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Coals and evaporites are commonly used as qualitative indicators of wet and dry environments in deep-time climate studies, respectively. Here, we combine geological records with climate simulations to establish quantitative relationships of coals and evaporites with temperature and precipitation over the Phanerozoic. We show that coal records were associated with a median temperature of 25°C and precipitation of 1300 mm yr-1 before 250 Ma. Afterwards, coal records appeared with temperatures between 0°C and 21°C and precipitation of 900 mm yr-1. Evaporite records were associated with a median temperature of 27°C and precipitation of 800 mm yr-1. The most remarkable result is that net precipitation associated with coal and evaporite records remained constant across time. The results here have important implications for quantifying climate conditions for other lithologic indicators of climate and for predicting exogenetic ore deposits.
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Although great successes have been achieved, the preparation of closed-loop recyclable polyesters with high working temperatures still remains as a big challenge. Herein, we present the syntheses of a series of enantiopure bicyclic ether-ester monomers by upcycling of poly(3-hydroxybutyrate) bioplastic. The "living"/controlled ring-opening polymerizations of these enantiopure monomers to produce stereoregular polyesters with controlled molecular weights and well-defined chain ends were achieved. The effects of stereoconfiguration and substituent on polymerization kinetics and thermodynamics as well as the thermal properties of resultant polyesters were investigated. Of note, the stereoregular polyesters are semi-crystalline materials with melting temperatures up to 176 °C, even higher than the commodity polyolefin plastics. These polyesters can be depolymerized back to recover pristine monomers, thus successfully establishing a closed-loop life cycle.
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Chemoselective terpolymerization can produce polymer materials with diverse compositions and sequential structures, and thus have attracted considerable attention in the field of polymer synthesis. However, the intrinsic complexity of three-component system also brings great chanllenge, in regard to the reactivity and selectivity of different monomers. Herein, we report the terpolymerization of CO2 /epoxide/anhydride by a binary organocatalytic C3 N3 -Py-P3 /TEB (triethylborane) system. Both the activity and chemoselectivity were highly dependent upon the molar ratio of C3 N3 -Py-P3 to TEB, and sequence-controlled poly(ester-carbonate) copolymers were readily synthesized through one-pot/one-step methodology by tuning the stoichiometric ratio of phosphazene/TEB. In particular, C3 N3 -Py-P3 /TEB with a molar ratio of 1/0.5 exhibited an unprecedentedly high chemoselectivity for ring-opening alternating copolymerization (ROAC) of cyclohexene oxide (CHO) and phthalic anhydride (PA) first and then ROAC of CO2 /CHO. Thus, well-defined triblock polycarbonate-b-polyester-b-polycarbonate copolymers can be produced from the mixture of CO2 , CHO and PA using a bifunctional initiator. With C3 N3 -Py-P3 /TEB=1/1, tapered copolymers were obtained, while random copolymers with high content of polycarbonate (PC) were synthesized with further increasing the amount of TEB. The mechanism of the unexpected chemoselectivity was further investigated by DFT calculations.
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Cytotoxic peptides derived from spider venoms have been considered as promising candidates for anticancer treatment. The novel cell penetrating peptide LVTX-8, which is a 25-residue amphipathic α-helical peptide isolated from spider Lycosa vittata, exhibited potent cytotoxicity and is a potential precursor for further anticancer drug development. Nevertheless, LVTX-8 may be easily degraded by multiple proteases, inducing the proteolytic stability problem and short half-life. In this study, ten LVTX-8-based analogs were rationally designed and the efficient manual synthetic method was established by the DIC/Oxyma based condensation system. The cytotoxicity of synthetic peptides was systematically evaluated against seven cancer cell lines. Seven of the derived peptides exhibited high cytotoxicity towards tested cancer in vitro, which was better than or comparable to that of natural LVTX-8. In particular, both N-acetyl and C-hydrazide modified LVTX-8 (825) and the conjugate methotrexate (MTX)-GFLG-LVTX-8 (827) possessed more durable anticancer efficiency, higher proteolytic stability, as well as lower hemolysis. Finally, we confirmed that LVTX-8 could disrupt the integrity of cell membrane, target the mitochondria and reduce the mitochondrial membrane potential to induce the cell death. Taken together, the structural modifications were conducted on LVTX-8 for the first time and the stability significantly improved derivatives 825 and 827 may provide useful references for the modifications of cytotoxic peptides.
