Silicon-Containing Thiol-Specific Bioconjugating Reagent.

A new bioconjugation reagent containing silicon has been developed for the selective reaction with thiols. The inclusion of silicon significantly improves chemoselectivity and suppresses retro processes, thereby exceeding the capabilities of traditional reagents. The method is versatile and compatible with a broad range of thiols and unsaturated carbonyl compounds and yields moderate to high results. These reactions can be conducted under biocompatible conditions, thereby making them suitable for protein bioconjugation. The resulting conjugates display good stability in the presence of various biomolecules, which suggests their potential application for the synthesis of antibody-drug conjugates. Furthermore, the presence of a silicon moiety within the conjugated products opens up new avenues for drug release and bridging inorganics with other disciplines. This new class of silicon-containing thiol-specific bioconjugation reagents has significant implications for researchers working in bioanalytical science and medicinal chemistry and leads to innovative opportunities for advancing the field of bioconjugation research and medicinal chemistry.

Inhibiting IL11RA to mitigate hepatic metastasis in skin cutaneous melanoma: Comprehensive insights from in vitro and in vivo investigations.

OBJECTIVE: This study aimed to investigate the role of Interleukin-11 receptor alpha (IL11RA) in skin cutaneous melanoma (SKCM) metastasis to the liver. METHODS: Human SKCM cell lines (A375, A375-MA2, SK-MEL-28, RPMI-7951) and primary dermal fibroblasts (HDFa) were utilized to assess IL11RA expression. IL11RA siRNA was transfected into RPMI-7951 and A375-MA2 cells for Wound healing and Transwell invasion assays. Il11ra knockout (KO) mice and wild-type (WT) mice were injected with B16-F10 cells into the spleen to evaluate hepatic melanoma metastasis. Correlation between IL11RA and MMP family genes was explored using online databases, including LinkedOmics, TIMER (Tumor Immune Estimation Resource), and GEPIA (Gene Expression Profiling Interactive Analysis). RT-qPCR and Western blotting were performed for expression analysis of Mmp2 and Mmp9 in liver tissues of mice. The impact of IL11RA on the STAT3 pathway was investigated in vitro and in vivo. RESULTS: Elevated expression of IL11RA was observed in SKCM cell lines compared to normal cells. IL11RA downregulation significantly inhibited migratory and invasive capabilities of A375-MA2 and RPMI-7951 in vitro. Il11ra gene knockout in mice demonstrated a substantial reduction in hepatic melanoma metastasis. Correlation analyses revealed associations between IL11RA and MMP2/MMP8. Il11ra gene knockout significantly decreased Mmp2 expression while increasing Mmp8 in liver tissues. IL11RA correlated positively with STAT3, and its inhibition led to a suppressed STAT3 pathway in SKCM cells and mouse liver tissue. CONCLUSION: IL11RA plays a crucial role in SKCM metastasis, affecting migratory and invasive abilities. Targeting IL11RA may offer a promising avenue for therapeutic interventions in cutaneous melanoma progression.

Triaryl Carbenium Ion Pair Mediated Electrocatalytic Benzylic C-H Oxygenation in Air.

The selective oxidation of benzylic C-H bonds is a pivotal transformation in organic synthesis. Undoubtedly, achieving efficient and highly selective aerobic oxidation of methylarenes to benzaldehydes has been highly challenging due to the propensity of benzaldehyde to undergo overoxidation under typical aerobic conditions. Herein, we propose an innovative approach to address this issue by leveraging electrocatalytic processes, facilitated by ion-pair mediators [Ph3C]+[B(C6F5)4]-. By harnessing the power of electrochemistry, we successfully demonstrated the effectiveness of our strategy, which enables the selective oxidation of benzylic C-H bonds in benzylic molecules and toluene derivatives. Notably, our approach exhibited high efficiency, excellent selectivity, and compatibility with various functional groups, underscoring the broad applicability of our methodology.

Model-Free Adaptive Positioning Control of the Bidirectional Stick-Slip Piezoelectric Actuator with Coupled Asymmetric Flexure-Hinge Mechanisms.

