bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of polychlorinated biphenyl (Aroclor 1254) on steroidogenesis and antioxidant system in cultured adult rat Leydig cells
Authors: Murugesan Palaniappan , Balaganesh Muthusamy , Balasubramanian Karundevi , Arunakaran Jagadeesan
Published: February 2007

Polychlorinated biphenyls (PCBs) are ubiquitous and persistent environmental contaminants that disturb normal endocrine functions, including gonadal functions in humans and mammals. In the present study, we examined the direct effects of PCB on rat Leydig cells in vitro. Adult Leydig cells were purified by Percoll gradient centrifugation method and the purity of Leydig cells was also determined by 3β-hydroxysteroid dehydrogenase (3β-HSD) staining method. Purified Leydig cells were exposed to different concentrations (10− 10–10− 7 M) of PCB (Aroclor 1254) for 24 h under basal and LH-stimulated conditions. After the experimental period, cultured media were collected and used for the assay of testosterone and estradiol. The treated cells were used for the quantification of cell-surface LH receptors and activities of steroidogenic enzymes, such as cytochrome P450 side-chain cleavage enzyme (P450scc), 3β-HSD, and 17β-hydroxysteroid dehydrogenase (17β-HSD). Leydig cellular enzymatic antioxidants, such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, γ-glutamyl transpeptidase, glutathione-S-transferase, and nonenzymatic antioxidants, such as vitamins C and E, were assayed. Lipid peroxidation (LPO) and reactive oxygen species (ROS) were also estimated in Leydig cells. In addition, total RNA was isolated from control and Aroclor 1254-exposed Leydig cells to monitor the steady-state mRNA levels by reverse transcription(RT)-PCR for steroidogenic acute-regulatory (StAR) protein, cytochrome P450scc, 3β-HSD, and 17β-HSD. Our results indicated that Aroclor 1254 (10− 9, 10− 8, and 10− 7 M) treatments significantly inhibit basal and LH-stimulated testosterone and estradiol production. In addition, the activities of steroidogenic enzymes, enzymatic and nonenzymatic antioxidants were significantly diminished in a dose-dependent manner. However, LPO and ROS were elevated in a dose-dependent manner under basal and LH-stimulated conditions. RT-PCR analysis of StAR mRNA level showed a decrease only in 10− 7 M dose of Aroclor 1254 treatment, while cytochrome P450scc, 3β-HSD, and 17β-HSD mRNAs were drastically decreased in both 10− 8 and 10− 7 M Aroclor 1254 treatment. These findings suggest that PCBs can act directly on Leydig cells to diminish testosterone production by inhibiting gene expression of steroidogenic enzymes and antioxidant system.
Changes in thrombospondin-1 levels in the endothelial cells of the anterior pituitary during estrogen-induced prolactin-secreting pituitary tumors
Authors: Sarkar Abby J , Chaturvedi Kirti , Chen Cui Ping , Sarkar Dipak K
Published: February 2007

Thrombospondin-1 (TSP-1), a multifunctional matrix glyco-protein, has been shown to control tumor growth by inhibiting angiogenesis in various tissues. However, the role of this glycoprotein in pituitary angiogenesis is not well studied. In this report, we determined the changes in the production and action of TSP-1 on endothelial cells in anterior pituitary following estradiol treatment, which is known to increase prolactin-secreting tumor growth and vascularization in this tissue. We showed that TSP-1 immunoreactive protein is distributed in the anterior pituitary, particularly in the endothelial cells. Estradiol treatment for 2 and 4 weeks decreased the total tissue immunoreactive level of TSP-1 as well as the endothelial cell-specific immunoreactive level of this protein in the anterior pituitary. The steroid treatment also decreased the protein levels of TSP-1 in anterior pituitary tissues and in purified pituitary endothelial cells in primary cultures. Determination of the effects of TSP-1 on proliferation and migration of pituitary-derived endothelial cells in primary cultures elucidated an inhibitory action of TSP-1 on these vascular cell functions. These results suggest that locally produced TSP-1 may regulate estrogen angiogenic action on the pituitary.
The possible mechanisms by which phanoside stimulates insulin secretion from rat islets
Authors: Hoa Nguyen Khanh , Norberg Åke , Sillard Rannar , Van Phan Dao , Thuan Nguyen Duy , Dzung Dang Thi Ngoc , Jörnvall Hans , Östenson Claes-Göran
Published: February 2007

We recently showed that phanoside, a gypenoside isolated from the plant Gynostemma pentaphyllum, stimulates insulin secretion from rat pancreatic islets. To study the mechanisms by which phanoside stimulates insulin secretion. Isolated pancreatic islets of normal Wistar (W) rats and spontaneously diabetic Goto-Kakizaki (GK) rats were batch incubated or perifused. At both 3.3 and 16.7 mM glucose, phanoside stimulated insulin secretion several fold in both W and diabetic GK rat islets. In perifusion of W islets, phanoside (75 and 150 μM) dose dependently increased insulin secretion that returned to basal levels when phanoside was omitted. When W rat islets were incubated at 3.3 mM glucose with 150 μM phanoside and 0.25 mM diazoxide to keep K-ATP channels open, insulin secretion was similar to that in islets incubated in 150 μM phanoside alone. At 16.7 mM glucose, phanoside-stimulated insulin secretion was reduced in the presence of 0.25 mM diazoxide (P<0.01). In W islets depolarized by 50 mM KCl and with diazoxide, phanoside stimulated insulin release twofold at 3.3 mM glucose but did not further increase the release at 16.7 mM glucose. When using nimodipine to block L-type Ca2+ channels in B-cells, phanoside-induced insulin secretion was unaffected at 3.3 mM glucose but decreased at 16.7 mM glucose (P<0.01). Pretreatment of islets with pertussis toxin to inhibit exocytotic Ge-protein did not affect insulin response to 150 μM phanoside. Phanoside stimulated insulin secretion from Wand GK rat islets. This effect seems to be exerted distal to K-ATP channels and L-type Ca2+ channels, which is on the exocytotic machinery of the B-cells.
Regulation of the expression and secretion of urocortin 2 in rat pituitary
Authors: Nemoto Takahiro , Iwasaki-Sekino Azusa , Yamauchi Naoko , Shibasaki Tamotsu
Published: February 2007

