Ion Substitution Strategy of Manganese-Based Layered Oxide Cathodes for Advanced and Low-Cost Sodium Ion Batteries.

Sodium ion batteries (SIBs) have recently been promising in the large-scale electric energy storage system, due to the low cost, abundant sodium resources. Mn-based layered oxide cathode materials have been widely investigated, because of the high theoretical specific capacity, low cost, and abundant reserves. However, their development is limited by the problems of Jahn-Teller distortion, Na+ /vacancy ordering, complex phase transitions, and irreversible anionic redox during cycling. Ion substitution strategy is one simple and effective way to regulate the crystal structure and boost sodium-storage performances of Mn-based cathode materials. In this review, we summarize the progress and mechanism of ion-substituted Mn-based oxides, establish a composition-crystal structure-electrochemical performance relationship, and also offer perspectives for guiding the design of high-performance Mn-based oxides for SIBs.

Design and synthesis of new indole containing biaryl derivatives as potent antiproliferative agents.

A new series of indole containing biaryl derivatives were designed and synthesized, and further biological evaluations of their antiproliferative activity against cancer cell lines (MGC-803 and TE-1 cells) were also conducted. Of these synthesized biaryls, compound 4-methyl-2-((5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)methyl)quinazoline (23) performed as the most potent antiproliferative agent that inhibited cell viability of MGC-803 cells with an IC50 value of 8.28 µM. In addition, investigation of mechanism exhibited that the compound 4-methyl-2-((5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)methyl)quinazoline (23) could inhibit the expression of c-Myc and glycolysis related proteins, decrease the ATP and lactate production, and further induce apoptosis by activating the AMP-activated protein kinase (AMPK) and p53 signaling pathways.

CuBr/NHPI co-catalyzed aerobic oxidative [3 + 2] cycloaddition-aromatization to access 5,6-dihydro-pyrrolo[2,1-a]isoquinolines.

An efficient and enviromentally friendly CuBr/NHPI co-catalyzed aerobic oxidative [3 + 2] cycloaddition-aromatization cascade was realized with N-substituted tetrahydroisoquinolines and electron-deficient olefins. Under the mild conditions, the reaction proceeded smoothly and displayed excellent functional group tolerance, affording 5,6-dihydro-pyrrolo[2,1-a]isoquinolines in good to high yields. This protocol exhibits a broad substrate scope to both N-alkyl tetrahydroisoquinolines and dipolarophile substrates.

Lichen endophyte derived pyridoxatin inactivates Candida growth by interfering with ergosterol biosynthesis.

BACKGROUND: This study is to characterize the antifungal effects of pyridoxatin (PYR), a small natural product isolated from an endolichenic fungus. METHODS: The susceptibility tests in vitro and in vivo by using Caenorhabditis elegans as an infectious model were performed to evaluate the antifungal efficacy of PYR against Candida species. The cytotoxicity of PYR against normal human cells was tested using MTT assay. The transcriptional levels of genes related to sterol synthesis and cell cycle regulation were measured using real-time quantitative PCR (qPCR). The contents ergosterol, squalene, lanosterol were detected by liquid chromatography/tandem mass spectrometry (LC/MS). RESULTS: PYR was effective against four tested Candida species with its minimal inhibitory concentrations (MICs) ranging from 1-4µg/ml. No obvious cytotoxicity was observed for PYR against normal human cells. PYR inhibited the growth of Candida albicans, preventing the biofilm formation. And the antifungal action was independent on efflux pumps. The in vivo test showed PYR greatly prolonged the survival of infected C. elegans. qPCR results revealed that most of the genes related to sterol biosynthesis were considerably down-regulated in PYR-treated cells. Determination of the sterol content found that PYR inhibited the ergosterol synthesis dose dependently and caused the accumulation of squalene and lanosterol. Moreover, analysis of the structure-activity relationship revealed the heterocyclic hydroxamic acid in PYR was the key group for the antifungal action. CONCLUSIONS: PYR interferes with the ergosterol synthesis to exert antifungal action. GENERAL SIGNIFICANCE: The elucidated mechanism provides possible applications of PYR in fighting clinical relevant fungal infections.

Chromium(II)-catalyzed enantioselective arylation of ketones.

The chromium-catalyzed enantioselective addition of carbo halides to carbonyl compounds is an important transformation in organic synthesis. However, the corresponding catalytic enantioselective arylation of ketones has not been reported to date. Herein, we report the first Cr-catalyzed enantioselective addition of aryl halides to both arylaliphatic and aliphatic ketones with high enantioselectivity in an intramolecular version, providing facile access to enantiopure tetrahydronaphthalen-1-ols and 2,3-dihydro-1H-inden-1-ols containing a tertiary alcohol.

