To enhance the sensitivity of graphene aerogel‐based piezoresistive sensors by weakening their compressive strength while keeping their elasticity, lightweight and lamellar graphene aerogels (LGAs) ...with high elasticity and satisfactory electrical conductance networks are fabricated by bidirectional‐freezing of aqueous suspensions of graphene oxide in the presence of small amounts of organic solvents, followed by lyophilizing and thermal annealing. Because of the lamellar structure of the LGA, its compressive strength along the direction perpendicular to the lamellar surface is much lower than those of both isotropic and unidirectionally aligned graphene aerogels with similar apparent densities, leading to an ultrasensitive LGA‐based piezoresistive sensor with a high sensitivity of −3.69 kPa−1 and a low detection limit of 0.15 Pa. The ultrahigh sensitivity and low detection limit of LGA‐based piezoresistive sensor contribute to detecting subtle pressure at room temperature and in liquid nitrogen with ability to detect dynamic force frequency and sound vibration. Besides, thanks to the fewer junction points between the graphene lamellae, LGAs slices can be integrated as a wide‐range and sensitive bending sensor, which can detect arbitrary bending angles from 0° to 180° with a low detection limit of 0.29°, and is efficient in detecting biosignals of wrist pulse and finger bending.
Soft yet elastic lamellar graphene aerogels are fabricated by bidirectional‐freezing graphene oxide suspension with the addition of ethanol, followed by freeze‐drying and thermal annealing. An aerogel‐derived piezoresistive sensor exhibits both a high sensitivity of −3.69 kPa−1 and a low detection limit of 0.15 Pa, while the aerogel‐based bending sensor shows a wide detecting range and a low detection limit of 0.29°.
Chiral perovskites have emerged as a significant class of materials showing promising optoelectronic and spintronic applications. Reports of chiral perovskite ferroelectrics, however, have been ...scarce. In this work, we have successfully synthesized homochiral lead–iodide perovskite ferroelectrics (R)‐N‐(1‐phenylethyl)ethane‐1,2‐diaminiumPbI4 and (S)‐N‐(1‐phenylethyl)ethane‐1,2‐diaminiumPbI4 by introducing a methyl group into the organic cation of the parent (N‐benzylethane‐1,2‐diaminium)PbI4. Vibrational circular dichroism spectra identify the chiral mirroring relationship. They both undergo 222F2‐type paraelectric–ferroelectric behavior at around 378 K coupled with clear ferroelastic domain “ON/OFF” switching. Besides, they exhibit an evident thermochromism with color change from orange–yellow to orange–red. To our knowledge, the discovery of integrated ferroelectricity, ferroelasticity, and reversible thermochromism in chiral perovskites is unprecedented.
2D homochiral lead‐iodide perovskites were constructed by the introduction of a chiral center. The perovskites exhibit coexisting ferroelectricity, ferroelasticity, and reversible thermochromism, offering great application prospects for next‐generation smart devices.
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.
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.
Renal tubulointerstitial fibrosis was a crucial pathological feature of diabetic nephropathy (DN), and renal tubular injury might associate with abnormal mitophagy. In this study, we investigated the ...effects and molecular mechanisms of AMPK agonist metformin on mitophagy and cellular injury in renal tubular cell under diabetic condition. The high fat diet (HFD) and streptozotocin (STZ)-induced type 2 diabetic mice model and HK-2 cells were used in this study. Metformin was administered in the drinking water (200 mg/kg/d) for 24 weeks. Renal tubulointerstitial lesions, oxidative stress and some indicators of mitophagy (e.g., LC3II, Pink1, and Parkin) were examined both in renal tissue and HK-2 cells. Additionally, compound C (an AMPK inhibitor) and Pink1 siRNA were applied to explore the molecular regulation mechanism of metformin on mitophagy. We found that the expression of p-AMPK, Pink1, Parkin, LC3II, and Atg5 in renal tissue of diabetic mice was decreased obviously. Metformin reduced the levels of serum creatinine, urine protein, and attenuated renal oxidative injury and fibrosis in HFD/STZ induced diabetic mice. In addition, Metformin reversed mitophagy dysfunction and the over-expression of NLRP3. In vitro pretreatment of HK-2 cells with AMPK inhibitor compound C or Pink1 siRNA negated the beneficial effects of metformin. Furthermore, we noted that metformin activated p-AMPK and promoted the translocation of Pink1 from the cytoplasm to mitochondria, then promoted the occurrence of mitophagy in HK-2 cells under HG/HFA ambience. Our results suggested for the first time that AMPK agonist metformin ameliorated renal oxidative stress and tubulointerstitial fibrosis in HFD/STZ-induced diabetic mice via activating mitophagy through a p-AMPK-Pink1-Parkin pathway.