We previously demonstrated that urocortin 2 (Ucn 2) is expressed in the proopiomelanocortin (POMC) cells of rat pituitary. However, the regulatory mechanism of pituitary synthesis and secretion of Ucn 2 remained to be clarified. We hypothesized that hypothalamic hormones and glucocorticoids may control the expression and secretion of pituitary Ucn 2, as Ucn 2 is expressed in POMC-expressing cells in the pituitary. Thus, in the present study, we tested this hypothesis using primary culture of rat pituitary cells. The secretion of Ucn 2 from the anterior and intermediate pituitary cells was significantly increased by 50 mM KCl. In the anterior pituitary cells, corticotropin-releasing factor (CRF) increased mRNA expression levels and secretion of Ucn 2, although arginine vasopressin (AVP) did not induce any significant change in Ucn 2 expression or secretion. Under these conditions, both CRF and AVP increased ACTH secretion, but only CRF increased the level of POMC mRNA expression. Dexamethasone inhibited Ucn 2 and POMC mRNA expression levels, while it inhibited the secretion of only Ucn 2. In the intermediate pituitary, CRF increased both the mRNA expression levels and secretion of Ucn 2. Furthermore, dopamine did not affect either the mRNA expression level or secretion of Ucn 2 although it inhibited β-endorphin secretion in the intermediate pituitary cells. These results suggest that the mRNA expression and secretion of Ucn 2 in POMC cells of the pituitary are positively regulated by CRF and negatively regulated by glucocorticoids.
Magnetic Resonance Imaging Characteristics of LGI1-Antibody and CASPR2-Antibody Encephalitis
Authors: Kelly Mark J. , Grant Eleanor , Murchison Andrew G. , Binks Sophie , Ramanathan Sudarshini , Michael Sophia , Handel Adam E. , Handunnetthi Lahiru , Uy Christopher E. , Soltys John N. , Dubey Divyanshu , Day Gregory S. , Lopez-Chiriboga A. Sebastian , Flanagan Eoin P. , Sheerin Fintan , Irani Sarosh R.
Published: March 2024

Importance

Rapid and accurate diagnosis of autoimmune encephalitis encourages prompt initiation of immunotherapy toward improved patient outcomes. However, clinical features alone may not sufficiently narrow the differential diagnosis, and awaiting autoantibody results can delay immunotherapy.

Objective

To identify simple magnetic resonance imaging (MRI) characteristics that accurately distinguish 2 common forms of autoimmune encephalitis, LGI1- and CASPR2-antibody encephalitis (LGI1/CASPR2-Ab-E), from 2 major differential diagnoses, viral encephalitis (VE) and Creutzfeldt-Jakob disease (CJD).

Design, Setting, and Participants

This cross-sectional study involved a retrospective, blinded analysis of the first available brain MRIs (taken 2000-2022) from 192 patients at Oxford University Hospitals in the UK and Mayo Clinic in the US. These patients had LGI1/CASPR2-Ab-E, VE, or CJD as evaluated by 2 neuroradiologists (discovery cohort; n = 87); findings were validated in an independent cohort by 3 neurologists (n = 105). Groups were statistically compared with contingency tables. Data were analyzed in 2023.

Main Outcomes and Measures

MRI findings including T2 or fluid-attenuated inversion recovery (FLAIR) hyperintensities, swelling or volume loss, presence of gadolinium contrast enhancement, and diffusion-weighted imaging changes. Correlations with clinical features.

Results

Among 192 participants with MRIs reviewed, 71 were female (37%) and 121 were male (63%); the median age was 66 years (range, 19-92 years). By comparison with VE and CJD, in LGI1/CASPR2-Ab-E, T2 and/or FLAIR hyperintensities were less likely to extend outside the temporal lobe (3/42 patients [7%] vs 17/18 patients [94%] with VE; P < .001, and 3/4 patients [75%] with CJD; P = .005), less frequently exhibited swelling (12/55 [22%] with LGI1/CASPR2-Ab-E vs 13/22 [59%] with VE; P = .003), and showed no diffusion restriction (0 patients vs 16/22 [73%] with VE and 8/10 [80%] with CJD; both P < .001) and rare contrast enhancement (1/20 [5%] vs 7/17 [41%] with VE; P = .01). These findings were validated in an independent cohort and generated an area under the curve of 0.97, sensitivity of 90%, and specificity of 95% among cases with T2/FLAIR hyperintensity in the hippocampus and/or amygdala.

Conclusions and Relevance

In this study, T2 and/or FLAIR hyperintensities confined to the temporal lobes, without diffusion restriction or contrast enhancement, robustly distinguished LGI1/CASPR2-Ab-E from key differential diagnoses. These observations should assist clinical decision-making toward expediting immunotherapy. Their generalizability to other forms of autoimmune encephalitis and VE should be examined in future studies.
The Most Difficult Question in a Cognitive Disorders Clinic
Authors: Arshad Faheem , Alladi Suvarna
Published: March 2024

This essay describes the difficulty in diagnosing dementia and the experiences and questions caregivers have regarding its diagnosis.
Orbital‐Morphology‐Based Oxygen Reduction in a Correlated Oxide
Authors: Zhang Zhihua , Zhu Yangyu , Shi Xiaoyue , Qi Baotong , Ding Yu , Du Yan , Shi Wanfeng , Zhang Jian , Liu Jian , Sang Yuanhua , Wang Zeyan , Zhang Lei , Yu Haohai , Zhang Huaijin , Cai Bin , Zhao Mingwen , Li Yangyang
Published: March 2024

