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In the robust secure aggregation problem, a server wishes to learn and only learn the sum of the inputs of a number of users while some users may drop out (i.e., may not respond). The identity of the dropped users is not known a priori and the server needs to securely recover the sum of the remaining surviving users. We consider the following minimal two-round model of secure aggregation. Over the first round, any set of no fewer than $U$ users out of $K$ users respond to the server and the server wants to learn the sum of the inputs of all responding users. The remaining users are viewed as dropped. Over the second round, any set of no fewer than $U$ users of the surviving users respond (i.e., dropouts are still possible over the second round) and from the information obtained from the surviving users over the two rounds, the server can decode the desired sum. The security constraint is that even if the server colludes with any $T$ users and the messages from the dropped users are received by the server (e.g., delayed packets), the server is not able to infer any additional information beyond the sum in the information theoretic sense. For this information theoretic secure aggregation problem, we characterize the optimal communication cost. When $U \leq T$ , secure aggregation is not feasible, and when $U > T$ , to securely compute one symbol of the sum, the minimum number of symbols sent from each user to the server is 1 over the first round, and $1/(U-T)$ over the second round. [ABSTRACT FROM AUTHOR]

Shape editability combined with a self‐healing capability and long‐term cycling durability are highly desirable properties for wearable supercapacitors. Most wearable supercapacitors have rigid architecture and lack the capacity for editability into desirable shapes. Through sandwiching hydrogel electrolytes between two electrodes, a suite of wearable supercapacitors that integrate desirable properties namely: repeated shape editability, excellent self‐healing capability, and long‐term cycling durability is demonstrated. A strategy is proposed to enhance the long‐term cycling durability by utilizing hydrogel electrolytes with unique cross‐linking structures. The dynamic crosslinking sites are formed by quadruple H bonds and hydrophobic association, stabilizing the supercapacitors from inorganic ion disruption during charge–discharge processes. The fabricated supercapacitors result in the capacitance retention rates of 99.6% and 95.8% after 5000 and 10 000 charge–discharge cycles, respectively, which are much higher than others reported in the literature. Furthermore, the supercapacitor sheets can be repeatedly processed into various shapes without any capacitance loss. The supercapacitors exhibit a 95% capacitance retention rate after five cutting/self‐healing cycles, indicative of their excellent self‐healing performance. To demonstrate real‐life applicability, the wearable supercapacitors are successfully used to power a light‐emitting diode and an electronic watch. [ABSTRACT FROM AUTHOR]

Inspired by the unique band structure of CsPbBr3, we have developed an asymmetric Cl‐exchange strategy based on the CsPbBrxCl3‐x/TiO2 heterojunction‐type catalyst and achieved photocatalytic activation of C(sp3)−H bond using the toluene oxidation reaction as a proof‐of‐concept application. The anion exchange at the supported CsPbBr3 surface results in the CsPbBrxCl3‐x/TiO2 structure with an asymmetric distribution of halide. The resultant heterojunction‐type catalysts exhibit significantly improved photocatalytic activity for toluene oxidation reaction with the highest benzaldehyde production rate at 1874 μmol g−1 h−1 (∼4 times that of the naked CsPbBr3 nanocrystals). The remarkable photocatalytic performance can be ascribed to the improved carrier transport at CsPbBrxCl3‐x/TiO2 interface enabled by the unique band structure due to the asymmetric halide distribution, verified by the micro‐strain discovered through the X‐ray diffraction. This work demonstrates a new pathway to fabricate highly‐efficient halide perovskite heterojunction‐type catalysts for photocatalytic activation of C(sp3)−H bond. [ABSTRACT FROM AUTHOR]

A CsPbBr3@Ag-C3N4 ternary heterojunction photocatalyst with g-C3N4 as ballistic electron transport "tunnel" is designed and synthesized. The photogenerated electrons of CsPbBr3 dots can be efficiently transferred to Ag nanoparticles via g-C3N4 sheets, resulting in efficient CO2 reduction. The structured design of catalyst provides a novel insight for the development of perovskite-based photocatalysts. [Display omitted] • CsPbBr 3 @Ag-C 3 N 4 ternary heterojunction photocatalyst is designed and synthesized. • The photogenerated electrons of CsPbBr 3 QDs can be efficiently transferred to Ag nanoparticles via g-C 3 N 4 as the electron transport tunnel. • The CsPbBr 3 @Ag-C 3 N 4 ternary photocatalyst achieves a conversion rate of 19.49 μmol·g−1·h−1 with almost 100 % CO selectivity. • In situ DRIFT and DFT calculations reveal the photocatalytic mechanism for CO 2 reduction. Perovskite CsPbBr 3 quantum dot shows great potential in artificial photosynthesis, attributed to its outstanding optoelectronic properties. Nevertheless, its photocatalytic activity is hindered by insufficient catalytic active sites and severe charge recombination. In this work, a CsPbBr 3 @Ag-C 3 N 4 ternary heterojunction photocatalyst is designed and synthesized for high-efficiency CO 2 reduction. The CsPbBr 3 quantum dots and Ag nanoparticles are chemically anchored on the surface of g-C 3 N 4 sheets, forming an electron transfer tunnel from CsPbBr 3 quantum dots to Ag nanoparticles via g-C 3 N 4 sheets. The resulting CsPbBr 3 @Ag-C 3 N 4 ternary photocatalyst, with spatial separation of photogenerated carriers, achieves a remarkable conversion rate of 19.49 μmol·g−1·h−1 with almost 100 % CO selectivity, a 3.13-fold enhancement in photocatalytic activity as compared to CsPbBr 3 quantum dots. Density functional theory calculations reveal the rapid CO 2 adsorption/activation and the decreased free energy (0.66 eV) of *COOH formation at the interface of Ag nanoparticles and g-C 3 N 4 in contrast to the g-C 3 N 4 , leading to the excellent photocatalytic activity, while the thermodynamically favored CO desorption contributes to the high CO selectivity. This work presents an innovative strategy of constructing perovskite-based photocatalyst by modulating catalyst structure and offers profound insights for efficient CO 2 conversion. [ABSTRACT FROM AUTHOR]

