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Stories are widely used around the world to try to teach children moral lessons. However, it is often difficult for children to figure out how lessons from stories can be applied to real-life settings. In the present research, we tested whether encouraging children to be like the protagonists helps explain the success of positive moral stories (i.e., emphasizing positive consequence of truth-telling) in promoting honesty. Participants were 3- to 6-year-old children (N = 383), and honesty was operationalized in terms of truthful admission to cheating in the Temptation Resistance Paradigm (TRP). The results showed that stories were only effective at promoting honesty among young children when they were encouraged to try being like the protagonist in positive moral stories. Theoretical implications for moral development and practical implications for moral education are discussed.

The traditional concept of "tonic food" and demand for traditional Chinese medicine make pangolins the largest population of illegally smuggled mammals in the world. Illegal hunting and trade are not only responsible for the sharp decline in pangolin populations but also provide conditions for pathogenic transmission. In 2021, we rescued 21 confiscated unhealthy Malayan pangolins, none of which survived. This study aimed to investigate the reasons for their unexpected deaths and the potential pathogens that may be transmitted during smuggling. Physical examination found that more than 80% pangolins were parasitized with A. javanense ticks. Autopsy and pathological staining analysis revealed multiple organ damage in the deceased pangolins. Pathogens nucleic acid detection of 33 tick samples showed that the positive rate of Rickettsia spp., Anaplasma spp., Ehrlichia spp. Babesia spp., and Colpodella spp. were 90.91%, 6.06%, 6.06%, 15.15% and 18.18%, respectively. Furthermore, pangolin samples were positive for Rickettsia spp. (42.86%, 9/21), Ehrlichia sp. (4.76%, 1/21), and Babesia sp. (4.76%, 1/21). This study confirmed that spotted fever triggered by Rickettsia spp. from A. javanense might accelerate the most death of confiscated pangolins, while Ehrlichia sp., and Babesia sp. infection potentially accelerating a few deaths. Of note, A. javanense ticks carrying Colpodella spp. were detected for the first time in Malayan pangolins. However, whether Colpodella spp. are pathogenic to pangolins is unknown. Further research on the diagnosis, treatment, surveillance, and elimination of ticks and tick-borne diseases in humans, livestock, and wildlife should provide insight into wildlife conservation and zoonotic disease prevention.

Parathyroid carcinoma (PC) is a rare and aggressive endocrine malignancy with limited treatment options. Current treatments such as chemotherapy and radiotherapy have demonstrated limited efficacy. Here, we report the case of a male patient who presented with symptoms including polydipsia, polyuria, and joint pain. Further examination revealed a neck lump, hypercalcemia, and hyperparathyroidism, leading to a diagnosis of PC after en bloc surgery. Seven months later, the patient developed local recurrence and lung metastases, which were resected via left lateral neck dissection and thoracoscopic wedge resection. A 422-gene panel test revealed the presence of epidermal growth factor receptor ( EGFR ) p.L858R (c. T2573G) mutation, which may sensitize the EGFR-tyrosine kinase inhibitor response, and phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha ( PIK3CA ) p.E545KV (c. G1633A) mutation. After multidisciplinary treatment discussions, the patient was treated with the multi-target tyrosine kinase inhibitor, anlotinib, resulting in survival benefits for 19 months. This case highlights the potential of targeted therapy in terms of long-term survival in patients with distant metastatic PC, as well as the importance of precision therapy guided by genome sequencing to identify potential therapeutic targets.

Abstract Background Osteoarthritis (OA), a degenerative disease with a high global prevalence, is characterized by the degradation of the extracellular matrix (ECM) and the apoptosis of chondrocytes. Ajugol, a extract derived from the herb Rehmannia glutinosa, has not yet been investigated for its potential in modulating the development of OA. Methods We employed techniques such as western blotting, immunofluorescence, immunohistochemistry, X-ray imaging, HE staining, and SO staining to provide biological evidence supporting the role of Ajugol as a potential therapeutic agent for modulating OA. Furthermore, in an in vivo experiment, intra-peritoneal injection of 50 mg/kg Ajugol effectively mitigated the progression of OA following destabilization of the medial meniscus (DMM) surgery. Results Our findings revealed that treatment with 50 μM Ajugol activated TFEB-mediated autophagy, alleviating ER stress-induced chondrocyte apoptosis and ECM degradation caused by TBHP. Furthermore, in an in vivo experiment, intra-peritoneal injection of 50 mg/kg Ajugol effectively mitigated the progression of OA following destabilization of the medial meniscus (DMM) surgery. Conclusion These results provide compelling biological evidence supporting the role of Ajugol as a potential therapeutic agent for modulating OA by activating autophagy and attenuating ER stress-induced cell death and ECM degradation. The promising in vivo results further suggest the potential of Ajugol as a treatment strategy for OA progression.

