bluuebunny/crossref_metadata_2025 huggingface dataset:
Visible‐light‐induced Catalyzed Dehydrogenative Coupling of Quinoxalin‐2(1H)‐ones with Azoles Using Carbon Nitride
Authors: Xie Shihua , Wang Hui , Wang Yong , Yang Qifan , Zhu Hongjun
Published: June 2022

An efficient visible‐light‐induced catalyzed dehydrogenation coupling of quinoxalin‐2(1H)‐ones with azoles was developed, a protocol that did not require prefunctionalization of the substrates and produced hydrogen (H2). Meanwhile, this reaction proceeded without the addition of other metal and oxidant and provided a broad range of 3‐aminoquinoxalin‐2(1H)‐ones in medium to good yield. Furthermore, this protocol provided advantages of easy and simple operation, high chemoselectivity, and a recyclable catalyst. A preliminary mechanistic investigation revealed that the reaction involved a radical process.
Hexaphenylbenzene‐Based Deep Blue‐Emissive Metallacages as Donors for Light‐Harvesting Systems
Authors: Liu Haifei , Zhang Zeyuan , Mu Chaoqun , Ma Lingzhi , Yuan Hongye , Ling Sanliang , Wang Heng , Li Xiaopeng , Zhang Mingming
Published: June 2022

We herein report the preparation of a series of hexaphenylbenzene (HPB)‐based deep blue‐emissive metallacages via multicomponent coordination‐driven self‐assembly. These metallacages feature prismatic structures with HPB derivatives as the faces and tetracarboxylic ligands as the pillars, as evidenced by NMR, mass spectrometry and X‐ray diffraction analysis. Light‐harvesting systems were further constructed by employing the metallacages as the donor and a naphthalimide derivative (NAP) as the acceptor, owing to their good spectral overlap. The judiciously chosen metallacage serves as the antenna, providing the suitable energy to excite the non‐emissive NAP, and thus resulting in bright emission for NAP in the solid state. This study provides a type of HPB‐based multicomponent emissive metallacage and explores their applications as energy donors to light up non‐emissive fluorophores in the solid state, which will advance the development of emissive metallacages as useful luminescent materials.
Intramolecular Tricarbonyl‐Ene Reactions and α‐Hydroxy‐β‐Diketone Rearrangements Inspired by the Biosynthesis of Polycyclic Polyprenylated Acylphloroglucinols
Authors: zur Bonsen Andreas B. , Peralta Ricardo A. , Fallon Thomas , Huang David M. , George Jonathan H.
Published: June 2022

Structurally unique natural products pose biosynthetic puzzles whose solution can inspire new chemical reactions. Herein, we propose a unified biosynthetic pathway towards some complex meroterpenoids—the hyperireflexolides, biyoulactones, hybeanones and hypermonones. This hypothesis led to the discovery of uncatalyzed, intramolecular carbonyl‐ene reactions that are spontaneous at room temperature. We also developed an anionic cascade reaction featuring an α‐hydroxy‐β‐diketone rearrangement and an intramolecular aldol reaction to access four distinct natural product scaffolds from a common intermediate.
Biodegradable Ca2+ Nanomodulators Activate Pyroptosis through Mitochondrial Ca2+ Overload for Cancer Immunotherapy
Authors: Zheng Pan , Ding Binbin , Zhu Guoqing , Li Chunxia , Lin Jun
Published: June 2022

Pyroptosis provides a new direction and broad prospects for cancer immunotherapy. However, the development of a nanoplatform as a pyroptosis inducer is limited, and the discovery of a new type of nano‐pyroptosis inducer for cancer immunotherapy is still imminent. Herein, biodegradable Ca2+ nanomodulators (CaNMs) are prepared as pyroptosis inducers for cancer immunotherapy via mitochondrial Ca2+ overload. The obtained CaNMs can decompose under low pH to release Ca2+ and curcumin, leading to a sudden surge in mitochondrial Ca2+ ions, eventually resulting in pyroptosis. We not only confirm the occurrence of mitochondrial Ca2+ overload‐triggered pyroptosis for the first time but also reveal the robust immune responses via CaNMs, along with remarkably suppressing tumor proliferation and lung metastasis. This work will provide new strategies and inspiration for pyroptosis‐mediated cancer treatments, greatly contributing to the further development of Ca2+ nanomodulators.
Proton‐Gradient‐Driven Sensitivity Enhancement of Liposome‐Encapsulated Supramolecular Chemosensors
Authors: Nilam Mohamed , Karmacharya Shreya , Nau Werner M. , Hennig Andreas
Published: June 2022

