolidines] with two nonadjacent tetra- and tri-substituted stereocenters in 83-99% yields, moderate to excellent diastereoselectivities (up to >20:1 diastereomeric ratio (dr)), and excellent enantioselectivities (up to >99% enantiomeric excess (ee)) under mild conditions.

The potential role of reprogrammed glucose metabolism: an emerging actionable codependent target in thyroid cancer.

Although the incidence of thyroid cancer is increasing year by year, most patients, especially those with differentiated thyroid cancer, can usually be cured with surgery, radioactive iodine, and thyroid-stimulating hormone suppression. However, treatment options for patients with poorly differentiated thyroid cancers or radioiodine-refractory thyroid cancer have historically been limited. Altered energy metabolism is one of the hallmarks of cancer and a well-documented feature in thyroid cancer. In a hypoxic environment with extreme nutrient deficiencies resulting from uncontrolled growth, thyroid cancer cells utilize "metabolic reprogramming" to satisfy their energy demand and support malignant behaviors such as metastasis. This review summarizes past and recent advances in our understanding of the reprogramming of glucose metabolism in thyroid cancer cells, which we expect will yield new therapeutic approaches for patients with special pathological types of thyroid cancer by targeting reprogrammed glucose metabolism.

Prediction of asialoglycoprotein receptors by correlated liver function parameters before hepatectomy.

Flow cytometric analysis of asialoglycoprotein receptor (ASGPR) levels on the surface of hepatocytes, which were obtained from the liver specimens of patients that received hepatectomy, were used as predictors of liver dysfunction after major hepatectomy for primary hepatocellular carcinoma (HCC) in Chinese patients, based on our previous study which confirmed the value of ASGPR levels on the surface of hepatocytes in evaluating the liver reserve function. The current study was planned to establish a conversion formula for the value of ASGPR with correlated liver function parameters. It was conducted from January 1, 2014, to June 30, 2015, at Beijing DiTan Hospital, Beijing, China, and comprised 55 patients having undergone major hepatectomy. The outcomes of hepatectomy were compared with ASGPR levels and preoperative liver function parameters. A multiple linear regression model was used to identify the converted ASGPR value. The calculated ASGPR level was derived as: 80.695 + 0.002 × cholinesterases (CHE) (IU/L) - 0.620 × indocyanine green retention rate at 15 min (ICGR15)(%) - 0.655 × total bilirubin (TB) (umol/L). Receiver-operator characteristic curve analysis showed that the sensitivity and specificity of the ASGPR value <68.18% were 100% and 77.3% respectively for predicting liver dysfunction after hepatectomy. The converted ASGPR value may be reliable index for hepatic functional reserve in patients undergoing hepatectomy.

Emerging role of exosome-derived non-coding RNAs in tumor-associated angiogenesis of tumor microenvironment.

The tumor microenvironment (TME) is an intricate ecosystem that is actively involved in various stages of cancer occurrence and development. Some characteristics of tumor biological behavior, such as proliferation, migration, invasion, inhibition of apoptosis, immune escape, angiogenesis, and metabolic reprogramming, are affected by TME. Studies have shown that non-coding RNAs, especially long-chain non-coding RNAs and microRNAs in cancer-derived exosomes, facilitate intercellular communication as a mechanism for regulating angiogenesis. They stimulate tumor growth, as well as angiogenesis, metastasis, and reprogramming of the TME. Exploring the relationship between exogenous non-coding RNAs and tumor-associated endothelial cells, as well as their role in angiogenesis, clinicians will gain new insights into treatment as a result.

Comprehensive analysis of the effect of Hashimoto's thyroiditis on the diagnostic efficacy of preoperative ultrasonography on cervical lymph node lesions in papillary thyroid cancer.

Purpose: Hashimoto's thyroiditis often leads to reactive hyperplasia of the central compartment lymph nodes in papillary thyroid carcinoma (PTC) patients. However, the effect and clinical significance of Hashimoto's thyroiditis (HT) on ultrasonography evaluation for cervical lymph node (LN) lesions remain unknown. This study aims to investigate the effect of Hashimoto's thyroiditis on the diagnostic efficacy of preoperative ultrasonography on cervical lymph node lesions in PTC patients. Patients and methods: This study consecutively enrolled 1,874 PTC patients who underwent total thyroidectomy and radical cervical lymph node dissection between January 2010 and December 2021. Eligible patients were categorized as with HT and without HT. The diagnostic performance of preoperative ultrasonography for cervical LN lesions (including central LNs and lateral LNs) was evaluated between PTC patients with HT and those without HT, respectively. Results: Among the 1,874 PTC patients, 790 (42.1%) had central cN+ and 1,610 (85.9%) had lateral cN+. Compared with PTC patients without HT, the preoperative US for central LNs displays a higher false-positive rate (27.9% vs. 12.2%, p <0.001) and a lower specificity (72.1% vs. 87.8%, p < 0.001) in PTC patients with HT. Moreover, in PTC patients with HT, the ratio of the absence of fatty hilum in central LNs without metastasis was higher than in PTC patients without HT (13.02% vs. 7.46%, p = 0.013). However, no such differences were observed in lateral LNs. Conclusion: HT will interfere with the preoperative US evaluation for central LNs and increase the incidence of the absence of fatty hilum in central benign LNs. When PTC patients have concomitant HT, clinicians should thoroughly evaluate the central LNs, thereby decreasing the incidence of misdiagnosis and unnecessary surgery.