Ready-to-eat meat (RTE) products are potential to contaminate bacteria, yeasts and molds during the processing, transport, storage, and sale periods, causing food spoilage and foodborne diseases. As a new non-thermal sterilization technology, atmospheric cold plasma (ACP) is effective and green and has shown great potential in food sterilization and preservation. This paper summarizes the inactivation effects of ACP on microorganisms as well as the factors influencing the antimicrobial efficacy of ACP. The recent progress in the applications of ACP in the sterilization and preservation of RTE meat products is also reviewed in this article. Meanwhile, the effects of ACP treatments on the lipids, proteins, color parameter and sensory quality parameters of RTE meat products are also well discussed. This paper provides references for the potential application of ACP technology in the sterilization and preservation of RTE meat products.

Summary: Nuclear factor kappa B (NF-κB) is a key regulator in immune signaling and is known to exhibit a digital activation pattern. Yet the molecular basis underlying the heterogeneity in NF-κB activation at single-cell level is not entirely understood. Here, we show that NF-κB activation in single cells is largely regulated by intrinsic differences at the receptor level. Using the genome editing and time-lapse imaging, we directly characterize endogenous TNFR1 dynamics and NF-κB activation from the same single cells. Total internal reflection fluorescence (TIRF) microscopy shows that endogenous TNFR1 forms pre-ligand clusters in the resting cells. Upon tumor necrosis factor (TNF) stimulation, the diffusion coefficient of membrane TNFR1 was significantly decreased and a substantial level of TNFR1 undergoes oligomerization to form trimers and hexamers. Moreover, multi-color cell imaging reveals that both digital and graded information processing regulate NF-κB activation across different TNFR1 expression levels. Our results indicate that single-cell NF-κB activation potential strongly correlates with its TNFR1 characteristics.

Abstract Background TMVP1 is a novel tumor targeting polypeptide screened by our laboratory with a core sequence of five amino acids LARGR. It specially binds to vascular endothelial growth factor receptor-3 (VEGFR-3), which is mainly expressed on neo-lymphatic vessels in sentinel lymph node (SLN) with tumor metastasis in adults. Here, we prepared a targeted nanoprobe using TMVP1-modified nanomaterials for tumor metastasis SLN imaging. Results In this study, TMVP1-modified polymer nanomaterials were loaded with the near-infrared (NIR) fluorescent dye, indocyanine green (ICG), to prepare a molecular imaging TMVP1-ICG nanoparticles (NPs) to identify tumor metastasis in SLN at molecular level. TMVP1-ICG-NPs were successfully prepared using the nano-precipitation method. The particle diameter, morphology, drug encapsulation efficiency, UV absorption spectrum, cytotoxicity, safety, and pharmacokinetic properties were determined. The TMVP1-ICG-NPs had a diameter of approximately 130 nm and an ICG loading rate of 70%. In vitro cell experiments and in vivo mouse experiments confirmed that TMVP1-ICG-NPs have good targeting ability to tumors in situ and to SLN with tumor metastasis by binding to VEGFR-3. Effective photothermal therapy (PTT) with TMVP1-ICG-NPs was confirmed in vitro and in vivo. As expected, TMVP1-ICG-NPs improved ICG blood stability, targeted tumor metastasis to SLN, and enhanced PTT/photodynamic (PDT) therapy, without obvious cytotoxicity, making it a promising theranostic nanomedicine. Conclusion TMVP1-ICG-NPs identified SLN with tumor metastasis and were used to perform imaging-guided PTT, which makes it a promising strategy for providing real-time NIR fluorescence imaging and intraoperative PTT for patients with SLN metastasis.