Practical metal-free C(sp(3))-H functionalization: construction of structurally diverse α-substituted N-benzyl and N-allyl carbamates.

Described is a practical and universal CH functionalization of readily removable N-benzyl and N-allyl carbamates, with a wide range of nucleophiles at ambient temperature promoted by Ph3 CClO4 . The metal-free reaction has an excellent functional-group tolerance, and displays a broad scope with respect to both N-carbamates and nucleophile partners (a variety of organoboranes and CH compounds). The synthetic utility in target- as well as diversity-oriented syntheses is demonstrated.

Face privacy protection scheme by security-enhanced encryption structure and nonlinear dynamics.

This article proposes a secure communication enhancement scheme based on face detection and chaotic partition permutation. The scheme uses edge detection technology to detect facial information, which is then used as an encryption object. The hash value of the plaintext image is extracted as the secret key to the chaotic sequence generated by the chaotic system. Then a series of encryption operations are performed on the face image to obtain the final ciphertext image. In this article, two chaotic systems are used to generate pseudo-random chaotic sequences for different encryption steps. The initial key is computed by combining the hash function of the image and external parameters. The experimental results and security analysis show that the algorithm has excellent encryption effectiveness and security performance against various typical attacks.

Aggregation-induced emission enhancement (AIEE) active bispyrene-based fluorescent probe: "turn-off" fluorescence for the detection of nitroaromatics.

The detection of nitroaromatic explosives in real samples is essential for environmental monitoring because of their strongly powerful nature and wide applications in industries. Aggregation-induced emission enhancement (AIEE) active fluorescent probe has been widely employed to detect nitroaromatic explosives. Hereby, a simple V-shaped bispyrene-based fluorescent probe (called py-o) with AIEE properties was designed and synthesized, which was fully charactered by 1D NMR, ESI, FTIR, and 2D NOESY spectra. The py-o displayed bright blue-green fluorescence excimer emission at 480 nm in DMF/H2O (v/v 1:1). It is observed that the fluorescence excimer emission of py-o at 480 nm was quenched by PA in solution with a quenching constant of 5.45 × 104 M-1, and the limit of detection was approximately 0.139 µM. The details of the sensing mechanism were explained using 1H NMR titrations, Job's plot and Bensi-Hildebrand methods, which revealed a 1:1 binding ratio via the π-π interactions between PA and py-o. Meanwhile, it exhibited outstanding anti-interference ability in the detection of PA when interfering analytes were added under the same conditions. Furthermore, low-cost thin-layer chromatography (TLC) plates coated with py-o were developed as fluorescent tools for naked-eye detection of PA in the solid state. Therefore, this work provides a new method for constructing an AIEE fluorescent probe for the detection of nitroaromatic explosives to utilize in environmental monitoring.

Structure-Based Optimization of Novel Sterol 24-C-Methyltransferase Inhibitors for the Treatment of Candida albicans Infections.

Interfering with sterol biosynthesis is an important strategy for developing safe and effective antifungal drugs. We previously identified compound H55 as an allosteric inhibitor of the fungal-specific C-24 sterol methyltransferase Erg6 for treating Candida albicans infections. Herein, 62 derivatives of H55 were designed and synthesized based on target-ligand interactions to identify more active candidates. Among them, d28 displayed the most potent antivirulence ability (MHIC50 = 0.25 µg/mL) by targeting Erg6, exhibiting an 8-fold increase in potency compared with H55. Moreover, d28 significantly outperformed H55 in inhibiting cell adhesion and biofilm formation, and exhibited minimal cytotoxicity and negligible potential to induce drug resistance. Of note, the coadministration of d28 and other sterol biosynthesis inhibitors, such as tridemorph or terbinafine, demonstrated a strong synergistic antifungal action in vitro and in vivo in a murine skin infection model. These results support the potential application of d28 in the treatment of C. albicans infections.

Manganese dioxide-methanesulfonic acid promoted direct dehydrogenative alkylation of sp3 C-H bonds adjacent to a heteroatom.

A manganese dioxide (MnO2)-methanesulfonic acid (CH3SO3H) oxidation system has been developed to efficiently promote direct coupling of benzylic ethers and carbamates with simple ketones via oxidative C-H bond activation. The alkylation proceeds smoothly under air atmosphere to afford the corresponding products in good to excellent yields (53-87%). The employment of the combination of MnO2 and CH3SO3H is attractive on the basis of economical and environmental issues.

Chaos-based block permutation and dynamic sequence multiplexing for video encryption.