While the life expectancy of cancer survivors has substantially improved over time in the United States, the extent to which cancer patients are cured is not known. Population‐level cure patterns are ...important indicators to quantify cancer survivorships. This population‐based cohort study included 8978,721 cancer patients registered in the Surveillance, Epidemiology and End Results (SEER) databases between 1975 and 2018. The primary outcome was cure fractions. Five‐year cure probability, time to cure and median survival time of uncured cases were also assessed. All four measures were calculated using flexible parametric models, according to 46 cancer sites, three summary stages, individual age and calendar year at diagnosis. In 2018, cure fractions ranged from 2.7% for distant liver cancer to 100.0% for localized/regional prostate cancer. Localized cancer had the highest cure fraction, followed by regional cancer and distant cancer. Except for localized breast cancer, older patients generally had lower cure fractions. There were 38 cancer site and stage combinations (31.2%) that achieved 95% of cure within 5 years. Median survival time of the uncured cases ranged from 0.3 years for distant liver cancer to 10.9 years for localized urinary bladder cancer. A total of 117 cancer site and stage combinations (93.6%) had increased cure fraction over time. A considerable proportion of cancer patients were cured at the population‐level, and the cure patterns varied substantially across cancer site, stage and age at diagnosis. Increases in cure fractions over time likely reflected advances in cancer treatment and early detection.
What's new?
While the life expectancy of cancer survivors has substantially improved in the United States, the extent to which cancer patients are cured is not known. Measuring cure at the population level offers a comprehensive picture of the patterns and disparities in the lifelong outcomes of cancer patients. The cure fractions quantified in this study using population‐based data from the SEER program between 1975 and 2018 for 46 cancer sites in the United States suggest that a considerable proportion of cancer patients were cured at the population level. The cure patterns varied substantially across cancer site, stage, and age at diagnosis.
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.
Epidemiological studies suggest that chronic periodontitis (CP) is closely associated with the incidence and progression of cognitive impairment. The present study investigated the causal ...relationship between CP and cognitive decline and the underlying mechanism in mice. Long-term ligature around the left second maxillary molar tooth was used to induce CP in mice. Severe alveolar bone loss and inflammatory changes were observed in gingival tissues, accompanied by progressive cognitive deficits during a 12-month period. We also observed cerebral neuronal and synaptic injury and glial activation in this mouse model of CP. Furthermore, CP mice exhibited significant dysbiosis of the oral and gut microbiota, disruption of the intestinal barrier and blood-brain barrier, increases in the serum contents of proinflammatory cytokines and lipopolysaccharide (LPS), and increases in brain LPS levels, Toll-like receptor 4 (TLR4) expression, nuclear factor-κB (NF-κB) nuclear translocation and proinflammatory cytokine mRNA levels. These results indicate that CP may directly induce progressive cognitive decline and its mechanism is probably related to microbiota-gut-brain axis disorders, LPS/TLR4/NF-κB signaling activation and neuroinflammatory responses in mice. Therefore, the microbiota-gut-brain axis may provide the potential strategy for the prevention and treatment of CP-associated cognitive impairment.