Orbital degree of freedom plays a crucial role in governing the physical and chemical properties of solid materials, and it is widely investigated in the fields of physics, material science, and chemistry. Typically, orbital‐energy‐related scenarios, such as d‐band center or electron occupancy, have been discussed in the catalytic materials, since they can control the surface‐adsorbate bonding strength to modulate the catalytic activity. However, the impact of orbital morphology, that is the “posture” of orbitals on catalysts' surfaces, has never been studied. Here the importance of 3d‐orbital morphology on the activity of oxygen reduction reaction (ORR) in a strongly correlated oxide α‐Ti2O3 is highlighted. Superior ORR performance is observed in α‐Ti2O3 (Ti3+:3d1) than that of the anatase and rutile TiO2 (Ti4+:3d0), with higher Faradaic efficiency (87.3%) and H2O2 selectivity (93.2%). More importantly, a novel orbital‐morphology‐based mechanism is developed and the orbital morphology dominates the catalytic activity by determining the surface‐adsorbates d–p orbital hybridization via orbitals' overlap, resulting in a crystal‐plane‐dependent ORR activity in α‐Ti2O3. The work reveals the strong interplay between the orbital morphology, d–p hybridization, and ORR activity, which broadens the fundamental understanding of catalysts from a new view of the orbital degree of freedom.
Robust and Seamless Integration of Thiol‐Ene‐Epoxy Thermosets with Thermoplastics and Glass as Hybrid Microfluidic Devices Suitable for Drug Studies
Authors: Harris Peter , Kaveh Javad , Kemas Aurino M. , Mikaelsson Henrik , Fielden Matthew , Lauschke Volker M. , Zandi Shafagh Reza
Published: March 2024

Facile, durable and biocompatible integration of hybrid Lab‐on‐a‐Chip devices has remained an important challenge in microengineering. Here, the robust and seamless integration of off‐stoichiometry thiol‐ene‐epoxy (OSTE+) thermosets with a diverse range of thermoplastic and glass materials is demonstrated. While direct bonding offers sturdy proprieties for the majority of the material hybrids (up to 1.5 MPa), further surface priming enhances the bonding strength for those of lower surface energy (up to seven‐fold). Using microfluidic devices with a unique configuration of chambers and microchannels down to 100 µm, the impact of various bonding methods on their fluidic functionality is further shown. To investigate the utility of hybrid devices for pharmacological and toxicological studies, both pristine and primed devices are benchmarked against polydimethylsiloxane (PDMS) with regard to cell biocompatibility and drug absorption. While being on par with PDMS in terms of cell viability, pristine OSTE+ devices show an 11‐fold lower absorption of hydrophobic drug molecules. Although surface priming enhances the bonding strength, it compromises other criteria in device performance and biological applications. Combined, results demonstrate a novel integration approach for facile manufacturing of hybrid microfluidic devices using a material toolbox suitable for cell and pharmaceutical studies.
Electrochemical Oxidative Ring‐Opening Reactions of 2H‐Indazoles with Alcohols to Obtain Ortho‐alkoxycarbonylated Azobenzenes
Authors: Hu Yibin , Liu Xin , Feng Chenglong , Wang Jiaxu , Li Meichao , Shen Zhenlu
Published: March 2024

A strategy for synthesis of azo‐derived compounds by electrochemical oxidative ring‐opening reactions of 2H‐indazoles with alcohols is reported. The reactions are carried out under galvanostatic electrolysis conditions in an undivided cell without the use of transition metal catalysts. On the basis of cyclic voltammetry and control experiments, a plausible mechanism for this ring‐opening reaction involving the radical pathway is proposed. Furthermore, various 2H‐indazoles and alcohols are suitable in this system, giving the desired ortho‐alkoxycarbonylated azobenzenes in 9–84% yields.
Tumor Exosomal ENPP1 Hydrolyzes cGAMP to Inhibit cGAS‐STING Signaling
Authors: An Yu , Zhu Jinchao , Xie Qihui , Feng Jianzhou , Gong Yanli , Fan Qian , Cao Jiao , Huang Zhi , Shi Weixiong , Lin Qingyuan , Wu Lingling , Yang Chaoyong , Ji Tianhai
Published: March 2024

To evade immune surveillance, tumor cells express ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) on the surface of their membrane, which degrades extracellular cyclic GMP‐AMP (cGAMP), thereby inhibiting the cyclic GMP‐AMP synthase (cGAS) stimulator of interferon gene (STING) DNA‐sensing pathway. To fully understand this tumor stealth mechanism, it is essential to determine whether other forms of ENPP1 with hydrolytic cGAMP activity also are present in the tumor microenvironment to regulate this innate immune pathway. Herein, it is reported that various tumor‐derived exosomes carry ENPP1, and can hydrolyze synthetic 2′3′‐cGAMP and endogenous 2′3′‐cGAMP produced by cells to inhibit cGAS‐STING pathway in immune cells. Moreover, tumor exosomal ENPP1 also can hydrolyze 2′3′‐cGAMP bound to LL‐37 (an effective transporter of 2′3′‐cGAMP) to inhibit STING signaling. Furthermore, high expression of ENPP1 in exosomes is observed isolated from human breast and lung cancer tissue, and tumor exosomal ENPP1 inhibited the immune infiltration of CD8+ T cells and CD4+ T cells. The results elucidate the essential function of tumor exosomal ENPP1 in the cGAS‐STING pathway, furthering understanding of the crosstalk between the tumor cells and immune system.
New and facile recovery strategy for silver, copper, and nickel from waste silver contacts using polyiodide ionic liquids
Authors: Yin Xiaolu , Wang Shuping , Liu Ronghao , Liu Xiaoxia , Liu Peng , Yang Yanzhao
Published: March 2024