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Antineoplásicos , Peptídeos Penetradores de Células , Neoplasias , Venenos de Aranha , Humanos , Venenos de Aranha/farmacologia , Venenos de Aranha/química , Venenos de Aranha/metabolismo , Antineoplásicos/farmacologia , Metotrexato/química , Peptídeos Penetradores de Células/químicaRESUMO
The fine-tuning of metal-organic framework (MOF) pore structures is of critical importance in developing energy-efficient xenon/krypton (Xe/Kr) separation techniques. Capitalizing on reticular chemistry, we constructed a robust Y-based MOF (NU-1801) that is isoreticular to NPF-500 with a shortened organic ligand and a larger metal radius while maintaining the 4,8-connected flu topology, giving rise to a narrowed pore structure for the efficient separation of a Xe/Kr mixture. At 298 K and 1 bar, NU-1801 possessed a moderate Xe uptake of 2.79 mmol/g but exhibited a high Xe/Kr selectivity of 8.2 and an exceptional Xe/Kr uptake ratio of about 400%. NU-1801 could efficiently separate a Xe/Kr mixture (20:80, v/v), as validated by breakthrough experiments, due to the outstanding discrimination in van der Waals interactions of Xe and Kr toward the framework confirmed by grand canonical Monte Carlo simulations. This work highlights the importance of reticular chemistry in designing structure-specific MOFs for gas separation.
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Shifts in the position of the intertropical convergence zone (ITCZ) have great importance for weather, climate, and society. The ITCZ shifts have been extensively studied in current and future warmer climate; however, little is known for its migration in the past on geological time scales. Using an ensemble of climate simulations over the past 540 million years, we show that ITCZ migrations are controlled primarily by continental configuration through two competing pathways: hemispheric radiation asymmetry and cross-equatorial ocean heat transport. The hemispheric asymmetry of absorbed solar radiation is produced mainly by land-ocean albedo contrast, which can be predicted using only the landmass distribution. The cross-equatorial ocean heat transport is strongly associated with the hemispheric asymmetry of surface wind stress, which is, in turn, controlled by the hemispheric asymmetry of ocean surface area. These results allow the influence of continental evolution on global ocean-atmosphere circulations to be understood through simple mechanisms that depend primarily on the latitudinal distribution of land.
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Applying reactive polymer materials sensitive to biological stimuli has recently attracted extensive research interest. The special physiological effects of reactive oxygen species (ROS) on tumors or inflammation and the application of ROS-responsive polymers as drug-delivery systems in organisms have attracted much attention. ROS is a vital disease signal molecule, and the unique accumulation of ROS-responsive polymers in pathological sites may enable ROS-responsive polymers to deliver payload (such as drugs, ROS-responsive prodrugs, and gene therapy fragments) in a targeted fashion. In this paper, the research progress of ROS-responsive polymers and their application in recent years were summarized and analyzed. The research progress of ROS-responsive polymers was reviewed from the perspective of nanoparticle drug delivery systems, multi-responsive delivery systems, and ROS-responsive hydrogels. It is expected that our work will help understand the future development trends in this field.
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In recent decades, the global incidence of dengue has risen sharply, with more than 75% of infected people showing mild or no symptoms. Since the year 2000, dengue in China has spread quickly. At this stage, there is an urgent need to fully understand its transmission intensity and spread in China. Serological data provide reliable evidence for symptomatic and recessive infections. Through a literature search, we included 23 studies that collected age-specific serological dengue data released from 1980 to 2021 in China. Fitting four catalytic models to these data, we distinguished the transmission mechanisms by deviation information criterion and estimated force of infection and basic reproduction number (R0), important parameters for quantifying transmission intensity. We found that transmission intensity varies over age in most of the study populations, and attenuation of antibody protection is identified in some study populations; the R0 of dengue in China is between 1.04-2.33. Due to the scarceness of the data, the temporal trend cannot be identified, but data shows that transmission intensity weakened from coastal to inland areas and from southern to northern areas in China if assuming it remained temporally steady during the study period. The results should be useful for the effective control of dengue in China.