An overarching challenge in the development of supramolecular sensor systems is to enhance their sensitivity, which commonly involves the synthesis of refined receptors with increased affinity to the analyte. We show that a dramatic sensitivity increase by 1–2 orders of magnitude can be achieved by encapsulating supramolecular chemosensors inside liposomes and exposing them to a pH gradient across the lipid bilayer membrane. This causes an imbalance of the influx and efflux rates of basic and acidic analytes leading to a significantly increased concentration of the analyte in the liposome interior. The utility of our liposome‐enhanced sensors was demonstrated with various host–dye reporter pairs and sensing mechanisms, and we could easily increase the sensitivity towards multiple biologically relevant analytes, including the neurotransmitters serotonin and tryptamine.
Spherical boron nitride/pitch‐based carbon fiber/silicone rubber composites for high thermal conductivity and excellent electromagnetic interference shielding performance
Authors: Xie Jian , Li Chenjian , Fu Yuheng , Chen Zhimin , Wang Xuelin , Qin Hongmei , Zhang Xiaolin , Zhang Shixian , Wang Shan , Xiong Chuanxi , Zhu Shipeng
Published: June 2022

Composites with high thermal conductivity and excellent electromagnetic interference (EMI) shielding performance are very important for the long‐term stable operation of electronic equipment. In this work, we report a simple and effective method to construct thermally and electrically conductive network pathways by hybridizing pitch‐based carbon fiber (PCF) and spherical boron nitride (s‐BN), in which PCF plays the role in building the framework, and s‐BN acts as a bridge to connect the PCF framework. This can simultaneously enhance the thermal conductivity and EMI shielding efficiency (SE) of silicone rubber (SR) composites. The s‐BN10/PCF20/SR composite could achieve 5.81 W m−1 K−1 of bulk thermal conductivity. The total EMI SE reached 51 dB at the X‐band of 8.2–12.4 GHz. In addition, the s‐BN10/PCF20/SR would have a good heat resistance index (HRI). The tensile strength and elongation at break of the s‐BN10/PCF20/SR were 1.08 MPa and 21.98%, respectively, and its density was only 1.391 g/cm3. In brief, this work provides a simple and effective method to fabricate SR composites with light weight, good thermal stability and suitable mechanical properties to be applied in thermal management and EMI shielding of current electronic equipment.
Improvement in anti‐biofouling property of polyamide thin‐film composite membranes by using copper nanoparticles
Authors: Ngo Thu Hong Anh , Nguyen Tung Duc , Nguyen Vuong Duy , Tran Dung Thi
Published: June 2022

Membrane biofouling is a major problem of the membrane process owing to microbial growth and biofilm on the membrane surface. In this work, a thin‐film composite polyamide membrane was modified with poly(ethylene glycol) and copper nanoparticles. Results demonstrated that surface modification induced changes in membrane‐surface characteristics and enhanced filtration property. The membrane surfaces became more hydrophilic (decreased water contact angle from around 48° to 28°) and had better antibacterial properties than the original ones. The separation property of modified membranes improved, increasing the membrane flux (up to 40%) and antifouling property simultaneously. In particular, the maintained flux ratio (anti‐biofouling property) significantly increased after 4 days of immersing the membranes in Escherichia coli bacterial solution. The membranes were then used for filtration tests with different foulants, such as humic acid and bovine serum albumin solutions.
Finite‐time estimation for a class of systems with unknown time‐delay using modulating functions‐based method
Authors: Asiri Sharefa , Liu Da‐Yan
Published: June 2022

Time‐delay systems are widely used to model real problems. Most of the works on such systems assume prior knowledge of the delay, which is mostly unknown in real applications. This paper aims to fast and robustly estimate unknown delay, parameters, and output derivatives for a class of linear time‐delay systems in noisy environment. First, the classical modulating functions method is combined with the recursive least square algorithm and the Gauss–Newton method to estimate the coefficients and the time‐delay, respectively. Second, the generalized modulating functions method is adopted to provide algebraic integral formulas to estimate the output derivatives using the estimated parameters. Finally, numerical simulations are given to demonstrate the efficiency and robustness of the proposed methods.
The association of 20 short tandem repeat loci of autosomal chromosome with male schizophrenia
Authors: Yang Chun , Ba Huajie , Zou Huihui , Zhou Xianju
Published: June 2022

Introduction

Schizophrenia's heritability and familial transmission have been known for several decades. The male‐specific Y chromosome plays an important role in schizophrenia. Short tandem repeats (STRs)have been recognized as risk genes in the development of schizophrenia. Here, we investigated the association between male schizophrenia and Y‐chromosomal STRs loci.