This work proposed a novel strategy for recovering Ag, Cu, and Ni from waste silver contacts (WSCs) using polyiodide ionic liquids (ILs). Our method exhibited exceptional leaching efficiency (Ag: 98.7%, Cu: 99.1%) and remarkable reusability (over 6 cycles). In contrast to a traditional three‐step leaching‐extraction‐striping process, our polyiodide ILs present a significant simplification. This approach is ideal for practical applications due to its low viscosity (49.6 cP) and gentle (55°C) leaching conditions of polyiodide ILs. Additionally, the redox leaching mechanism was successfully elucidated by XPS, XRD, and UV‐vis spectra. Based on our findings, a closed‐loop route for the recovery and separation of Ag, Cu, and Ni was suggested. Moreover, economic analysis revealed that the recovery of 1.0 kg WSCs could generate a considerable profit of 58 ± 7 USD. Overall, this new method provides a rapid, high profit, and sustainable recovery strategy with significant potential for industrial applications.
Spaced‐confined capsule catalysts with tunable micro‐environments for efficient CO2 conversion
Authors: Wu Hao , Guo Lisheng , Wang Xianbiao , Zhou Wenjie , Chen Fang , Li Da , Liu Kai , Ai Peipei , Wei Yuxue , Cai Mengdie , Sun Song
Published: March 2024

CO2 as a greenhouse gas causes a series of issues, and catalytic utilization of CO2 to fuels is a favorable strategy. Herein, we report the discovery in CO2 hydrogenation reaction where C5+ yield can be evidently improved by encapsulating ZnFe2O4 inside ZSM‐5, in which the micro‐environments of core‐shell components can be tuned. For the ZnFe2O4, the K promoter makes the FeC structure more electron deficient than the Na, which contributes to the formation of long‐chain olefins. ZSM‐5 with K or Ce modification presents enhanced adsorption ability of alkene, then promoting aromatization and isomerization reactions of alkenes. Compared with Ce, K‐ZSM‐5 contributes to isomerization rather than aromatization, forming more isoparaffins. In this work, regulating the microenvironment of capsule catalysts provides a new idea for the design of efficient tandem catalysts, and expands the ability of hybrid catalysts against other catalysts, thus presenting an excellent catalytic efficiency for CO2 upgrading.
Dementia and mild cognitive impairment screening in an emergency homeless shelter
Authors: Ross Heather M. , Dzenga Primrose , Myers Martha , Squires Alisa , Duncan Stephanie , Caradine Jamilyn , Scharf Phillip , Bowman Diana M.
Published: March 2024

INTRODUCTION

Older adults represent the fastest growing segment of the homeless community. Little is known about the prevalence of dementia and mild cognitive impairment (MCI) in this population.

METHODS

Dementia and MCI screening using the Montreal Cognitive Assessment (MoCA) was incorporated into the standard senior evaluation for adult clients aged ≥ 55 in a large emergency homeless shelter.

RESULTS

In a 6‐week period, 104 of 112 (92.9%) assessments were positive for dementia or MCI using a standard cutoff of 26, and 81 (72.3%) were positive using a conservative cutoff of 23. There was no significant difference in MoCA scores based on sex or education level, and no significant correlation between age and MoCA score.

DISCUSSION

Older adults experiencing homelessness may have a high likelihood of dementia or MCI. Routine MoCA screening in older adults experiencing homelessness is feasible and can help to identify services needed to successfully exit homelessness.
Iso‐E‐Codelock: A Rebuilding‐free Electrochemical Chip with a Customizable Decoding Probe for Real‐Time and Portable Pathogen Diagnostics
Authors: Liu Yichen , Tang Yidan , Bao Yin , Cai Kaiwei , Lu Baiyang , Zhao Rujian , Yu Chunxu , Du Yan , Li Bingling
Published: March 2024

In order to realize portable pathogen diagnostics with easier quantitation, digitization and integration, we develop a ready‐to‐use electrochemical sensing strategy (Iso‐E‐Codelock) for real‐time detection of isothermal nucleic acid amplification. Bridged by a branched DNA as codelock, the isothermal amplicon is transduced into increased current of an electrochemical probe, holding multiple advantages of high sensitivity, high selectivity, signal‐on response, “zero” background and one‐pot operation. Through a self‐designed portable instrument (BioAlex PHE−T), the detection can be implemented on a multichannel microchip and output real‐time amplification curves just like an expensive commercial PCR machine. The microchip is a rebuilding‐free and disposable component. The branch codelock probe can be customized for different targets and designs. Such high performance and flexibility have been demonstrated utilizing four virus (SARS‐CoV‐2, African swine fever, FluA and FluB) genes as targets, and two branch (3‐way and 4‐way) DNAs as codelock probes.
Poly(O‐Toluidine)‐polyvinylpyrrolidone copolymer submerged MgFe2O4/CS‐OXSWCNTs nanocomposite for removal of acid red dye from aqueous solutions
Authors: Katowah Dina F. , Sadek Ahmed H.
Published: March 2024