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N6-methyladenosine (m6A) RNA methylation and its associated RNA-binding protein insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) are involved in tumor initiation and progression. Here, we explored the biological function and clinical significance of IGF2BP1 in intrahepatic cholangiocarcinoma (iCCA). We found that IGF2BP1 expression was upregulated by H3K27 acetylation enrichment of its promoter, which positively correlated with poor clinicopathological characteristics and survival. Gain- and loss-of-function experiments showed that IGF2BP1 overexpression (knockdown) enhanced (attenuated) iCCA growth and metastasis in vitro and in vivo. Mechanistically, IGF2BP1 not only regulated the c-Myc/p16 axis to promote iCCA growth and inhibit senescence, but also activated the ZIC2/PAK4/AKT/MMP2 axis to induce tumor metastasis. More importantly, BTYNB, a recently identified IGF2BP1 inhibitor, exerted promising anti-tumor efficacy in a patient-derived xenograft (PDX) model, and IGF2BP1 conditional knockout (cKO) reduced the tumor burden. These results demonstrate the crucial role of IGF2BP1 in iCCA progression via m6A-dependent modification, highlighting IGF2BP1 as a potential therapeutic target in iCCA.
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Colangiocarcinoma , Humanos , Linhagem Celular Tumoral , Colangiocarcinoma/patologia , Quinases Ativadas por p21RESUMO
Laser sensing and vision sensing smart canes can improve the convenience of travel for the visually impaired, but for the present, most of the system functions of laser sensing and vision sensing smart canes are still defective. Guide equipment and smart blind canes are introduced and classified first, and the smart blind canes based on vision sensing, laser sensing and laser vision sensing are investigated, respectively, and the research status of laser vision sensing smart blind canes is sorted out. The advantages and disadvantages of various laser vision sensing smart blind canes are summarized, especially the research development of laser vision fusion as the core of new smart canes. The future development prospects of laser vision sensing smart blind cane are overviewed, to boost the development of laser vision sensing smart blind cane, to provide safe and efficient travel guarantee for the visually impaired.
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Bengala , Pessoas com Deficiência Visual , Humanos , Desenho de Equipamento , CegueiraRESUMO
Two types of bifunctional amido-ether ligands (syn-L and anti-L) with the rigid anthracene skeleton were designed to support dinuclear group 4 metal complexes. All organic ligands and organometallic complexes (syn-M2 and anti-M2; M = Hf, Zr, and Ti) were fully characterized by 1H and 13C NMR spectroscopies and elemental analyses. The anti-Hf2 complex showed two confirmations at room temperature with C2-symmetry or S2-symmetry that can inter-exchange, as indicated by VT NMR, while only a C2-symmetric isomer was observed for syn-Hf2 complex at room temperature. However, for Zr and Ti analogues, both syn and anti complexes exhibited only one conformation at room temperature. The molecular structures of complexes syn-Hf2, anti-Hf2, and syn-Ti2 in the solid state were further determined by single-crystal X-ray diffraction, revealing the distances between two metal centers in syn-M2 from 7.138 Å (syn-Ti2) to 7.321 Å (syn-Hf2) but a much farther separation in anti-M2 (8.807 Å in C2-symmetric anti-Hf2). The mononuclear complex (2-CH3O-C6H4-N-C14H9)Zr(NMe2)3 (mono-Zr1) was also prepared for control experiments. In the presence of alkyl aluminum (AlEt3) as the alkylating agent and trityl borate ([Ph3C][B(C6F5)4]) as the co-catalyst, all metal complexes were tested for copolymerization of ethylene with 1-octene at high temperature (130 °C). The preliminary polymerization results revealed that the activity was highly dependent upon the nature of metal centers, and syn-Zr2 showed the highest activity of 9600 kg(PE)·mol-1 (Zr)·h-1, which was about 17- and 2.2-fold higher than those of syn-Hf2 and syn-Ti2, respectively. Benefitting from both steric proximity and electronical interaction of two metal centers, syn-Zr2 exhibited significant cooperativity in comparison to anti-Zr2 and mono-Zr1, with regard to activity and molecular weight and 1-octene incorporation of resultant copolymers.