Biling Weitong Granules (BLWTG) are a newly developed traditional Chinese medicine prescription based on the ancient prescription Jinlingzi San and Zuojin Wan. It is used for the treatment of functional gastrointestinal disorders (FGIDs) featured as visceral hypersensitivity (VH). However, its active ingredients and protein targets involved still remain unknown. To explore the potential targets of BLWTG for the treatment of visceral hypersensitivity. Active components and their protein targets of BLWTG were screened from TCMSP database and the component-target network were constructed with Cytoscape software. Irritable bowel syndrome (IBS) was the representative disease in this study and information on its linked pathways was obtained from NCBI, Drugbank and Genecard. Target pathways of BLWTG were analyzed through KEGG to verify the correlation with IBS related pathways.Then, the VH mouse models was induced by maternal separation (MS), randomly divided into normal saline (NS),BLWTG1 (low-dosage) and BLWTG2 (high-dosage) group. After intervention, threshold intensity of colorectal distension (CRD) and body weight were measured to evaluate relief of IBS symptoms. Elisa was performed to evaluate 5-HT concentration changes of colon tissues. Flow cytometry was performed to assess changes of colon eosinophils and mast cells proportion. Transcriptome sequencing was employed to analyze changes of pathways and differential genes. 199 protein targets and 132 active components of BLWTG were identified. KEGG analysis revealed the overlap between BLWTG target pathways and IBS related pathways such as neuroactive ligand-receptor interaction, tryptophan metabolism and inflammatory reaction. 34 genes were not only BLWTG target proteins but also recognized targets for treating IBS. After maternal separation (MS), the mice showed a significant decrease in threshold intensity of CRD, a progressive decrease in body weight and an increase of 5-HT concentration of colon tissue. The proportion of mast cells and eosinophils in the colon increased. Differential genes including Hp,Ido1 and Aqp7 were significantly increased in MS mice group and IBS-related pathways were upregulated. After treatment of BLWTG, threshold intensity of CRD and body weight were significantly improved and IBS related pathways were downregulated. In addition, among BLWTG protein targets, Il1b,Tnf,Adrb1 and Nos2 were found upregulated in MS+NS mice and downregulated after BLWTG intervention through combination of transcriptome sequencing. In maternal separation-induced mouse models, BLWTG could alleviate visceral hypersensitivity, possibly through downregulation of 5-HT concentration and eosinophils and mast cells proportion in colon and critical pathways such as neuroactive ligand-receptor pathway. Potential targets of BLWTG including Il1b,Tnf,Adrb1 and Nos2 were found through integration of network pharmacology database and transcriptome sequencing, providing evidence for further study on mechanisms underlying visceral hypersensitivity. [Display omitted] • 132 active components and 199 protein targets of BLWTG were identified through network pharmacology analysis. • Visceral hypersensitivity can be simulated by maternal separation in mouse model and alleviated after BLWTG intervention. • Potential BLWTG targets including Il1b,Tnf,Adrb1 and Nos2 were found by combining network pharmacology and in vivo analysis. [ABSTRACT FROM AUTHOR]

Summary of main observation and conclusion: The heterojunction‐type structure has shown significant merits in tuning the optical properties and carrier physics. Inspired by the excellent absorption capability of halide perovskite materials for visible light, a series of CsPbBr3/TiO2 heterojunction‐type photocatalysts with various all‐inorganic‐perovskite/TiO2 ratios are successfully fabricated by the ligand‐assisted reprecipitation (LARP) method. The heterojunction structure extends the light absorption of TiO2 with good chemical and structural stability. A Pb‐O interaction at the CsPbBr3/TiO2 interface is observed by the XPS and confirmed by the TRPL showing improved interface carrier transport and stability. The heterojunction‐type catalyst shows drastically enhanced photocatalytic activity towards the direct oxidation of toluene with O2 molecule, as an important reaction for organic chemical synthesis. The optimized sample shows an activity of 2356 μmol·g–1·h–1 at 75 °C, 4 times of that of the naked CsPbBr3 nanocrystals, and 3 times of that of the bare TiO2. Based on the investigation with trapping agents, a reaction mechanism is hence proposed suggesting that the photo‐generated hole may be involved in the rate‐limiting step. This work demonstrates the potential of inorganic halide perovskite‐based heterojunction structure for photocatalytic applications. [ABSTRACT FROM AUTHOR]

Background: For stereotactic body radiotherapy (SBRT) to central (C) and ultracentral (UC) lung tumors, our provincial practice has been to prioritize organs at risk (OARs) constraints by compromising target volume coverage if needed. The objectives are to report the treatment's efficacy and safety.Methods: We conducted a retrospective analysis of all provincial patients who underwent SBRT at 60Gy in 8 fractions to C and UC lung tumors, from 2013 to 2017.Results: Ninety-eight lesions were treated, 57 (58.2%) C and 41 (41.8%) UC. The median follow-up was 22.9 months (range 2.5-64.8 months). The 1- and 3-year local control (LC) was 97.8 and 84.5% respectively, with no differences between C and UC groups (p = 0.662). Fifty-three (54.1%) cases had optimal dose coverage (V60Gy ITV&PTV > 95%), 29 (29.6%) had compromised PTV coverage (V60Gy ITV > 95%/PTV < 95%), and 16 (16.3%) had both compromised ITV and PTV coverage (V60Gy ITV&PTV < 95%). No significant difference in LC was detected at 2 years between the 3 groups (95.6, 91.8 and 90.9%, p = 0.717). There were 3 episodes of grade 3 toxicity in the C group (2 dyspnea, 1 pneumonitis) and 2 in the UC group (1 dyspnea, 1 hemoptysis). There were no gr4/5 toxicities. On multivariable Cox regression analysis, ITV size was found to be a predictor for LC (p = 0.001).Conclusions: SBRT at 60Gy in 8 fractions achieves high rates of LC with low risks of significant toxicities, even if target volume coverage is reduced to meet OARs constraints. [ABSTRACT FROM AUTHOR]

The conventional method of using montmorillonite hemostatic materials affects the hemostatic effect due to easy dislodgement on the wound surface. In this paper, a multifunctional bio-hemostatic hydrogel (CODM) was prepared based on hydrogen bonding and Schiff base bonding using modified alginate, polyvinylpyrrolidone (PVP), and carboxymethyl chitosan. The amino group-modified montmorillonite was uniformly dispersed in the hydrogel by its amido bond formation with the carboxyl groups of carboxymethyl chitosan and oxidized alginate. The catechol group, –CHO, and PVP can form hydrogen bonds with the tissue surface to afford the firm tissue adhesion to afford the wound hemostatic. The addition of montmorillonite-NH 2 further improves the hemostatic ability, making it better than commercial hemostatic materials. Moreover, the photothermal conversion ability (derived from the polydopamine) was synergized with the phenolic hydroxyl group, quinone group, and the protonated amino group to effectively kill the bacteria in vitro and in vivo. Based on its in vitro and in vivo biosafety and satisfactory degradation ratio anti-inflammatory, antibacterial, and hemostatic properties, the CODM hydrogel holds promising potential for emergency hemostasis and intelligent wound management. [ABSTRACT FROM AUTHOR]

The conventional method of using montmorillonite hemostatic materials affects the hemostatic effect due to easy dislodgement on the wound surface. In this paper, a multifunctional bio-hemostatic hydrogel (CODM) was prepared based on hydrogen bonding and Schiff base bonding using modified alginate, polyvinylpyrrolidone (PVP), and carboxymethyl chitosan. The amino group-modified montmorillonite was uniformly dispersed in the hydrogel by its amido bond formation with the carboxyl groups of carboxymethyl chitosan and oxidized alginate. The catechol group, –CHO, and PVP can form hydrogen bonds with the tissue surface to afford the firm tissue adhesion to afford the wound hemostatic. The addition of montmorillonite-NH 2 further improves the hemostatic ability, making it better than commercial hemostatic materials. Moreover, the photothermal conversion ability (derived from the polydopamine) was synergized with the phenolic hydroxyl group, quinone group, and the protonated amino group to effectively kill the bacteria in vitro and in vivo. Based on its in vitro and in vivo biosafety and satisfactory degradation ratio anti-inflammatory, antibacterial, and hemostatic properties, the CODM hydrogel holds promising potential for emergency hemostasis and intelligent wound management. [ABSTRACT FROM AUTHOR]

A direct and selective method for the α,β-dehydrogenation of esters using palladium catalysis in the presence of free O H and N H functionalities is reported herein. Allyl-palladium catalysis allows for preservation of readily oxidizable functionalities such as amines and alcohols. Furthermore, an economical protocol using LDA was developed for the dehydrogenation of β-amino esters. [ABSTRACT FROM AUTHOR]

A highly practical and step-economic α,β-dehydrogenation of carboxylic acids via enediolates is reported through the use of allyl-palladium catalysis. Dianions underwent smooth dehydrogenation when generated using Zn(TMP)2⋅2 LiCl as a base in the presence of excess ZnCl2, thus avoiding the typical decarboxylation pathway of these substrates. Direct access to 2-enoic acids allows derivatization by numerous approaches. [ABSTRACT FROM AUTHOR]