This paper proposes a video security transmission enhancement algorithm based on block permutation and dynamic multiplexing sequences encryption based on 4D autonomous hyperchaotic system. Firstly, we employ the block permutation encryption and diffusion confusion encryption module, which is based on dynamic multiplexing chaotic sequences, to encrypt the plaintext and obtain the ciphertext. Subsequently, the hash value of this round's ciphertext is utilized to generate the chaotic key, produced by the multiplexing sequence of this round after mathematical processing. Then, the key is used to generate the chaotic sequence to confuse the N-th of the multiplexed sequence, and the next round of multiplexed sequence is obtained. If the current round of chaotic sequence has been completely confused, the chaotic sequence is re-generated to generate a new multiplex sequence by using the key generated by the current round key and the initial key. Finally, the above steps are repeated for the encryption of each frame of the video. Compared with the traditional permutation coding algorithm, it increases the difficulty of estimation or recognition while ensuring efficiency, and effectively improves the avalanche effect of the algorithm. Through frame by frame ciphertext closed-loop feedback, it has the ability to resist known plaintext attack and selected plaintext attack. The results show that the scheme has high security and significant diffusion characteristics, and can effectively resist various common cryptographic attacks.

Cu/Ti co-doping boosting P2-type Fe/Mn-based layered oxide cathodes for high-performance sodium storage.

Environmentally friendly P2-type layered iron manganese oxides appear to be one of the most potential cathode materials for sodium-ion batteries (SIBs). However, their practical application is hindered by the unfavorable phase transitions, dissolution of transition metals, and poor air stability. One effective strategy by either single-cation doping or high-cost Li involved co-doping is used to alleviate the problems. Here, low-cost Cu/Ti co-doping is introduced to boost P2-Na0.7Cu0.2Fe0.2Mn0.5Ti0.1O2 as an air and electrochemical stable cathode material for SIBs. The resulting electrode delivers an initial capacity of 130 mAh g-1 at 0.1C within 2.0-4.2 V, a reversible discharge capacity of 61.0 mAh g-1 at a high rate of 5C and a capacity retention ratio exceeding 71.1% after 300 cycles. In particular, the co-doped crystal structure is well-maintained after 1 month of exposure to air, and even 3 days of soaking in water. Furthermore, the enhancement is elucidated by the effectively mitigated P2-Z and the completely suppressed P2-P'2 phase transitions, the decreased volume variation proved by in-situ X-ray diffraction (XRD), as well as the lowered transition-metal dissolution evidenced by inductively coupled plasma optical emission spectrometer (ICP-OES) and X-ray photoelectron spectroscopy (XPS). The low-lost Cu/Ti doping strategy could thus be effective for designing and preparing environmentally friendly and high-performance cathode materials for SIBs.

Benzamidine Conjugation Converts Expelled Potential Active Agents into Antifungals against Drug-Resistant Fungi.

Fungal infections present a growing global public health concern, necessitating the development of novel antifungal drugs. However, many potential antifungals, particularly the expelled potential active agents (EPAAs), are often underestimated owing to their limitations in cellular entry or expulsion by efflux pumps. Herein, we identified 68 EPAAs out of 2322 candidates with activity against a Candida albicans efflux pump-deficient strain and no inhibitory activity against the wild-type strain. Using a novel conjugation strategy involving benzamidine (BM) as a mitochondrion-targeting warhead, we successfully converted EPAAs into potent antifungals against various urgent-threat azole-resistantCandida strains. Among the obtained EPAA-BM conjugates, IS-2-BM (11) exhibited excellent antifungal activities and induced negligible drug resistance. Furthermore, IS-2-BM prevented biofilm formation, eradicated mature biofilms, and exhibited excellent therapeutic effects in a murine model of systemic candidiasis. These findings provide a promising strategy for increasing the possibilities of discovering more antifungals.

Diagnostic Potential of Endometrial Cancer DNA from Pipelle, Pap-Brush, and Swab Sampling.

