1,4‐Diazabicyclo2.2.2octane (dabco) and its derivatives have been extensively utilized as building units of excellent molecular ferroelectrics for decades. However, the homochiral dabco‐based ...ferroelectric remains a blank. Herein, by adding a methyl (Me) group accompanied by the introduction of homochirality to the H2dabco2+ in the non‐ferroelectric H2dabcoTFSA2 (TFSA=bis(trifluoromethylsulfonyl)ammonium), we successfully designed enantiomeric ferroelectrics R and S‐2‐Me‐H2dabcoTFSA2. The two enantiomers show two sequential phase transitions with transition temperature (Tc) as high as 405.8 K and 415.8 K, which is outstanding in both dabco‐based ferroelectrics and homochiral ferroelectrics. To our knowledge, R and S‐2‐Me‐H2dabcoTFSA2 are the first examples of dabco‐based homochiral ferroelectrics. This finding opens an avenue to construct dabco‐based homochiral ferroelectrics and will inspire the exploration of more eminent enantiomeric molecular ferroelectrics.
The first examples of homochiral dabco‐based (dabco=1,4‐diazabicyclo2.2.2octane) ferroelectrics, R‐ and S‐2‐Me‐H2dabcoTFSA2 (TFSA=bis(trifluoromethylsulfonyl)ammonium), were designed from the non‐ferroelectric H2dabcoTFSA2. They show two phase transitions with a transition temperature (Tc) up to 405.8 K and 415.8 K, higher than the Tc of most dabco‐based or homochiral ferroelectrics.
The laurel family within the Magnoliids has attracted attentions owing to its scents, variable inflorescences, and controversial phylogenetic position. Here, we present a chromosome-level assembly of ...the Litsea cubeba genome, together with low-coverage genomic and transcriptomic data for many other Lauraceae. Phylogenomic analyses show phylogenetic discordance at the position of Magnoliids, suggesting incomplete lineage sorting during the divergence of monocots, eudicots, and Magnoliids. An ancient whole-genome duplication (WGD) event occurred just before the divergence of Laurales and Magnoliales; subsequently, independent WGDs occurred almost simultaneously in the three Lauralean lineages. The phylogenetic relationships within Lauraceae correspond to the divergence of inflorescences, as evidenced by the phylogeny of FUWA, a conserved gene involved in determining panicle architecture in Lauraceae. Monoterpene synthases responsible for production of specific volatile compounds in Lauraceae are functionally verified. Our work sheds light on the evolution of the Lauraceae, the genetic basis for floral evolution and specific scents.
A high transition temperature (Tc) is essential for the practical application of ferroelectrics as electronic devices under extreme thermal conditions in the aerospace, automotive, and energy ...industries. In recent decades, the isotope effect and strain engineering are found to effectively modulate Tc; however, these strategies are limited to certain systems. Developing simple, universal, and practical methods to improve Tc has become an imminent challenge for expanding the applications of ferroelectrics. Here, by adopting a molecular design strategy involving H/F substitution on an organic–inorganic hybrid perovskite (1‐azabicyclo2.2.1heptane)CdCl3 at a Tc of 190 K, the successful synthesis of a multiaxial, ferroelectric hybrid perovskite (4‐fluoro‐1‐azabicyclo2.2.1heptane)CdCl3 is reported, which demonstrates a large spontaneous polarization of 11.2 µC cm−2 (greater than that of polyvinylidene difluoride) and a Tc of 419 K (greater than that of BaTiO3). This temperature enhancement (229 K) is the largest reported for molecular ferroelectrics, far exceeding the reported enhancements induced by the isotope effect and other techniques. This pioneering technique provides an effective and universal method for improving Tc in ferroelectrics and represents an important step toward the development of high‐performance ferroelectric technology.
From (1‐azabicyclo2.2.1heptane)CdCl3, a molecular design strategy of H/F substitution is applied to synthesize a multiaxial organic–inorganic hybrid perovskite ferroelectric (4‐fluoro‐1‐azabicyclo2.2.1heptane)CdCl3. The phase transition temperature is successfully increased from 190 to 419 K, which is a record enhancement of 229 K for molecular ferroelectrics, significantly outperforming those induced by the isotope effect and other techniques.
Overexpression of Twist, a highly conserved basic helix-loop-helix transcription factor, is associated with epithelial-mesenchymal transition (EMT) and predicts poor prognosis in various kinds of ...cancers, including breast cancer. In order to further clarify Twist's role in breast cancer, we detected Twist expression in breast cancer tissues by immunohistochemistry. Twist expression was observed in 54% (220/408) of breast cancer patients and was positively associated with tumor size, Ki67, VEGF-C and HER2 expression. Conversely, Twist was negatively associated with estrogen receptor (ER), progesterone receptor (PgR) and E-cadherin expression. Patients with Twist expression had a poorer prognosis for 30-month disease free survival (DFS) (82.9%) than patients with negative Twist (92.3%). Overexpression of Twist led to dramatic changes in cellular morphology, proliferation, migratory/invasive capability, and expression of EMT-related biomarkers in breast cancer cells. Moreover, we show that Twist serves as a driver of tumorigenesis, as well as an inducer of EMT, at least in part, through activation of the Akt and extracellular signal-regulated protein kinase (ERK) pathways which are critical for Twist-mediated EMT. Our results demonstrate that Twist expression is an important prognostic factor in breast cancer patients.