A highly practical and step-economic α,β-dehydrogenation of carboxylic acids via enediolates is reported through the use of allyl-palladium catalysis. Dianions underwent smooth dehydrogenation when generated using Zn(TMP)2⋅2 LiCl as a base in the presence of excess ZnCl2, thus avoiding the typical decarboxylation pathway of these substrates. Direct access to 2-enoic acids allows derivatization by numerous approaches. [ABSTRACT FROM AUTHOR]

Three-dimensional (3D) printing is suitable for the fabrication of complex radiotherapy bolus. Although investigated from dosimetric and feasibility standpoints, there are few reports to date of its use for actual patient treatment. This study illustrates the versatile applications of 3D printing in clinical radiation oncology through a selection of patient cases, namely, to create bolus for photon and modulated electron radiotherapy (MERT), as well as applicators for surface high-dose rate (HDR) brachytherapy. Photon boluses were 3D-printed to treat a recurrent squamous cell carcinoma (SCC) of the nasal septum and a basal cell carcinoma (BCC) of the posterior pinna. For a patient with a mycosis fungoides involving the upper face, a 3D-printed MERT bolus was used. To treat an SCC of the nose, a 3D-printed applicator for surface brachytherapy was made. The structures' fit to the anatomy and the radiotherapy treatment plans were assessed. Based on the treatment planning computed tomography (CT), the size of the largest air gap at the interface of the 3D-printed structure was 3 mm for the SCC of the nasal septum, 3 mm for the BCC of the pinna, 2 mm for the mycosis fungoides of the face, and 2 mm for the SCC of the nose. Acceptable treatment plans were obtained for the SCC of the nasal septum (95% isodose to 99.8% of planning target volume [PTV]), the BCC of the pinna (95% isodose to 97.7% of PTV), and the mycosis fungoides of the face (90% isodose to 92.5% of PTV). For the latter, compared with a plan with a uniform thickness bolus, the one featuring the MERT bolus achieved relative sparing of all the organs at risk (OARs) distal to the target volume, while maintaining similar target volume coverage. The surface brachytherapy plan for the SCC of the nose had adequate coverage (95% isodose to 95.6% of clinical target volume [CTV]), but a relatively high dose to the left eye, owing to its proximity to the tumor. 3D printing can be implemented effectively in the clinical setting to create highly conformal bolus for photon and MERT, as well as applicators for surface brachytherapy. [ABSTRACT FROM AUTHOR]

We consider the secure computation problem in a minimal model, where Alice and Bob each holds an input and wish to securely compute a function of their inputs at Carol without revealing any additional information about the inputs. For this minimal secure computation problem, we propose a novel coding scheme built from two steps. First, the function to be computed is expanded such that it can be recovered while additional information might be leaked. Second, a randomization step is applied to the expanded function such that the leaked information is protected. We implement this expand-and-randomize coding scheme with two algebraic structures—the finite field and the modulo ring of integers, where the expansion step is realized with the addition operation and the randomization step is realized with the multiplication operation over the respective algebraic structures. [ABSTRACT FROM AUTHOR]

In their Full Paper, Y. Zhao et al. show that a designed CsPbBr SB x sb Cl SB 3-x sb /TiO SB 2 sb photocatalyst with asymmetric halide distribution can efficiently improve charge transfer that expedites the toluene oxidation reaction. Inorganic halide perovskite, Heterojunction structure, Photocatalysis, Toluene oxidation Keywords: Inorganic halide perovskite; Heterojunction structure; Photocatalysis; Toluene oxidation EN Inorganic halide perovskite Heterojunction structure Photocatalysis Toluene oxidation 2539 2539 1 06/10/21 20210608 NES 210608 B The Cover Feature b shows a CsPbBr SB x sb Cl SB 3-x sb /TiO SB 2 sb photocatalyst during toluene oxidation reaction. [Extracted from the article]

• Push-out tests were carried out on 13 steel-plate HSC shear wall specimens with group studs. • High-strength concrete/recycled aggregate concrete is used. • Replacement of some studs with tie bar connectors is considered. • The bond-slip constitutive relationship of specimens is given. Steel-plate-reinforced concrete composite shear walls have been widely used in high-rise and super-high-rise buildings. To improve the bond behaviour between the steel plate and high-strength concrete (HSC) in shear walls, 13 steel-plate HSC shear wall (SPHSCSW) specimens with group studs were designed for push-out tests. Specimens were constructed using HSC or high-strength recycled aggregate concrete (HSRAC). Concrete strength, concrete type, stud length-to-diameter ratio, and replacement of studs with tie bar connectors are considered. The influence of different parameters on the interfacial bond behaviour of specimens is discussed by analysing the load-slip curves, bond strength, and interface damage energy dissipation. The equations for the shearing capacity of studs and the interfacial bond-slip constitutive relationship under different connectors were obtained. Results show that the influence of concrete strength on the bond strength of SPHSCSWs is positively correlated, and the bond behaviour with HSRAC is similar to that of normal HSC. When the stud length-to-diameter ratio exceeds four, increasing the ratio has little effect on improving the shearing capacity, and a further increase reduces the residual bond strength. Replacing some studs with tie bars can significantly improve the residual bond strength and interfacial bond energy dissipation capacity. The proposed equations for the shearing capacity of studs in SPHSCSWs and the bond-slip constitutive relationship agree well with the test results, which can be used for engineering applications and further research. [ABSTRACT FROM AUTHOR]

Summary: This paper proposes a wireline serial link transceiver for on‐package die‐to‐die links based on 12‐nm fin field‐effect transistor (FinFET) technology. The link is crucial for improving the computational performance of larger systems built from chiplets. To achieve high pin/energy efficiency and prevent traditional single‐ended signaling disadvantages, the transceiver adopts single‐ended ground‐reference signaling (GRS) to transfer information. To precompensate for the frequency‐dependent loss, retain the advantages of GRS, and avoid the disadvantages of traditional AC‐coupled equalizer, the transmitter in the transceiver adopts a DC‐coupled switched‐capacitor charge pump equalizer that can transmit GRS and its equilibrium value can be adjusted according to the channel attenuation. This paper proposes a method for timing de‐skew using digital control delay lines to eliminate the timing skew between data and the clock. In addition, this paper presents a duty cycle corrector to avoid duty cycle distortion, with an adjustment range of 44.5% to 52% and a power dissipation of only 30 μW. The transceiver has an area of 1.016 × 0.676 mm2, including one clock lane link and four data lane links. At a nominal 0.8‐V power supply voltage, the aggregate eye‐opening of the measured 25 Gb/s data on an organic substrate channel with an attenuation of −2.2 dB over 6 mm is 0.675 UI, with a bit error rate (BER) of less than 10−12 and an energy efficiency of 1.01 pJ/bit. [ABSTRACT FROM AUTHOR]

