Construction of Photothermo-Electro Coupling Field Based on Surface Modification of Hydrogenated TiO2 Nanotube Array Photoanode and Its Improved Photoelectrochemical Water Splitting.

Solar water splitting has gained increasing attention in converting solar energy into green hydrogen energy. However, the construction of a photothermo-electro coupling field by harnessing light-induced heat and its enhancement on solar water splitting were seldom studied. Herein, we developed a full-spectrum responsive photoanode by depositing CdxZn1-xS onto the surface of hydrogenated TiO2 nanotube array (H-TNA), followed by modification with Ni2P. The resulting ternary photoanode exhibits a photocurrent density of 4.99 mA·cm-2 at 1.23 V vs. RHE with photoinduced heating, which is 11.9-fold higher than that of pristine TNA, with an optimal ABPE of 2.47%. The characterization results demonstrate that the ternary photoanode possesses superior full-spectrum absorption and efficient photogenerated carrier separation driven by the interface electric fields. Additionally, Ni2P reduces the hole injection barrier and increases surface active sites, accelerating the consumption of holes accumulating on the relatively unstable CdxZn1-xS to simultaneously improve the activity and stability of water splitting. Moreover, temperature-dependent measurements reveal that H-TNA and Ni2P significantly motivate the photothermal conversion to construct a photothermo-electro coupling field, optimizing photoelectric conversion and charge carrier-induced surface reactions. This work contributes to understanding the synergistic effect of the photothermo-electro coupling field on the photoelectrochemical water splitting.

Mechanism Analysis and Property Prediction of Extended Surfactants Based on the Respectively Optimized Force Field.

Extended surfactants represent a novel class of anionic-nonionic surfactants with exceptional performance and unique application value in chemically enhanced oil recovery. Although molecular dynamics (MD) simulations can efficiently screen these surfactants, the current research is limited. Here, it is proven for the first time that existing generic force fields (GAFF and CHARMM) cannot accurately describe extended surfactants, and traditional approaches are insufficient for obtaining precise charge parameters. The concept of the respectively optimized force field (ROFF) with the purports of specialization and accuracy is proposed to construct high-accuracy models for MD simulations, and a new approach is developed to simulate the interface model. By combining the newly specialized alkane model, ROFF-based surfactant models, and the innovative simulation protocol, high accuracy and reliability can be obtained in predicting hydration free energies, minimum of area per molecule, and critical micelle concentration of extended surfactants. Key properties of the newly designed extended surfactants in conventional oil-water interfaces and oil reservoir environments are comprehensively predicted by using advanced analytical and characterization methods. Furthermore, the more rigorous mechanism underlying the special amphiphilicity of the extended surfactant is revealed, potentially offering significant improvements over previous empirical perspectives.

Novel Indole-Containing Hybrids Derived from Millepachine: Synthesis, Biological Evaluation and Antitumor Mechanism Study.

Millepachine, a bioactive natural product isolated from the seeds of Millettia pachycarpa, is reported to display potential antitumor activity. In this study, novel indole-containing hybrids derived from millepachine were designed, synthesized and evaluated for their antitumor activities. Among all the compounds, compound 14b exhibited the most potent cytotoxic activity against five kinds of human cancer cell lines, with IC50 values ranging from 0.022 to 0.074 µM, making it almost 100 times more active than millepachine. Valuable structure-activity relationships (SARs) were obtained. Furthermore, the mechanism studies showed that compound 14b induced cell-cycle arrest at the G2/M phase by inhibiting tubulin polymerization and further induced cell apoptosis through reactive oxygen species (ROS) accumulation and mitochondrial membrane potential (MMP) collapse. In addition, the low cytotoxicity toward normal human cells and equivalent sensitivity towards drug-resistant cells of compound 14b highlighted its potential for the development of antitumor drugs.

Improving Semantic Segmentation via Decoupled Body and Edge Information.