Methods

We recruited 355 patients with schizophrenia and 473 healthy males for physical examination and amplified them with a PowerPlex 21 System fluorescence‐labeled composite amplification System. Then, the resultant products were separated by electrophoresis and further detected. Finally, differences in allele and genotype frequency distributions of STR loci were observed.

Results

Our results showed that all 20 STR loci were in accordance with Hardy–Weinberg's law (p > .05). There were statistically significant differences in alleles of D13S317 and D5S818 loci and genotype frequency distribution between the two groups (alleles: p = .039, p = .022, respectively; genotype: p = .0004, p = .011, respectively). However, there was no difference in the other autosomal 18 STR loci between the two groups (p > .05). Univariate analysis showed that the frequency distribution differences of allele 11 and genotype 10‐11 at the D13S317 locus between the two groups were significant (compared to the controls, p = 0.005, odds ratio (OR) = 1.37, 95%b confidence interval (CI) = 1.10–1.71, compared to the controls, p = .0000002, OR = 3.92, 95% CI = 2.27–6.77, respectively). The frequency distribution differences of allele 7 and genotype 7‐10 at D5S818 between the two groups were significant (compared to the controls, p = .0006, OR = 3.42, 95% CI = 1.63–7.16, compared to the controls, p = .0011, OR = 8.24, 95% CI = 1.83–37.05, respectively).

Conclusion

Polymorphisms of the D13S317 and D5S818 loci may be predisposing factors for schizophrenia.
Chemical Constituents of the Stem Bark of the Hybrid Plant Citrus × paradisi Macfad. (Rutaceae)
Authors: Essombe Malolo Fanny‐Aimée , Bellier Tabekoueng George , Dongmo Tekapi Tsopgni Willifred , Nguemdjo Chimeze Valery Wilfried , Kenmogne Kouam Ariane , Mas‐Claret Eduard , Langat Moses K. , Ndom Jean Claude , Frese Marcel , Sewald Norbert , Duplex Wansi Jean
Published: June 2022

The stem bark of Citrus × paradisi Macfad. (Rutaceae) gave (23S)‐isolimonexic acid (1), limonin (2), citracridone II (3), citpressine II (4), citpressine I (5), grandisine (6), 2‐hydroxynoracronycine (7), citracridone I (8), 5‐methoxyseselin (9), umbelliferone (10), scopoletin (11), naringenin (12), apigenin (13), friedelin (14), agrostophyllinone (15) and stigmasterol‐3‐O‐β‐D‐glucopyranoside (16). The structures of the compounds were determined using NMR and MS spectroscopic data, and by comparison with published data. The relative configuration of 1 was proposed as (23S)‐isolimonexic acid using NOE studies. Hydrogenation reaction of compound 3 led to the new derivative 3’,4’‐dihydrocitracridone II (3a). Cytotoxicity activities against the human adenocarcinoma alveolar basal epithelial cell lines A549 and the Caucasian prostate adenocarcinoma cell lines PC3, using the MTT assays showed that the methanol crude extract was significant with IC50 values of 30.1 and 31.7 μg/mL, respectively, with the positive control, doxorubicin giving an IC50 of 0.9 μM. In addition, compounds 3, 7 and 8 gave moderate cytotoxic activities with IC50 values of 33.1, 31.2 and 32.5 μM for A549 cells and 35.7, 33.8 and 34.9 μM for PC3 cells, respectively. The hydrogenated 3a was less active than 3, suggesting that the presence of the double bond in pyrans is important for structure‐activity relationship.
The binding between NPM and H2B proteins signals for the diabetes‐associated centrosome amplification
Authors: Xu Si X. , Han Ya W. , Guo Jia Li , Bian Xue K. , Hu Hong M. , Lee Shao C.
Published: June 2022