In this study, a new hybrid material was created that exhibits excellent adsorption performance and high stability. POT‐PVP/MgF/CS‐OXSWCNTs NCs were synthesized using a three‐step approach. The process involved the chemical polymerization of poly(o‐toluidine)‐polyvinylpyrrolidone (POT‐PVP) with MgFe2O4 nanoparticles (MgF NPs) and chitosan‐oxidized single‐wall carbon nanotubes (CS‐OXSWCNTs). The synthesis process involved the use of an egg white method to synthesize MgF NPs and cross‐linking chitosan with OXSWCNTs using glutaraldehyde (GA) to obtain CS‐OXSWCNTs. The POT‐PVP copolymer was then used to coat MgF NPs and CS‐OXSWCNTs NCs. The successful synthesis of the NCs with strong component interaction was confirmed by several characterization techniques, including X‐ray diffraction spectroscopy (XRD), Fourier‐transform infrared spectroscopy (FTIR), and Raman spectroscopy. Microscopy analysis using scanning electron microscopy (SEM) and transmission electron microscopy (TEM) verified that the POT‐PVP copolymer had properly coated the MgF NPs and CS‐OXSWCNTs NCs. The N2 adsorption–desorption isotherm verified that the specific surface area of NCs had increased with the addition of MgF NPs and CS‐OXSWCNTs NCs. Furthermore, the composite structure greatly improved the thermal stability of POT‐PVP/MgF/CS‐OXSWCNTs NCs. To evaluate how well the nanocomposites (NCs) eliminated pollutants, an artificially produced toxic effluent that contained acid red dye (A.R) was applied. To investigate their impact on dye removal, several parameters were changed, including pH, adsorbent dosage, time, temperature, and ionic strength. The POT‐PVP/MgF/CS‐OXSWCNTs NCs showed a higher removal rate based on a greater surface area, stability, and conducting power than MgF NPs and POT‐PVP. It was found that 25 mg L−1 and 7.5 mg were the optimal dye concentration and adsorbent dosage, respectively. The POT‐PVP/MgF/CS‐OXSWCNTs NCs achieved 99.46% removal efficiency at an acidic pH of 2. The NCs were found to have a maximum dye adsorption capacity of 107.4 mg g−1, and the adsorption process followed the pseudo‐second‐order kinetics. Thermodynamic analyses revealed that the dye adsorption onto POT‐PVP/MgF/CS‐OXSWCNTs NCs was endothermic, implying a spontaneous and physical adsorption mechanism. It can be inferred from these results that POT‐PVP/MgF/CS‐OXSWCNTs NCs are useful for eliminating dye pollutants from water.
Exploring rhodanine linked enamine–carbohydrazide derivatives as mycobacterial carbonic anhydrase inhibitors: Design, synthesis, biological evaluation, and molecular docking studies
Authors: Maddipatla Sarvan , Bakchi Bulti , Gadhave Rutuja Rama , Ammara Andrea , Sau Shashikanta , Rani Bandela , Nanduri Srinivas , Kalia Nitin Pal , Supuran Claudiu T. , Yaddanapudi Venkata Madhavi
Published: March 2024

With the rise of multidrug‐resistant tuberculosis, the imperative for an alternative and superior treatment regimen, incorporating novel mechanisms of action, has become crucial. In pursuit of this goal, we have developed and synthesized a new series of rhodanine‐linked enamine–carbohydrazide derivatives, exploring their potential as inhibitors of mycobacterial carbonic anhydrase. The findings reveal their efficacy, displaying notable selectivity toward the mycobacterial carbonic anhydrase 2 (mtCA 2) enzyme. While exhibiting moderate activity against human carbonic anhydrase isoforms, this series demonstrates promising selectivity, positioning these compounds as potential antitubercular agents. Compound 6d was the best one from the series with a Ki value of 9.5 µM toward mtCA 2. Most of the compounds displayed moderate to good inhibition against the Mtb H37Rv strain; compound 11k showed a minimum inhibitory concentration of 1 µg/mL. Molecular docking studies revealed that compounds 6d and 11k show metal coordination with the zinc ion, like classical CA inhibitors.
Synthesis of R–GABA Derivatives via Pd(II) Catalyzed Enantioselective C(sp3)−H Arylation and Virtual Validation with GABAB1 Receptor for Potential leads
Authors: Mohanlal Smitha , Saha Diprupa , Pandey Shubhant , Acharya Rudresh , Sharma Nagendra K.
Published: March 2024

GABA (γ–amino butyric acid) analogues like baclofen, tolibut, phenibut, etc., are well–known GABAB1 inhibitors and pharmaceutically important drugs. However, there is a huge demand for more chiral GABA aryl analogues with promising pharmacological actions. Here, we demonstrate the chiral ligand acetyl–protected amino quinoline (APAQ) mediated enantioselective synthesis of GABAB1 inhibitor drug scaffolds from easily accessible GABA via Pd–catalyzed C(sp3)−H activation. The synthetic methodology shows moderate to good yields, up to 74% of ee. We have successfully demonstrated the deprotection and removal of the directing group to synthesize R–tolibut in 86% yield. Further, we employed computation to probe the binding of R–GABA analogues to the extracellular domain of the human GABAB1 receptor. Our Rosetta–based molecular docking calculations show better binding for four R–enantiomers of GABA analogues than R–baclofen and R–phenibut. In addition, we employed GROMACS MD simulations and MMPB(GB)SA calculations to identify per–residue contribution to binding free energy. Our computational results suggest analogues (3R)‐4‐amino‐3‐(3,4‐dimethylphenyl) butanoic acid, (3R)‐4‐amino‐3‐(3‐fluorophenyl) butanoic acid, (3R)‐3‐(4‐acetylphenyl)‐4‐aminobutanoic acid, (3R)‐4‐amino‐3‐(4‐methoxyphenyl) butanoic acid, and (3R)‐4‐amino‐3‐phenylbutanoic acid are potential leads which could be synthesized from our methodology reported here.
Pfeilersanierung an der Alten Brücke Heidelberg
Authors: Groß Thomas , Schneider Marcel
Published: March 2024