In this paper, we propose a method that uses the idea of decoupling and unites edge information for semantic segmentation. We build a new dual-stream CNN architecture that fully considers the interaction between the body and the edge of the object, and our method significantly improves the segmentation performance of small objects and object boundaries. The dual-stream CNN architecture mainly consists of a body-stream module and an edge-stream module, which process the feature map of the segmented object into two parts with low coupling: body features and edge features. The body stream warps the image features by learning the flow-field offset, warps the body pixels toward object inner parts, completes the generation of the body features, and enhances the object's inner consistency. In the generation of edge features, the current state-of-the-art model processes information such as color, shape, and texture under a single network, which will ignore the recognition of important information. Our method separates the edge-processing branch in the network, i.e., the edge stream. The edge stream processes information in parallel with the body stream and effectively eliminates the noise of useless information by introducing a non-edge suppression layer to emphasize the importance of edge information. We validate our method on the large-scale public dataset Cityscapes, and our method greatly improves the segmentation performance of hard-to-segment objects and achieves state-of-the-art result. Notably, the method in this paper can achieve 82.6% mIoU on the Cityscapes with only fine-annotated data.

Design, synthesis and biological evaluation of phthalimide-alkylamine derivatives as balanced multifunctional cholinesterase and monoamine oxidase-B inhibitors for the treatment of Alzheimer's disease.

A series of novel phthalimide-alkylamine derivatives were synthesized and evaluated as multi-functions inhibitors for the treatment of Alzheimer's disease (AD). The results showed that compound TM-9 could be regarded as a balanced multi-targets active molecule. It exhibited potent and balanced inhibitory activities against ChE and MAO-B (huAChE, huBuChE, and huMAO-B with IC50 values of 1.2µM, 3.8µM and 2.6 µM, respectively) with low selectivity. Both kinetic analysis of AChE inhibition and molecular modeling study suggested that TM-9 binds simultaneously to the catalytic active site and peripheral anionic site of AChE. Interestingly, compound TM-9 abided by Lipinski's rule of five. Furthermore, our investigation proved that TM-9 indicated weak cytotoxicity, and it could cross the blood-brain barrier (BBB) in vitro. The results suggest that compound TM-9, an interesting multi-targeted active molecule, offers an attractive starting point for further lead optimization in the drug-discovery process against Alzheimer's disease.

Design, synthesis and biological evaluation of 2-acetyl-5-O-(amino-alkyl)phenol derivatives as multifunctional agents for the treatment of Alzheimer's disease.

A series of 2-acetyl-5-O-(amino-alkyl)phenol derivatives was designed, synthesized and evaluated as multi-function inhibitors for the treatment of Alzheimer's disease (AD). The results revealed that compound TM-3 indicated selective AChE inhibitory potency (eeAChE, IC50 = 0.69 µM, selective index (SI) = 32.7). Both kinetic analysis of AChE inhibition and molecular modeling study suggested that TM-3 could simultaneously bind to the catalytic active site and peripheral anionic site of AChE. And TM-3 was also a highly selective MAO-B inhibitor (IC50 = 6.8 µM). Moreover, TM-3 could act as antioxidant (ORAC value was 1.5eq) and neuroprotectant, as well as a selective metal chelating agent. More interestingly, compound TM-3 could cross the blood-brain barrier (BBB) in vitro and abided by Lipinski's rule of five. Therefore, compound TM-3, a promising multi-targeted active molecule, offers an attractive starting point for further lead optimization in the drug-discovery process against AD.

Design, synthesis and biological evaluation of 3,4-dihydro-2(1H)-quinoline-O-alkylamine derivatives as new multipotent cholinesterase/monoamine oxidase inhibitors for the treatment of Alzheimer's disease.

A new family of multitarget molecules able to interact with acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), as well as with monoamino oxidase (MAO) A and B, has been synthesized. Novel 3,4-dihydro-2(1H)-quinoline-O-alkylamine derivatives have been designed using a conjunctive approach that combines the JMC49 and donepezil. The most promising compound TM-33 showed potent and balance inhibitory activities toward ChE and MAO (eeAChE, eqBuChE, hMAO-A and hMAO-B with IC50 values of 0.56µM, 2.3µM, 0.3µM and 1.4µM, respectively) but low selectivity. Both kinetic analysis of AChE inhibition and molecular modeling study suggested that TM-33 binds simultaneously to the catalytic active site and peripheral anionic site of AChE. Furthermore, our investigation proved that TM-33 could cross the blood-brain barrier (BBB) in vitro, and abided by Lipinski's rule of five. The results suggest that compound TM-33, an interesting multi-targeted active molecule, offers an attractive starting point for further lead optimization in the drug-discovery process against Alzheimer's disease.

