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MXenes have attracted increasing research enthusiasm owing to their unique physical and chemical properties. Although MXenes exhibit exciting potential in cations adsorption due to their unique surface groups, the adsorption capacity is limited by the low specific surface area and undeveloped porosity. Our work aims at enhancing the adsorption performance of a well-known MXene, Ti3C2Tx, for methylene blue (MB) by decorating tiny ZIF-8 nanoparticles in the interlayer. After the incorporation of ZIF-8, suitable interspace in the layers resulting from the distribution of tiny ZIF-8 appears. When employing in MB, the adsorption capacity of composites can reach up to 107 mg∙g–1 while both ZIF-8 (3 mg∙g–1) and Ti3C2Tx (9 mg∙g–1) show nearly no adsorption capacity. The adsorption mechanism was explored, and the good adsorption capacity is caused by the synergistic effect of ZIF-8 and Ti3C2Tx, for neither of them is of suitable interspace or surface groups for MB adsorption. Our work might pave the way for constructing functional materials based on the introduction of nanoparticles into layered materials for various adsorption applications.

Amines in porous materials have been employed as active species for the selective CO2 adsorption from natural gas because of their target-specific interactions. Nevertheless, it is difficult to modulate such strong interactions to reach a high efficiency in the adsorption processes. Herein, we fabricated light-responsive adsorbents with tunable adsorbent–adsorbate interactions for CO2 capture. The adsorbents were synthesized by introducing primary and secondary amines into a mesoporous silica that had been grafted with azobenzene groups on the surfaces. The target-specific amine sites render the adsorbents significantly selective in the uptake of CO2 over CH4, and the azobenzene groups were used as light-responsive switches to influence the adsorbent–adsorbate interactions. The adsorbents can freely adsorb CO2 when the azobenzene groups are in the trans state. Ultraviolet-light irradiation makes the azobenzene groups transform to the cis configuration, which greatly hinders amines in the uptake of CO2. The caused difference of adsorption capacity can reach 34.9%. The alternative irradiation by ultraviolet- and visible-light can lead to a recyclable regulation on adsorption performance. The changes of the electrostatic potentials of amines are responsible for the light-induced regulation on adsorption.

The objective of this study was to investigate the influence of mental abacus calculation training (MACT) on subliminal cognitive processes.Twenty children with intensive MACT (MACT group) and 20 children without MACT (non-MACT group) were selected. The two groups of children were matched in age, sex, handedness and academic grade. The participants were tested with subthreshold arithmetic priming task while their neural activities were recorded with a 32-channel electroencephalogram system.We found that MACT changed the subliminal cognitive mechanism of computational processing, speeding up the computation. MACT affected the computational processing mode. Specifically, in the identification stage, both groups of children adopted the visual space processing mode, while in the computing stage, the MACT group adopted a visual space processing mode, but the non-MACT group adopted a semantic processing mode. Moreover, MACT improved children's executive functions.These results yielded insights into the effect of early abacus training on children's cognitive processing, providing a theoretical basis for the development and promotion of abacus training.

The first rate-limiting enzyme of the serine synthesis pathway (SSP), phosphoglycerate dehydrogenase (PHGDH), is hyperactive in multiple tumors, which leads to the activation of SSP and promotes tumorigenesis. However, only a few inhibitors of PHGDH have been discovered to date, especially the covalent inhibitors of PHGDH. Here, we identified withangulatin A (WA), a natural small molecule, as a novel covalent inhibitor of PHGDH. Affinity-based protein profiling identified that WA could directly bind to PHGDH and inactivate the enzyme activity of PHGDH. Biolayer interferometry and LC–MS/MS analysis further demonstrated the selective covalent binding of WA to the cysteine 295 residue (Cys295) of PHGDH. With the covalent modification of Cys295, WA blocked the substrate-binding domain (SBD) of PHGDH and exerted an allosteric effect to induce PHGDH inactivation. Further studies revealed that with the inhibition of PHGDH mediated by WA, the glutathione synthesis was decreased and intracellular levels of reactive oxygen species (ROS) were elevated, leading to the inhibition of tumor proliferation. This study indicates WA as a novel PHGDH covalent inhibitor, which identifies Cys295 as a novel allosteric regulatory site of PHGDH and holds great potential in developing anti-tumor agents for targeting PHGDH., Graphical abstract WA is a novel covalent-allosteric inhibitor of phosphoglycerate dehydrogenase (PHGDH), and inhibits the serine synthesis pathway and proliferation of colon cancer cells with overexpression of PHGDH.Image 1

A new porous liquid system based on the coalition of MOPs and bulky IL was designed. The liquid materials exhibit permanent cavities, long-term durability, and good ability to separate CO2 from N2 and CH4 not only as an entity but also as a membrane.

