Blocking the Hype‐Hypocrisy‐Falsification‐Fakery Pathway is Needed to Safeguard Science

In chemistry and other sciences, hype has become commonplace, compounded by the hypocrisy of those who tolerate or encourage it while disapproving of the consequences. This reduces the credibility and trust upon which all science depends for support. Hype and hypocrisy are but first steps down a slippery slope towards falsification of results and dissemination of fake science. Systemic drivers in the contemporary structure of the science establishment encourage exaggeration and may lure the individual into further steps along the hype‐hypocrisy‐falsification‐fakery continuum. Collective, concerted intervention is required to effectively discourage entry to this dangerous pathway and to restore and protect the probity and reputation of the science system. Chemists must play and active role in this effort.     

Modulation of the PGE2-Mediated Pathway in the Eclosion Blocking Effect of Flumethrin and Terpenoid Subfraction Isolated from Artemesia nilagirica in Rhipicephalus annulatus

Prostaglandins are a group of important cell-signaling molecules involved in the regulation of ovarian maturation, oocyte development, egg laying and associated behaviors in invertebrates. However, the presence of prostaglandin E₂ (PGE₂), the key enzymes for PGE₂ biosynthesis and its interference by drugs were not investigated previously in the ovary of ticks. The present study was undertaken to assess the modulation of the PGE₂-mediated pathway in the eclosion blocking effect of flumethrin and terpenoid subfraction isolated from Artemisia nilagirica in Rhipicephalus annulatus ticks. The acaricidal activities and chemical profiling of the terpenoid subfraction were performed. The localization of the cyclooxygenase1 (COX1) and prostaglandin E synthase (PGES) enzymes and the quantification of PGE₂ in the ovaries of the ticks treated with methanol (control), flumethrin and terpenoid subfraction were also undertaken. In addition, the vitellogenin concentration in hemolymph was also assayed. Both flumethrin and the terpenoid subfraction of A. nilagirica elicited a concentration-dependent inhibition of fecundity and blocking of hatching of the eggs. The COX1 could not be detected in the ovaries of treated and control ticks, while there was no significant difference observed in the concentration of vitellogenin (Vg) in them. The presence of PGES in the oocytes of control ticks was confirmed while the immunoreactivities against PGES were absent in the vitellogenic oocytes of ticks treated with flumethrin and terpenoid subfraction. The levels of PGE₂ were below the detection limit in the ovaries of the flumethrin-treated ticks, while it was significantly lower in the ovaries of the terpenoid subfraction-treated ticks. Hence, the prostaglandin E synthase and PGE₂ were identified as very important mediators for the signaling pathway for ovarian maturation and oviposition in ticks. In addition, the key enzyme for prostaglandin biosynthesis, PGES and the receptors for PGE₂ can be exploited as potential drug targets for tick control. The detection of PGES by immunohistochemistry and quantification of PGE₂ by LC-MSMS can be employed as valuable tools for screening newer compounds for their eclosion blocking acaricidal effects.     

Fluorinated Analogues to the Pentuloses of the Pentose Phosphate Pathway

Fluorinated carbohydrates are valuable tools for enzymological studies due to their increased metabolic stability compared to their non-fluorinated analogues. Replacing different hydroxyl groups within the same monosaccharide by fluorine allows to influence a wide range of sugar–receptor interactions and enzymatic transformations. In the past, this principle was frequently used to study the metabolism of highly abundant carbohydrates, while the metabolic fate of rare sugars is still poorly studied. Rare sugars, however, are key intermediates of many metabolic routes, such as the pentose phosphate pathway (PPP). Here we present the design and purely chemical synthesis of a set of three deoxyfluorinated analogues of the rare sugars d -xylulose and d -ribulose: 1-deoxy-1-fluoro-d -ribulose ( 1DFRu ), 3-deoxy-3-fluoro-d -ribulose ( 3DFRu ) and 3-deoxy-3-fluoro-d -xylulose ( 3DFXu ). Together with a designed set of potential late-stage radio-fluorination precursors, they have the potential to become useful tools for studies on the complex equilibria of the non-oxidative PPP.     