Cp*CoIII-Catalyzed Synthesis of Pyrido[2',1':2,3]pyrimido[1,6-a]indol-5-iums via Tandem C-H Activation and Subsequent Annulation from 1-(Pyridin-2-yl)-1H-indoles and Internal Alkynes.

A Cp*CoIII-catalyzed C2-selective C-H alkenylation/annulation cascade transformation of 1-(pyridin-2-yl)-1H-indoles with internal alkynes to afford pyrido[2',1':2,3]pyrimido[1,6-a]indol-5-iums is presented. Moreover, 6,7-dihydro-4H-pyrido[2',1':2,3]pyrimido[1,6-a]indole, a new functionalized N-fused indole core heterocycle, could be constructed effectively via reduction of pyrido[2',1':2,3]pyrimido[1,6-a]indol-5-ium by NaBH4.

Design, synthesis and evaluation of novel ferulic acid-memoquin hybrids as potential multifunctional agents for the treatment of Alzheimer's disease.

A novel series of ferulic acid-memoquin hybrids were designed, synthesized and evaluated as multifunctional agents for the treatment of Alzheimer's disease (AD). The in vitro studies showed that most of the compounds exhibited a significant ability to inhibit acetylcholinesterase (AChE) (IC50 of 3.2-34.7µM) and self-induced ß-amyloid (Aß1-42) aggregation (30.8-39.1%, 25µM), to act as potential antioxidants (ORAC-FL value of 0.9-1.3). In particular, compound 17d had the greatest ability to inhibit AChE (IC50=3.2µM), and Aß1-42 aggregation (30.8%) was also an excellent antioxidant and neuroprotectant. Moreover, it is capable of disaggregating self-induced Aß aggregation. Furthermore, 17d could cross the blood-brain barrier (BBB) in vitro. The results showed that compound 17d is a potential multifunctional agent for the treatment of AD.

Copper-catalyzed oxidative amination of sp(3) C-H bonds under air: synthesis of 1,3-diarylated imidazo[1,5-a]pyridines.

A copper(II)-catalyzed tandem reaction between pyridine ketone and benzylamine was developed by using clean O2 as an oxidant. This transformation proceeded via an efficient condensation-amination-oxidative dehydrogenation process, affording 1,3-diarylated imidazo[1,5-a]pyridines in excellent yields.

Synthesis of N-vinylindoles through copper catalyzed cyclization reaction of N-(2-alkynylphenyl)imine.

A copper(II)-catalyzed cyclization reaction of N-(2-alkynylphenyl)imine was developed. This strategy provided an effective procedure for the synthesis of substituted N-vinylindoles in moderate to good yields.

Establishment and clinical application of a candidate reference measurement procedure for quantification of urinary vanillylmandelic acid and homovanillic acid using ID-LC-MS/MS method.

Neuroblastoma (NB), an embryonic tumor of the autonomous nervous system, poses a significant threat to the health and lives of children. Accurate measurement of vanillylmandelic acid (VMA) and homovanillic acid (HVA) in human urine is crucial for screening and diagnosis of NB. Although various laboratories have developed liquid chromatography tandem mass spectrometry (LC-MS/MS) method to detect VMA and HVA, the comparability between the results obtained from different laboratories and methods was poor. The absence of reference method for VMA and HVA hinders the standardization of their measurements. Therefore, a candidate reference measurement procedure (cRMP) based on isotope dilution LC-MS/MS (ID-LC-MS/MS) for the detection of VMA and HVA in human urine was established. Urine samples were spiked with VMA-d3 and HVA-d5 as internal standards and extracted using a protein precipitation method. The cRMP exhibited desirable precision with the total imprecision below 5 %. The accuracy of this cRMP was demonstrated by the high analytical recovery (98.64 % - 102.22 % and 98.41 % - 100.97 % for VMA and HVA, respectively), and comparability between different reference systems. The limit of detection for HVA and VMA were 15.625 ng/mL and 3.906 ng/mL, respectively; the quantification limits were 62.5 ng/mL and 7.813 ng/mL, respectively, which can meet the clinical detection requirements. The linear range was from 78.125 ng/mL to 20 µg/mL. Specificity evaluations showed no corresponding interference from structurally similar analogs. In conclusion, we have established a cRMP based on ID-LC-MS/MS for the measurement of VMA and HVA in urine samples, demonstrating well-defined method performance including accuracy, precision, and specificity. This newly established cRMP is suitable for routine assay standardization and evaluation of clinical samples. Furthermore, this method has the potential to significantly enhance the diagnostic accuracy for neuroblastoma.