Endometrial cancer (EC) is a major gynecological malignancy with rising morbidity and mortality worldwide. The aim of this study was to explore a safe and readily available sample and a sensitive and effective detection method and its biomarkers for early diagnosis of EC, which is critical for patient prognosis. This study designed a panel targeting variants for EC-related genes, assessed its technical performance by comparing it with whole-exon sequencing, and explored the diagnostic potential of endometrial biopsies using the Pipelle aspirator, cervical samples using the Pap brush, and vaginal specimens using the swab from 38 EC patients and 208 women with risk factors for EC by applying targeted panel sequencing (TPS). TPS produced high-quality data (Q30 > 85% and mapping ratios > 99.35%) and was found to have strong consistency with whole-exome sequencing (WES) in detecting pathogenic mutations (92.11%), calculating homologous recombination deficiency (HRD) scores (r = 0.65), and assessing the microsatellite instability (MSI) status of EC (100%). The sensitivity of TPS in detection of EC is slightly better than that of WES (86.84% vs. 84.21%). Of the three types of samples detected using TPS, endometrial biopsy using the Pipelle aspirator had the highest sensitivity in detection of pathogenic mutations (81.87%) and the best consistency with surgical tumor specimens in MSI (85.16%). About 84% of EC patients contained pathogenic mutations in PIK3CA, PTEN, TP53, ARID1A, CTNNB1, KRAS, and MTOR, suggesting that this small gene set can achieve an excellent pathogenic mutation detection rate in Chinese EC patients. The custom panel combined with ultra-deep sequencing serves as a sensitive method for detecting genetic lesions from endometrial biopsy using the Pipelle aspirator.

Inhibitory effects of a maleimide compound on the virulence factors of Candida albicans.

Candidiasis caused by Candida albicans infection has long been a serious human health problem. The pathogenicity of C. albicans is mainly due to its virulence factors, which are novel targets of antifungal drugs for low risk of resistance development. In this study, we identified a maleimide compound [1-(4-methoxyphenyl)-1hydro-pyrrole-2,5-dione, MPD] that exerts effective anti-virulence activity. It could inhibit the process of adhesion, filamentation, and biofilm formation in C. albicans. In addition, it exhibited low cytotoxicity, hemolytic activity, and drug resistance development. Moreover, in Galleria mellonella-C. albicans (in vivo) infection model, the survival time of infected larvae was significantly prolonged under the treatment of MPD. Further, mechanism research revealed that MPD increased farnesol secretion by upregulating the expression of Dpp3. The increased farnesol inhibited the activity of Cdc35, which then decreased the intracellular cAMP content resulting in the inhibition of virulence factors via the Ras1-cAMP-Efg1 pathway. In all, this study evaluated the inhibitory effect of MPD on various virulence factors of C. albicans and identified the underlying mechanisms. This suggests a potential application of MPD to overcome fungal infections in clinics.

Selective Metal Chelation by a Thiosemicarbazone Derivative Interferes with Mitochondrial Respiration and Ribosome Biogenesis in Candida albicans.

Metal chelation is generally considered as a promising antifungal approach but its specific mechanisms are unclear. Here, we identify 13 thiosemicarbazone derivatives that exert broad-spectrum antifungal activity with potency comparable or superior to that of fluconazole in vitro by screening a small compound library comprising 89 thiosemicarbazone derivatives as iron chelators. Among the hits, 19ak exhibits minimal cytotoxicity and potent activity against either azole-sensitive or azole-resistant fungal pathogens. Mechanism investigations reveal that 19ak inhibits mitochondrial respiration mainly by retarding mitochondrial respiratory chain complex I activity through iron chelation, and further reduces mitochondrial membrane potential and ATP synthesis in Candida albicans. In addition, 19ak inhibits fungal ribosome biogenesis mainly by disrupting intracellular zinc homeostasis. 19ak also stimulates the activities of antioxidant enzymes and decreases reactive oxygen species formation in C. albicans, resulting in an increase in detrimental intracellular reductive stress. However, 19ak has minor effects on mammalian cells in depleting intracellular iron and zinc. Moreover, 19ak exhibits low capacity to induce drug resistance and in vivo efficacy in a Galleria mellonella infection model. These findings uncover retarded fungal mitochondrial respiration and ribosome biogenesis as downstream effects of disruption of iron and zinc homeostasis in C. albicans and provide a basis for the thiosemicarbazone 19ak in antifungal application. IMPORTANCE The increasing incidence of fungal infections and resistance to existing antifungals call for the development of broad-spectrum antifungals with novel mechanisms of action. In this study, we demonstrate that a thiosemicarbazone derivative 19ak selectively inhibits mitochondrial respiration mainly by retarding mitochondrial respiratory chain complex I activity through iron chelation and inhibits ribosome biogenesis mainly by disrupting intracellular zinc homeostasis in C. albicans. In addition, 19ak exhibits low capacity to induce fungal resistance, minimal cytotoxicity, and in vivo antifungal efficacy. This study provides the basis of thiosemicarbazone derivative 19ak as a metal chelator for the treatment of fungal infections.

How Leader-Member Exchange Affects Creative Performance: An Examination From the Perspective of Self-Determination Theory.