Water pathways through the ages: Integrated laundry wastewater treatment for pollution prevention.

Rapid urbanization and the rising global population have led to the generation of substantial volumes of laundry wastewater. Accordingly, treatment of laundry wastewater has been advocated to curb water pollution and achieve water sustainability. However, technological limitations in treating (specifically) laundry wastewater and the lack of regulations governing the levels of contaminants for such discharges have been perennial problems. This review bridges the knowledge gap by delineating the feasibility of current technologies in laundry wastewater treatment and the experiences of various countries in adopting different approaches. Besides, the feasible methods for collecting laundry wastewater are elaborated. The development of the treatment technologies is highlighted, in which the integrated-treatment processes (physicochemical, biological, and combination of both) are critically discussed based on their functions and methods. A judicious selection of the technologies not only improves the energy efficiency and quality of the treated wastewater, but also mitigates capitals and operational costs. This is projected to enhance public acceptance towards the reuse of laundry wastewater. Thus, the comprehensive assessment herein is envisioned to insightfully guide national policymakers in exploring the viability of the technologies and water-recycling projects. Future research should focus on the techno-economic aspects of the treatment processes, especially their industrial scale-up.

MicroRNA-574-5p directly targets FOXN3 to mediate thyroid cancer progression via Wnt/ß-catenin signaling pathway.

OBJECTIVE: Thyroid cancer is the most common endocrine tumor. A large number of thyroid cancer-related miRNAs have been studied and identified. However, the detailed roles of miR-574-5p in thyroid cancer remain poorly understood. This work mainly aimed to investigate the role of miR-574-5p/FOXN3 axis and its mechanism in the thyroid cancer progression. METHODS: MiR-574-5p, FOXN3, Wnt/ß-catenin pathway, and apoptosis-related markers were measured by quantitative real-time PCR (qRT-PCR) and western blotting analysis, respectively. Luciferase reporter assay was employed to validate the direct targeting of FOXN3 by miR-574-5p. MTT, flow cytometry, wound healing and transwell experiments were applied to analyze the functions of FOXN3 and miR-574-5p in thyroid cancer cells. RESULTS: Knockdown of miR-574-5p up-regulated FOXN3 expression and miR-574-5p directly targeted FOXN3 in thyroid cancer cells. Biological function experiments showed that knockdown of miR-574-5p inhibited proliferation, migration, invasion and promoted apoptosis of thyroid cancer cells. The activation of Wnt/ß-catenin pathway was suppressed by MiR-574-5p silencing. FOXN3 silencing reversed the effects of miR-574-5p inhibitor on FOXN3 level and Wnt/ß-catenin singling pathway, also reversed the effects on cell migration, proliferation, invasion and apoptosis. CONCLUSION: The miR-574-5p/FOXN3 axis is a novel molecular mechanism that promotes thyroid cancer progression, suggesting their potential for clinical therapy of thyroid cancer.

NF-κB-Activated miR-574 Promotes Multiple Malignant and Metastatic Phenotypes by Targeting BNIP3 in Thyroid Carcinoma.

Thyroid cancer is the most common endocrine malignancy, and miR-574 is significantly upregulated in thyroid cancer. However, the role and underlying mechanism of miR-574 in thyroid cancer development are poorly understood. In this study, we showed that NF-κB/p65 signaling pathway was activated and miR-574 was upregulated in thyroid cancer cells. p65 directly bound to the promoter of miR-574 and activated miR-574 transcription. Functionally, miR-574 inhibited apoptosis, promoted proliferation and migration of thyroid cancer cells, and stimulated thyroid cancer-induced tube formation of endothelial cells. On the molecular level, miR-574 inhibited the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3) by binding to 3'-UTR of BNIP3. miR-574 also downregulated the expression of apoptosis-inducing factor (AIF), while elevated the levels of MMP2, MMP9, and VEGFA. In vivo, miR-574 promoted xenograft growth, which was associated with reduced apoptosis and enhanced angiogenesis. NF-κB/miR-574 signaling presents multiple oncogenic activities on thyroid cancer development by directly regulating the BNIP3/AIF pathway. Therefore, targeting NF-κB/miR-574 signaling may reduce the aggressiveness of thyroid cancer. IMPLICATIONS: miR-574, directly regulated by NF-κB/p65, promotes tumorigenesis of thyroid cancer via inhibiting BNIP3/AIF pathway.