Development of simultaneous quantitation method for 20 free advanced glycation end products using UPLC-MS/MS and clinical application in kidney injury.

Advanced glycation end products (AGEs), derived from the non-enzymatic glycation reaction, are defined as glycotoxins in various diseases including aging, diabetes and kidney injury. Exploring AGEs as potential biomarkers for these diseases holds paramount significance. Nevertheless, the high chemical structural similarity and great heterogeneity among AGEs present a formidable challenge when it comes to the comprehensive, simultaneous, and accurate detection of multiple AGEs in biological samples. In this study, an UPLC/MS/MS method for simultaneous quantification of 20 free AGEs in human serum was firstly established and applied to quantification of clinical samples from individuals with kidney injury. Simple sample preparation method through protein precipitation without derivatization was used. Method performances including imprecision, accuracy, sensitivity, linearity, and carryover were systematically validated. Intra- and inter- imprecision of 20 free AGEs were 1.93-5.94 % and 2.30-8.55 %, respectively. The method accuracy was confirmed with good recoveries ranging from 96.40 % to 103.25 %. The LOD and LOQ were 0.1-3.13 ng/mL and 0.5-6.25 ng/mL, respectively. Additionally, the 20 free AGEs displayed excellent linearity (R2 >0.9974) across a wide linear range (1.56-400 ng/mL). Finally, through simultaneous quantitation of 20 Free AGEs in 100 participants including kidney injury patient and healthy controls, we identified six free AGEs, including N6-carboxyethyl-L-arginine (CEA), N6-carboxymethyl-L-lysine (CML), methylglyoxal-derived hydroimidazolones (MG-H), N6-formyl-lysine, N6-carboxymethyl-L-arginine (CMA), and glyoxal-derived hydroimidazolone (G-H), could well distinguish kidney injury patients and healthy individuals. Among them, the levels of four free AGEs including CML, CEA, MG-H, and G-H strongly correlate with traditionally clinical markers of kidney disease. The high area under the curve (AUC) values (AUC=0.965) in receiver operating characteristic (ROC) curve indicated that these four free AGEs can be served as combined diagnostic biomarkers for the diagnosis of kidney disease.

In-situ observation of silk nanofibril assembly via graphene plasmonic infrared sensor.

Silk nanofibrils (SNFs), the fundamental building blocks of silk fibers, endow them with exceptional properties. However, the intricate mechanism governing SNF assembly, a process involving both protein conformational transitions and protein molecule conjunctions, remains elusive. This lack of understanding has hindered the development of artificial silk spinning techniques. In this study, we address this challenge by employing a graphene plasmonic infrared sensor in conjunction with multi-scale molecular dynamics (MD). This unique approach allows us to probe the secondary structure of nanoscale assembly intermediates (0.8-6.2 nm) and their morphological evolution. It also provides insights into the dynamics of silk fibroin (SF) over extended molecular timeframes. Our novel findings reveal that amorphous SFs undergo a conformational transition towards ß-sheet-rich oligomers on graphene. These oligomers then connect to evolve into SNFs. These insights provide a comprehensive picture of SNF assembly, paving the way for advancements in biomimetic silk spinning.

Multifunctional Protection Layers via a Self-Driven Chemical Reaction To Stabilize Lithium Metal Anodes.

