Associations of psychological status and ultrasonic characteristics of thyroid nodules in adults during the COVID-19 pandemic.

Background: The morbidity of thyroid cancer has been increasing in the last decades all over the world. In addition to the more sensitive thyroid nodule screening technology, several social and environmental factors might represent credible candidates for this increase. They include psychological stress, lifestyle-associated risk factors, nutritional deficiencies, and environmental pollutants. Foremost, psychological stress had gained high interest as a possible promoter and a modifiable risk factor for thyroid nodules in recent years. The present study was to investigate the clinical characteristics and psychological status of the population during the peak of coronavirus disease 2019 (COVID-19) and assessed the association of psychosocial determinants and the ultrasonic characteristics of thyroid nodules. Methods: In this cross-sectional study, 490 adult subjects who had received at least two doses of COVID-19 vaccine and were not infected with COVID-19, and did not know whether they had thyroid nodules, received thyroid color ultrasound examination and psychological questionnaire survey. Depression, anxiety, and stress were assessed using Depression Anxiety Stress Scales-21 (DASS-21). Sleep quality was rated using the Pittsburgh sleep quality index (PQSI). The characteristics of 243 subjects with thyroid nodules were described and recorded in detail by thyroid color ultrasound, and the correlations between anxiety, depression, sleep quality, clinical indicators, and thyroid nodule ultrasound characteristics were analyzed. Associations between psychological status (mutually adjusted predictors) and ultrasonic characteristics of thyroid nodules (outcome) were modeled using binary logistic regression controlling for sex, age, BMI, TSH, FT3, and FT4. Results: Depression was positively correlated with thyroid hypoechoic nodule (OR = 3.720, 95%CI 1.615-8.570), microcalcification of thyroid nodule (OR = 3.638, 95%CI 1.476-8.966), the aspect ratio of thyroid nodule>1 (OR = 3.860, 95%CI 1.052-14.161), the unclear boundary of thyroid nodule (OR = 4.254, 95%CI 1.359-13.312), and the irregular edge of thyroid nodule (OR = 4.134, 95%CI 1.810-9.439). Anxiety was positively correlated with microcalcification of thyroid nodules (OR = 4.319, 95%CI 1.487-11.409). Stress was positively correlated with thyroid hypoechoic nodules (OR = 4.319, 95%CI 1.487-11.409), microcalcification of thyroid nodules (OR = 2.724, 95%CI 1.038-7.151), and the irregular edge of thyroid nodules (OR = 2.478, 95%CI 1.077-5.705). Conclusion: This study demonstrates that depression, anxiety, and stress were associated with the morbidity of thyroid nodules and thyroid ultrasound characteristics. During COVID-19, people's negative emotions increased significantly compared to before. Negative emotions might be harmful to thyroid health. Therefore, during periods of high stress, strategies to prevent psychological problems should be implemented to improve thyroid health.

Identification of novel B-1 transitional progenitors by B-1 lymphocyte fate-mapping transgenic mouse model Bhlhe41 dTomato-Cre.

B-1 lymphocytes exhibit specialized roles in host defense against multiple pathogens. Despite the fact that CD19+CD93+B220lo/- B cells have been identified as B-1 progenitors, the definition for B-1 progenitors remains to be elucidated as CD19+CD93+B220+ B cells are capable to give rise to B-1 cells. Given that transcription factor Bhlhe41 is highly and preferentially expressed in B-1 cells and regulates B-1a cell development, we generated a transgenic mouse model, Bhlhe41dTomato-Cre , for fate mapping and functional analysis of B-1 cells. Bhlhe41dTomato-Cre mice efficiently traced Bhlhe41 expression, which was mainly restricted to B-1 cells in B-cell lineage. We showed an efficient and specific Cre-mediated DNA recombination in adult B-1 cells and neonatal B-1 progenitors rather than B-2 cells by flow cytometric analysis of Bhlhe41 dTomato-Cre/+ Rosa26 EYFP mice. Treatment of Bhlhe41 dTomato-Cre/+ Rosa26 iDTR mice with diphtheria toxin revealed a robust efficacy of B-1 cell depletion. Interestingly, using Bhlhe41 dTomato-Cre mice, we demonstrated that neonatal B-1 progenitors (CD19+CD93+B220lo/-) expressed Bhlhe41 and were identical to well-defined transitional B-1a progenitors (CD19+CD93+B220lo/-CD5+), which only gave rise to peritoneal B-1a cells. Moreover, we identified a novel population of neonatal splenic CD19hidTomato+B220hiCD43loCD5lo B cells, which differentiated to peritoneal B-1a and B-1b cells. Bhlhe41 deficiency impaired the balance between CD19hidTomato+B220lo/-CD5hi and CD19hidTomato+B220hiCD5lo cells. Hence, we identified neonatal CD19hidTomato+B220hiCD43loCD5lo B cells as novel transitional B-1 progenitors. Bhlhe41 dTomato-Cre/+ mouse can be used for fate mapping and functional studies of B-1 cells in host-immune responses.

The hypoxia-driven crosstalk between tumor and tumor-associated macrophages: mechanisms and clinical treatment strategies.