It has been shown that leadership is a major factor that influences creative performance. Although past studies have found that leader-member exchange (LMX) has direct effects on employee creative performance, there continues to be a lack of research examining how the LMX relationship mediates creative performance. This study used self-determination theory to examine the mediating effects of the LMX relationship on creative performance through attitudinal and emotional processes. Participants were supervisors and subordinates of township enterprises in the Pearl River Delta in China. There were 386 valid supervisor-subordinate dyads. Supervisors were responsible for assessing creative performance and the remaining variables were completed by employees. Results showed that high LMX increased the positive moods of subordinates, improved creative performance, and stimulated intrinsic motivation for improvement. Based on the results, we have proposed academic and practical recommendations such as organizations that want to encourage creativity, could begin by training managers to demonstrate high LMX by strengthening their relationships with employees. We also described study limitations, and suggested directions for future studies.

Determination of the in vitro metabolic stability and metabolites of the anticancer derivative riccardin D-N in human and mouse hepatic S9 fractions using HPLC-Q-LIT-MS.

Riccardin D-N (RD-N) is an aminomethylated derivative of the macrocyclic bisbibenzyl compound riccardin D (RD), which has shown stronger activity against cancer cells than RD. However, there has been no research on the metabolism of RD-N. The present study aimed to characterize the in vitro metabolism and metabolic stability of RD-N after incubation with mouse and human hepatic S9 fractions using high performance liquid chromatography-hybrid triple quadrupole/linear ion trap mass spectrometry (HPLC-Q-LIT-MS). Multiple ion monitoring (MIM) and multiple reaction monitoring (MRM)-information dependent acquisition-enhanced product ion (MIM/MRM-IDA-EPI) scans were used to identify the metabolites formed. MRM scans were also used to quantify the changes in the amount of RD-N and to semi-quantify the main metabolites. Twenty-eight metabolic products were detected and 25 structures were predicted. Hydroxylation, dehydrogenation, glucuronidation, and methylation were proposed to be the principle metabolic pathways in the in vitro incubation with human and mouse hepatic S9 fractions. There were differences in the number and abundance of RD-N metabolites between the human and mouse hepatic S9 fractions. RD-N was shown to have good metabolic stability. After 2 h of incubation, 44% of the original RD-N remained in the human hepatic S9 fraction compared with 22% in the mouse. The major metabolites of RD-N, M4, M8, M20 and M21, were monitored semi-quantitatively using the typical transitions. Finally, HPLC-Q-LIT-MS was used for the identification and quantitation of the metabolites of R D-N, which is a simple and efficient method to rapidly screen potential drug candidates.

Design and synthesis of furyl/thineyl pyrroloquinolones based on natural alkaloid perlolyrine, lead to the discovery of potent and selective PDE5 inhibitors.

Based on perlolyrine (1), a natural alkaloid with weak PDE5 potency from the traditional Chinese aphrodisiac plant Tribulus terrestris L., a series α-substituted tetrahydro-ß-carboline (THßC) derivatives were synthesized via T+BF4--mediated oxidative C-H functionalization of N-aryl THßCs with diverse potassium trifluoroborates. Following Winterfeldt oxidation afforded the corresponding furyl/thienyl pyrroloquinolones, of which 5-ethylthiophene/ethylfuran derivatives 20a-b were identified as the most potent and selective PDE5 inhibitors. Among the enantiomers, (S)-20a and (S)-20b (IC50 = 0.52 and 0.39 nM) were found to be more effective than their (R)-antipode, display favorable pharmacokinetic profiles, exert in vitro vasorelaxant effects on the isolated thoracic aorta, and exhibit in vivo efficacy in the anesthetized rabbit erectile model.

Discovery of furyl/thienyl ß-carboline derivatives as potent and selective PDE5 inhibitors with excellent vasorelaxant effect.

Based on our previous studies and predictive docking results, furans and thiophenes were introduced to the privileged tetrahydro-ß-carboline scaffold to generate more potent and selective PDE5 inhibitors. A total of 66 novel furyl/thienyl tetrahydro-ß-carboline derivatives were designed, synthesized and evaluated for PDE5 inhibition. Tetrahydro-ß-carboline-piperazinedione 19f and tetrahydro-ß-carboline-hydantoin 26b with optimized pendant 5-ethylfuran/5-ethylthiophene were identified as the most potent PDE5 inhibitors, and showed high selectivity towards PDE5 versus other PDE isozymes, especially PDE6 and PDE11. Further vasorelaxant activity assessments revealed that these PDE5 inhibitors also exhibited significant angiectasis on the norepinephrine-precontracted 3rd-order mesenteric arteries (110-150 µm) via NO-sGC-cGMP pathway, implying their further application for the treatment of vascular diseases.