The Li metal anode is considered one of the most potential anodes due to its highest theoretical specific capacity and the lowest redox potential. However, the scalable preparation of safe Li anodes remains a challenge. In the present study, a LiF-rich protection layer has been developed using self-driven chemical reactions between the Li3xLa2/3-xTiO3/polyvinylidene fluoride/dimethylacetamide (LLTO/PVDF/DMAc) solution and the Li metal. After coating the LLTO/PVDF/DMAc solution to Li foil, PVDF reacted with Li spontaneously to form LiF, and the accompanying Ti4+ ions (in LLTO) were reduced to Ti3+ to form a mixed ionic and electronic conductor LixLLTO. The protective layer can redistribute the Li-ion transport, regulate the even Li deposition, and inhibit the Li dendrite growth. When paired with LiFePO4, NCM811, and S cathodes, the batteries have demonstrated excellent capacity retention and cycling stability. More importantly, a volumetric energy density of 478 Wh L-1 and 78% capacity retention after 310 cycles have been achieved by using a S/LixLLTO-Li pouch cell. This work provides a feasible avenue to provide large-scale preparation of safe Li anodes for the next-generation pouch-type Li-S batteries as ideal power sources for flexible electronic devices.

Tuning the Band Structure of MoS2 via Co9S8@MoS2 Core-Shell Structure to Boost Catalytic Activity for Lithium-Sulfur Batteries.

The introduction of a dual-functional interlayer into lithium-sulfur batteries (LSBs) provides many opportunities for restraining the "shuttle effect" and enhancing sluggish sulfur conversion kinetics. Tuning the band structure of the metal sulfide provides an opportunity to enhance its catalytic activity, which plays an important role in suppressing the "shuttle effect" of lithium polysulfides (LiPSs) in LSBs. Here were present a Co9S8@MoS2 core-shell heterostructure anchored to a carbon nanofiber (Co9S8@MoS2/CNF), developed as an interlayer for suppressing the shuttle effect of LiPSs. The fabricated composite heterostructure is determined to be an effective alternative material that combines the synergistic relationship between chemisorption and electrochemical catalysis. We find that the band structure of the MoS2 shell can be effectively tuned by the Co9S8 core and that the Co9S8@MoS2/CNF can capture the LiPSs, providing excellent catalytic ability to convert LiPSs into Li2S2, with subsequent transformation from Li2S2 to Li2S. Importantly, high capacities of 1002 and 986 mAh g-1 can be retained after 50 cycles with high-sulfur loadings of 6 and 10 mg cm-2. Our results highlight the design of an atomic-scale heterostructure as a multifunctional interlayer providing a synergistic relationship between adsorption and catalysis. The net result is an effective retardation of the shuttling of LiPSs and an enhancement of the electrochemical redox reactions of LiPSs. This work shows great promise toward the development of practical applications of LSBs.

Apigenin-rivastigmine hybrids as multi-target-directed liagnds for the treatment of Alzheimer's disease.

Here we reported novel apigenin-rivastigmine hybrids were rationally designed and synthesized by the multi-target-directed ligands (MTDLs) strategy, their activity in vitro results revealed that compound 3d showed significant antioxidant potency (ORAC = 1.3 eq), and it was a reversible huAChE (IC50 = 6.8 µM) and huBChE (IC50 = 16.1 µM) inhibitor. 3d also served as a selective metal chelator, and it significantly inhibited and disaggregated self-mediated and Cu2+-mediated Aß1-42 aggregation, and also inhibited hAChE-mediated induced Aß1-40 aggregation. Compound 3d exhibited remarkable neuroprotective effect and hepatoprotective activity. In addition, compound 3d presented favourable blood-brain barrier penetration in vitro and drug-like property. Further, the in vivo assay displayed that 3d indicated remarkable dyskinesia recovery rate and response efficiency on AD zebrafish, and exhibited surprising protective effect on Aß1-40-mediated zebrafish vascular injury. More importantly, 3d did not indicate obvious acute toxicity at dose up to 2000 mg/kg, and could improve scopolamine-induced memory impairment. Subsequently, the regulation of multi-targets for 3d were further confirmed through transcriptome sequencing of brain hippocampi, which also offered novel potential targets and opened a new way to treat Alzheimer's disease. More interestingly, the metabolism of 3din vitro indicated that 4 metabolites in rat liver microsome metabolism, 2 metabolites in human liver microsome metabolism, and 4 metabolites in intestinal flora metabolism, which offered supports for the preclinical study of 3d. Overall, this study exhibited that compound 3d was a promising advanced compound targeted multiple factors associated with AD.