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The low temperature condition, long reaction time and associated high energy inputs involved in the polymerization process still hampered the scalable production of poly(γ-butyrolactone) (PγBL) via ring-opening polymerization (ROP) of low strained γBL due to its unfavorable thermodynamics. In this contribution, we presented the rapid ROP of γBL using a bisurea in combination with an organophosphazene base as the binary catalyst. Well-defined PγBL samples with various terminal groups were prepared by using different alcohol initiators. The bisurea as a co-catalyst exhibited much higher catalytic activity even compared to the most active monourea in previous report as supported by the kinetic experiments. A moderate monomer conversion of 61% was achieved within 10â mins, producing high-molecular-weight PγBL with Mn up to 37.5â kDa and good mechanical properties. The short polymerization time considerably reduced the energy cost for the ROP of γBL conducted at low temperature condition. This study may clear away obstacles for the scalable production and practical applications for PγBL.
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A fully π-conjugated nitrogen-rich three-dimensional covalent organic framework (PYTRI-COF-2) containing both pyrazine and triazine units was prepared through a post-synthetic strategy. The imine linkages in the pre-prepared PYTRI-COF-1 were converted into heterocyclic quinoline by the Povarov reaction. The obtained PYTRI-COF-2 displayed high Li-ion storage capacity and excellent cycling stability when it was used as the lithium (Li)-ion battery electrode.
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Photothermal therapy has become a promising approach as precision medicine to allow spatial control of therapeutic effect only in the site of interest. However, the full potential of PTT has not been realized due to the lack of simple photosensitizers (PSs) that can overcome multistage biological barriers and improve theranostic efficiency. Here, we develop a small molecule-based PS to enhance tumor-specific PTT by programming multistage transport and activation properties in molecular architecture. This PS can self-assemble into stable nanoparticles that accumulate passively in tumor, and then actively internalize through ligand-mediated endocytosis. Subsequently, the programmable degradable linkers are selectively cleaved, enabling size shrinkage for better tumor penetration, binding albumin to enhance the near-infrared fluorescence for low-background imaging, and activating photothermal conversion for tumor suppression. The self-delivery process can be programmed, representing the first multistage small-molecule nano-photosensitizer that overcomes multiple biological barriers and improves the PTT index of tumor. STATEMENT OF SIGNIFICANCE: Photothermal therapy has become a promising approach as precision medicine, but has not been realized due to the lack of simple photosensitizers that can overcome multistage biological barriers and improve theranostic efficiency. In this contribution, we solve this dilemma by developing a small molecule-based photosensitizer by programming multistage transport and activation properties in molecular architecture, which could self-assemble into stable nanoparticles that accumulate passively in tumor, and actively internalized through ligand-mediated endocytosis. Subsequently, the programmable activation by ROS triggered size reduction for tumor penetration and minimized the phototoxicity to normal tissue. The activatable fluorescence and photothermal properties made the photosensitizer intrinsically suitable for multimodal imaging-guided PTT, providing a promising supramolecular nanomedicine towards tumor precise diagnosis and therapy.