Direct Prebiotic Pathway to DNA Nucleosides

It is assumed that RNA played a key role in the origin of life, and the transition to more complex but more stable DNA for continuous information storage and replication requires the development of a ribonucleotide reductase to obtain the deoxyribonucleotides from ribonucleotides. This step, as well as an alternative path from abiotic molecules to DNA‐based life is completely unknown. Shown here is the formation of deoxyribonucleosides under relevant prebiotic conditions in water in high regio‐ and stereoselectivity, from all canonical purine and pyrimidine bases, by condensation with acetaldehyde and sugar‐forming precursors. Thus, a continuous path to deoxyribonucleosides, starting from simple, prebiotically available molecules has been discovered. Furthermore, the deoxyapionucleosides (DApiNA) were identified as a potential DNA progenitor. The results suggest that the DNA world evolved much earlier than previously assumed.     

Blocking of the silver catalyst surface in the conversion of ethylene to ethylene oxide

The conversion of ethylene oxide on silver catalysts of varying degree of oxidation has been studied. The formation of an adsorbed layer partially blocks the surface under catalytic conditions.

---

, , .

     

Extending the Total Pore Blocking method to normal phase high performance liquid chromatography

It has been demonstrated that it is possible to extend the Total Pore Blocking (TBP)-method for the determination of the external porosity (ε(e)) of packed bed columns from reversed-phase (RP) chromatography to normal-phase (NP) chromatography conditions by switching the nature of the blocking agent and the interstitial void flushing liquid, i.e., by using a hydrophilic blocking agent (pure or buffered water at pH 3.0 or pH 7.0) and a hydrophobic flushing liquid (linear alkanes such as decane). Several parameters that might influence the accuracy of the method, such as the applicable range of flow rates and the meso-pore size of the particles have been investigated. The influence of several different parameters on the obtained external porosity value has been investigated. From a wide selection of possible t(0)-markers, the class of linear alkanes has been shown to be the single possible one. This brings along the need to use refractive index detection to measure the signal of the linear alkane tracer (e.g., dodecane) in a stream of (another) linear alkane. The results of the newly established NP-TPB method have been compared to the values of the external porosity obtained by ISEC and proved to generate the same results, however with a much smaller read-out error (being only of the order of 0.1%).     

New Pathway to the Synthesis of Substituted 4H-3,1-Benzoxazines

The intramolecular rearrangement of N-acyl-2-cyclopropylanilines by the action of protic acids gives substituted 4H-3,1-benzoxazines. The reaction proceeds in high yield through the formation of benzoxazine precursors, namely, the corresponding 3,1-benzoxazinium ions, which are stable in acid solution. N-Acylamino-2-alkenylbenzenes, in which the double bond of the alkyl chain is conjugated with the benzene ring, are capable of undergoing a similar rearrangement.     

Proteome Analysis: A Pathway to the Functional Analysis of Proteins

The protein equivalent of genomes , proteomes are quantitative protein patterns of an organism, a cell, or a body fluid, and are determined by the development state and environmental parameters. Changes in protein expression and their consequences can be investigated at the molecular level and provide biologically relevant information not obtainable from experiments with mRNA.     

f-block MOFs: A Pathway to Heterometallic Transuranics

A novel series of heterometallic f-block-frameworks including the first examples of transuranic heterometallic ²³⁸U/²³⁹Pu-metal–organic frameworks (MOFs) and a novel monometallic ²³⁹Pu-analog are reported. In combination with theoretical calculations, we probed the kinetics and thermodynamics of heterometallic actinide(An)-MOF formation and reported the first value of a U-to-Th transmetallation rate. We concluded that formation of uranyl species could be a driving force for solid-state metathesis. Density of states near the Fermi edge, enthalpy of formation, band gap, proton affinity, and thermal/chemical stability were probed as a function of metal ratios. Furthermore, we achieved 97 % of the theoretical maximum capacity for An-integration. These studies shed light on fundamental aspects of actinide chemistry and also foreshadow avenues for the development of emerging classes of An-containing materials, including radioisotope thermoelectric generators or metalloradiopharmaceuticals.     