Li0.35La0.55TiO3 Nanofibers Enhanced Poly(vinylidene fluoride)-Based Composite Polymer Electrolytes for All-Solid-State Batteries.

Using polymer electrolytes with relatively high mechanical strength, enhanced safety, and excellent flexibility to replace the conventional liquid electrolytes is an effective strategy to curb the Li-dendrite growth in Li-metal batteries (LMBs). However, low ionic conductivity, unsatisfactory thermal stability, and narrow electrochemical window still hinder their applications. Here, we fabricate Li0.35La0.55TiO3 (LLTO) nanofiber-enabled poly(vinylidene fluoride) (PVDF)-based composite polymer electrolytes (CPEs) with enhanced mechanical property and wide electrochemical window. The results show that 15 wt % of LLTO nanofibers synergize with PVDF, giving a flexible electrolyte membrane with significantly improved performance, such as high ionic conductivity (5.3 × 10-4 S cm-1), wide electrochemical window (5.1 V), high mechanical strength (stress 9.5 MPa, strain 341%), and good thermal stability (thermal degradation 410 °C). In addition, an all-solid-state Li-metal battery of sandwich-type LiFePO4/PVDF-CPE (15 wt % of LLTO)/Li delivers satisfactory cycling stability and outstanding rate performance. A reversible capacity of 121 mA h g-1 is delivered at 1 C after 100 cycles. This work exemplifies that the introduction of LLTO nanofibers can improve the electrochemical performances of PVDF-based CPEs used as electrolytes for all-solid-state LMBs.

Polydatin prevents the induction of secondary brain injury after traumatic brain injury by protecting neuronal mitochondria.

Polydatin is thought to protect mitochondria in different cell types in various diseases. Mitochondrial dysfunction is a major contributing factor in secondary brain injury resulting from traumatic brain injury. To investigate the protective effect of polydatin after traumatic brain injury, a rat brain injury model of lateral fluid percussion was established to mimic traumatic brain injury insults. Rat models were intraperitoneally injected with polydatin (30 mg/kg) or the SIRT1 activator SRT1720 (20 mg/kg, as a positive control to polydatin). At 6 hours post-traumatic brain injury insults, western blot assay was used to detect the expression of SIRT1, endoplasmic reticulum stress related proteins and p38 phosphorylation in cerebral cortex on the injured side. Flow cytometry was used to analyze neuronal mitochondrial superoxide, mitochondrial membrane potential and mitochondrial permeability transition pore opened. Ultrastructural damage in neuronal mitochondria was measured by transmission electron microscopy. Our results showed that after treatment with polydatin, release of reactive oxygen species in neuronal mitochondria was markedly reduced; swelling of mitochondria was alleviated; mitochondrial membrane potential was maintained; mitochondrial permeability transition pore opened. Also endoplasmic reticulum stress related proteins were inhibited, including the activation of p-PERK, spliced XBP-1 and cleaved ATF6. SIRT1 expression and activity were increased; p38 phosphorylation and cleaved caspase-9/3 activation were inhibited. Neurological scores of treated rats were increased and the mortality was reduced compared with the rats only subjected to traumatic brain injury. These results indicated that polydatin protectrd rats from the consequences of traumatic brain injury and exerted a protective effect on neuronal mitochondria. The mechanisms may be linked to increased SIRT1 expression and activity, which inhibits the p38 phosphorylation-mediated mitochondrial apoptotic pathway. This study was approved by the Animal Care and Use Committee of the Southern Medical University, China (approval number: L2016113) on January 1, 2016.

N-(4-Chloro-phen-yl)-4-(2-oxocyclo-pent-yl)butyramide.

In the title compound, C(15)H(18)ClNO(2), the amide group is coplanar with the chloro-phenyl group, making a dihedral angle of 1.71 (12)°. The cyclo-penta-none ring adopts a twist conformation. A weak intra-molecular C-H⋯O hydrogen bond is observed. Mol-ecules are linked into cyclic centrosymmetric dimers by paired N-H⋯O hydrogen bonds.