Adsorptive separation plays a critical role in chemical, food, pharmaceutical, and environmental industries, as well as in many other industrial areas. Adsorbents are most important for adsorptive separation and undergo adsorption and desorption processes to accomplish the specific tasks of separation. In the process of adsorption, adsorbates diffuse into the pore spaces of adsorbents through pore openings, adsorb on active sites via physical or chemical interactions, and subsequently are regenerated by temperature or pressure swings during desorption. In the process of adsorption and desorption, however, the requirements for pore structures and surface properties of adsorbents are different. In general, adsorbents with small pore openings can realize selective adsorption and do not favor desorption; on the other hand, adsorbents with large pore openings are efficient in desorption but at the expense of adsorption selectivity. Remarkably, active sites possessing strong interactions with adsorbates contribute to high selectivity for adsorption, while desorption becomes difficult. The trade-off between adsorption and desorption presents an enormous challenge to develop high-efficiency adsorbents. Restricted by their fixed structures and surface properties, conventional adsorbents are unable to meet the demands of adsorption and desorption processes simultaneously.To confront the obstacles, the development of advanced adsorbents to meet the demand of adsorptive separation are urgent. A key strategy to address such issues lies in dynamically adjusting the pore structures or the surface properties of adsorbents with controllability according to the demands of adsorption/desorption. For instance, pursuant to the requirements of varying pore structures during adsorption/desorption, the pore openings of adsorbents can be customized through dynamic structural change of the decorated stimuli-sensitive motifs by suitable external intervention. In addition, the active sites within the adsorbents can be exposed to enhance the adsorption selectivity or sheltered to accelerate the desorption through stimuli-triggered adsorbent-adsorbate interactions. Hence, we proposed a concept of process-oriented smart adsorbents (POSAs) on the basis of the requirements of the adsorption/desorption processes. The design and development of such POSAs are based on three aspects, namely, pore openings, pore spaces, and adsorption sites of adsorbents.In this Account, we present the progress in the development of POSAs according to the demands of adsorption/desorption processes. A series of POSAs with incorporated stimuli-sensitive motifs were successfully achieved. The versatility of incorporated motifs allows them to tune the pore structures and surface properties of adsorbents dynamically and further to enhance the adsorption and desorption efficiency simultaneously. Based on the concept of POSAs, we hope that this Account could contribute to the development of high-efficiency adsorbents and ultimately promote their applications in practical industrial separation. Moreover, we present an outlook on future trends and challenges on the road toward the development and applications of POSAs.

Graphical abstract, Introduction Previously, we have reported a withanolide-type steroid, named tubocapsenolide A (TA), which shows potent anti-proliferative activity in several cancer cell lines. However, its inhibitory effect on the Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) pathway and therapeutic potential on osteosarcoma have not been reported. Objectives In the present study, we aimed to investigate the effect and molecular mechanism of TA in osteosarcoma. Methods The biological functions of TA in U2OS cells were investigated using colony formation, 5-ethynyl-20-deoxyuridine (EDU) staining, and cell cycle/apoptosis assays. The interaction between TA and Src homology 2 phosphatase 2 (SHP-2) was detected by enzyme activity and validated by target-identification methods such as drug affinity responsive target stability (DARTS), cellular thermal shift assay (CETSA), and biolayer interferometry (BLI). The in vivo anti-tumor efficacy of TA was analyzed in the xenograft tumor model. Western blotting analysis was performed to detect the protein expression levels. Results TA exhibited antitumor activity against osteosarcoma both in vitro and in vivo by regulating the JAK/STAT3 signaling pathway. Mechanically, TA interacted with SHP-2 directly and activated its phosphatase activity. Importantly, protein tyrosine phosphatase (PTP) inhibitor, SHP-2 inhibitor, and SHP-2 siRNA could reverse the inhibitory effect of TA on the JAK/STAT3 signaling pathway and restored the TA-induced cell death. Conclusion TA activated the phosphatase activity of SHP-2, which resulted in the inhibition of the JAK/STAT3 pathway and contributed to the antitumor efficacy of TA. Collectively, these findings suggested that TA could serve as a novel therapeutic agent for the treatment of osteosarcoma.

Taiwania cryptomerioides Hayata is an endangered relict plant belonging to Taxodiaceae, and it is also an endemic plant to China. The decay-resistant of Taiwania timber can provide highly quality wood for building and furniture. Plenty of regenerative of leaves of T. cryptomerioides also has been used as a resource for the discovery of new dimeric diterpenoids. In a search for structurally diverse dimeric diterpenoids and potent bioactive isolates, ten new heterodimeric diterpenoids, taiwaniadducts K-T (1-4, 6, 8-11, 14), along with five known ones (5, 7, 12, 13, 15), were isolated from the leaves of T. cryptomerioides. These new compounds were defined by comprehensive spectroscopic analyses, putative biosynthetic pathways, and the value of optical. Biologically, anti-multidrug resistance (MDR) activities of compounds were evaluated. Compounds 4 and 10 exerted a 9.18-fold potentiation effect on bortezmib (BTZ) susceptibility at a tested concentration (20 μM) better than the positive control verapamil. The research of the leaves of T. cryptomerioides not only added the new data to the structural diversity and activities of dimeric diterpenoids but also could provide support for the medical and industrial application of the leaves of this endangered relict plant.

