Twist Promotes Tumor Metastasis in Basal-Like Breast Cancer by Transcriptionally Upregulating ROR1

Rationale: Twist is a key transcription factor for induction of epithelial-mesenchymal transition (EMT), which promotes cell migration, invasion, and cancer metastasis, confers cancer cells with stem cell-like characteristics, and provides therapeutic resistance. However, the functional roles and targeted genes of Twist in EMT and cancer progression remain elusive. Methods: The potential targeted genes of Twist were identified from the global transcriptomes of T47D/Twist cells by microarray analysis. EMT phenotype was detected by western blotting and immunofluorescence of marker proteins. The dual-luciferase reporter and chromatin immunoprecipitation assays were employed to observe the direct transcriptional induction of ROR1 by Twist. A lung metastasis model was used to study the pro-metastatic role of Twist and ROR1 by injecting MDA-MB-231 cells into tail vein of nude mice. Bio-informatics analysis was utilized to measure the metastasis-free survival of breast cancer patients. Results: Twist protein was proved to directly activate the transcription of ROR1 gene, a receptor of Wnt5a in non-canonical WNT signaling pathway. Silencing of ROR1 inhibited EMT process, cell migration, invasion, and cancer metastasis of basal-like breast cancer (BLBC) cells. Knockdown of ROR1 also ameliorated the pro-metastatic effect of Twist. Furthermore, analyses of clinical specimens indicated that high expression of both ROR1 and Twist tightly correlates with poor metastasis-free survival of breast cancer patients. Conclusion: ROR1 is a targeted gene of Twist. Twist/ROR1 signaling is critical for invasion and metastasis of BLBC cells

Enhancement of thermoelectric performance in n-type PbTe1−ySey by doping Cr and tuning Te:Se ratio

Lead telluride and its alloys have been extensively studied for medium temperature thermoelectric applications due to decent figure-of-merit (ZT) at temperature close to 900 K. However, little emphasis has been given to improve the ZT near room temperature. In this investigation, we report a systematic study of Cr doping in PbTe[subscript 1−y]Se[subscript y] with y=0, 0.25, 0.5, 0.75, 0.85, and 1. We found the peak ZT temperature increased with increasing concentration of Se. The highest ZT of ~0.6 at room temperature in Te-rich Cr[subscript 0.015]Pb[subscript 0.985]Te[subscript 0.75]Se[subscript 0.25] was obtained due to a lowered thermal conductivity and enhanced power factor resulted from high Seebeck coefficient of about −220 µV K[superscript −1] and high Hall mobility ~1120 cm[superscript 2] V[superscript −1] s[superscript −1] at room temperature. A room temperature ZT of ~0.5 and peak ZT of ~1 at about 573–673 K is shown by Se-rich sample Cr[subscript 0.01]Pb[subscript 0.99]Te[subscript 0.25]Se[subscript 0.75]. This improvement of the room temperature ZT improved the average ZT over a wide temperature range and could potentially lead to a single leg efficiency of thermoelectric conversion for Te-rich Cr[subscript 0.015]Pb[subscript 0.985]Te[subscript 0.75]Se[subscript 0.25] up to ~11% and Se-rich Cr[subscript 0.01]Pb[subscript 0.99]Te[subscript 0.25]Se[subscript 0.75] up to ~13% with cold side and hot side temperature at 300 K and 873 K, respectively, if matched with appropriate p-type legs

Selenium‐doping induced two antiferromagnetic transitions in thiospinel compounds CuCo₂S_(4‐x)Se_x (0 ≤ x ≤ 0.8)

A series of copper thiospinels compounds, CuCo₂S_(4‐x)Se_x (x = 0, 0.2, 0.4, 0.6, 0.8), have been successfully synthesized by solid state reaction and their structure and magnetic properties have been studied. The Rietveld refinements of X‐Ray diffractions indicate that both the lattice constants and the nearest neighbor Cu‐Cu distances increase with increasing selenium doping. A weakly antiferromagnetic transition occurring at about 4 K is observed in CuCo₂S₄. Two antiferromagnetic transitions at about 3.5 K and 6 K are observed in selenium‐doped samples, which suggest that the exchange couplings associated with Cu‐S(Se)‐Cu and Cu‐Se(S)‐Cu, respectively, are responsible for the two antiferromagnetic transitions. Detailed analysis of the experimental results further indicate that the nearest‐neighbor molecular field coefficient is comparable to the next‐neighbor molecular field coefficient. We propose a reasonable model to explain this phenomenon