The traditional concept of "tonic food" and demand for traditional Chinese medicine make pangolins the largest population of illegally smuggled mammals in the world. Illegal hunting and trade are not only responsible for the sharp decline in pangolin populations but also provide conditions for pathogenic transmission. In 2021, we rescued 21 confiscated unhealthy Malayan pangolins, none of which survived. This study aimed to investigate the reasons for their unexpected deaths and the potential pathogens that may be transmitted during smuggling. Physical examination found that more than 80% pangolins were parasitized with A. javanense ticks. Autopsy and pathological staining analysis revealed multiple organ damage in the deceased pangolins. Pathogens nucleic acid detection of 33 tick samples showed that the positive rate of Rickettsia spp., Anaplasma spp., Ehrlichia spp. Babesia spp., and Colpodella spp. were 90.91%, 6.06%, 6.06%, 15.15% and 18.18%, respectively. Furthermore, pangolin samples were positive for Rickettsia spp. (42.86%, 9/21), Ehrlichia sp. (4.76%, 1/21), and Babesia sp. (4.76%, 1/21). This study confirmed that spotted fever triggered by Rickettsia spp. from A. javanense might accelerate the most death of confiscated pangolins, while Ehrlichia sp., and Babesia sp. infection potentially accelerating a few deaths. Of note, A. javanense ticks carrying Colpodella spp. were detected for the first time in Malayan pangolins. However, whether Colpodella spp. are pathogenic to pangolins is unknown. Further research on the diagnosis, treatment, surveillance, and elimination of ticks and tick-borne diseases in humans, livestock, and wildlife should provide insight into wildlife conservation and zoonotic disease prevention. Author summary: As a globally distributed obligate bloodthirsty ectoparasite, ticks are the vector second only to mosquitoes, capable of transmitting a variety of pathogenic viruses, bacteria, and protozoa to humans, livestock, and wildlife. Illegal poaching and smuggling pose a serious threat to the survival of pangolins and are also a potential route for the spread of tick-borne diseases. The present study was conducted to investigate the reasons for the unexpected death of Malayan pangolins confiscated in 2021, as well as to explore the potential pathogens that may be transmitted during smuggling. Based on the clinical symptoms, autopsy, and molecular detection results, we speculate that the primary cause was the spotted fever triggered by Rickettsia spp. from A. javanense, which accelerated the death of smuggled pangolins. Ehrlichia sp. or Babesia sp. infection might be associated with the death of a few pangolins. Moreover, A. javanense carrying Colpodella spp. were detected for the first time in Malayan pangolins, and whether Colpodella spp. are pathogenic to pangolins awaits further study. The findings suggest that more attention should be paid to the diagnosis and treatment of tick-borne diseases in the rescue operation of pangolins and other wildlife. [ABSTRACT FROM AUTHOR]

To efficiently remove all recurrent lymph nodes (rLNs) and minimize complications, we developed a combination approach that consisted of 68Gallium prostate-specific membrane antigen (PSMA) ligand positron emission tomography (PET)/computed tomography (CT) and integrated indocyanine green (ICG)-guided salvage lymph node dissection (sLND) for rLNs after radical prostatectomy (RP). Nineteen patients were enrolled to receive such treatment. 68Ga-PSMA ligand PET/CT was used to identify rLNs, and 5 mg of ICG was injected into the space between the rectum and bladder before surgery. Fluorescent laparoscopy was used to perform sLND. While extensive LN dissection was performed at level I, another 5 mg of ICG was injected via the intravenous route to intensify the fluorescent signal, and laparoscopy was introduced to intensively target stained LNs along levels I and II, specifically around suspicious LNs, with 68Ga-PSMA ligand PET/CT. Next, both lateral peritonea were exposed longitudinally to facilitate the removal of fluorescently stained LNs at levels III and IV. In total, pathological analysis confirmed that 42 nodes were rLNs. Among 145 positive LNs stained with ICG, 24 suspicious LNs identified with 68Ga-PSMA ligand PET/CT were included. The sensitivity and specificity of 68Ga-PSMA ligand PET/CT for detecting rLNs were 42.9% and 96.6%, respectively. For ICG, the sensitivity was 92.8% and the specificity was 39.1%. At a median follow-up of 15 (interquartile range [IQR]: 6–31) months, 15 patients experienced complete biochemical remission (BR, prostate-specific antigen [PSA] 0.2 ng ml−1. Therefore, 68Ga-PSMA ligand PET/CT integrating ICG-guided sLND provides efficient sLND with few complications for patients with rLNs after RP.