Given that hypoxia is a persistent physiological feature of many different solid tumors and a key driver for cancer malignancy, it is thought to be a major target in cancer treatment recently. Tumor-associated macrophages (TAMs) are the most abundant immune cells in the tumor microenvironment (TME), which have a large impact on tumor development and immunotherapy. TAMs massively accumulate within hypoxic tumor regions. TAMs and hypoxia represent a deadly combination because hypoxia has been suggested to induce a pro-tumorigenic macrophage phenotype. Hypoxia not only directly affects macrophage polarization, but it also has an indirect effect by altering the communication between tumor cells and macrophages. For example, hypoxia can influence the expression of chemokines and exosomes, both of which have profound impacts on the recipient cells. Recently, it has been demonstrated that the intricate interaction between cancer cells and TAMs in the hypoxic TME is relevant to poor prognosis and increased tumor malignancy. However, there are no comprehensive literature reviews on the molecular mechanisms underlying the hypoxia-mediated communication between tumor cells and TAMs. Therefore, this review has the aim to collect all recently available data on this topic and provide insights for developing novel therapeutic strategies for reducing the effects of hypoxia.

Bioadhesive poly(methyl vinyl ether-co-maleic anhydride)-TPGS copolymer modified PLGA/lipid hybrid nanoparticles for improving intestinal absorption of cabazitaxel.

A bioadhesive nanocarrier, PTNP, was constructed by utilizing a novel poly(methyl vinyl ether-co-maleic anhydride)- D-α-Tocopheryl polyethylene glycol succinate (PVMMA-TPGS) copolymer in the PLGA/lipid hybrid nanoparticles (PLGA NPs) for improving oral delivery of cabazitaxel (CTX). The PVMMA-TPGS was synthesized by the ring-opening polymerization of the anhydride groups with the hydroxyl groups, combining the bioadhesive property of PVMMA with P-glycoprotein (P-gp) inhibitory effect of TPGS. The CTX-loaded PTNPs (CTX-PTNPs) were prepared by an emulsification-solvent evaporation method and performed a spherical appearance with a uniform particle size of 192.2 nm. The CTX-PTNPs were surface negatively charged, and exhibited good drug loading (10.2%) and encapsulation efficiency (92.1%). A sustained drug release and high stability in simulated gastrointestinal environment were confirmed in in vitro studies. The in vitro mucin adhesion and in vivo intestinal retention experiments indicated that the PTNPs had a stronger bioadhesive effect and a notably longer intestinal retention than the control PLGA NPs, due to the interaction of PVMMA on the PTNP surface with the intestinal mucosa. Moreover, an enhanced intestinal permeability of the PTNPs was also verified in in vivo and ex vivo intestinal permeation studies, which was probably attributed to the extended retention of PTNPs in intestinal mucosa and the P-gp inhibitory effect of TPGS. As respected, in in vivo pharmacokinetic study, the Tmax and oral bioavailability of CTX were dramatically improved to 1.08 h and 28.84% by the PTNPs, respectively, obviously superior to the CTX solution and the PLGA NPs, further demonstrating the high-efficiency in oral delivery of CTX. Hence, this bioadhesive carrier is proposed to be a potential and promising strategy for increasing oral absorption of small molecule insoluble drugs.

Muscle-Mimetic Synergistic Covalent and Supramolecular Polymers: Phototriggered Formation Leads to Mechanical Performance Boost.

A thin filament stimulated by Ca2+ to combine with myosin is the structural basis to achieve filament sliding and muscle contraction. Though a large variety of artificial materials has been developed by mimicking muscle, the on-demand combination of the actin filament and myosin has never been precisely reproduced in polymeric systems. Herein, we show that both the combination process and the combined structure of actin filament and myosin have been mimicked to construct synergistic covalent and supramolecular polymers (CSPs). Specifically, photoirradiation as a stimulus induces the independently formed covalent polymers (CPs) and supramolecular polymers (SPs) to interact with each other through activated quadruple H-bonding. The resultant CSPs possess a unique network structure which not only facilitates the synergistic effect of CPs and SPs to afford stiff, strong, yet tough materials but also provides efficient pathways to dissipate energy with the damping capacity of the representative material being higher than 95%. Furthermore, muscle functions, for example, by becoming stiff during contraction and self-growth by training, are imitated well in our system via in situ phototriggered formation of CSP in the solid state. We hope that the fundamental understanding gained from this work will promote the development of synergistic CSP systems with emergent functions and applications by mimicking the principle of muscle movements.

Liposome-loaded thermo-sensitive hydrogel for stabilization of SN-38 via intratumoral injection: optimization, characterization, and antitumor activity.

Main challenges of the clinical use of 7-ethyl-10-hydroxycamptothecin (SN-38) are its facile transition between the active lactone form (SN-38 A) and the inactive carboxylate form (SN-38I) under physiological conditions and its low solubility. The purpose of this study was to develop a thermo-sensitive hydrogel system with acidic SN-38 liposomes (SN-38-Lip-Gel) for local chemotherapy to solve these problems and to evaluate its antitumor activity and tissue distribution in tumor-bearing mice. A study of structural conversion between SN-38I and SN-38 A under various pH conditions indicated that acidic solution could inhibit the conversion. Namely, a preparation with low pH was essential to stabilize lactone form of SN-38. SN-38-Lip-Gel had an appropriate gelation time (GT) at 25/37 °C. The particle size of SN-38-Lip-Gel was similar to that of SN-38-Lip. SN-38-Lip-Gel showed a slower release than SN-38-Lip in vitro. SN-38-Lip-Gel suggested pH-dependent stability, the percentage of SN-38 A remaining decreased along with the increasing pH. In vivo studies SN-38-Lip-Gel showed better antitumor efficacy and lower systemic toxicity compared with other groups at the same drug dose. In conclusion, SN-38-Lip-Gel could improve the effective use of SN-38 by stabilizing the lactone form, extending the drug release, providing a high local drug concentration, and reducing systemic toxicity.