After UV illumination at 254 nm for 10 min, the incorporated LiYGeO4:Bi3+ in the PCN-PLM can continuously provide light irradiation at 365 nm to regulate the CO2 adsorption capacity of PCN-250.

Olanzapine is widely used for treating schizophrenia and bipolar I disorder. Due to its high pharmacokinetic variability, several population pharmacokinetic studies have been performed to identify factors contributing to the variability and thus facilitate individualized dosing. This review aims to provide a comprehensive overview of published population pharmacokinetic studies and explore potential covariates. We systematically searched PubMed, Web of Science, and EMBASE databases from their inception to 31 December 2022. Information on the study design, characteristics, and final parameter estimates was summarized and compared. Monte Carlo simulations provided visual predictive distributions to compare eligible studies. Forest plots were constructed to explore the effects of covariates on olanzapine pharmacokinetics. A total of 10 population pharmacokinetic and three population pharmacokinetic/pharmacodynamic studies involving infants, children, adolescents, and adults were finally included. The median apparent clearance was 0.253 L/h/kg in adults, 27–43% lower than that of infants and children. Men and smokers increased the apparent clearance of olanzapine by 32% and 34%, respectively. The concentration required to achieve half of the maximum effect for the Positive and Negative Syndrome Scale total score was 24.80 ng/mL, comparable with 22.32 ng/mL for dopamine D2 receptor occupancy. A higher dosage may be required for men or heavy smokers than for women or nonsmokers to reach the same exposure. Moreover, further population studies are essential to be conducted to clarify the dose-exposure-response relationship of olanzapine. CRD42022368637

Photoresponsive covalent organic frameworks (PCOFs) have emerged as attractive candidates for adsorption, but it is challenging to construct PCOF adsorbents due to structural order loss of covalent organic frameworks (COFs) after introducing photoresponsive motifs and/or tedious steps of postmodification. Here, a facile strategy is developed, by dispersing photoresponsive metal-organic polyhedra (PMOP) into COFs, to endow COFs with photoresponsive adsorption sites. As a proof-of-concept study, a COF with pore size of 4.5 nm and PMOP with suitable molecular size (4.0 and 3.1 nm for trans and cis configuration, respectively) are selected to meet the requirements of proper accommodation space, good guest dispersion, and free isomerization. The structure of COF is well preserved after introducing PMOPs. Interestingly, the obtained photoresponsive host-guest composite (PHGC) adsorbents exhibit photomodulated adsorption capacity on propylene (C

Ordered porous solid strong bases (OPSSBs) have attracted great research interest due to the excellent performance as heterogeneous catalysts in various reactions. The main obstacle for fabricating OPSSBs is the requirement of high temperature to produce strong basicity on ordered porous materials. For example, the temperatures of 600–650 °C are required for the decomposition of base precursor NaNO3 to basic sites on mesoporous silica SBA-15 and zeolite Y. Such high decomposition temperatures are energy-intensive and harmful to the structure of supports. Herein, we report the fabrication of OPSSBs by utilizing the redox interaction between base precursor and low-valence metal centers (e.g., Cr3+) in metal-organic frameworks (MOFs). The base precursor NaNO3 on MIL-101(Cr) can be converted to basic sites entirely at 300 °C, which is quite lower than those of the conventional thermal conversion on SBA-15 and zeolite Y (600–650 °C). The exploration on decomposition mechanism reveals that the valence change of Cr3+ to Cr6+ takes place during the conversion of NaNO3 to basic sites. In this way, MOFs-derived base catalysts have been synthesized successfully by the host–guest redox strategy and exhibit high catalytic activity in typical base-catalyzed reactions.

Porous liquid is a unique liquid medium that combines permanent porosity of porous solid with the fluidity of liquid, and this special characteristic makes it potential in various applications. Here we report the first photoresponsive porous ionic liquid (PPIL) by solubilizing photoresponsive metal-organic polyhedron (PMOP, constructed from dicopper and azobenzene-containing carboxylate) in polyethylene-glycol-functionalized bulky ionic liquid (IL). Owing to favorable ion interactions, bulky IL molecules encircle outside PMOP cages, and the inter cavities are maintained. The azobenzene moieties can be isomerized freely in the obtained PPILs to expose and shelter active sites upon visible and UV light irradiations. Hence, the adsorption capacity of PPILs is controllable by light irradiation, and the change in CO2 uptake is up to 30% which is different from neat IL with negligible change. This study might inspire the development of new adsorption process regulated by light instead of conventional pressure and temperature swing adsorption technologies.