Background: Cancer rehabilitation is gaining recognition in response to treatment advances, with more survivors living with functional impairments. This study aims to describe the outcomes from neuro-oncological rehabilitation within an inpatient neurorehabilitation setting, focusing on patients with malignancy. Subjects and Methods: A review of neuro-oncological admissions from 2009 to 2017 was performed comparing length of stay (LOS), changes in United Kingdom Functional Independence Measure + Functional Assessment Measure (UK FIM + FAM) scores, discharge outcome, and survival between patients with benign and malignant diagnoses. Results: One hundred and twenty patients were included (40% with malignancy). Eighteen percent required transfer back to acute setting due to cancer- or treatment-related complications. Having malignancy was associated with a higher rate of acute transfer (34% vs. 7%, x2 = 13.8, P < 0.01). LOS was not significantly different between the two groups (median difference: 5 days, 95% confidence interval [CI]: −8–18, P = 0.187). While UK FIM + FAM change was significantly lower in the malignant group, the corresponding lower UK FIM + FAM efficiency was not (mean difference: 16, 95% CI: 1–31, P = 0.043 and 0.18, −0.42–0.05, P = 0.114, respectively). The median survival in the malignant group was 3.2 months (95% CI: 2.0–8.4), with survival up to 40.4 months. Conclusion: While patient outcomes with benign and malignant diagnoses were similar, the UK FIM + FAM does not capture the full benefit of rehabilitation. Given that patients with malignancy have limited survival, quality of life measures and goal attainment scaling may be more appropriate. Effective and efficient inpatient neuro-oncological rehabilitation in malignancy is deliverable, but collaboration with both oncology and palliative care services is crucial.

Abstract Background Long non-coding RNAs (lncRNAs) are novel regulatory molecules in breast cancer development. LncRNA LUCAT1 is a potential tumor promoter in human cancers. In this study, we aimed to explore the role of LUCAT1 in human breast cancer tissues and cells. Methods A total of 31 breast cancer patients who underwent tumor resection, but without chemo- or radiotherapy or acute lung/heart/kidney diseases, provided tumor and adjacent normal tissues. Bioinformatic analysis, qRT-PCR, and luciferase reporter assay were carried out during the study. Results qRT-PCR analysis indicated that, compared with the adjacent tissues and MCF-10A normal breast epithelial cells, LUCAT1 was markedly up-regulated in the breast cancer tissues and five BC cell lines, including MDA-MB-231, MDA-MB-468, MDA-MB-435, SKBR3, and MCF-7. The knockdown of LUCAT1, through the transfection of small interfering RNA (siRNA) specific to LUCAT1, resulted in inhibition of proliferation in breast cancer cells. The expression levels of miR-181a-5p were decreased in the breast cancer tissues and five BC cell lines. Bioinformatic analysis and luciferase reporter assay suggested the interaction between miR-181a-5p and LUCAT1. In addition, the effects of LUCAT1 on promoting cell proliferation were attenuated by overexpression of miR-181a-5p through the transfection of miR-181a-5p mimic. Moreover, bioinformatics and luciferase reporter assay confirmed that miR-181a-5p targeted the 3′-UTR region of KLF6 and KLF15 mRNA, which were two tumor suppressor genes. LUCAT1/miR-181a-5p axis regulated the expression of KLF6 and KLF15 both in vitro and in vivo. Conclusions Our data indicate that LUCAT1/miR-181a-5p axis can serve as a novel therapeutic target in breast cancer.

Abstract Background Recently, the roles of long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) in human diseases have been unveiled, this research was conducted to explore the impacts of lncRNA SET-binding factor 2-antisense RNA1 (SBF2-AS1), miR-143 and resistance to ralstonia solanacearum 1 (RRS1) on breast cancer (BC) development. Methods The expression of SBF2-AS1, miR-143 and RRS1 in BC tissues, as well as in MDA-MB-231 and MCF-7 cell lines were assessed. Subsequently, the cells were transfected with miR-143 mimics or/and silenced or overexpressed SBF2-AS1 plasmids, and their negative controls. Then the proliferation, colony formation ability, cell cycle arrest, apoptosis, invasion and migration of the cells were assessed through gain- and loss-of-function experiments. Furthermore, the tumor growth, ki-67 expression and apoptosis in vivo were observed by subcutaneous tumorigenesis in nude mice. Binding relation between SBF2-AS1 and miR-143, and that between miR-143 and RRS1 were confirmed. Results SBF2-AS1 and RRS1 were amplified, while miR-143 was reduced in BC tissues and cells. Reduced SBF2-AS1 and elevated miR-143 could repress the proliferation, invasion and migration via restraining RRS1 expression. Moreover, knockdown of SBF2-AS1 up-regulated miR-143 to promote the apoptosis of BC cells by downregulating RRS1, resulting in a prohibitive effect on the tumorigenesis and progression of BC. Results of in vivo experiments indicated that the inhibited SBF2-AS1 and overexpressed miR-143 could restrict BC cell proliferation and promote apoptosis, and decelerate tumor growth in xenografts. Conclusion We have discovered in this study that down-regulated SBF2-AS1 could inhibit tumorigenesis and progression of BC by up-regulation miR-143 and repressing RRS1, which provides basic therapeutic considerations for a novel target against BC.