The use of indirect calorimetry (IC) is increasing due to its precision in resting energy expenditure (REE) measurement in critically ill patients. Thus, we aimed to evaluate the clinical outcomes of ...an IC-guided nutrition therapy compared to predictive equations strategy in such a patient population.
We searched PubMed, EMBASE, and Cochrane library databases up to October 25, 2020. Randomized controlled trials (RCTs) were included if they focused on energy delivery guided by either IC or predictive equations in critically ill adults. We used the Cochrane risk-of-bias tool to assess the quality of the included studies. Short-term mortality was the primary outcome. The meta-analysis was performed with the fixed-effect model or random-effect model according to the heterogeneity.
Eight RCTs with 991 adults met the inclusion criteria. The overall quality of the included studies was moderate. Significantly higher mean energy delivered per day was observed in the IC group, as well as percent delivered energy over REE targets, than the control group. IC-guided energy delivery significantly reduced short-term mortality compared with the control group (risk ratio = 0.77; 95% CI 0.60 to 0.98; I
= 3%, P = 0.03). IC-guided strategy did not significantly prolong the duration of mechanical ventilation (mean difference MD = 0.61 days; 95% CI - 1.08 to 2.29; P = 0.48), length of stay in ICU (MD = 0.32 days; 95% CI - 2.51 to 3.16; P = 0.82) and hospital (MD = 0.30 days; 95% CI - 3.23 to 3.83; P = 0.87). Additionally, adverse events were similar between the two groups.
This meta-analysis indicates that IC-guided energy delivery significantly reduces short-term mortality in critically ill patients. This finding encourages the use of IC-guided energy delivery during critical nutrition support. But more high-quality studies are still needed to confirm these findings.
Berberine (BBR) has been confirmed to have multiple bioactivities in clinic, such as cholesterol-lowering, anti-diabetes, cardiovascular protection and anti- inflammation. However, BBR's plasma level ...is very low; it cannot explain its pharmacological effects in patients. We consider that the in vivo distribution of BBR as well as of its bioactive metabolites might provide part of the explanation for this question. In this study, liquid chromatography coupled to ion trap time-of-flight mass spectrometry (LC/MS(n)-IT-TOF) as well as liquid chromatography that coupled with tandem mass spectrometry (LC-MS/MS) was used for the study of tissue distribution and pharmacokinetics of BBR in rats after oral administration (200 mg/kg). The results indicated that BBR was quickly distributed in the liver, kidneys, muscle, lungs, brain, heart, pancreas and fat in a descending order of its amount. The pharmacokinetic profile indicated that BBR's level in most of studied tissues was higher (or much higher) than that in plasma 4 h after administration. BBR remained relatively stable in the tissues like liver, heart, brain, muscle, pancreas etc. Organ distribution of BBR's metabolites was also investigated paralleled with that of BBR. Thalifendine (M1), berberrubine (M2) and jatrorrhizine (M4), which the metabolites with moderate bioactivity, were easily detected in organs like the liver and kidney. For instance, M1, M2 and M4 were the major metabolites in the liver, among which the percentage of M2 was up to 65.1%; the level of AUC (0-t) (area under the concentration-time curve) for BBR or the metabolites in the liver was 10-fold or 30-fold higher than that in plasma, respectively. In summary, the organ concentration of BBR (as well as its bioactive metabolites) was higher than its concentration in the blood after oral administration. It might explain BBR's pharmacological effects on human diseases in clinic.