Solid superbases can catalyze diverse reactions under mild conditions, while they suffer from aggregation of basic sites and poor stability during recycling. Here we report a new generation of solid superbases derived from K single atoms (SAs) prepared by a tandem redox strategy. The initial redox reaction takes place between base precursor KNO

To investigate the effect of BECN1 expression on proliferation and invasion of human multiple myeloma (MM) cell line RPMI-8226.RPMI-8226 cells were cultured in vitro, the recombinant plasmid pcDNA3.1-BECN1 was constructed and transfected into RPMI-8226 cells, then the cells were divided into three groups: control group, negative transfection group and BECN1 transfection group. The expression of BECN1 mRNA in cells of each group was detected by real-time fluorescent quantitative polymerase chain reaction (qRT-PCR); the effect of BECN1 overexpression on cell proliferation inhibition rate was detected by cell counting kit 8 (CCK-8); the effect of BECN1 overexpression on the colony formation rate was detected by plate cloning assay; the effect of BECN1 overexpression on cell invasion was detected by Transwell assay; the effects of BECN1 overexpression on the expression of cell proliferation, invasion and autophagy-related proteins were detected by Western blot.The expression of BECN1 mRNA in BECN1 transfection group was significantly higher than that in control group and negative transfection group (P0.05); the inhibition rate of cell proliferation and the expression of autophagy-related proteins Beclin1, Atg5 and invasion-related protein E-cadherin in BECN1 transfection group were significantly higher than those in control group and negative transfection group; the colony formation rate, invasion number and the expression of proliferation-related proteins CyclinD1, β-catenin and invasion-related protein N-cadherin were significantly lower than those in control group and negative transfection group (P0.05).Overexpression of BECN1 can inhibit the proliferation and invasion of human MM cells RPMI-8226, which may be a potential research target of MM.BECN1表达对人骨髓瘤细胞RPMI-8226增殖、侵袭的影响.探讨BECN1表达对人多发性骨髓瘤（MM）细胞RPMI-8226增殖、侵袭的影响.体外培养RPMI-8226细胞，构建重组质粒pcDNA3.1-BECN1，并转染至RPMI-8226细胞，将细胞分为对照组、阴性转染组、BECN1转染组。实时荧光定量聚合酶链反应（qRT-PCR）检测各组细胞中BECN1 mRNA的表达；CCK-8法检测过表达BECN1对各组细胞增殖抑制率的影响；平板克隆法检测过表达BECN1对各组细胞克隆形成率的影响；Transwell实验检测过表达BECN1对各组细胞侵袭的影响；蛋白免疫印迹法检测过表达BECN1对各组细胞增殖、侵袭、自噬相关蛋白表达的影响.BECN1转染组细胞BECN1 mRNA的表达显著高于对照组和阴性转染组（P0.05）；BECN1转染组细胞增殖抑制率及细胞自噬蛋白Beclin1和Atg5、侵袭蛋白E-cadherin的表达显著高于对照组和阴性转染组，而细胞克隆形成率、侵袭数目及细胞增殖蛋白CyclinD1、β-catenin、侵袭蛋白N-cadherin表达显著低于对照组和阴性转染组（P0.05）.过表达BECN1能够抑制人MM细胞RPMI-8226的增殖和侵袭，可能是MM的潜在研究靶点.

This paper is to design an objective evaluation algorithm that automatically evaluates image quality and is consistent with the human visual system.In view of the fact that most traditional full reference image quality assessment methods only analyze images in the spatial domain,and have shortcomings in pooling strategies,this paper proposes a random forest based spatial-frequency domain joint feature full reference color image quality evaluation method.Firstly,this method extracts the chroma and gradient features in the spatial domain,which are used to characterize the color information and spatial structure information of images.The texture detail information of the response of the log-Gabor filter bank and spatial frequency features are extracted in the frequency domain,which are used to be joint features.Then,random forest is implemented for learning the mapping relationship between the feature vector and the subjective opinion score to predict the objective quality score.Experiments conducted on three standard databases,i.e.TID2013,TID2008,and CSIQ show that the comprehensive evaluation performance by our method is better than the state-of-the-art full reference assessment algorithms,especially on TID2013 database,the Pearson linear correlation coefficient value can reach 0.9397.