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Nanopartículas , Neoplasias , Humanos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Fármacos Fotossensibilizantes/química , Terapia Fototérmica , Linhagem Celular Tumoral , Ligantes , Nanopartículas/uso terapêutico , Nanopartículas/química , Neoplasias/tratamento farmacológico , Imagem Multimodal , Nanomedicina Teranóstica/métodos , Fototerapia/métodosRESUMO
BACKGROUND AND PURPOSE: Gut microbiota dysbiosis induced by acute pancreatitis (AP) exacerbates pancreatic injury and systemic inflammatory responses. The alleviation of gut microbiota dysbiosis through faecal microbiota transplantation (FMT) is considered a potential strategy to reduce tissue damage and inflammation in many clinical disorders. Here, we aim to investigate the effect of gut microbiota and microbiota-derived metabolites on AP and further clarify the mechanisms associated with pancreatic damage and inflammation. EXPERIMENTAL APPROACH: AP rat and mouse models were established by administration of caerulein or sodium taurocholate in vivo. Pancreatic acinar cells were exposed to caerulein and lipopolysaccharide in vitro to simulate AP. KEY RESULTS: Normobiotic FMT alleviated AP-induced gut microbiota dysbiosis and ameliorated the severity of AP, including mitochondrial dysfunction, oxidative damage and inflammation. Normobiotic FMT induced higher levels of NAD+ (nicotinamide adenine dinucleotide)-associated metabolites, particularly nicotinamide mononucleotide (NMN). NMN administration mitigated AP-mediated mitochondrial dysfunction, oxidative damage and inflammation by increasing pancreatic NAD+ levels. Similarly, overexpression of the NAD+ -dependent mitochondrial deacetylase sirtuin 3 (SIRT3) alleviated the severity of AP. Furthermore, SIRT3 deacetylated peroxiredoxin 5 (PRDX5) and enhanced PRDX5 protein expression, thereby promoting its antioxidant and anti-inflammatory activities in AP. Importantly, normobiotic FMT-mediated NMN metabolism induced SIRT3-PRDX5 pathway activation during AP. CONCLUSION AND IMPLICATIONS: Gut microbiota-derived NMN alleviates the severity of AP by activating the SIRT3-PRDX5 pathway. Normobiotic FMT could be served as a potential strategy for AP treatment.
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An effective fault diagnosis method of bearing is the key to predictive maintenance of modern industrial equipment. With the single use of equipment failure mechanism or operation of data, it is hard to resolve multiple complex variable working conditions, multiple types of fault and equipment malfunctions and failures related to knowledge and data. In order to solve these problems, a fault diagnosis method based on the fusion of deep learning with a knowledge graph is proposed in this paper. Firstly, the knowledge rules of bearing data is used for entity extraction. Next, the multiscale optimized convolutional neural network (MOCNN) proposed in this paper is used for fault classification to achieve relationship extraction. Finally, the fault diagnosis graph of the bearing is constructed for fault-assisted decision-making as well as the detailed display of fault information. According to experiment analysis, the fault diagnosis model based on MOCNN proposed in this paper, which integrates the end-to-end convolutional neural network and the attention mechanism, still achieves an accuracy of 97.86% under the data set of 160 types of faults. Compared with the deep learning models such as Resnet and Inception in the noise environment of multiple working conditions and variable working conditions, the model proposed in this paper not only shows a faster convergence speed and stable performance, but also a higher accuracy in evaluation indicators, which is beneficial to practical use.
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We evaluate the performance of Coupled Model Intercomparison Project Phase 6 (CMIP6) models in simulating the observed global terrestrial near-surface wind speed (NSWS) and project its future changes under three different Shared Socioeconomic Pathways (SSPs). Results show that the CESM2 has the best ability in reproducing the observed NSWS trends, although all models examined are generally not doing well. Based on projections of CESM2, the global NSWS will decrease from 2021 to 2100 under all three SSPs. The projected NSWS declines significantly over the north of 20°N, especially across North America, Europe, and the mid-to-high latitudes of Asia; meanwhile, it increases over the south of 20°N. Under SSP585, there would be more light-windy days and fewer strong-windy days than those under SSP245, which leads to a significant global NSWS decline. Robust hemispheric-asymmetric changes in the NSWS could be due to the temperature gradient in the two hemispheres under global warming, with -1.2%, -3.5%, and -4.1% in the Northern Hemisphere, and 0.8%, 1.0%, and 1.5% in the Southern Hemisphere, for the near-term (2021-2040), mid-term (2041-2060), and long-term (2081-2100), respectively.