A model-free adaptive positioning control strategy for piezoelectric stick-slip actuators (PSSAs) with uncertain disturbance is proposed. The designed controller consists of a data-driven self-learning feedforward controller and a model-free adaptive feedback controller with a radial basis function neural network (RBFNN)-based observer. Unlike the traditional model-based control methods, the model-free adaptive control (MFAC) strategy avoids the complicated modeling process. First, the nonlinear system of the PSSA is dynamically linearized into a data model. Then, the model-free adaptive feedback controller based on a data model is designed to avoid the complicated modeling process and enhance the robustness of the control system. Simultaneously, the data-driven self-learning feedforward controller is improved to realize the high-precision control performance. Additionally, the convergence of the tracking error and the boundedness of the control output signal are proved. Finally, the experimentally obtained results illustrate the advantages and effectiveness of the developed control methodology on the bidirectional stick-slip piezoelectric actuator with coupled asymmetric flexure-hinge mechanisms. The positioning error through the proposed controller reaches 30 nm under the low-frequency condition and 200 nm under the high-frequency condition when the target position is set to 100 µm. In addition, the target position can be accurately tracked in less than 0.5 s in the presence of a 100 Hz frequency.

Thiol-Specific Silicon-Containing Conjugating Reagent: ß-Silyl Alkynyl Carbonyl Compounds.

Site-specific modification of thiol-containing biomolecules has been recognized as a versatile and powerful strategy for probing our biological systems and discovering novel therapeutics. The addition of lipophilic silicon moiety opens up new avenues for multi-disciplinary research with broad applications in both the medicinal and material sciences. However, adhering to the strict biocompatibility requirements, and achieving the introduction of labile silicon handle and high chemo-selectivity have been formidable. In this paper, we report silicon-based conjugating reagents including ß-trialkylsilyl and silyl ether-tethered alkynones that selectively react with thiols under physiological conditions. The pH-neutral, metal-free and additive-free reaction yields stable products with broad substrate compatibility and full retention of silicon handles in most cases. Besides simple aliphatic and aromatic thiols, this approach is applicable in the labeling of thiols present in proteins, sugars and payloads, thereby expanding the toolbox of thiol conjugation.

Fluoride Anion Catalyzed Mukaiyama-Aldol Reaction: Rapid Access to α-Fluoro-ß-hydroxy Esters.

The Mukaiyama-aldol reaction is probably one of the most efficient strategies to prepare synthetically useful ß-hydroxy carbonyl compounds. However, only several reported methods were concerned with the accesses to α-fluoro-ß-hydroxy esters. Herein, we report a protocol for a fluoride anion-mediated Mukaiyama aldol reaction with low catalytic loading in a short reaction time to incorporate fluorine at the α position into ß-hydroxy esters. The method shows good functional-group tolerance and scale-up potential, moreover, is applicable to the late-stage modification of natural products and small molecular drugs.

Prolonged low-salt immersion effectively controls Flavobacterium columnare infection in Murray cod Maccullochella peelii peelii.

A disease outbreak occurred in Murray cod Maccullochella peelii peelii in a recirculating aquaculture farm in Tianjin city, China, in 2019. Strain MRX-2019 was isolated and considered to be the etiological pathogen; it was identified as Flavobacterium columnare based on a 16S rDNA gene sequence analysis and physiological and biochemical tests. The effect of salinity on the growth of MRX-2019 was investigated in vitro. Salinity >4‰ (i.e. 6‰) inhibited MRX-2019 growth, whereas 8 and 10‰ salinity killed it. The effect of 4‰ salinity on F. columnare was not significant (p > 0.05). When MRX-2019-infected Murray cod were treated with 4, 6, or 8‰ salinity, the mortality rate was reduced by 8.9, 67.76, or 75.56%, respectively, compared with that of the control. However, the mortality rate increased by 7.77% at 10‰ salinity. In this study, we found that maintaining the fish in freshwater with 6-8‰ salinity effectively reduced the mortality of these fish when infected with F. columnare. The findings provide an environmentally friendly control strategy for columnaris disease in Murray cod.

Induction of cell cycle arrest and apoptosis by CPUC002 through stabilization of p53 and suppression of STAT3 signaling pathway in multiple myeloma.