Die Alte Brücke Heidelberg ist weithin als Fotomotiv bekannt. Die im Jahr 1788 als Mauerwerksbrücke aus Sandstein erbaute Brücke überspannt, mit Sicht auf das Heidelberger Schloss, mit sieben Brückenbögen den Neckar. Was in den vergangenen Jahren im Schatten der Brücke geschah, blieb jedoch von den meisten unentdeckt. Während der Bauwerksprüfungen in den Jahren 2008 und 2016 wurden an allen Pfeilern der Alten Brücke Heidelberg sowohl in der Wasserwechselzone als auch im ständig eingestauten Bereich Schäden festgestellt und dokumentiert. Hierbei handelte es sich vorrangig um Fugenausspülungen und Beschädigungen an den Natursandsteinen. Zusätzlich wurden bei diesen Untersuchungen auch Steinklammern überarbeitet sowie Anprallwinkel an den Pfeilerspitzen ausgetauscht und ergänzt. Um notwendige Sanierungsarbeiten durchführen zu können, mussten die Pfeiler trockengelegt werden. Aufgrund der angrenzenden Schifffahrtsöffnungen und dadurch bedingter enger Platzverhältnisse musste hierzu ein schlanker Senkkasten hergestellt werden, der exakt auf den Fundamentsockel der Pfeiler aufgesetzt werden konnte und die laufende Schifffahrt nicht behinderte. Der zweiteilige Senkkasten hatte ein Gesamtgewicht von knapp 32 t und wurde in kurzen Schifffahrtssperren in der Nacht mit zwei eigens hierfür zusammengebauten Spezialpontons um den jeweiligen Brückenpeiler eingeschwommen. Anschließend wurden die beiden Senkkastenhälften verbunden, abgesenkt und auf dem Grund verankert, sodass ein geschlossener, dichter Arbeitsraum um den Brückenpfeiler entstand.
Bauteilversuche Oberesslingen – Teil 2
Authors: Kötz Harold , Begemann Christoph , Ebers‐Ernst Jeannette
Published: March 2024

Die Angebotsbearbeitung der Ausschreibung „Bauteilversuche an der Neckarschleuse in Oberesslingen (BTV OES)“ war sowohl hinsichtlich der Inhalte als auch durch das vom Auftraggeber gewählte Vergabeverfahren besonders. Die Planungen im Rahmen der Konzepterstellung als Teil des Angebots mussten eine Vielzahl von vorgegebenen Randbedingungen, Anforderungen und Leistungsumfängen berücksichtigen. Die Bearbeitung erfolgte durch eine auf ein späteres Totalunternehmen ausgerichtete Bietergemeinschaft. Das gesamte Vergabeverfahren erstreckte sich über einen Zeitraum von mehr als zwei Jahren mit einer intensiven Zeit der Angebotsbearbeitung und Konzeptfortschreibungen von ca. einem Jahr. Der Konzeptinhalt und folglich die Detailtiefe wuchsen dabei stetig an. Diese Konzentration auf die Konzeptinhalte und der damit verbundene hohe Stellenwert der technischen Lösungsansätze spiegelten sich in der entsprechend hohen Gewichtung bei der Angebotsbewertung mit einem Wertungsanteil von 80 % wider. Um die vielfältigen Leistungsanforderungen hinsichtlich Planung und Ausführung zu bedienen, erfolgte die Angebotsbearbeitung als Bietergemeinschaft aus Planungsbüros und bauausführenden Unternehmen. Die frühzeitige Beteiligung der Baufirmen bot im Hinblick auf die Sicherstellung der späteren Ausführbarkeit optimale Voraussetzungen. Im Folgenden werden die Herangehensweise sowie die Konzepte zu Trockenlegung, Abtrag und Reprofilierung sowie vorlaufende Maßnahmen genauer beschrieben.
Enhancing Electrochemical Properties of Walnut Shell Activated Carbon with Embedded MnO Clusters for Supercapacitor Applications
Authors: Esteban Daniel Arenas , Chamocho Elena García , Carretero González Javier , Urones Garrote Esteban , Otero Díaz Luis Carlos , Brande David Ávila
Published: March 2024

Activated carbon (AC) materials from renewable sources are widely used in electrochemical applications due to their well‐known high surface area. However, their application as electrode material in double‐layer electrochemical devices may be limited due to their relatively low electrical conductivity and lightweight. To overcome these limitations, the incorporation of pseudocapacitance metal oxide nanoparticles is an optimum approach. These nanoparticles can provide a second energy storage mechanism to the composite, mitigating the loss of surface area associated with their incorporation. As a result, the composite material is endowed with increased conductivity and higher density, making it more suitable for practical implementation in real devices. In this study, we have incorporated a fine dispersion of 1 % of MnO clusters into a highly porous activated carbon synthesized from walnut shells (WAC). The high‐resolution electron microscopy studies, combined with their related analytical techniques, allow us to determine the presence of the cluster within the matrix carbon precisely. The resulting MnO@WAC composite demonstrated significantly improved capacitive behavior compared with the WAC material, with increased volumetric capacitance and higher charge retention at higher current densities. The composite‘s electrochemical performance suggests its potential as a promising electrode material for supercapacitors, addressing drawbacks associated with traditional AC materials.
Bioburden detection on surface and water samples in a rapid, ultra‐sensitive and high‐throughput manner
Authors: Hasan Md Sadique , Sundberg Chad , Gilotte Elias , Ge Xudong , Kostov Yordan , Rao Govind
Published: March 2024

Bioburden detection is crucial for food, water, and biopharmaceutical applications as it can directly impact public health. The objective of this study is to develop and validate an assay and protocol for detecting bioburden on solid surfaces, as well as in water, with high sensitivity and accuracy in a rapid manner. Henceforth, a resazurin‐based assay optimized for detecting bioburden has been integrated with a previously developed portable multichannel fluorometer. The microbes were isolated from solid surfaces in different laboratory settings by swabbing technique, and stream water was collected for contamination analysis. Based on the results, the assay and protocol can successfully detect bioburden as low as 20 CFU/cm2 and 10 CFU/mL present in both surface and water samples, respectively.
Yinxieling decoction ameliorates psoriasis by regulating the differentiation and functions of Langerhans cells via the TGF‐β1/PU.1/IL‐23 signal axis
Authors: Li Ning , Ke Jiagu , Yu Qihua , Li Xiong , Tang Lipeng , Zhang Miaomiao , Chai Xiaoshu , Wu Qiaoling , Lu Chuanjian , Wu Dinghong
Published: March 2024