Purpose. Serum cytokines/chemokines play important roles in cryptococcal meningitis, but it is unclear whether cytokines/chemokines in cerebrospinal fluid (CSF) contribute to high intracranial pressure (HICP) in HIV-associated cryptococcal meningitis (HCM). Methods. CSF cytokines/chemokines were assayed in 17 HIV-uninfected patients, 26 HIV-infected patients without CNS infection, and 39 HCM patients at admission. Principal component analysis and correlation and logistic regression analyses were used to assess the relationships between these parameters. Results. The CSF Th1, Th2, and macrophage cytokines showed an obvious increase in HCM patients as compared to the HIV-uninfected patients and HIV-infected patients without CNS infection. CSF IL-6, GM-CSF, and IL-8 were positively correlated with CSF fungal burden. Serum CD4 count, CSF Th1 cytokines (TNF-α, TNF-β, IL-12, IL-1β, and INF-α2), and Th2 cytokines (IL-5 and IL-6) were closely related to cryptococcal meningitis. Furthermore, both Th1 cytokines (TNF-α, TNF-β, INF-γ, and IL-12) and Th2 cytokines (IL-4 and IL-10) contribute to HICP. Conclusion. Overall, the present findings indicated that both pro- and anti-inflammatory cytokines of Th1, Th2, and macrophage origin contributed to the development of HCM. Specifically, the chemokine and cytokine cascade caused by skewing of the Th1-Th2 balance and reduced CD4 count were found to be important contributors to HICP. Summary. Our research suggested that chemokine and cytokine cascade caused by skewing of the Th1-Th2 balance in HIV-infected patients played more important role than Cryptococcus numbers and size in CSF on the development of high intracranial pressure in HIV-associated cryptococcal meningitis, providing a new understanding of mechanisms of HCM. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract Proteasome-mediated degradation of proteins is a vital cellular process and is performed by the ubiquitin-dependent proteasome system (UPS) and the ubiquitin-independent proteasome system (UIPS). While both systems are necessary to maintain healthy cell function, many disease states are characterized by reduced activity of the UPS, and the UIPS cannot by itself maintain proper protein levels. It has been suggested that the 20S core particle (20S CP), the isoform of the proteasome in the UIPS that can degrade proteins without a ubiquitin tag, can be stimulated with a small molecule to assist the 20S CP to accept and hydrolyze substrates more rapidly. Several small molecule stimulators of the 20S CP have since been discovered, including AM-404, an arachidonic acid derivative. AM-404 has previously been shown to inhibit fatty acid amide hydrolase activity. We wished to evaluate what structural components of AM-404 are required to stimulate the 20S CP with the long-term goal of using this information to design a stimulator with better drug-like qualities. We synthesized numerous derivatives of AM-404, varying the chain length, substitutions, and degree of unsaturation. Through this endeavor, we obtained several molecules capable of stimulating the 20S CP to various degrees. We discovered that though chain length is important, the presence of a cis -alkene in a specific location in the aliphatic chain has the greatest impact on the ability to stimulate the 20S CP. Two of the derivatives maintain modest stimulatory activity, and have improved toxicity over AM-404. [ABSTRACT FROM AUTHOR]

We overview global clinical trials of targeted protein degradation (TPD) drugs for oncology across the past decade. The most common classes of TPD drugs in oncology clinical trials are selective estrogen receptor degraders (SERDs), immunomodulatory drugs (ImiDs), and proteolysis-targeting chimeras (PROTACs), all of which target protein degradation via the ubiquitin–proteasome system. Second-generation IMiDs with improved degradation potency could overcome resistance to lenalidomide and can treat more types of hematologic malignancies. The clinical development of oral SERDs still has many challenges, but several drugs have recently shown promising results in breast cancer patients with ESR1 mutations. Oral bioavailability and pharmacokinetics are two main issues that need to be addressed when developing clinically applicable PROTACs. Anticancer-targeted therapies inhibit various kinases implicated in cancer and have been used in clinical settings for decades. However, many cancer-related targets are proteins without catalytic activity and are difficult to target using traditional occupancy-driven inhibitors. Targeted protein degradation (TPD) is an emerging therapeutic modality that has expanded the druggable proteome for cancer treatment. With the entry of new-generation immunomodulatory drugs (IMiDs), selective estrogen receptor degraders (SERDs), and proteolysis-targeting chimera (PROTAC) drugs into clinical trials, the field of TPD has seen explosive growth in the past 10 years. Several challenges remain that need to be tackled to increase successful clinical translation of TPD drugs. We present an overview of the global landscape of clinical trials of TPD drugs over the past decade and summarize the clinical profiles of new-generation TPD drugs. In addition, we highlight the challenges and opportunities for the development of effective TPD drugs for future successful clinical translation. [ABSTRACT FROM AUTHOR]

An abstract of the article "Diastereoselective Formation of Aziridines from Diazocarbonyl Compounds and N-(O-Pivaloylated D-Galactosyl)benzylideneamines and Ring-Opening Reactions with P-Toluenethiol" by Y. Zhao, and G. Wang, S. Zhou is presented.

The telescoping of allyl-palladium catalyzed ketone dehydrogenation with organocuprate conjugate addition chemistry allows for the introduction of aryl, heteroaryl, vinyl, acyl, methyl, and other functionalized alkyl groups chemoselectively to a wide variety of unactivated ketone compounds via their enone counterparts. The compatibility of the dehydrogenation conditions additionally allows for efficient trapping of the intermediate enolate with various electrophiles. The utility of this approach is demonstrated by comparison to several previously reported multistep sequences. [ABSTRACT FROM AUTHOR]

The telescoping of allyl-palladium catalyzed ketone dehydrogenation with organocuprate conjugate addition chemistry allows for the introduction of aryl, heteroaryl, vinyl, acyl, methyl, and other functionalized alkyl groups chemoselectively to a wide variety of unactivated ketone compounds via their enone counterparts. The compatibility of the dehydrogenation conditions additionally allows for efficient trapping of the intermediate enolate with various electrophiles. The utility of this approach is demonstrated by comparison to several previously reported multistep sequences. [ABSTRACT FROM AUTHOR]

Special attention should be devoted to the thermal stability of hybrid perovskite solar cells (PSCs), because they are often operated at elevated temperatures. However, effective strategies are lacking for manipulation of heat flow in PSCs to improve their thermal stability. Here, a holistic solution is reported for the rapid removal of dissipated heat within the absorber by introducing hexagonal boron nitride (h‐BN) inside and radiator fin outside of the device. This strategy significantly improves the thermal conductivity of perovskite and speeds up the heat transfer of device, which effectively reduces the cell temperature under illumination of simulated AM 1.5G standard spectrum by ≈6.5 °C. Regardless of device configurations, the corresponding PSCs exhibit prolonged lifetimes aged at different temperatures, continuously operated under white light‐emitting diode (LED) lamp or full‐spectrum illumination. Of particular note, the optimized h‐BN/Cu device with n–i–p structure keeps 88% and 93% of its initial PCE after 1776 h of 85 °C thermal aging and 2451 h of maximum power point (MPP) tracking, respectively, and the device with p–i–n structure maintains 96% and 92% of its original PCE after 1704 h of 85 °C thermal aging and 2164 h of MPP tracking. [ABSTRACT FROM AUTHOR]