基于概念通路的科学教科书微观设计探微——以“三态粒子模型”为例

教科书是知识的载体,是教与学的重要依据,教科书内容的微观设计需反映学生知识获取的认知过程。本文在对“三态粒子模型“形成的概念通路进行理论构建基础上,通过对香港初中科学教科书“化学分支“中“三态粒子模型“的内容设计进行深入分析,以解答基于概念通路的教科书内容微观设计的操作性问题。     

Total Synthesis Establishes the Biosynthetic Pathway to the Naphterpin and Marinone Natural Products

The naphterpins and marinones are naphthoquinone meroterpenoids with an unusual aromatic oxidation pattern that is biosynthesized from 1,3,6,8‐tetrahydroxynaphthalene (THN). We propose that cryptic halogenation of THN derivatives by vanadium‐dependent chloroperoxidase (VCPO) enzymes is key to this biosynthetic pathway, despite the absence of chlorine in these natural products. This speculation inspired a total synthesis to mimic the naphterpin/marinone biosynthetic pathway. In validation of this biogenetic hypothesis, two VCPOs were discovered that interconvert several of the proposed biosynthetic intermediates.     

ATR/Chk1 Pathway is Activated by Oxidative Stress in Response to UVA Light in Human Xeroderma Pigmentosum Variant Cells

The crucial role of DNA polymerase eta in protecting against sunlight‐induced tumors is evidenced in Xeroderma Pigmentosum Variant (XP‐V) patients, who carry mutations in this protein and present increased frequency of skin cancer. XP‐V cellular phenotypes may be aggravated if proteins of DNA damage response (DDR) pathway are blocked, as widely demonstrated by experiments with UVC light and caffeine. However, little is known about the participation of DDR in XP‐V cells exposed to UVA light, the wavelengths patients are mostly exposed. Here, we demonstrate the participation of ATR kinase in protecting XP‐V cells after receiving low UVA doses using a specific inhibitor, with a remarkable increase in sensitivity and γH2AX signaling. Corroborating ATR participation in UVA‐DDR, a significant increase in Chk1 protein phosphorylation, as well as S‐phase cell cycle arrest, is also observed. Moreover, the participation of oxidative stress is supported by the antioxidant action of N‐acetylcysteine (NAC), which significantly protects XP‐V cells from UVA light, even in the presence of the ATR inhibitor. These findings indicate that the ATR/Chk1 pathway is activated to control UVA‐induced oxidatively generated DNA damage and emphasizes the role of ATR kinase as a mediator of genomic stability in pol eta defective cells.     

Inhibition of HER2‐Positive Breast Cancer Growth by Blocking the HER2 Signaling Pathway with HER2‐Glycan‐Imprinted Nanoparticles

Blocking the HER2 signaling pathway has been an effective strategy in the treatment of HER2‐positive breast cancer. It mainly relies on the use of monoclonal antibodies and tyrosine‐kinase inhibitors. Herein, we present a new strategy, the nano molecularly imprinted polymer (nanoMIP). The nanoMIPs, imprinted using HER2 N‐glycans, could bind almost all HER2 glycans and suppress the dimerization of HER2 with other HER family members, blocking the downstream signaling pathways, thereby inhibiting HER2+ breast cancer growth. In vitro experiments demonstrated that the nanoMIPs specifically targeted HER2+ cells and inhibited cell proliferation by 30 %. In vivo experiments indicated that the mean tumor volume of the nanoMIP‐treated group was only about half of that of the non‐treated groups. This study provides not only a new possibility to treat of HER2+ breast cancer but also new evidence to boost further development of nanoMIPs for cancer therapy.     

In vitro Reconstitution of the Biosynthetic Pathway to the Nitroimidazole Antibiotic Azomycin

Nitroimidazoles are one of the most effective ways to treat anaerobic bacterial infections. Synthetic nitroimidazoles are inspired by the structure of azomycin, isolated from Streptomyces eurocidicus in 1953. Despite its foundational role, no biosynthetic gene cluster for azomycin has been found. Guided by bioinformatics, we identified a cryptic biosynthetic gene cluster in Streptomyces cattleya and then carried out in vitro reconstitution to deduce the enzymatic steps in the pathway linking l ‐arginine to azomycin. The gene cluster we discovered is widely distributed among soil‐dwelling actinobacteria and proteobacteria, suggesting that azomycin and related nitroimidazoles may play important ecological roles. Our work sets the stage for development of biocatalytic approaches to generate azomycin and related nitroimidazoles.     