Multiple myeloma has always been an important health problem in human beings due to its high morbidity, high mortality, and lack of effective therapeutic drugs. This study investigated the anticancer effect and mechanism of the newly synthesized small molecule compound CPUC002 on multiple myeloma. Our results confirmed that CPUC002 inhibited proliferation and induced G0/G1 cell cycle arrest in multiple myeloma cells. Moreover, CPUC002 also induced apoptosis by mitochondrial pathway and exogenous pathway. In mechanism, CPUC002 triggered apoptosis by stabilizing p53 in NCI-H929 cells which expressed wt-p53. Knockdown of p53 partially suppressed CPUC002-induced apoptosis. This suggests that there are other molecular mechanisms underlying CPUC002's antitumor effect. Further studies showed that the CPUC002 also inhibited the STAT3 signaling pathway, while knockdown of STAT3 abolished CPUC002-induced apoptosis and cell cycle arrest. In vivo, CPUC002 has significant antitumor activity through the same mechanism as our in vitro studies, and is highly safe in xenograft models. Together these findings indicate that CPUC002 induces apoptosis and G0/G1 cell cycle arrest in multiple myeloma cells by stabilizing p53 and inhibiting the STAT3 signaling pathway.

First report of a disease caused by Bacillus cereus in cultured loach Paramisgurnus dabryanus.

Bacillus cereus is commonly considered a bacterium pathogenic to mammals, but several studies have suggested that it also induces diseases in fish. In 2017 and 2018, 2 strains of B. cereus, NQ-2017-17 and NQ-2018-8, were isolated from diseased large-scale loach Paramisgurnus dabryanus in Tianjin, China, and were considered to be the pathogens responsible for the disease. These stains were identified as B. cereus based on the results of 16S rDNA gene sequence analysis, Vitek biochemical tests, physiological and biochemical tests, and B. cereus group species-specific PCR. Strains NQ-2017-7 and NQ-2018-8 were found to contain virulence genes (e.g. hblA, hblC, hblD, entFM, and bceT) causing pathological damage to the spleen, kidneys, liver, and gills of loach. The median lethal dose (LD50) of NQ-2017-7 and NQ-2018-8 for loach were 1.0 ×106.64 and 1.0 ×106.49 CFU ml-1, respectively. To our knowledge, this is the first report of loach disease caused by a member of the genus Bacillus.

Electrochemical Sensors for Detection of Markers on Tumor Cells.

In recent years, the increasing incidence and mortality of cancer have inspired the development of accurate and rapid early diagnosis methods in order to successfully cure cancer; however, conventional methods used for detecting tumor cells, including histopathological and immunological methods, often involve complex operation processes, high analytical costs, and high false positive rates, in addition to requiring experienced personnel. With the rapid emergence of sensing techniques, electrochemical cytosensors have attracted wide attention in the field of tumor cell detection because of their advantages, such as their high sensitivity, simple equipment, and low cost. These cytosensors are not only able to differentiate tumor cells from normal cells, but can also allow targeted protein detection of tumor cells. In this review, the research achievements of various electrochemical cytosensors for tumor cell detection reported in the past five years are reviewed, including the structures, detection ranges, and detection limits of the cytosensors. Certain trends and prospects related to the electrochemical cytosensors are also discussed.

Enantioselective vinylogous aldol/lactonization cascade reaction between ß,γ-unsaturated amides and trifluoromethyl ketones: facile access to chiral trifluoromethyl dihydropyranones.

An efficient asymmetric vinylogous aldol/lactonization cascade reaction between ß,γ-unsaturated amides and trifluoromethyl ketones has been developed. Using a chiral cyclohexanediamine-based tertiary amine-thiourea catalyst, optically active trifluoromethyl dihydropyranones have been constructed in moderate-to-excellent yields (up to 99%) with excellent stereoselectivities (96-> 99.5% ee).

UWB quadruplet signal generation based on a DP-QPSK modulator and a delay-line filter.