The process of atherosclerosis (AS) is complicated. Transcriptomics technology can assist in discovering the underlying mechanisms and exploring the key targets of Traditional Chinese Medicine (TCM) against atherosclerosis. This study aimed to investigate targets and signaling pathways significantly related to AS and the potential intervention targets of Xuefu Zhuyu decoction by transcriptomics. AS models were established by subjecting ApoE-/-mice to an 8-week high-fat diet. Structural changes and plaque formation in the aortic root were observed using hematoxylin-eosin staining (HE staining), while Oil Red O staining was employed to visualize lipid deposition within the aortic root plaque. Movat staining and immunohistochemical staining were conducted to examine the components present in the aortic root plaque. Macrophage content within the plaque was observed through immunofluorescence. Additionally, mRNA sequencing was performed on aortic tissues to identify differentially expressed genes. Enrichment analysis was performed using GO and KEGG analysis. Visualization of the protein-protein interaction (PPI) network was achieved using Cytoscape 3.7.1 and STRING. Western blotting (WB) was employed to assess the protein expression of major differentially expressed genes in the aortic tissue. The drug freeze-dried powder of Xuefu Zhuyu decoction was prepared and the RAW264.7 cells were induced by lipopolysaccharide (LPS) to build an in vitro model. Real-time quantitative PCR was employed to measure the mRNA expression of major differential genes. After ApoE-/- mice were fed with an 8-week high-fat diet, observable changes included the thinning of the aortic root wall, the accumulation of foam cells within the plaque, and the formation of cholesterol crystals in the model group. Treatment with Xuefu Zhuyu (XFZY) decoction for 12 weeks significantly reduced the lipid deposition and the number of macrophages (P < 0.05) and significantly increased the collagen content within the plaque (P < 0.01). Enrichment analysis revealed a high enrichment of the Cytokine-cytokine receptor interaction pathway and Chemokine signaling pathway. Noteworthy genes involved in this response included Ccl12 , Ccl22 , Cx3cr1 , Ccr7 , Ccr2 , Tnfrsf25 , and Gdf5. Xuefu Zhuyu decoction significantly downregulated the expression of CX3CL1 and CX3CR1 (P < 0.05) and upregulated the expression of GDF5 (P < 0.01). Compared with control group, in cell models, the mRNA expressions of Ccl12 , Ccl22 , and Ccr2 were significantly upregulated (P < 0.05 or P < 0.01). Xuefu Zhuyu decoction significantly downregulated the expression of Ccl12 , Ccl22 , Cx3cr1 , Ccr7 and Ccr2 (P < 0.05 or P < 0.01). Xuefu Zhuyu decoction demonstrates effective regulation of plaque components, retarding plaque progression and preserving plaque stability by modulating lipid metabolism and inflammatory responses. Subsequent transcriptome analysis identified the Cytokine-cytokine receptor interaction and Chemokine signaling pathway as potential key pathways for the therapeutic effects of Xuefu Zhuyu decoction. This insight not only provides crucial avenues for further exploration into the mechanisms underlying Xuefu Zhuyu decoction but also offers valuable perspectives and hypotheses for enhancing disease prevention and treatment strategies. [Display omitted] • XFZY reduced lipid deposition and macrophage infiltration, increased collagen of plaques. • Cytokine-cytokine receptor interaction and Chemokine signaling pathways were enriched in AS. • XFZY downregulated CX3CL1 and CX3CR1, and upregulated GDF5. [ABSTRACT FROM AUTHOR]

The phase ratio of a chromatographic system is an important measurement that has long been estimated or calculated, but rarely directly measured. This study utilized a nanoflow liquid chromatography instrument to more accurately measure the phase ratio for a lauryl acrylate porous polymer monolith. Direct measurement of the phase ratio, and its dependence on temperature, allows for a better understanding of the thermodynamics of retention of small analytes. This study investigates the retention of an alkyl benzene series, toluene to octylbenzene, via capillary electrochromatography. The phase ratio was determined to be 0.202 at 303 K and 0.213 at 333 K. Using the directly measured phase ratio, entropic contributions to retention can also be obtained. Therefore, the Gibbs free energy calculations from these measurements and methods can give insight to modes of retention. The free energy of retention for toluene is –3.97 kJ/mol at 303 K and –3.78 kJ/mol at 333 K. The trends for enthalpy, entropy, and Gibbs free energy of transfer show that retention is enthalpically driven in this capillary electrochromatography (CEC) porous polymer monolith system. [ABSTRACT FROM AUTHOR]

Context. About 15 million people worldwide suffer strokes each year and 5 million people are left with permanent disabilities which is due to the loss of local blood supply to the brain, resulting in a neurologic deficit. Panax notoginseng (Bruk.) F. H. Chen (Araliaceae) is a traditional Chinese herbal medicine widely used in the treatment of cardio-cerebrovascular diseases. Objective. This study investigated whether Panax notoginseng saponins (PNS) extracted from Panax notoginseng (Bruk.) F. H. Chen played a neuroprotective role by affecting the EGFR/PI3K/AKT pathway in oxygen-glucose deprived (OGD) SH-SY5Y cells. Materials and Methods. Different groups of OGD SH-SY5Y cells were treated with varying doses of PNS, PNS + AG1478 (a specific inhibitor of EGFR), or AG1478 for 16 hours. CCK8, Annexin V-FITC/PI apoptosis analysis, and LDH release analysis were used to determine cell viability, apoptosis rate, and amounts of LDH. Quantitative real-time PCR (q-RT-PCR) and western blotting were used to measure mRNA and proteins levels of p-EGFR/EGFR, p-PI3K/PI3K, and p-AKT/AKT in SH-SY5Y cells subjected to OGD. Results. PNS significantly enhanced cell viability, reduced apoptosis, and weakened cytotoxicity by inhibiting the release of LDH. The mRNA expression profiles of EGFR, PI3K, and AKT showed no difference between model and other groups. Additionally, ratios of p-EGFR, p-PI3K, and p-AKT to EGFR, PI3K, and AKT proteins expression, respectively, all increased significantly. Conclusions. These findings indicate that PNS enhanced neuroprotective effects by activating the EGFR/PI3K/AKT pathway and elevating phosphorylation levels in OGD SH-SY5Y cells. [ABSTRACT FROM AUTHOR]

Patients with heart failure (HF) are more susceptible to cognitive impairment, but the mechanism is still unclear. This study aimed to observe the dynamic changes in brain glucose metabolism and neuronal structure in different stages of HF. An HF rat model was established by ligating the anterior descending branch of the left coronary artery. To simulate acute heart failure (AHF) and chronic heart failure (CHF) in the clinic, relevant laboratory indexes were detected 10 and 60 days after ligation. The results showed that the model rats had systolic HF. Cognitive function was not obviously impaired in 10-day rats with HF, while the memory and learning functions were significantly impaired in 60-day rats with HF. The brain glucose metabolism in 10-day rats compensatorily increased in the prefrontal cortex (PFC), medial PFC (mPFC), cingulate gyrus, and basal ganglia (BG). In contrast, the metabolism of 60-day rats reduced in the PFC and BG. Meanwhile, the neuronal structure slightly changed in 10-day rats with HF, but neuronal karyopyknosis, reduced Nissl bodies, and swollen organelles were found in 60-day rats with HF. In conclusion, brain glucose metabolism and neuronal structure showed a dynamic evolution. Rats with AHF were in a compensatory state for increased glucose metabolism and slight neuronal damage. As a result, no significant cognitive impairment was observed. However, rats with CHF had significantly decreased cerebral glucose metabolism and neuronal degeneration, contributing to the cognitive function after HF. [ABSTRACT FROM AUTHOR]