Inorganic phosphate-triggered release of anti-cancer arsenic trioxide from a self-delivery system: an in vitro and in vivo study.

On-demand drug delivery is becoming feasible via the design of either exogenous or endogenous stimulus-responsive drug delivery systems. Herein we report the development of gadolinium arsenite nanoparticles as a self-delivery platform to store, deliver and release arsenic trioxide (ATO, Trisenox), a clinical anti-cancer drug. Specifically, unloading of the small molecule drug is triggered by an endogenous stimulus: inorganic phosphate (Pi) in the blood, fluid, and soft or hard tissue. Kinetics in vitro demonstrated that ATO is released with high ON/OFF specificity and no leakage was observed in the silent state. The nanoparticles induced tumor cell apoptosis, and reduced cancer cell migration and invasion. Plasma pharmacokinetics verified extended retention time, but no obvious disturbance of phosphate balance. Therapeutic efficacy on a liver cancer xenograft mouse model was dramatically potentiated with reduced toxicity compared to the free drug. These results suggest a new drug delivery strategy which might be applied for ATO therapy on solid tumors.

Haplotype diversity in mitochondrial DNA hypervariable region I, II and III in northeast China Han.

Sequence polymorphism of the mitochondrial DNA (mtDNA) control region, hypervariable regions HVR I, HVR II and HVR III, from 51 unrelated China Han (Yan Bian area) were determined by PCR amplification and cycle sequencing.

Flow cytometric analysis of asialoglycoprotein receptor expression predicts hepatic functional reserve after hepatectomy.

OBJECTIVE: To validate a cheaper and more accessible flow cytometry-based method of assessing Asialoglycoprotein Receptor (ASGPR) expression for hepatic functional reserve. STUDY DESIGN: A retrospective analysis. PLACE AND DURATION OF STUDY: Beijing Ditan Hospital, Capital Medical University, Beijing, from January 2011 to October 2013. METHODOLOGY: Patients with Hepatocellular Carcinoma (HCC) undergoing major hepatectomy at Beijing Ditan Hospital, during the study period were retrospectively studied. The fraction of hepatocytes expressing ASGPR in liver tissues was assessed by flow cytometry. Patients were grouped according to the presence or absence of postoperative hepatic dysfunction. The correlation between ASGPR expression and pre-operative liver function parameters with the outcomes of hepatectomy were analyzed. RESULTS: Fewer hepatocytes from patients with postoperative hepatic dysfunction expressed ASGPR [63.3 (57.3 - 68.2)] than from patients without postoperative hepatic dysfunction [72.4 (70.6 - 76.3), p < 0.001]. Multiple logistic regression demonstrated ASGPR levels to be independently correlated with postoperative hepatic dysfunction (Odds ratio 3.34, 95% CI: 2.61-6.02, p < 0.001), and the Receiver Operating Characteristic (ROC) curve for prediction of postoperative liver dysfunction at ≤ 68.95% ASGPR+ hepatocytes achieved a sensitivity of 100% and specificity of 90.6%. The ROC curve for prediction of postoperative liver failure related death at ≤ 58.53% ASGPR+ hepatocytes achieved a sensitivity of 100% and specificity of 99%. CONCLUSION: Flow cytometric assessment of ASGPR expression may be a useful predictor of liver dysfunction following major hepatectomy for HCC in Chinese patients.

The management of retroperitoneal giant schwannomas in AIDS patients: A case report.

Retroperitoneal schwannomas are a rare disease. During the potent antiretroviral therapy era, the incidence of AIDS-defining cancers has decreased, while the incidence of non-AIDS defining cancers has increased; however, the existence of a relationship between benign or malignant schwannomas and AIDS remains unclear. Although a case of ethmoid malignant schwannoma in an AIDS patient was first reported in 1993, no additional reports of schwannomas associated with AIDS have been published since. In the current study, the case of a 30-year-old male AIDS patient with a large benign retroperitoneal schwannoma is presented. The ideal treatment of retroperitoneal schwannomas is complete excision. However, controversy exists over the necessity of negative soft tissue margins, particularly when adjacent tissue or viscera must also be removed. In the current case study, due to the immune dysfunction in AIDS patients, the incidence of malignancy could not be completely excluded prior to surgery and a significant risk of short-term relapse or malignancy following partial tumor resection was present. The patient underwent complete resection with partial superior mesenteric artery excision in order to attain negative margins, and recovered well. A follow-up was performed 1 year after the procedure and the patient was well and a CT scan demonstrated no evidence of recurrence. However, the long term efficacy of this procedure requires continued observation in this patient.