Solid strong bases can catalyze a variety of organic reactions under mild conditions. Their preparation consists of loading base precursors (e.g. KNO3) on porous supports followed by activating to convert base precursors to basic sites (e.g. K2O). However, high temperatures are usually required for activation, which consumes lots of energy and damages the structure of supports. Moreover, filtration or centrifugation is mainly adopted for the recovery of solid base catalysts, which is tedious and limits their applications to some extent. In this paper, we constructed multifunctional core–shell structured Fe3O4@C microspheres as the supports owing to the reducibility of carbon shell and the magnetism of Fe3O4 core, thus creating magnetically responsive solid strong bases under mild conditions. Strong basic sites can be formed at a low temperature of 400 °C due to the redox reaction between the carbon shell and the base precursor, yielding the solid base K-400@Fe3O4@C. Such a temperature is obviously lower than the temperature for the decomposition of KNO3 on the frequently used supports SiO2 (750 °C) and Al2O3 (500−700 °C). The resultant solid base K-400@Fe3O4@C exhibits excellent catalytic activity in transesterification reaction, and the yield of target product dimethyl carbonate is higher than some benchmarks like MgO, CsX, and Na2O/Al2O3. In addition, thanks to the superparamagnetism, the solid base catalysts can be recovered within 10 s with the assistance of external magnetic fields.

Four new highly oxidized sesquiterpene lactones, Argyoxynolides A–D, along with two known analogs were isolated from the leaves of Artemisia argyi H.Lev. & Vaniot. Their structures were characterized utilizing extensive spectroscopic methods. All isolates were evaluated for the LPS-induced nitric oxide (NO) production inhibitory activity and one compound exhibited activity with IC50 = 37.95 ± 4.39 μM.

Metal–organic polyhedra (MOPs) have emerged as versatile platforms for artificial models of biological systems due to their discrete structure and modular nature. However, the design and fabricatio...

Mono-ubiquitination of histone H2B plays a critical role in the regulation of gene transcription, DNA replication, and DNA damage repair. In Schizosaccharomyces pombe, Brl2 is an E3 ubiquitin ligase and required for the ubiquitination of H2B at lysine residue 119. Currently, there are few studies related to the function of Brl2 in DNA damage repair. Using camptothecin (CPT) to induce DNA double-strand breaks (DSBs) in S. pombe, we investigated the effect of Brl2 on DSB repair, and found that brl2-null mutants showed greater sensitivity to CPT when compared with wild-type (WT) cells, as well as having a drastically reduced spontaneous recombinant frequency. The fluorescent analysis demonstrated that Brl2 was co-localized with the recombination factor Rad52 at DSBs. Moreover, Brl2 promoted the recruitment of Rad52 to DSBs. Under CPT-induced DSBs, Brl2 was phosphorylated. These findings indicate that Brl2 plays a critical role in DNA homologous recombination and its mediated repair of DSBs.组蛋白H2B单泛素化在基因转录、DNA复制及损伤修复中发挥着重要的调控作用。在裂殖酵母(Schizosaccharomyces pombe)中,Brl2作为一个泛素化连接酶,调节H2B的119位赖氨酸的单泛素化。目前,有关Brl2在DNA损伤修复中的作用研究较少,本研究利用药物喜树碱(camptothecin, CPT)处理裂殖酵母产生高毒性的DNA双链断裂(DNA double-strand breaks, DSBs),探索Brl2在DSB修复过程中的作用。研究发现,brl2基因缺失的菌株对CPT高度敏感,并导致细胞内DNA自发重组频率下降。荧光分析表明Brl2和重组修复蛋白Rad52共定位到DSB处,且Brl2促进Rad52在DSB处的募集。在CPT产生的DSB条件下,Brl2会发生磷酸化。以上研究发现揭示了Brl2在DSB修复过程中起重要作用,为具体阐明Brl2在DNA同源重组及双链断裂修复的分子机制奠定了进一步研究的基础。.

Metal-organic frameworks (MOFs) have attracted increasing research enthusiasm owing to their tunable functionality, diverse structure characteristics, and large surface area. However, poor hydrothermal stability restricts the utilization of some MOFs in practical applications. Our work aims at improving the hydrothermal stability of a representative MOF, namely, HKUST-1, by incorporating a two-dimensional material Ti3C2Tx MXene for the first time. A new type of hybrid material is synthesized through the hybridization of HKUST-1 and Ti3C2Tx, and the obtained hybrids show improved hydrothermal stability as well as catalytic performance. The porosity of hybrids is enhanced when incorporating an appropriate amount of Ti3C2Tx, and the surface area can reach 1380 m2·g-1, while the pristine HKUST-1 is 1210 m2·g-1. After the hydrothermal treatment (hot water vapor, 70 °C), the structure of hybrid materials maintains well, while the framework of HKUST-1 is severely destroyed. When catalyzing the ring-opening reaction of styrene oxide, the conversion reaches 76.7% only for 20 min, which is much higher than that of pure HKUST-1 (23.1% for 20 min). More importantly, the catalytic activity could recover without loss even after six cycles. Our hybrid materials are promising in practical catalytic applications due to their excellent hydrothermal stability, catalytic activity, and reusability.