Clinical and genetic characteristics of adult cerebral adrenoleukodystrophy

Objective·To summarize and analyze the clinical and genetic characteristics of adult cerebral adrenoleukodystrophy(ACALD ).Methods·The data of eight patients with ACALD who attended the Shanghai Sixth People′s Hospital, Shanghai Jiao Tong University School of Medicine from June 2018 to September 2022 were collected and comprehensively analyzed. Clinical data included age at onset, duration of disease, family history, present history and physical examination. Imaging examinations included magnetic resonance imaging (MRI) of the cranial, cervical spine and thoracic spine. Laboratory tests included serum very-long-chain fatty acids (VLCFA), adrenal cortical function and genetic test. Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (Moca) were used to assess patients′ cognitive function.Results·A total of 8 male patients with ACALD were included in this study. Ageat onset ranged from 23 to 40 years old with an average age of (32.75±5.80) years, and the disease duration ranged from 4 to 59 months. Patients′ first symptoms were highly variable. Three patients showed memory loss and cognitive dysfunction, two showed irritability and personality change, one showed mental and behavioral abnormalities, one showed dysarthria and ataxia, and one showed persistent dizziness, occipital numbness and insomnia. All the patients had multiple white matter demyelination lesions, and white matter demyelination in parietal occipital lobe and posterior corpus callosum was the most common. Enhancement MRI showed patchy Gd-enhancement of partial lesions in three cases. In two patients, magnetic resonance spectroscopy showed that choline (Cho) peak increased and N-acetyl-aspartate (NAA) peak decreased. Serum VLCFA levels of C26, C24/C22 and C26/C22 were elevated in six patients who underwent serum VLCFA examination. Seven patients underwent adrenal cortical function testing, of which six experienced adrenal cortical dysfunction. Six patients were cognitively impaired, four of whom had decreased MMSE and MoCA scores, and two of whom were unable to cooperate with the assessment due to severe cognitive impairment. Eight different ABCD1 gene mutations were identified, among which c.1750delC (p.H584Tfs*52) and c.160_170delACGCAGGAGGC (p.T54Lfs*137) were novel mutations.Conclusion·The initial symptoms of ACALD vary, among which memory loss and cognitive dysfunction are the most common. White matter demyelination lesions in the parietal and corpus callosum pressure are the most common, and imaging abnormalities precede neurological symptoms. The clinical features of the disease are hair thinning and skin pigmentation, and the biochemical features are elevated serum VLCFA and adrenal insufficiency. Missense mutations are more common in the ABCD1 gene, and exons 1 and 6 are the hot mutant exons in Chinese

Targeting Inhibition of Accumulation and Function of Myeloid-Derived Suppressor Cells by Artemisinin via PI3K/AKT, mTOR, and MAPK Pathways Enhances Anti-PD-L1 Immunotherapy in Melanoma and Liver Tumors

Despite the remarkable success and efficacy of immune checkpoint blockade (ICB) therapy such as anti-PD-L1 antibody in treating cancers, myeloid-derived suppressor cells (MDSCs) that lead to the formation of the protumor immunosuppressive microenvironment are one of the major contributors to ICB resistance. Therefore, inhibition of MDSC accumulation and function is critical for further enhancing the therapeutic efficacy of anti-PD-L1 antibody in a majority of cancer patients. Artemisinin (ART), the most effective antimalarial drug with tumoricidal and immunoregulatory activities, is a potential option for cancer treatment. Although ART is reported to reduce MDSC levels in 4T1 breast tumor model and improve the therapeutic efficacy of anti-PD-L1 antibody in T cell lymphoma-bearing mice, how ART influences MDSC accumulation, function, and molecular pathways as well as MDSC-mediated anti-PD-L1 resistance in melanoma or liver tumors remains unknown. Here, we reported that ART blocks the accumulation and function of MDSCs by polarizing M2-like tumor-promoting phenotype towards M1-like antitumor one. This switch is regulated via PI3K/AKT, mTOR, and MAPK signaling pathways. Targeting MDSCs by ART could significantly reduce tumor growth in various mouse models. More importantly, the ART therapy remarkably enhanced the efficacy of anti-PD-L1 immunotherapy in tumor-bearing mice through promoting antitumor T cell infiltration and proliferation. These findings indicate that ART controls the functional polarization of MDSCs and targeting MDSCs by ART provides a novel therapeutic strategy to enhance anti-PD-L1 cancer immunotherapy

Evidences for pressure-induced two-phase superconductivity and mixed structures of NiTe₂ and NiTe in type-II Dirac semimetal NiTe_(2-x) (x = 0.38 ± 0.09) single crystals

Bulk NiTe₂ is a type-II Dirac semimetal with non-trivial Berry phases associated with the Dirac fermions. Theory suggests that monolayer NiTe₂ is a two-gap superconductor, whereas experimental investigation of bulk NiTe_(1.98) for pressures (P) up to 71.2 GPa do not reveal any superconductivity. Here we report experimental evidences for pressure-induced two-phase superconductivity as well as mixed structures of NiTe₂ and NiTe in Te-deficient NiTe_(2-x) (x = 0.38±0.09) single crystals. Hole-dominant multi-band superconductivity with the P3M1 hexagonal-symmetry structure of NiTe₂ appears at P ≥ 0.5 GPa, whereas electron-dominant single-band superconductivity with the P2/m monoclinic-symmetry structure of NiTe emerges at 14.5 GPa < P < 18.4 GPa. The coexistence of hexagonal and monoclinic structures and two-phase superconductivity is accompanied by a zero Hall coefficient up to ∼ 40 GPa, and the second superconducting phase prevails above 40 GPa, reaching a maximum T_c = 7.8 K and persisting up to 52.8 GPa. Our findings suggest the critical role of Te-vacancies in the occurrence of superconductivity and potentially nontrivial topological properties in NiTe_(2-x)