•Chronic periodontitis (CP) mice displayed progressive cognitive deficits.•Murine CP aggravated neuronal injury and neuroinflammation.•Murine CP caused the oral and gut microbiota dysbiosis.•Murine CP induced intestinal barrier damage and inflammation.•Murine CP injured blood-brain barrier and activated TLR4 pathway in the brain.
Our study measures the impact of diagnosing cancers early before they metastasise on reducing the burden of cancer death. A cohort of 716 501 people aged 15 to 89 years diagnosed with a solid cancer ...in New South Wales, Australia, during 1985 to 2014 were followed‐up to December 2015. Crude probabilities of cancer death by stage at diagnosis were calculated for all solid cancers combined and five individual cancers using flexible parametric relative survival models. These probabilities were used to estimate the number of avoided cancer deaths within 10 years of diagnosis in three 10‐year diagnostic periods if all cases with known distant stage were instead diagnosed at an earlier stage. Cancers are known to be diagnosed at distant stage composed ~16% of all solid cancers diagnosed during 2005 to 2014. Assuming all these cases were instead diagnosed at regional stage, an annual average of 2064 cancer deaths would have been potentially avoided within 10 years of diagnosis. This equated to ~21% of modelled observed deaths. Alternatively, if half of all known distant cases diagnosed during 2005 to 2014 were diagnosed as regional and half as localised, the average number of deaths avoided per year would increase to 2677 (~28%). Estimates varied by diagnostic period, sex and cancer type, reflecting both the different stage distributions for the cancer types, and the respective survival differences between cancer stages. While prevention is the most effective pillar of cancer control, these findings quantify the potential benefits of diagnosing all cancer types when they are less advanced to reduce the burden of cancer mortality.
What's new?
Population‐based cancer survival rates have improved significantly in developed countries in recent decades. Whether such improvements are due to advances in early cancer detection, more effective treatment strategies or a combination thereof remains unclear. Here, the authors investigated the impact of early cancer diagnosis on cancer mortality burden in an Australian cohort. Analyses show that annually, more than one‐fifth of cancer deaths that occurred within 10 years of diagnosis may have been avoided if cases of metastatic disease were diagnosed when disease was in regional stages. These observations highlight the importance of cancer screening and early detection in cancer control.
DNA alkylating agents generally kill tumor cells by covalently binding with DNA to form interstrand or intrastrand cross-links. However, in the case of cisplatin, only a few DNA adducts (<1%) are ...highly toxic irreparable interstrand cross-links. Furthermore, cisplatin is rapidly detoxified by high levels of intracellular thiols such as glutathione (GSH). Since the discovery of its mechanism of action, people have been looking for ways to directly and efficiently remove intracellular GSH and increase interstrand cross-links to improve drug efficacy and overcome resistance, but there has been little breakthrough. Herein, we hypothesized that the anticancer efficiency of cisplatin can be enhanced through iodo-thiol click chemistry mediated GSH depletion and increased formation of DNA interstrand cross-links via mild hyperthermia triggered by near-infrared (NIR) light. This was achieved by preparing an amphiphilic polymer with platinum(IV) (Pt(IV)) prodrugs and pendant iodine atoms (iodides). The polymer was further used to encapsulate IR780 and assembled into Pt–I–IR780 nanoparticles. Induction of mild hyperthermia (43 °C) at the tumor site by NIR light irradiation had three effects: (1) it accelerated the GSH-mediated reduction of Pt(IV) in the polymer main chain to platinum(II) (Pt(II)); (2) it boosted the iodo-thiol substitution click reaction between GSH and iodide, thereby attenuating the GSH-mediated detoxification of cisplatin; (3) it increased the proportion of highly toxic and irreparable Pt-DNA interstrand cross-links. Therefore, we find that mild hyperthermia induced via NIR irradiation can enhance the killing of cancer cells and reduce the tumor burden, thus delivering efficient chemotherapy.
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