Enantioenriched indole derivatives are widely found in natural products, pharmaceuticals and bioactive compounds. Therefore, developing efficient methods for the synthesis of enantioenriched indole derivatives has become an important goal in the community of organic chemistry. To this end, chemists have designed and developed a variety of indole-containing platform molecules and their related catalytic asymmetric reactions. Among these approaches, vinylindoles have proved to be versatile platform molecules for accessing enantioenriched indole derivatives via catalytic asymmetric reactions, especially organocatalytic asymmetric reactions. Based on this approach, a plethora of chiral indole derivatives have been synthesized with optical purity and structural complexity. This review summarizes advances in vinylindole-based organocatalytic asymmetric reactions since 2008 and includes the applications of some methodologies in the total synthesis of natural products. In addition, this review points out the remaining challenges in this research area to be confronted by organic chemists, which will shed light on the future development of this area.

CuI-Functionalized materials show high potential in numerous applications such as adsorptive desulfurization. Nonetheless, the instability of CuI against oxidation limits its practical applications, and exposure of CuI to air can lead to the formation of CuII owing to the presence of oxygen and moisture. Herein, an unexpected way to stabilize CuI against oxidation was designed by constructing a superhydrophobic microenvironment in original hydrophilic metal–organic frameworks (MOFs) via polystyrene (PS) coating. A pre-polymerization strategy is developed to coat PS on the surface of CuI-functionalized MIL-101(Cr) (CuIM) rather than entering the pores (producing CuIM@PS), and the access of moisture to CuI is hindered, thus stabilizing CuI regardless of the existence of oxygen. CuI in CuIM@PS is stable in the air with a constant relative humidity of 75% for 200 days, while almost all CuI is converted to CuII in CuIM in only 14 days. The optimal CuIM@PS material after air exposure can adsorb 0.208 mmol g−1 of thiophene, which is much superior to that of CuIM (0.024 mmol g−1) despite the comparable adsorption capacity for unexposed materials. Moreover, the present CuIM@PS adsorbents exhibit excellent adsorption performance for water-containing model fuels.

Reproducing the highly efficient catalytic cascade system to mimic life behaviors in vitro has been intensively investigated over the past few decades. However, except for biocatalysis with enzymes, most chemocatalytic cascades in essence combine several reactions that occur over mutually independent catalytic sites in a container. Herein, with a series of control experiments and stepwise theoretical derivation based on the calculations of density functional theory and a semi-empirical method, a generalized cascade catalysis is discovered for the chemocatalytic conversion of CO2 to higher alcohols over a porphyrinic zirconium metal–organic framework, PCN-224-Cu. Two types of catalytic sites in PCN-224-Cu, i.e., the Zr6 cluster and TCPP-Cu unit, act like organelles, which can complete a class of reactions instead of particular one. The Zr6 cluster is in charge of molecular dissociation, while the TCPP-Cu unit is responsible for molecular assembly. Therefore, semi-finished intermediates repeatedly transfer between the two types of catalytic sites until the ultimate formation of ethanol with high efficiency (ethanol yield, 4.53 mmol h−1 gcat.−1 at 403 K) and selectivity (∼100%).

Light-responsive metal–organic frameworks (LMOFs) are intriguing materials for CO2 capture owing to their tunable structures and performances. However, conventional LMOFs are reported to regulate C...

Camrelizumab, a programmed cell death 1 (PD-1) inhibitor, has been approved for the treatment of patients with relapsed or refractory classical Hodgkin lymphoma, nasopharyngeal cancer and non-small cell lung cancer. The aim of this study was to perform a population pharmacokinetic (PK) analysis of camrelizumab to quantify the impact of patient characteristics and to investigate the appropriateness of a flat dose in the dosing regimen. A total of 3092 camrelizumab concentrations from 133 patients in four clinical trials with advanced melanoma, relapsed or refractory classical Hodgkin lymphoma and other solid tumor types were analyzed using nonlinear mixed effects modeling. The PKs of camrelizumab were properly described using a two-compartment model with parallel linear and nonlinear clearance. Then, covariate model building was conducted using stepwise forward addition and backward elimination. The results showed that baseline albumin had significant effects on linear clearance, while actual body weight affected intercompartmental clearance. However, their impacts were limited, and no dose adjustments were required. The final model was further evaluated by goodness-of-fit plots, bootstrap procedures, and visual predictive checks and showed satisfactory model performance. Moreover, dosing regimens of 200 mg every 2 weeks and 3 mg/kg every 2 weeks provided similar exposure distributions by model-based Monte Carlo simulation. The population analyses demonstrated that patient characteristics have no clinically meaningful impact on the PKs of camrelizumab and present evidence for no advantage of either the flat dose or weight-based dose regimen for most patients with advanced solid tumors.