Source and Evolution of Subduction–Related Hot Springs Discharged in Tengchong Geothermal Field, Southwest China: Constrained by Stable H, O, and Mg Isotopes

The hydrothermal system plays a crucial role in material and energy cycling between the lithosphere and hydrosphere. In general, seafloor hydrothermal systems are one of important Mg sinks, but the situation may not be the same as it is in terrestrial hydrothermal systems. In addition, the behavior of Mg isotopes during hydrothermal circulation is still unclear. Thus, in this study, we determined the Mg isotopic compositions of the hydrothermal fluids discharged in the Tengchong region to understand better the fate of Mg in the continental hydrothermal system. The δ2H and δ18O values of the Tengchong hydrothermal fluids indicate that the recharge water sources are primary from meteoric water and influenced by the evaporation process. In contrast, the subduction–related volcanic water input is limited, except in for the Rehai area. The Mg in most of the samples is contributed by percolated meteoric water. The measured δ26Mg values range from –0.969 to 0.173‰, which are enriched in light Mg compared to the volcanic rocks of Tengchong. Combined with the precipitation dissolution of carbonate, we calculated the δ26Mg value for the endmember fluid before precipitation, which shows that the process of carbonate precipitation changes the Mg isotope of the fluid, substantially. The Shiqiang (SQ) vent is unique among all of the samples, characterized by an extremely a high δ26Mg value and Mg concentration, and it is estimated that it could have been mixed with an upper crustal material. This also reveals the diversity of the hydrothermal fluid material sources in the subduction zone

Prognostic factors in transnasal endoscopic surgery for paediatric patients with ossifying fibroma of the paranasal sinuses and skull base

Abstract Background Ossifying fibroma of the paranasal sinuses and skull base in paediatric patients is difficult to operate and can recur easily after surgery. This study aimed to analyse factors associated with recurrence after transnasal endoscopic resection of ossifying fibroma in paediatric patients. Methods This retrospective observational study included 34 patients under 17 years of age who underwent transnasal endoscopic resection of ossifying fibroma of the paranasal sinuses and skull base from 2005 to 2021 at a single tertiary medical centre. Clinical indicators such as age; surgical history; pathological type; intraoperative bleeding; and orbit, anterior skull base, sphenoid bone, sella turcica, clivus, or frontal sinus involvement were subjected to univariate analysis using the χ2 test, to investigate whether any of these factors affected recurrence. Results All 34 patients underwent transnasal endoscopic resection. The follow-up period was 6–120 months (mean: 48.0 months). Five patients experienced local recurrence during the follow-up period (14.7%). Results of χ2 tests indicated that a history of previous surgery, the amount of intraoperative bleeding, and sphenoid and/or sella turcica and clivus involvement were significantly associated with recurrence (P  0.05). Conclusions The increased risk of recurrence after transnasal endoscopic resection of nasal–skull base ossifying fibroma should be considered during endoscopic surgery in paediatric patients with a history of previous surgery, intraoperative bleeding tendency, and sphenoid and/or sella turcica and clivus involvement. These patients require careful postoperative follow-up

Effectiveness of interventions to reduce aerosol generation in dental environments: A systematic review

Certain dental procedures produce high levels of aerosols containing pathogenic microorganisms, posing a risk for the transmission of infections in dental settings. This study aimed to assess the effectiveness of various aerosol mitigation interventions during clinical dental procedures in real-world environments. A systematic literature search was conducted in PubMed/MEDLINE, Scopus, Web of Science, and Embase for English studies up to March 2023 according to the PRISMA guidelines. Only peer-reviewed controlled clinical trials (CCT) or randomized controlled trials (RCT) studies involving human subjects were included. The risk of bias of selected researches were evaluated by two independent authors using the Cochrane Collaboration tool. The literature search yielded 3491 articles, of which 42 studies met the inclusion criteria and were included in this study. Most studies evaluated bacterial contamination in bio-aerosols, while the viral and fungal contamination was assessed in only three studies. Overall, various approaches have been applied in reducing aerosol contamination in clinical scenarios, including high-volume evacuators (HVE), mouse rinses and rubber dams, air cleaning systems, and high-efficiency particulate air (HEPA) filters. The available evidence suggests that various aerosol mitigation strategies could be implemented to decrease the risk of cross-infection during clinical dental procedures in real-world environments. However, further clinical trials are necessary to establish statistical validity in measuring aerosol contamination and mitigation, as well as to evaluate the risk of infection transmission for viral and fungal contamination