Planispine A Sensitized Cancer Cells to Cisplatin by Inhibiting the Fanconi Anemia Pathway

The use of cisplatin as a chemotherapeutic drug is impeded by the development of drug resistance. Combination therapies of a chemosensitizer for cisplatin have been studied, but with little success, and the search for an effective combination therapy is continuing. Our earlier reports have shown that Zanthoxylum armatum DC. extract enhances the apoptotic effect of cisplatin in cancer cell lines. In this study, we purified and identified the bioactive phytocompound through bio-assay-guided purification, using column chromatography and HPLC. Chemical characterization using NMR and mass spectrometry revealed the compound as planispine A, with molecular structure C₂₅H₃₀O₆ and molecular weight, 426.16 g/mol. Planispine A was found to inhibit cancer cell proliferation in a dose-dependent manner and to sensitize the cancer cells to cisplatin-augmented apoptotic cell death, in a caspase-dependent manner. A combination of planispine A and cisplatin induced S-phase cell cycle arrest, and reduced the expression of survival proteins such as cyclin D1. Interestingly, planispine A inhibits the Fanconi anemia pathway, as shown by reduced FANCD2 foci formation and FANCD2 monoubiquitination, which revealed the molecular mechanism of chemo-sensitization of cancer cells to cisplatin. Evaluation of this combination therapy in cisplatin-resistant tumors may lead to more efficient cisplatin treatment.     

Isoorientin Inhibits Amyloid β25–35-Induced Neuronal Inflammation in BV2 Cells by Blocking the NF-κB Signaling Pathway

Alzheimer’s disease (AD) is a severe neurodegenerative disorder. AD is pathologically characterized by the formation of intracellular neurofibrillary tangles, and extracellular amyloid plaques which were comprised of amyloid-beta (Aβ) peptides. Aβ induces neurodegeneration by activating microglia, which triggers neurotoxicity by releasing various inflammatory mediators and reactive oxygen species (ROS). Nuclear factor-kappa B (NF-κB) is expressed in human tissues including the brain and plays an important role in Aβ-mediated neuronal inflammation. Thus, the identification of molecules that inhibit the NF-κB pathway is considered an attractive strategy for the treatment and prevention of AD. Isoorientin (3′,4′,5,7-Tetrahydroxy-6-C-glucopyranosyl flavone; ISO), which can be extracted from several plant species, such as Philostachys and Patrinia is known to have various pharmacological activities such as anticancer, antioxidant, and antibacterial activity. However, the effect of ISO on Aβ-mediated inflammation and apoptosis in the brain has yet to be elucidated. In the present study, we investigated whether ISO regulated Aβ-induced neuroinflammation in microglial cells and further explored the underlying mechanisms. Our results showed that ISO inhibited the expression of iNOS and COX-2 induced by Aβ_25–35. And, it inhibited the secretion of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). In addition, ISO reduced the ROS production in Aβ_25–35-induced BV2 cells and inhibited NF-κB activation. Furthermore, ISO blocked Aβ_25–35-induced apoptosis of BV2 cells. Based on these findings, we suggest that ISO represents a promising therapeutic drug candidate for the treatment and prevention of AD.     

A Nanotechnology Pathway to Arresting Phase Separation in Soft Nanocomposites

Direct observation of the miscibility improving effect of ultra‐small polymeric nanoparticles (radius ≈4 nm) in model systems of soft nanocomposites is reported. We have found thermodynamically arrested phase separation in classical poly(styrene) (PS)/poly(vinyl methyl ether) blends when PS linear chains were totally replaced by ultra‐small, single chain PS nanoparticles, as determined by thermo‐optical microscopy measurements. Partial arrested phase splitting on heating was observed when only some of the PS chains were replaced by unimolecular PS nanoparticles, leading to a significant increase of the lower critical solution temperature (LCST) of the system (up to 40 °C at 15 vol.‐% nanoparticle content). Atomic force microscopy and rheological experiments supported these findings. Thermodynamic arrest of the phase separation process induced by replacement of linear polymer chains by unimolecular polymer nanoparticles could have significant implications for industrial applications requiring soft nanocomposite materials with excellent nanoparticle dispersion in a broad temperature range.

     

参加科技活动是提高大学生综合素质的重要环节

改变旧的教学模式、教学方法、教学内容,把培养重点放在学生综合素质的全面提高以及创造性思维和创业能力的培养上,是当前教育改革的重点,也是我们高等学校教育改革的焦点。 高等学校有较强的科研优势,很多教师都有相当强的研究能力,正如邓小平同志所强调的,高等学