Hypoxia is a parameter related to many diseases. Ratiometric hypoxia probes often rely on a combination of an O2 -insensitive fluorophore and an O2 -sensitive phosphor in a polymer matrix, which require high cost and multi-step synthesis of transition metal complexes. The two-chromophore hypoxia probes encounter unfavorable energy transfer processes and different stabilities of the chromophores. Reported herein is a pure organic ratiometric hypoxia nanoprobe, assembled by a monochromophore, naphthalimide ureidopyrimidinone (BrNpA-UPy), bridged by a bis-UPy-functionalized benzyl skeleton. The joint factors of quadruple hydrogen bonding, the rigid backbone of UPy, and bromine substitution of the naphthalimide derivative facilitate bright phosphorescence (ΦP =7.7 %, τP =3.2 ms) and fluorescence of the resultant nanoparticles (SNPs) at room temperature, which enable accurate, ratiometric, sensitive oxygen detection (Ksv =189.6 kPa-1 ) in aqueous solution as well as in living HeLa cells.

Palladium (Pd)-containing catalysts have gained extensive attention because of their outstanding activity in various heterogeneous catalytic reactions. The activity of these catalysts highly correl...

Eight new germacranolides, minusolides A–H (1–8), along with two known analogues, 9 and 10, were isolated from the whole plant of Carpesium minus. Their structures were elucidated by spectroscopic ...

Due to the good controllability and high energy efficiency in adsorption processes, photoresponsive adsorbents are intriguing for CO2 capture. Nevertheless, most reported photoresponsive adsorbents are designed based on weak adsorption sites, regulating CO2 adsorption through structural change or steric hindrance. In addition, ultraviolet (UV) light is commonly involved in the regulation of adsorption capacity. Here we report for the first time the smart adsorbents for CO2 capture, which makes strong adsorption sites respond to visible (Vis) light. The adsorbents were fabricated by introducing primary amine and Dispersed Red 1 (DR1, a kind of push-pull azobenzene that responds to Vis light rapidly) units to mesoporous silica, which act as strong adsorption sites and triggers, respectively. The primary amine sites make the adsorbents highly selective in the adsorption of CO2 over CH4. Without light irradiation, azobenzene is in the form of trans configuration, which leads to decreased electrostatic potential of primary amines and subsequently, exposure of active sites and liberal adsorption of CO2. Upon Vis-light irradiation, cis isomers are formed, which results in increased electrostatic potential of primary amines and subsequently shelter of active sites. Even on such strong adsorption sites, the alteration of CO2 adsorption capacity can reach 40% for the adsorbent with and without Vis-light irradiation. Moreover, the trans/cis isomerization of DR1 units can be triggered reversibly by Vis light. The present smart system endows adsorbents with selective adsorption capacity and avoids the employment of UV light, which is unlikely to be achieved by conventional photoresponsive adsorbents.

Due to the nontoxicity, low cost, and versatility, CuO-functionalized materials have received much attention. Their performances are intensely dependent on the dispersion state of CuO. Herein we re...

Polycarbonate diols (PCDLs) are intermediates used in the synthesis of polyurethanes (PU), and therefore their efficient and green synthesis is a necessity. In this work, KOH/K2CO3@γ-Al2O3 catalysts were prepared and employed in the synthesis of PCDLs. A 4 wt% KOH/40 wt% K2CO3@γ-Al2O3 catalyst and a DMC: 1,4-BDO molar ratio of 1.25:1 exhibited the best activity for the reaction and gave a PCDL yield of 95% with a molecular weight of 4527 g·mol−1. Moreover, the catalyst could be reused 4 times without a significant loss of the catalytic activity in transesterification. The effects of the catalyst composition and reaction conditions on the synthesis of PCDLs were investigated. The results indicate that the catalyst amount and the molar ratio of DMC: 1,4-BDO can influence the purity of PCDLs. The reaction equation Catalyst preparation The synthesis of PCDLs using DMC and 1,4-BDO

Background and Objectives: Antiepileptic drugs are the major treatment modality for patients with epilepsy. Delayed or missed doses are common during long-term or lifelong anti-epilepsy treatment. This study aims to explore optimal individualized remedial dosing regimens for delayed or missed doses of nine commonly used antiepileptic drugs. Methods Monte Carlo simulation based on previously published population pharmacokinetic models was employed to explore remedial regimens of carbamazepine, clobazam, eslicarbazepine acetate, lamotrigine, levetiracetam, oxcarbazepine, phenobarbital, topiramate, and valproic acid. Six remedial strategies for delayed or missed doses were investigated. The deviation time outside the individual therapeutic range was used to evaluate each remedial regimen. The influences of patients’ demographics, concomitant medication, and scheduled dosing intervals on remedial regimens were assessed. RxODE and Shiny in R were employed to perform Monte Carlo simulation and recommend individual remedial regimens. Results The recommended remedial regimens were highly correlated to delayed time, scheduled dosing interval, and half-life of the antiepileptic drug. Moreover, the recommended remedial regimens for pediatric and adult patients were different. The renal function, along with concomitant medication that affect the clearance of the antiepileptic drug, may also influence the remedial regimens. A web-based dashboard was developed to provide optimal individualized remedial regimens for nonadherent patients, and a user-defined module with all parameters that could be defined flexibly by the user was built. Discussion Monte Carlo simulation based on population pharmacokinetic models may provide a rational approach to propose remedial regimens for delayed or missed doses of antiepileptic drugs.