Langerhans cells (LCs) play a critical role in skin immune responses and the development of psoriasis. Yinxieling (YXL) is a representative Chinese herbal medicine for the treatment of psoriasis in South China. It was found to improve psoriasis without obvious side effects in the clinic. Here we attempted to clarify whether and how YXL regulates the differentiation and functions of LCs in Imiquimod (IMQ)‐induced psoriasis in vivo and induced LCs in vitro. The Psoriasis Area Severity Index (PASI) score was used to evaluate the efficacy of YXL for IMQ‐induced psoriasis‐like mice. Flow cytometry was utilized to analyze the effects of YXL, to regulate the differentiation, migration, maturation, and antigen presentation of LCs. The results show that YXL significantly alleviated skin inflammation, as reduced in PASI score and classic psoriasis characteristics in pathological sections. Although there was no effect on the proportion of total DCs in the skin‐draining lymph nodes, the expression of epidermal LCs and its transcription factor PU.1 were both markedly inhibited. LCs were also prevented from migrating from epidermal to skin‐draining lymph nodes and mature. In addition, the number of LCs carrying antigens in the epidermis increased, which suggested that YXL could effectively prevent LCs from presenting antigens. In vitro, YXL had a significant impact on inhibiting the differentiation of LCs. Further data showed that YXL decreased the relative expression of transforming growth factor‐β (TGFβ) messenger RNA (mRNA) and interleukin‐23 (IL‐23) mRNAs. Thus, YXL alleviates psoriasis by regulating differentiation, migration, maturation, and antigen presentation via the TGFβ/PU.1/IL‐23 signal axis.
The regulatory role of autophagy between TAMs and tumor cells
Authors: Hu Min , Fan Jiao‐Xiu , He Zi‐Yue , Zeng Jun
Published: March 2024

Cancer has become a global public health problem and its harmful effects have received widespread attention. Conventional treatments such as surgical resection, radiotherapy and other techniques are applicable to clinical practice, but new drugs are constantly being developed and other therapeutic approaches, such as immunotherapy are being applied. In addition to studying the effects on individual tumor cells, it is important to explore the role of tumor microenvironment on tumor cell development since tumor cells do not exist alone but in the tumor microenvironment. In the tumor microenvironment, tumor cells are interconnected with other stromal cells and influence each other, among which tumor‐associated macrophages (TAMs) are the most numerous immune cells. At the same time, it was found that cancer cells have different levels of autophagy from normal cells. In cancer therapy, the occurrence of autophagy plays an important role in promoting tumor cell death or inhibiting tumor cell death, and is closely related to the environment. Therefore, elucidating the regulatory role of autophagy between TAMs and tumor cells may be an important breakthrough, providing new perspectives for further research on antitumor immune mechanisms and improving the efficacy of cancer immunotherapy.
Does ejection fraction matter in choosing between percutaneous coronary intervention and coronary artery bypass surgery?
Authors: Seto Arnold H. , Yau Persephone
Published: March 2024

Key points

Left ventricular systolic dysfunction has traditionally been used as a risk factor favoring coronary artery bypass surgery over percutaneous coronary intervention (PCI), but recent data have challenged this.

Retrospective data from the BIOFLOW trials show no difference between normal and moderately abnormal LVEF (30%–50%) in acute complications or target vessel failure.

Abnormal LVEF may be a marker for comorbidities but no longer a relative contraindication to PCI.
Ring–Opening Mechanism of O‐heterocycles into α,ω‐Diols over Ni−La(OH)3: C−O Bond Hydrogenolysis of THFA to 1,5‐Pentanediol as a Case Study
Authors: Al‐Yusufi Mohammed , Michalik Dirk , Kubis Christoph , Murayama Toru , Ishida Tamao , Abdel‐Mageed Ali M. , Köckritz Angela
Published: March 2024

The elucidation of the ring–opening reaction mechanism is a critical step towards improving the catalytic performance for the conversion of biomass into value–added chemicals. Herein, we focused on the stepwise C−O bond hydrogenolysis mechanism of oxygen–containing heterocycles (O‐heterocycles) into α,ω‐diols, in particular THFA to 1,5‐PeD, over selective Ni−La(OH)3 in hydrogen–donor isopropanol. A mechanistic study was carried out on a structurally well–defined Ni−La(OH)3, where the mechanism was elucidated using a combination of kinetic and 13C NMR isotope labeling experiments. It was suggested that both Ni nanoparticles and La(OH)3 support play a critical role in the reaction mechanism, where basic hydroxide species of the support initially deprotonate the CH2OH and −OH modified furan, tetrahydrofuran and tetrahydropyran rings, adsorbing them chemically on the catalyst surface. This step is followed by a direct hydride attack on the second carbon atom of these rings, which is proposed to be the key step for ring cleavage, as indicated by the increased deuteration at this position. In addition to the direct hydrogenolysis using gaseous H2, it is assumed that a catalytic transfer hydrogenolysis reaction (CTH) reaction of THFA is proposed to proceed via the dehydrogenation of isopropanol over isolated Ni species, forming hydrogen species that can be adsorbed on the Ni surface or desorb as H2 molecules.
Influence of Acid‐Base Characteristics of Different Structural‐Type Zeolites (FER, MFI, FAU, BEA) on Their Activity and Selectivity in Isobutanol Dehydration
Authors: Zikrata Oksana V. , Larina Olga V. , Balakin Dmytro Yu. , Nychiporuk Yurii M. , Khalakhan Ivan , Švegovec Marija , Volavšek Janez , Yaremov Pavlo S. , Soloviev Sergiy O. , Orlyk Svitlana M.
Published: March 2024