Endoplasmic reticulum stress (ERS) and apoptosis of nucleus pulposus (NP) cells are considered to be the main pathological factors of intervertebral disc degeneration (IDD). Fucoxanthin (FX), a marine carotenoid extracted from microalgae, has antioxidant, anti‐inflammatory, and anticancer properties. The aim of this study was to investigate the effect of FX on NP cells induced by oxidative stress and its molecular mechanism. Primary NP cells of the lumbar vertebrae of rats were extracted and tested in vitro. qRT‐PCR, western blot, immunofluorescence, and TUNEL staining were used to detect apoptosis, ERS, extracellular matrix (ECM), and Sirt1‐related pathways. In vivo experiments, the recovery of IDD rats was determined by X‐ray, hematoxylin and eosin, Safranin‐O/Fast Green, Alcian staining, and immunohistochemistry. Our study showed that oxidative stress induced ERS, apoptosis, and ECM degradation in NP cells. After the use of FX, the expression of Sirt1 was up‐regulated, the activation of PERK‐eIF2α‐ATF4‐CHOP was decreased, and apoptosis and ECM degradation were decreased. At the same time, FX improved the degree of disc degeneration in rats in vivo. Our study demonstrates the effect of FX on improving IDD in vivo and in vitro, suggesting that FX may be a potential drug for the treatment of IDD. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) represents the most commonly diagnosed malignancy among women. Long non-coding RNAs (lncRNAs) can be transferred by extracellular vesicles (EVs) to participate in BC progression. This study demonstrated that SNHG16 expression was significantly increased in BC tissues and cells. Overexpression of SNHG16 promoted the migration, invasion, and epithelial–mesenchymal transition (EMT) of BC cells. SNHG16 was carried by EVs. Bioinformatics analysis predicted that SNHG16 regulated PPAPDC1A expression by sponging miR-892b, which was confirmed by RNA-fluorescence in situ hybridization (FISH), RT-qPCR, dual-luciferase gene reporter assay, and RNA immunoprecipitation (RIP). MDA-MB-157 and HS578T cells were transfected with pcDNA3.1-SNHG16, miR-892b-mimic, or si-PPAPDC1A for functional rescue experiments in vitro, and the cells were treated with MDA-MB-231 cell-derived EVs. The results confirmed that enhanced miR-892b expression partially eliminated the increase of migration, invasion, and EMT of BC cells mediated by SNHG16 or EVs. The lung metastasis model in nude mice was established by injecting HS578T cells via tail vein. The results showed that si-SNHG16 reduced the metastatic nodules and decreased the vimentin expression. In conclusion, EVs derived from BC cells transferred SNHG16 via the miR-892b/PPAPDC1A axis, thus promoting EMT, migration, and invasion of BC.

Abstract Background Breast cancer was dangerous to women health. A growing number of evidences indicate that long non-coding RNAs (lncRNAs) have many functions in the development and progression of breast cancer and may serve as the markers of diagnosis or prognosis. BLACAT1 is one of lncRNA and the roles of it in breast cancer is not clear. In this study, it is aimed to explore the roles and molecular mechanisms of BLACAT1 in breast cancer. Results We found BLACAT1 took part in breast cancer cell aggressive phenotype. The real-time PCR result showed that BLACAT1 was up-regulated in tumor tissues compared to adjacent normal tissues. The molecular mechanism experiments demonstrated that BLACAT1 down-regulation suppressed the proliferation and metastasis of human breast cancer cells by regulating miR-150-5p targeting CCR2. The clinical studies indicated that lack of BLACAT1 was related to tumor size, metastasis. Conclusion: The present study verified the involvement of the BLACAT1 in the mediation of cell survival and metastasis through miR-150-5p targeting CCR2 in breast cancer cells.