A photonic ultra-wideband (UWB) quadruplet signal generation based on a dual-polarization quadrature phase shift keying (DP-QPSK) modulator is presented. A Gaussian sequence is split into four parts and input to the four driving ports of the DP-QPSK. Through polarization rotation and polarization combination, a pair of polarization-orthogonal, polarity-reversed doublet signals are generated from the output of the DP-QPSK modulator. Subsequently, they are injected into a balanced photodetector (BPD) for further differentiation. After the heterodyne detection, a UWB quadruplet signal can be obtained. In this system, four electrical amplifiers are incorporated into the four electrical driving paths to adjust the modulation indices of the DP-QPSK. To attain the optimal spectral power efficiency (SPE), a relationship among the SPE, pulse width, delay time, and the two main modulation indices is created. Consequently, the optimal point is found with an SPE of 53.46%. Then, several impairments brought by the nonideal devices are considered in the simulation system. The distortion caused by impairments is compensated by properly adjusting the devices. The generated spectrum has a SPE of 53.38% and efficiently complies with the Federal Communications Commission (FCC) mask without any low-frequency components exceeding the FCC mask. In addition, on-off keying and pulse position modulation are realized in the system.

UWB quadruplet signal generation based on a DP-QPSK modulator and a delay-line filter: publisher's note.

This publisher's note corrects two sentences in Appl. Opt.59, 4404 (2020)APOPAI0003-693510.1364/AO.390663.

Multiple Coexisting Species and the First Known Case of a Cheater in Epicephala (Gracillariidae) Associated with a Species of Glochidion (Phyllanthaceae) in Tropical Asia.

Glochidion plants and Epicephala moths played different roles and kept the balance in the mutualism. We studied the four coexisting Epicephala species on Glochidion sphaerogynum in detail and reconstructed the phylogenic tree of 40 Gracillariidae species. The results showed that one of them (Epicephala impolliniferens) did not pollinate G. sphaerogynum, because of lacking the specialized structure of carrying pollen. These results suggested that E. impolliniferens acted as a 'cheater' in the system. The phylogenetic analyses suggested that E. impolliniferens derived from a pollinating species, and had secondarily gave up the ability to pollinate. This is a typical phenomenon of mutualism reversal. The phenomenon exhibits the co-evolutionary diversification under selection pressures.

Regioselective and Enantioselective Cu(II)-Catalyzed 1,4-Conjugate Addition of Diethylzinc Reagent to Nitrodienes.

The regioselective and enantioselective Cu(II)-catalyzed 1,4-conjugate addition of diethylzinc reagent to nitrodienes is described. With 0.25 mol % of Cu(OAc)2 and chiral amidophosphine ligand L3, the 1,4-addition products were produced with a complete regioselectivity, high yields (81-98%), and excellent enantioselectivities (87-97% ee) in a short reaction time.

Identification of novel peptidomimetics targeting the polo-box domain of polo-like kinase 1.

A series of new peptidomimetics targeting the polo-box domain (PBD) of polo-like kinase 1 (Plk1) was identified based on the potent and selective pentapeptide Plk1 PBD inhibitor PLHSpT. Unnatural amino acid residues were introduced to the newly designed compound and the N-terminal substituent of the peptidomimetic was investigated. The optimized compound 9 inhibited the Plk1 PBD with IC50 of 0.267 µM and showed almost no inhibition to Plk2 PBD or Plk3 PBD at 100 µM. Biolayer interferometry studies demonstrated that compound 9 showed potent binding affinity to Plk1 with a Kd value of 0.164 µM, while no Kd were detected against Plk2 and Plk3. Compound 9 showed improved stability in rat plasma compared to PLHSpT. Binding mode analysis was performed and in agreement with the observed experimental results. There are only two natural amino acids remained in the chemical structure of 9. This study may provide new information for further research on Plk1 PBD inhibitors.

Design, synthesis and evaluation of d-amino acid-containing peptidomimetics targeting the polo-box domain of polo-like kinase 1.