Background. A large number of proinflammatory/anti-inflammatory cytokines are produced in the extracellular matrix (ECM) after myocardial infarction (MI), and the inflammatory pathways activated by these inflammatory stimuli are involved in the regulation of lesions with excessive accumulation of ECM. Wenxin granules can play a protective role against MI, but the mechanism of its effect on the inflammatory pathway and ECM collagen expression is still unclear. Objective. To verify the effect of Wenxin granules on the inflammatory pathway and collagen expression after MI. Method. The proximal left anterior descending coronary artery in rats was ligated to induce acute MI. Then, animals were randomly assigned to the model group, the Carvedilol group, and the Wenxin Granules group. In addition, sham operation rats were used as the control group. 10 rats were allocated in each group. Gavage was given once a day for 4 weeks. The changes of cardiac hemodynamics were detected by the catheter method, morphological changes were observed by HE staining, and myocardial tissue collagen volume was counted by Immunohistochemistry combined with Masson staining, and the expression of inflammatory TGFβ-p38/JNK MAPK signal pathway markers was detected by Western blot. Results. Wenxin granules could significantly improve the hemodynamics, so that the fibrosis scar was relatively dense and uniform, and the residual myocardium was relatively neat, while Collagen type I and III volume and TGFβ expression levels were lessened. Although there were no differences in the expression of CTGF, p38, and JNK proteins, their phosphorylation levels showed significant differences. Conclusion. Wenxin granules can affect the inflammation-related TGFβ-p38/JNK MAPK signaling pathway and change the structural properties of myocardium and scar after MI by attenuated collagen deposition in the left ventricular myocardial tissue to improve cardiac function. [ABSTRACT FROM AUTHOR]

Qiliqiangxin capsule (QLC), a natural herb recipe with therapeutic effect from China, has been widely used in clinical practice for attenuating cardiac remodeling induced by myocardial infarction (MI). However, the pharmacological mechanism of QLC on cardiac remodeling after MI is not entirely clear. The present study aims to investigate the effectiveness and mechanisms of QLC on cardiac remodeling induced by MI in rats. The animal model was established by permanently ligating the left anterior descending coronary artery in rats. Subsequently, rats with successful ligation were randomly divided into model group, captopril group, and QLC group. And the control group was operated upon in parallel except ligation, namely, the sham group. All rats were treated through the intragastric administration once a day for 4 weeks. Cardiac hemodynamics was measured after treatment. Then, the left ventricular mass index (LVMI) was examined. The pathological changes were observed by HE staining. The collagen volume fraction (CVF) was detected by Masson trichrome staining. The apoptosis index was obtained by TUNEL fluorescent staining. The miR-133a and mRNA of TGF-β1, CTGF, Caspase9, and Caspase3 were examined by real-time PCR. The protein expressions of TGF-β1, CTGF, Caspase9, Caspase3, and cleaved-Caspase3 were tested by Western blot. Compared with the model group, QLC partially improved cardiac hemodynamics and decreased LVMI. miR-133a was significantly increased in QLC group. In addition, QLC declined CVF by downregulating TGF-β1 rather than CTGF. Meanwhile, QLC decreased the apoptosis index by attenuating Caspase9, Caspase3, and cleaved-Caspase3. This study suggested that QLC could improve cardiac function and partially attenuate cardiac remodeling by attenuating fibrosis and decreasing apoptosis, which might be partially related to miR-133a, TGF-β1, Caspase9, and Caspase3. [ABSTRACT FROM AUTHOR]

ABX3‐type halide perovskite nanocrystals (NCs) have been a hot topic recently due to their fascinating optoelectronic properties. It has been demonstrated that A‐site ions have an impact on their photophysical and chemical properties, such as the optical band gap and chemical stability. The pursuit of halide perovskite materials with diverse A‐site species would deepen the understanding of the structure–property relationship of the perovskite family. In this work we have attempted to synthesize rubidium‐based perovskite NCs. We have discovered that the partial substitution of Rb+ by Cs+ help to stabilize the orthorhombic RbPbBr3 NCs at low temperature, which otherwise can only be obtained at high temperature. The inclusion of Cs+ into the RbPbBr3 lattice results in highly photoluminescent Rb1−xCsxPbBr3 NCs. With increasing amounts of Cs+, the band gaps of the Rb1−xCsxPbBr3 NCs decrease, leading to a redshift of the photoluminescence peak. Also, the Rb1−xCsxPbBr3 NCs (x=0.4) show good stability under ambient conditions. This work demonstrates the high structural flexibility and tunability of halide perovskite materials through an A‐site cation substitution strategy and sheds light on the optimization of perovskite materials for application in high‐performance optoelectronic devices. Adding stability: Lead halide perovskite nanocrystals (NCs) attract tremendous attention due to their extraordinary optical properties. Herein, we show that the partial substitution of Rb+ by Cs+ helps to stabilize the orthorhombic RbPbBr3 NCs at low temperature, which otherwise could only be obtained at high temperature (above 300 °C, see figure). [ABSTRACT FROM AUTHOR]

Background/Aims: Qiliqiangxin (QL), a traditional Chinese medicine, has been demonstrated to be effective and safe for the treatment of chronic heart failure. Left ventricular (LV) remodeling causes depressed cardiac performance and is an independent determinant of morbidity and mortality after myocardial infarction (MI). Our previous studies have shown that QL exhibits cardiac protective effects against heart failure after MI. The objective of this study was to explore the effects of QL on myocardial fibrosis in rats with MI and to investigate the underlying mechanism of these effects. Methods: A rat model of acute myocardial infarction was induced by ligating the left anterior descending coronary artery. The rats were treated with QL (1.0 g/kg/day) for 4 weeks after surgery. Echocardiography and histology examination were performed to evaluate heart function and fibrosis, respectively. Protein levels of transforming growth factor-β1 (TGF-β1), phosphorylated Smad3 (p-Smad3), phosphorylated Smad7 (p-Smad7), collagen I (Col- I), alpha smooth muscle actin (a-SMA), tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), nuclear factor κB (NF-κB), and phosphorylated inhibitor of kappa B alpha (p-IκBα) were measured by western blot analysis. Results: QL treatment ameliorated adverse cardiac remodeling 8 weeks after AMI, including better preservation of cardiac function, decreased inflammation, and reduced fibrosis. In addition, QL treatment reduced Col-I, a-SMA, TGF-β1, and p-Smad3 expression levels but increased p-Smad7 levels in postmyocardial infarct rat hearts. QL administration also reduced the elevated levels of cardiac inflammation mediators, such as TNF-α and IL-6, as well as NF-κB and p-IκBα expression. Conclusions: QL therapy exerted protective effects against cardiac remodeling potentially by inhibiting TGF-β1/Smad3 and NF-κB signaling pathways, thereby preserving cardiac function, as well as reducing myocardial inflammation and fibrosis. [ABSTRACT FROM AUTHOR]

Currently, numerous thermal comfort models have been proposed; however, research on the combination of different models is lacking. This study aims to predict the overall thermal sensation (OTS*) and thermal comfort (OTC*) with different model combinations under hot and cold step changes. Three cold- and hot-shock processes are designed in the climate chamber. Accordingly, the skin temperature, thermal sensation, and thermal comfort votes of 16 participants are collected. The impacts of winter hot and cold step changes on subjective votes and skin temperatures are evaluated. Further, the OTS* and OTC* values are calculated, and their accuracy under different model combinations is analyzed. The results reveal that thermal sensation changes in human body exhibit distinct asymmetry under the cold and hot step-changes, except for the cycle of "15–30–15 °C" (I15). The parts farther from the core area become more asymmetrical after the step changes. The single models exhibit the highest accuracy in different model combinations. The combined form of a single model is recommended for thermal sensation or comfort prediction. • Discuss the thermal perception of the cold and hot impulse in winter. • Five model combinations in thermal sensation and comfort are obtained. • The parts farther from the core area become more asymmetrical after the step-changes. • The combination form of a single model is recommended for thermal sensation or comfort prediction. [ABSTRACT FROM AUTHOR]