The different structural‐type zeolites (FER, MFI, FAU, BEA) are investigated as catalysts in (bio)isobutanol conversion into linear butenes. The zeolites’ structure and morphology are confirmed by XRD, N2 (77 K) ad(de)sorption, SEM, EDX, XPS, and 27Al, 29Si, 1H MAS NMR, 1H‐29Si CP MAS NMR. The nature and strength of acid‐base sites are determined by FTIR spectroscopy of adsorbed pyridine, potentiometric titration, and TPD of NH3/CO2/H2O with MS control. The acid‐base properties of the zeolites′ surfaces influence their catalytic properties in the target process. The higher selectivity towards linear butene isomers achieved over FER and MFI can be explained by the high strength and density of Brønsted acid sites (over 90 % of the total surface acidity). MFI might be regarded as a potential material for the creation of novel catalysts for isobutanol conversion into linear butenes at moderate temperatures (448–473 K) since it offers greater operating stability throughout the process.
Electrowetting of Carbon‐based Materials for Advanced Electrochemical Technologies
Authors: Papaderakis Athanasios A. , Leketas Mantas , Wei Zixuan , Hwang Imgon , Carbone Paola , Juel Anne , Dryfe Robert A. W.
Published: March 2024

Wetting phenomena underpin a plethora of key processes occurring in nature and artificial systems. Subtle control over wetting can boost the performance of devices with applications in diverse technologies, spanning electrochemical energy conversion, storage, and capacitive deionization to variable micro‐/nano‐fluidics platforms and electro(nano)tribology. A common characteristic of these systems is their operation under application of an electric field that induces a series of electrochemical processes that can impact wetting. The dependence of wetting on the applied potential bias is referred to as electrowetting. Carbon‐based materials hold a central role as both active electrodes and additives in such systems due to their distinct physicochemical properties and versatile characteristics. Deciphering the mechanisms of electrowetting on carbon in contact with electrolytes of varied types and compositions requires the fundamental understanding of the underlying processes taking place at the carbon/electrolyte interface. Simultaneously, a systematic investigation of electrowetting can often provide significant insights into the properties of the interface. In this concept article, we discuss the latest advances in the area along with the current challenges and future directions of this recently revived research topic.
A new pressure control scheme on steam‐assisted gravity drainage for heavy oil production
Authors: Jia Xinfeng , Wang Kangkang , Xiong Jian , Jiao Binhai , Liu Dong , Chen Zhangxin , Jiang Liangliang , Pang Zhanxi
Published: March 2024

As one the most important recovery mechanisms of steam‐assisted gravity drainage (SAGD), gravity drainage is largely dependent on the inclination angle of the steam chamber edge. The existence of solution‐gas causes an ellipsoid‐shaped chamber that has small inclination angle at the bottom, which leads to inefficient gravity drainage and slows down oil production. To address this problem, this study proposes a new scheme, variable‐pressure SAGD (VP‐SAGD). It is basically a SAGD process, at certain stages of which pressure surge is induced by controlling the operating conditions so that the shape of steam chamber can be altered. This leads to a larger slip angle in the steam chamber at the bottom and more efficient heat transport between hot steam and crude oil. Results show that VP‐SAGD is able to increase oil recovery by up to 20% and decrease cumulative steam–oil ratio (cSOR) by up to 7%. Its special oil extraction mechanisms include swabbing effect, enlarged inclination angle of steam chamber boundary at the bottom, and enhanced heat transfer. Particularly, the inclination angle is increased by up to 40%. In addition, a lower producer bottom‐hole pressure (BHP) during pressure drawdown leads to a better production incremental in later stages. The optimal timing for pressure surge is the middle stage of steam chamber growth. The lower the producer BHP decrease, the better the yield increase. Moreover, The VP‐SAGD strategy works better in heavy oil reservoirs with a permeability of k = 0.5–10 Darcy or solution gas content of greater than 2%.
Historical analysis of accidents in the Saudi Arabian chemical industry
Authors: Palacios Adriana , Palacios‐Rosas Erika , Abdul‐Aziz‐Al‐Mughanam Tawfiq
Published: March 2024

The chemical industry oversees the transformation of raw materials into products through unit operations that require appropriate organization to avoid accidents. Hence, it is important to do analyses to identify any possible mistakes, substances involved, or common sources of accidents in the industry to avoid such errors and design better safety measures to create a safer space for the chemical industry, which is hugely important and boasts a worldwide presence. This document presents an analysis of chemical industry‐related accidents in Saudi Arabia, namely fires, explosions, and toxic clouds which occurred in the chemical and petrochemical industries and while transporting hazardous materials in the last 46 years. Three databases—one for each type of accident—were created with information collected from articles, newspapers, videos, and papers. ‘Explosion’, ‘fire’, and ‘toxic clouds’ were the key words used for the research, focusing on accident taking place in Saudi Arabia. Once the information had been collected, the accidents were filtered, checked, and moved to a fourth general database. It is shown that 54.0% of all related accidents were fires, 25.4% toxic clouds, and 20.6% were explosions. The provinces with the most registered accidents were Riyadh (15), Jeddah (10), and Jubail (6).
Concentration‐Gradient Structural LiFe0.5Mn0.5PO4/C Prepared via Co‐precipitation Reaction for Advanced Lithium‐Ion Batteries
Authors: Jiang Xiaoyan , Li Lanyan , Wang Xianyou , Luo Zhigao
Published: March 2024

The intrinsically low electronic conductivity and slow ion diffusion kinetics limit further development of olivine LiFexMn1‐xPO4 cathode materials. In this paper, with the aim of improving the performance of such materials and alleviating the Jahn‐Taller effect of Mn3+ ion, a bimetallic oxalate precursor with gradient distribution of elemental concentration followed with an efficient process is applied to synthesize LiFe0.5Mn0.5PO4 nanocomposite. The results shown that with certain structural modulation of the precursor, the discharge capacity of synthesized LiFe0.5Mn0.5PO4 increased from 149 mAh g−1 to 156 mAh g−1 at 0.1 C, the cycling capacity was also remarkably improved. the Fe0.5Mn0.5C2O4 ⋅ 2H2O‐1 precursor with gradient distribution of elemental concentration effectively restricts the reaction between electrode material and electrolyte, thereby alleviates the dissolution of Mn3+ ion, reduces the decay of capacity and improves the stability of the material.