Notch receptors (Notch1-4) play critical roles in tumorigenesis and metastasis of malignant tumors, including breast cancer. Although abnormal Notch activation is related to various tumors, the ...importance of single receptors and their mechanism of activation in distinct breast cancer subtypes are still unclear. Previous studies by our group demonstrated that Notch3 may inhibit the emergence and progression of breast cancer. PTEN is a potent tumor suppressor, and its loss of function is sufficient to promote the occurrence and progression of tumors. Intriguingly, numerous studies have revealed that Notch1 is involved in the regulation of PTEN through its binding to CBF-1, a Notch transcription factor, and the PTEN promoter. In this study, we found that Notch3 and PTEN levels correlated with the luminal phenotype in breast cancer cell lines. Furthermore, we demonstrated that Notch3 transactivated PTEN by binding CSL-binding elements in the PTEN promoter and, at least in part, inhibiting the PTEN downstream AKT-mTOR pathway. Notably, Notch3 knockdown downregulated PTEN and promoted cell proliferation and tumorigenesis. In contrast, overexpression of the Notch3 intracellular domain upregulated PTEN and inhibited cell proliferation and tumorigenesis in vitro and in vivo. Moreover, inhibition or overexpression of PTEN partially reversed the promotion or inhibition of cell proliferation induced by Notch3 alterations. In general, Notch3 expression positively correlated with elevated expression of PTEN, ER, lower Ki-67 index, and incidence of involved node status and predicted better recurrence-free survival in breast cancer patients. Therefore, our findings demonstrate that Notch3 inhibits breast cancer proliferation and suppresses tumorigenesis by transactivating PTEN expression.
For a century ferroelectricity has attracted widespread interest from science and industry. Inorganic ferroelectric ceramics have dominated multibillion dollar industries of electronic ceramics, ...ranging from nonvolatile memories to piezoelectric sonar or ultrasonic transducers, whose polarization can be reoriented in multiple directions so that they can be used in the ceramic and thin-film forms. However, the realization of macroscopic ferroelectricity in the polycrystalline form is challenging for molecular ferroelectrics. In pursuit of low-cost, biocompatible, and mechanically flexible alternatives, the development of multiaxial molecular ferroelectrics is imminent. Here, from quinuclidinium perrhenate, we applied fluorine substitution to successfully design a multiaxial molecular ferroelectric, 3-fluoroquinuclidinium perrhenate (3-F-QReO4), whose macroscopic ferroelectricity can be realized in both powder compaction and thin-film forms. The fluorination effect not only increases the intrinsic polarization but also reduces the coercive field strength. More importantly, it is also, as far as we know, the softest of all known molecular ferroelectrics, whose low Vickers hardness of 10.5 HV is comparable with that in poly(vinylidene difluoride) (PVDF) but almost 2 orders of magnitude lower than that in BaTiO3. These attributes make it an ideal candidate for flexible and wearable devices and biomechanical applications.
More and more evidence indicates that circular RNAs (circRNAs) have important roles in several diseases, especially in cancers. However, their involvement remains to be investigated in breast cancer. ...Through screening circRNA profile, we identified 235 differentially expressed circRNAs in breast cancer. Subsequently, we explored the clinical significance of two circTADA2As in a large cohort of triple-negative breast cancer (TNBC), and performed functional analysis of circTADA2A-E6 in vitro and in vivo to support clinical findings. Finally, we evaluated the effect of circTADA2A-E6 on miR-203a-3p and its target gene SOCS3. We detected two circRNAs, circTADA2A-E6 and circTADA2A-E5/E6, which were among the top five differentially expressed circRNAs in breast cancer. They were consistently and significantly decreased in a large cohort of breast cancer patients, and their downregulation was associated with poor patient survival for TNBC. Especially, circTADA2A-E6 suppressed in vitro cell proliferation, migration, invasion, and clonogenicity and possessed tumor-suppressor capability. circTADA2A-E6 preferentially acted as a miR-203a-3p sponge to restore the expression of miRNA target gene SOCS3, resulting in a less aggressive oncogenic phenotype. circTADA2As as promising prognostic biomarkers in TNBC patients, and therapeutic targeting of circTADA2As/miRNA/mRNA network may be a potential strategy for the treatment of breast cancer.
Near‐infrared (NIR) fluorescence imaging is an emerging noninvasive imaging modality, with unique advantages in guiding tumor resection surgery, thanks to its high sensitivity and instantaneity. In ...the past decade, studies on the conventional NIR window (NIR‐I, 750–900 nm) have gradually focused on the second NIR window (NIR‐II, 1000–1700 nm). With its reduced light scattering, photon absorption, and auto‐fluorescence qualities, NIR‐II fluorescence imaging significantly improves penetration depths and signal‐to‐noise ratios in bio‐imaging. Recently, several studies have applied NIR‐II imaging to navigating cancer surgery, including localizing cancers, assessing surgical margins, tracing lymph nodes, and mapping important anatomical structures. These studies have exemplified the significant prospects of this new approach. In this review, several NIR‐II fluorescence agents and some of the complex applications for guiding cancer surgeries are summarized. Future prospects and the challenges of clinical translation are also discussed.
Compared with traditional near‐infrared (NIR‐I) fluorescence imaging, NIR‐II imaging modality can significantly improve imaging penetration depth, spatial resolution, and inadequate signal‐to‐noise ratios. A variety of NIR‐II luminescent materials and imaging systems are developed, and widely applied to guide the surgery for malignancies in preclinical stage. Also, preliminary clinical translation is achieved, showing promising application prospects.
PDF