Two-dimensional (2D) organic-inorganic hybrid halide perovskites have gained extensive attention in photovoltaics, photodetectors and light-emitting diodes owing to their unique optoelectronic properties and superior stability compared with their three-dimensional (3D) counterparts. However, 2D perovskites have rarely been applied for photochemical conversion applications. Herein, a series of 2D BA 2 MA n-1 Pb n Br 3n+1 perovskite nanosheets have been synthesized through a facile, ligand-free precipitation (LFP) method at room temperature. Using the specific chemical trapping techniques, we show for the first time that the 2D perovskite nanosheets can effectively generate photosensitized singlet oxygen (1O 2) via energy transfer from triplet excitons to molecular oxygen in non-polar solvent. Based on this discovery, the as-prepared BA 2 PbBr 4 and BA 2 MAPb 2 Br 7 nanosheets successfully catalyze the ENE reaction and 1,2-addition reaction between olefin and singlet oxygen under visible light. Our study is anticipated to develop and demonstrate new mechanisms for 2D halide perovskite materials in photodynamic therapy and photocatalytic applications. 2D BA 2 MA n-1 PbnBr 3n+1 perovskite nanosheets are shown for first time to effectively generate photosensitized 1O 2 via energy transfer and can catalyze the ENE reaction and the 1,2-additional reaction between olefins and O 2. This study illustrates novel mechanisms of 2D perovskite materials in photodynamic therapy and photocatalytic applications. [Display omitted] • 2D BA 2 MA n-1 Pb n Br 3n+1 nanosheets are synthesized by ligand-free precipitation method. • Photosensitized 1O 2 generation in 2D perovskites via energy transfer is first studied. • BA 2 PbBr 4 and BA 2 MAPb 2 Br 7 nanosheets can drive olefins to react with O 2 for ENE reaction and 1,2-addition reaction. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Panax notoginseng saponins (PNS) extracted from a traditional Chinese herbal medicine, Panax notoginseng (Burkill) F.H. Chen (Araliaceae), which has been extensively used in treating coronary heart disease, ischemic cerebrovascular disease and hemorrhagic disorders in China over hundreds of years. Aims of the study This study explored whether panax notoginseng saponins (PNS) provided neuroprotective effects by inhibiting the expressions of NgR1, RhoA, and ROCK2 following middle cerebral artery occlusion in rats and oxygen-glucose deprivation/reoxygenation (OGD/R) injury in SH-SY5Y cells. Materials and methods 2,3,5-Triphenyltetrazolium chloride staining was used to determine successful middle cerebral artery occlusion establishment in sham-operated and operated Sprague–Dawley rats 1 day after injury. The rats were randomly separated into sham, model, NEP1-40, PNS, and NEP1-40 plus PNS (N+P) groups. After 7 days of treatment, body mass and neurological deficit scores were analyzed. Tissues were harvested and analyzed by hematoxylin-eosin staining and immunohistochemical analysis, western blotting, and quantitative real-time PCR (qRT-PCR). The optimal drug concentration of NEP1-40 and PNS on SH-SY5Y cells exposed to OGD/R injury was determined by CCK8 analysis. qRT-PCR was used to measure mRNA expression profiles of NgR1, RhoA, and ROCK2 in SH-SY5Y cells subjected to OGD/R. Results The results showed that MCAO surgery successfully produced an infarct, and the PNS, NEP1-40, and N+P groups exhibited increased body mass and ameliorated neurological deficits compared with the model group. NEP1-40 treatment markedly reduced NgR1 and RhoA overexpression when compared to the model group, although there was no significant difference in ROCK2 expression. PNS and N+P treatment significantly decreased NgR1, RhoA, and ROCK2 overexpression compared with the model group. However, N+P treatment did not result in a synergistic effect, as assessed by immunohistochemistry, western blotting, and qRT-PCR. Following optimal administration of PNS (160 μg/ml) and NEP1-40 (10 ng/ml) on SH-SY5Y cells exposed to OGD/R injury, cell viability in the NEP1-40, PNS, and N+P groups significantly increased compared with the model group, as assessed by CCK8 analysis. Additionally, NgR1, RhoA, and ROCK2 mRNA expression profiles were significantly less in the NEP1-40, PNS, and N+P groups compared with the model group. Conclusion PNS provided neuroprotective effects in a rat model of cerebral ischemia and SH-SY5Y cells exposed to oxygen/glucose deprivation injury by inhibiting the overexpression of NgR1, RhoA, and ROCK2. [ABSTRACT FROM AUTHOR]

Qili qiangxin (QL) capsule is a traditional Chinese medicine that is widely used for the treatment of patients with chronic heart failure (CHF) of all etiologies, although the exact mechanisms of action remain unclear. CHF leads to pulmonary vascular remodelling and thickening of the alveolar-capillary barrier that may be important mechanisms in the poor clinical outcome in patients with end-stage heart failure. We examined whether QL could improve lung injury in ischemic CHF by reducing lung remodeling. Rats with myocardial infarct received QL (1.0 g/kg/day) for 4 weeks. Echocardiographic and morphometric measurements were obtained followed by echocardiography, histological staining, and immunohistochemical analysis of lung sections. CHF caused significant lung structural remodeling evidenced by collagen deposition and thickening of the alveolar septa after myocardial infarct that were greatly improved by QL. Lung weight increased after infarct with no evidence of pulmonary edema and was normalized by QL. QL also reduced lung transforming growth factor-β1 (TGF-β1), p-Smad3, tumor necrosis factor-α (TNF-α), and Toll-like receptor-4 (TLR4) expression. Thus, QL reduces lung remodeling associated with CHF, mainly by suppressing the TGF-β1/Smad3 signaling pathway. The mechanism may also involve inhibition of TLR4 intracellular signaling. [ABSTRACT FROM AUTHOR]

Qili qiangxin capsule (QL), a traditional Chinese herbal compound, has been proved to be effective and safe for the treatment of chronic heart failure (CHF). Upregulation of aquaporin-2 (AQP2) accounts for the water retention in CHF. The aim of the present study was to evaluate the effects of QL on the expression of AQP2 in rats with CHF induced by acute myocardial infarction and to investigate the underlying mechanisms. The urine output of all rats was quantified and collected every day at the first week and the 4th week after administration of QL or Valsartan. The expression of AQP2, vasopressin type 2 receptor (V2R), and angiotensin II type 1 receptor (AT1R) were examined after treatment for 4 weeks. Urinary output increased significantly after administration of QL. Importantly, the protein expression of AQP2 and AQP2 phosphorylated at serine 256 (pS256-AQP2) was downregulated after administration of QL and Valsartan to CHF rats. Furthermore, QL reduced plasma arginine vasopressin (AVP) and angiotensin II (AngII) level and downregulated V2R and AT1R protein expression. Thus, QL exerts its diuretic effect and improves cardiac function in CHF rats by reversing the increases in both AQP2 and pS256-AQP2 expression. The possible mechanisms may involve inhibition of V2R and AT1R. [ABSTRACT FROM AUTHOR]