Background: Monitoring the level of anticoagulation by rivaroxaban in patients with non-valvular atrial fibrillation (NVAF) is valuable in clinical practice. Our study aimed to measure the plasma levels of rivaroxaban both by chromogenic anti-Xa assays and ultra-high performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS) in Chinese patients with NVAF, and compare with the expected drug levels. Materials and methods: A prospective clinical study was conducted to include NVAF patients taking rivaroxaban. Rivaroxaban levels were determined using UHPLC-MS/MS and chromogenic anti-Xa assays (Biophen DiXal and Zhenyuan anti-Xa). The correlation and agreement among measurements by different assays were evaluated. The rivaroxaban levels in Chinese patients were also compared with the expected drug levels, which were estimated from previous clinical trials and widely accepted. Results: A total of 243 plasma samples were collected from 182 patients. Results measured using the two chromogenic anti-Xa assays were both linearly correlated with those measured using UHPLC-MS/MS, especially in the range of 50–200 ng/mL, but the concentrations determined using anti-Xa assays were systematically underestimated. Rivaroxaban levels measured by either UHPLC-MS/MS or chromogenic anti-Xa assays were both larger than the expected ranges. There was no difference in the distribution of concentration whether the patients took an appropriate dose or not. However, for Chinese patients with an inappropriate lower dose, trough concentrations were less likely to exceed the expected concentration ranges.Conclusion: Rivaroxaban concentration in patients with NVAF were highly variable compared to the expected ranges estimated from clinical trials, whether measured by UHPLC-MS/MS or chromogenic anti-Xa assays. Chinese patients taking an appropriate rivaroxaban dose are more likely to obtain a rivaroxaban concentration level higher than expected, independent on the assay used.

Background and ObjectivesDelayed or missed antiseizure medications (ASMs) doses are common during long-term or lifelong antiepilepsy treatment. This study aims to explore optimal individualized remedial dosing regimens for delayed or missed doses of 11 commonly used ASMs.MethodsTo explore remedial dosing regimens, Monte Carlo simulation was used based on previously identified and published population pharmacokinetic models. Six remedial strategies for delayed or missed doses were investigated. The deviation time outside the individual therapeutic range was used to evaluate each remedial regimen. The influences of patients' demographics, concomitant medication, and scheduled dosing intervals on remedial regimens were assessed. RxODE and Shiny in R were used to perform Monte Carlo simulation and recommend individual remedial regimens.ResultsThe recommended remedial regimens were highly correlated with delayed time, scheduled dosing interval, and half-life of the ASM. Moreover, the optimal remedial regimens for pediatric and adult patients were different. The renal function, along with concomitant medication that affects the clearance of the ASM, may also influence the remedial regimens. A web-based dashboard was developed to provide individualized remedial regimens for the delayed or missed dose, and a user-defined module with all parameters that could be defined flexibly by the user was also built.DiscussionMonte Carlo simulation based on population pharmacokinetic models may provide a rational approach to propose remedial regimens for delayed or missed doses of ASMs in pediatric and adult patients with epilepsy.

Edoxaban is a non-vitamin K antagonist oral anticoagulant (NOAC) widely used for the long-term prevention of stroke in patients with non-valvular atrial fibrillation (NVAF). Adherence to NOAC therapy has been unsatisfactory and decreases over time. Remedial strategies are currently used to address the non-adherence events. Current recommendations, however, are generic and not well supported by evidence. The aim of this study was to explore appropriate remedial dosing regimens for non-adherent edoxaban-treated NVAF patients through Monte Carlo simulation.Six regimens were compared with the current recommendations of the European Heart Rhythm Association (EHRA) guide based on total deviation time. Both edoxaban plasma concentration and intrinsic Factor Xa activity were considered. Monte Carlo simulations were performed using RxODE based on a published population pharmacokinetic/pharmacodynamic (PK/PD) model.The proposed remedial strategies were different than the EHRA recommendations and were related to the delay time. However, it was found that the missed dose can be administered immediately if the delay time is within 11 h. When the delay is between 12 and 19 h, a half dose followed by a regular dosing schedule is recommended. When the delay time exceeds 19 h, a full dose followed by a half dose is preferred.PK/PD modelling and simulation are effective in developing and evaluating the remedial strategies of edoxaban, which can help maximise its therapeutic effect.