Diabetes not only increases the risk for cancer but also promotes cancer metastasis. Centrosome amplification (CA) is sufficient to initiate tumorigenesis and can enhance the invasion potential of cancer cells. We have reported that diabetes can induce CA, with diabetic pathophysiological factors as the triggers, which involves the signaling of nucleophosmin (NPM). Thus, CA can serve as a candidate biological link between diabetes and cancer. In the present study, we attempted to identify the NPM binding partners and investigated whether the binding between NPM and its partner mediated the CA. We confirmed that high glucose, insulin, and palmitic acid cancer could elicit CA in the HCT16 colon cancer cells and found that the experimental treatment increased the binding between NPM and H2B, but not between p‐NPM and H2B. The molecular docking analysis supported the fact that NPM and H2B could bind to each other through various amino acid residues. The treatment also increased the colocalization of NPM and H2B in the cytosol. Importantly, disruption of the NPM1–H2B complex by individual knockdown of the protein level of NPM or H2B led to the inhibition of the treatment‐evoked CA. In conclusion, our results suggest that the binding between NPM and H2B proteins signals for the CA by high glucose, insulin, and palmitic acid.
Percutaneous mechanical thrombectomy and extracorporeal membranous oxygenation: A case series
Authors: Mously Haytham , Hajjari Jamal , Chami Tarek , Hammad Tarek , Schilz Robert , Carman Teresa , Elgudin Yakov , Abu‐Omar Yasir , Pelletier Marc P. , Shishehbor Mehdi H. , Li Jun
Published: June 2022

Background

Massive or high‐risk pulmonary embolism (PE) is a potentially life‐threatening diagnosis with significant morbidity and mortality if treatment is delayed. Extracorporeal membrane oxygenation (ECMO) and large bore thrombectomy (LBT) in isolation have been used to stabilize and treat patients with massive PE, however, literature describing the combination of both modalities is lacking. We present a case series involving 9 patients who underwent combined ECMO and LBT and their outcomes.

Methods

This was a retrospective chart review of patients with confirmed PE, who underwent LBT and ECMO. We retrospectively captured clinical, therapeutic, and outcome data at the time of pulmonary embolism response team (PERT) activation and during the follow‐up period for up to 90 days.

Results

Nine patients who had PERT activation with confirmed PE diagnosis have undergone combined LBT and ECMO initiation since the advent of our PERT program. The median age was 57 (range 28–68) years. Six patients out of 9 (55%) had cardiac arrest before therapy. All patients exhibited right heart strain on computed tomography and echocardiogram. The median ECMO duration was 5 days (range 2.3–11.6 days), with mean hospitalization of 16.1 days (range 1.5–30.9). Mortality was 22% at 90‐day follow‐up period.

Conclusion

Patients with massive pulmonary embolism who suffer cardiac arrest have significant morbidity and mortality. ECMO in combination with LBT is a viable treatment option for patients with significant hemodynamic compromise.
Stability Enhancement of Iron‐based Perovskite Catalysts by A‐site Substitution for Oxidative Transposition of α‐Bromostyrene to Phenacyl Bromide
Authors: Shibata Satomi , Kamata Keigo , Hara Michikazu
Published: June 2022

LaFeO3 nanoparticles, which were synthesized by the sol‐gel method using aspartic acid, acted as efficient and stable heterogeneous catalysts for the oxidative transformation of α‐bromostyrene to phenacyl bromide using only air under mild conditions without the need for additives and light irradiation. The stability of Fe‐containing perovskite oxides was significantly improved by changing the A‐site metal cation from alkaline metals to lanthanum. LaFeO3 showed much higher catalytic activities than other Fe3+/Fe2+‐containing simple oxides. Mechanistic studies showed the involvement of a radical‐type mechanism involving surface adsorbed O2 species over p‐type LaFeO3. Such an active oxygen species was applicable to the aerobic oxidative cleavage of 1,1‐diphenylethylene and oxidative coupling of p‐toluenethiol.
Electron‐Rich Silicon Containing Phosphinanes for Rapid Pd‐Catalyzed C−X Coupling Reactions**
Authors: Kräh Sabrina , Kachel Iris , Trapp Oliver
Published: June 2022

Palladium‐catalyzed cross‐coupling reactions are among the most useful and efficient methods for direct access to complex structures in organic synthesis. However, heteroatom‐containing compounds can complicate such coupling reactions due to their competitive coordination with the palladium catalyst and electronic effects. As a result, good yields are often only obtained under harsher reaction conditions, such as high temperatures and long reaction times. Here the design of a highly active phosphine ligand is reported that provides excellent yields for C−N coupling reactions at ambient temperature. Incorporation of the phosphorus atom into a cyclohexane ring maintains the pyramidal structure of the phosphorus while reducing steric hindrance. This, and a silicon atom in the cyclohexane moiety, results in an electron‐rich phosphinane ligand. This novel silicon containing SabPhos ligand can be obtained in excellent yields in a straightforward synthesis. In palladium catalyzed reactions, this ligand facilitates the coupling of a broad range of heteroaryl chlorides via C−C bonds with boronic acids and C−N bonds with secondary amines in excellent yields under mild conditions.
Different Enzyme Conformations Induce Different Mechanistic Traits in HIV‐1 Protease
Authors: Coimbra João T. S. , Neves Rui P. P. , Cunha Ana V. , Ramos Maria J. , Fernandes Pedro A.
Published: June 2022