Yiqi Huoxue (YQHX) is widely used in traditional Chinese medical practice due to its reported cardioprotective effects. The aim of the present study was to investigate the mechanism underlying these effects of YQHX via the regulation of the Sigma-1 receptor. The Sigma-1 receptor is a chaperone protein located on the mitochondrion-associated endoplasmic reticulum (ER) membrane. It serves an important role in heart function by regulating intracellular Ca2+ homeostasis and enhancing cellular bioenergetics. In the present study, male Sprague Dawley rats with myocardial infarction (MI)-induced heart failure were used. MI rats were administered different treatments, including normal saline, YQHX and fluvoxamine, an agonist of the Sigma-1 receptor. Following four weeks of treatment, YQHX was revealed to improve heart function and attenuate myocardial hypertrophy in MI rats. Additionally, YQHX increased the ATP content and improved the mitochondrial ultrastructure in the heart tissues of MI rats in comparison with acontrol. Treatment was revealed to attenuate the decreased expression of the Sigma-1 receptor and increase the expression of inositol triphosphate type 2 receptors (IP3R2) in MI rats. By exposing H9c2 cells to angiotensin II (Ang II), YQHX prevented cell hypertrophy and normalized the decreased ATP content. However, these positive effects were partially inhibited when the Sigma-1 receptor was knocked down via small interfering RNA transfection. The results of the present study suggested that the Sigma-1 receptor serves an important role in the cardioprotective efficacy of YQHX by increasing ATP content and attenuating cardiomyocyte hypertrophy. [ABSTRACT FROM AUTHOR]

The accurate measurement of phase ratio is needed to determine the thermodynamic parameters of reversed phase retention on lauryl acrylate PPMs used in a CEC mode. DOI: 10.1002/jssc.202001285 The cover picture shows the elegant direct measurement of phase ratio via capillary electrochromatography (CEC), using a porous polymer monolith (PPM) as the stationary phase. Linear van't Hoff plots combined with the newly acquired phase ratios yield enthalpies, entropies, and Gibbs free energies of retention for an alkyl benzene series of analytes across a thirty-degree temperature range. [Extracted from the article]

Xuesaitong (XST) is a traditional Chinese medicine injection with neuroprotective properties and has been extensively used to treat stroke for many years. The main component of XST is Panax notoginseng saponins (PNS), which is the main extract of the Chinese herbal medicine Panax notoginseng. In this study, we investigated whether XST provided long-term neuroprotection by inhibiting neurite outgrowth inhibitor-A (Nogo-A) and the ROCKII pathway in experimental rats after middle cerebral artery occlusion (MCAO) and in SH-SY5Y cells exposed to oxygen-glucose deprivation/reperfusion (OGD/R). Rats with permanent MCAO were administered XST, Y27632, XST plus Y27632, and nimodipine for 14 and 28 days. Successful MCAO onset was confirmed by 2,3,5-triphenyl tetrazolium chloride (TTC) staining. Neurological deficit score (NDS) was used to assess neurological impairment. Hematoxylin-eosin (HE) staining and immunohistochemical (IHC) analysis of synaptophysin (SYN) and postsynaptic density protein-95 (PSD-95) were performed to evaluate cerebral ischemic injury and the neuroprotective capability of XST. Nogo-A levels and the ROCKII pathway were detected by IHC analysis, western blotting, and quantitative real-time polymerase chain reaction (qRT-PCR) to explore the protective mechanism of XST. OGD/R model was established in SH-SY5Y cells. Cell counting kit 8 (CCK8) was applied to detect the optimum OGD time and XST concentration. The expression levels Nogo-A and ROCKII pathway were determined using western blotting. Our results showed that XST reduced neurological dysfunction and pathological damage, promoted weight gain and synaptic regeneration, reduced Nogo-A mRNA and protein levels, and inhibited the ROCKII pathway in MCAO rats. CCK8 assay displayed that the optimal OGD time and optimal XST concentration were 7 h and 20 μg/mL respectively in SH-SY5Y cells. XST could evidently inhibit OGD/R-induced Nogo-A protein expression and ROCKII pathway activation in SH-SY5Y cells. The present study suggested that XST exerted long-term neuroprotective effects that assisted in stroke recovery, possibly through inhibition of the ROCKII pathway. [Display omitted] [ABSTRACT FROM AUTHOR]

• The synthesis of PPy nanoparticles (PPy-PVP NPs) using a vapor deposition method. • This method allows the formation of uniform PPy-PVP NPs at room temperature. • PVP 40kDa can ensure a better performance of the synthesized PPy-PVP NPs. In recent years, nanomaterials have aroused people's interest in the field of biomedicine. Polypyrrole (PPy) has become a research hotspot because of its simple synthesis, excellent photothermal conversion performance, and high biocompatibility. Here, we report the synthesis of PPy nanoparticles (PPy-PVP NPs) using a vapor deposition method, for tumor photothermal therapy. In this method, the slowly produced volatile pyrrole vapor was absorbed by the PVP (polyvinylpyrrolidone)/FeCl 3 aqueous solution. This slow vapor production and absorption allows the formation of uniform PPy-PVP NPs at room temperature. Then, the effects of the molecular weight of PVP on the photothermal property and anti-tumor efficiency of PPy-PVP NPs were compared. It was found that the selection of PVP 40kDa as the template and surface linker can ensure a better application performance of the synthesized nanomaterials. This work provides a theoretical basis for the rational design of nano-therapy carriers and biomedical applications. [ABSTRACT FROM AUTHOR]

• Push-out tests were carried out on 16 concrete-filled square steel tube specimens with different constructions. • The size of square steel tubes is 400 mm. • The in-filled concrete adopted high-strength concrete or recycled concrete. • The constitutive relationship of specimens is given. To solve the problem of insufficient interface bond strength of concrete-filled square steel tubes (CFSSTs), 16 large CFSST specimens with eight different types of connectors (no additional connectors, built-in studs, built-in circular ribs, built-in vertical ribs, built-in reinforcement cage, and various combinations of the above) were designed for push-out testing. Specimens were constructed using high-strength concrete or high-strength recycled aggregate concrete (RAC). The bond behavior and slip failure mechanism were analyzed by comparing the force-slip curves, slip displacements, and steel tube strains. The bond strength calculation method and bond-slip constitutive relationship of the interface under multiple parameters were obtained. Experiments revealed the following: bond-slip curves for CFSST without additional connectors were composed of an ascending section and a residual section; for tubes with different connectors, the peak values of the curves were higher; the performance-price ratio of studs and circular ribs for improving bond strength was high, and the combined use of studs and circular ribs can work well; the combination of circular ribs and vertical ribs can significantly improve bond strength and energy dissipation capacity; RAC had better bond behavior than normal concrete in HSCFSST without additional connectors or built-in vertical ribs. The predicted force-slip curves agreed well with the test curves, providing a theoretical basis for CFSST applications. [ABSTRACT FROM AUTHOR]

To investigate the bond-slip behavior of the interface in large high-strength concrete-filled circular steel tubes (HSCFCSTs), 18 specimens with 6 different constructions (HSCFCSTs with no additional construction, with built-in studs, with built-in circular ribs, with built-in vertical ribs, and with various combinations of the above) were examined using push-out tests. Specimens were constructed from high-strength concrete or recycled aggregate concrete (RAC). The bond-slip behavior and slip-failure mechanisms were analyzed through comparison of load-slip curves, slip displacements, and steel tube strain to generate predicted load-slip curves based on multiple parameters. Experiments revealed that the bond-slip curves of HSCFCSTs with no additional constructions contained an ascending section, a rapidly descending section, and a residual section. For tubes with special constructions, the descending section was either postponed or not visible, the interfacial bonding properties were enhanced when using special constructions, the concrete strength and bond strength were positively correlated, and the RAC had better bonding behavior than normal concrete. The predicted load-slip curves agreed with the test curves and provided a theoretical basis for HSCFCST applications. • Push-out tests were carried out on 18 HSCFCST specimens with 6 different constructions. • The diameter of circular steel tubes is 400 mm. • The in-filled concrete adopted 3 types of high-strength concrete. • The constitutive relationship of HSCFCSTs with different constructions is given. [ABSTRACT FROM AUTHOR]