A series of d-amino acid-containing peptidomimetics were designed, synthesized as novel polo-like kinase 1 (Plk1) polo-box domain (PBD) inhibitors based on the reported peptide Plk1 PBD inhibitor. Their inhibitory activity to Plk1, Plk2, and Plk3 PBD were evaluated using our fluorescence polarization (FP) assay. Compound 18 bound to Plk1 PBD with IC50 of 0.80 µM and showed nearly no inhibition to Plk2 PBD or Plk3 PBD at 100 µM. Compound 18 induced Hela cells to undergo apoptosis by increasing the ratio of the cells at the G2/M phase by decreasing the neosynthesized proteins in a dose-dependent manner from 50 to 150 µM. Compound 18 showed improved stability in rat plasma compared to l-peptide inhibitor LHSpTA. These novel d-amino acid modified selective Plk1 PBD inhibitors may provide new lead compounds for further optimization.

Translational compensation of gene copy number alterations by aneuploidy in Drosophila melanogaster.

Chromosomal or segmental aneuploidy-the gain or loss of whole or partial chromosomes-is typically deleterious for organisms, a hallmark of cancers, and only occasionally adaptive. To understand the cellular and organismal consequences of aneuploidy, it is important to determine how altered gene doses impact gene expression. Previous studies show that, for some Drosophila cell lines but not others, the dose effect of segmental aneuploidy can be moderately compensated at the mRNA level - aneuploid gene expression is shifted towards wild-type levels. Here, by analyzing genome-wide translation efficiency estimated with ribosome footprint data from the aneuploid Drosophila S2 cell line, we report that the dose effect of aneuploidy can be further compensated at the translational level. Intriguingly, we find no comparable translational compensation in the aneuploid Kc167 cell line. Comparing the properties of aneuploid genes from the two cell lines suggests that selective constraint on gene expression, but neither sequence features nor functions, may partly explain why the two cell lines differ in translational compensation. Our results, together with previous observations that compensation at the mRNA level also varies among Drosophila cell lines and yeast strains, suggest that dosage compensation of aneuploidy is not general but contingent on genotypic and/or developmental context.

Marine Observation Beacon Clustering and Recycling Technology Based on Wireless Sensor Networks.

Monitoring of marine polluted areas is an emergency task, where efficiency and low-power consumption are challenging for the recovery of marine monitoring equipment. Wireless sensor networks (WSNs) offer the potential for low-energy recovery of marine observation beacons. Reducing and balancing network energy consumption are major problems for this solution. This paper presents an energy-saving clustering algorithm for wireless sensor networks based on k-means algorithm and fuzzy logic system (KFNS). The algorithm is divided into three phases according to the different demands of each recovery phase. In the monitoring phase, a distributed method is used to select boundary nodes to reduce network energy consumption. The cluster routing phase solves the extreme imbalance of energy of nodes for clustering. In the recovery phase, the inter-node weights are obtained based on the fuzzy membership function. The Dijkstra algorithm is used to obtain the minimum weight path from the node to the base station, and the optimal recovery order of the nodes is obtained by using depth-first search (DFS). We compare the proposed algorithm with existing representative methods. Experimental results show that the algorithm has a longer life cycle and a more efficient recovery strategy.

The influence of amine structures on the stability and catalytic activity of gold nanoparticles stabilized by amine-modified hyperbranched polymers.

Amine-modified amphiphilic hyperbranched polymers (MePEG-H104-Nx) were prepared from hyperbranched 2,2-bis(methylol)propionic acid polyester (H104) by decoration with polyethylene glycol monomethyl ether (MePEG) and different classes of oligo(ethylenimine)s. By using the MePEG-H104-Nx polymers as stabilizers, gold nanoparticles (AuNPs) were prepared in an aqueous medium by the reduction of HAuCl4 with NaBH4. The AuNPs were sphere-like with diameters of 2-4 nm, which were dependent on the structure of the amines. Further, the catalytic activity of these AuNPs was evaluated by monitoring the reduction reaction of 4-nitrophenol by sodium borohydride. The results demonstrate that the longer chain length and the branched structure of the amine moieties are beneficial for the stability and catalytic activity of the AuNPs. The AuNPs stabilized by MePEG-H104-N4 and MePEG-H104-Nb3 showed high catalytic activity for the reduction of 4-nitrophenol to 4-aminophenol.