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Compared with traditional hot mix asphalt (HMA), wax based warm mix asphalt (WWMA) can be mixed with the aggregate at a lower temperature and achieve the desired compaction. However, the adhesion performance of WWMA on aggregate is uncertain. To evaluate the adhesion performance of asphalt and aggregate, researchers used contact angle test, pull-off test, and ultrasonic washing experiments. However, these tests cannot adequately explain the microscopic mechanism of the interface between asphalt and aggregate. Molecular dynamics (MD) can better explain the adhesion mechanism of asphalt aggregates because they can be simulated at the molecular scale. So, the purpose of this research is to use the MD method to study the adhesion performance between WWMA and aggregate. Two aggregate oxides (CaCO3 and SiO2) models, the matrix asphalt model and WWMA models, were built in Materials Studio (MS) software. The adhesion work of asphalt and aggregate oxides was calculated. With the increase of wax modifier content, the adhesion work of asphalt and aggregate oxides (CaCO3 and SiO2) first increases and then decreases. When the wax modifier is increased to 3 wt%, the adhesion works of the WWMA-SiO2 and WWMA-CaCO3 increase by 31.2% and 14.0%, compared with that of matrix asphalt. In this study, the accuracy of the MD calculation result was verified by the pull-off experiments and the contact angle experiments. WWMA was prepared by a high-shear mixer emulsifier. In the pull-off experiments and the contact angle experiments, the tensile strength and the adhesion work between the aggregate and the asphalt containing 3% wax modifier reaches peak values. These values are 140.7% and 124.9%, compared with those between the aggregate and the matrix asphalt. In addition, the results of the pull-off experiments and the contact angle experiments are in good agreement with that of the MD simulation. Finally, Fourier transform infrared spectroscopy (FTIR) shows that the carbonyl content of WWMA is greater than that of matrix asphalt. It explains well that the wax modifier promotes the adhesion between asphalt and aggregate. This paper provides an important theoretical basis to understand the adhesion performance of WWMA and aggregate.
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Although significant advances have been achieved, highly stereocontrolled polymerization using organocatalysts is still a great challenge, such as ring-opening polymerization of racemic lactide (rac-LA) for the synthesis of stereoregular polylactide (PLA). In this context, a series of binary organocatalysts consisting of different phosphazenes (CTPB, C3N3-Me-P3, C3N3-Py-P3, t-BuP2, and t-BuP4) and achiral ureas (U1-U6) were applied for the stereocontrolled ROP of rac-LA under mild conditions. It is remarkable that C3N3-Py-P3/U4 with the compatible basicity/acidity showed both high activity (92% conversion within 10 min) and great stereoselectivity (Pm = 0.92) at room temperature (20 °C), and the resultant stereoblock PLA had predictable molar mass, narrow distribution (D = 1.07), and high melting temperature (Tm = 190 °C). Interactions involved among phosphazene, urea, and initiator were investigated by an in situ NMR technique. It was found that C3N3-Py-P3 reacted with benzyl alcohol (BnOH) to form a relatively loose ion pair in the presence of U4, which accounted for both high activity and stereoselectivity. Kinetics studies for different LA monomers at 20 °C showed kobs-1 (rac-LA) = 0.212 min-1, kobs-1 (D-LA) = 0.311 min-1, and kobs-1 (L-LA) = 0.317 min-1, indicative of the chain end control mechanism for stereocontrolled ROP.
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Poliésteres , Ureia , Álcoois Benzílicos , Dioxanos , Poliésteres/química , Polimerização , TemperaturaRESUMO
Volume dynamics is a two-compartment dynamical model using hemoglobin (Hb) derived plasma diluted level as input data and urine output as input variable through consecutive repeated measurements of Hb concentration in the blood during infusion. It could be applied to evaluate and guide crystalloid fluid rehydration for patients with dehydration or hypovolemia and during anesthesia or surgery. Volume dynamics could be also used to quantificate of strains, hypovolume, and the change of fluid distribution and elimination caused by anesthesia or surgery. The factors which influence the volume resuscitation are complex, including gender, age, hemodynamic state [mean arterial pressure (MAP)], health and stress state, renal function, consciousness, surgical or anesthesia state and so on, which may affect the half-life, distribution, and volume of the fluid. This article summarizes and analyzes the pathophysiological changes of crystalloids fluid in vivo, in order to provide reference for volume management in critically ill patients.