The influence of the dynamical flexibility of enzymes on reaction mechanisms is a cornerstone in biological sciences. In this study, we aim to 1) study the convergence of the activation free energy by using the first step of the reaction catalysed by HIV‐1 protease as a case study, and 2) provide further evidence for a mechanistic divergence in this enzyme, as two different reaction pathways were seen to contribute to this step. We used quantum mechanics/molecular mechanics molecular dynamics simulations, on four different initial conformations that led to different barriers in a previous study. Despite the sampling, the four activation free energies still spanned a range of 5.0 kcal ⋅ mol−1. Furthermore, the new simulations did confirm the occurrence of an unusual mechanistic divergence, with two different mechanistic pathways displaying equivalent barriers. An active‐site water molecule is proposed to influence the mechanistic pathway.
Natural Products from Annonaceae as Potential Antichagasic Agents
Authors: Barros de Menezes Renata Priscila , Fechine Tavares Josean , Kato Massuo Jorge , da Rocha Coelho Francisco Alex , Sousa dos Santos Airton Lucas , da Franca Rodrigues Klinger Antonio , Sessions Zoe L. , Muratov Eugene N. , Scotti Luciana , Tullius Scotti Marcus
Published: June 2022

Chagas disease, a neglected tropical disease, is endemic in 21 Latin American countries and particularly prevalent in Brazil. Chagas disease has drawn more attention in recent years due to its expansion into non‐endemic areas. The aim of this work was to computationally identify and experimentally validate the natural products from an Annonaceae family as antichagasic agents. Through the ligand‐based virtual screening, we identified 57 molecules with potential activity against the epimastigote form of T. cruzi. Then, 16 molecules were analyzed in the in vitro study, of which, six molecules displayed previously unknown antiepimastigote activity. We also evaluated these six molecules for trypanocidal activity. We observed that all six molecules have potential activity against the amastigote form, but no molecules were active against the trypomastigote form. 13‐Epicupressic acid seems to be the most promising, as it was predicted as an active compound in the in silico study against the amastigote form of T. cruzi, in addition to having in vitro activity against the epimastigote form.
Amyloid‐β Inspired Short Peptide Amphiphile Facilitates Synthesis of Silver Nanoparticles as Potential Antibacterial Agents
Authors: Tripathi Satyendra K. , Kesharwani Khushboo , Kaul Grace , Akhir Abdul , Saxena Deepanshi , Singh Ramesh , Mishra Narendra K. , Pandey Archna , Chopra Sidharth , Joshi Khashti B.
Published: June 2022

An amyloid‐β inspired biocompatible short peptide amphiphile (sPA) molecule was used for controlled and targeted delivery of bioactive silver nanoparticles via transforming sPA nanostructures. Such sPA‐AgNPs hybrid structures can be further used to develop antibacterial materials to combat emerging bacterial resistance. Due to the excellent antibacterial activity of silver, the growth of clinically relevant bacteria was inhibited in the presence of AgNPs‐sPA hybrids. Bacterial tests demonstrated that the high biocompatibility and low cytotoxicity of the designed sPA allow it to work as a model drug delivery agent. It therefore shows great potential in locally addressing bacterial infections. The results of our study suggest that these nanodevices have the potential to trap and then engage in the facile delivery of their chemical payload at the target site, thereby working as potential delivery materials. This system has potential therapeutic value for the treatment of microbiota triggered progression of neurodegenerative diseases.
Confinement Effects in Dynamics of Ionic Liquids with Polymer‐Grafted Nanoparticles
Authors: Liu Siqi , Li Ruhao , Tyagi Madhusudan , Akcora Pinar
Published: June 2022

Ionic liquid mixed with poly(methyl methacrylate)‐grafted Fe3O4 nanoparticle aggregates at low particle concentrations was found to exhibit different dynamics and ionic conductivity than that of pure ionic liquid in our previous studies. In this work, we report on the quasi‐elastic neutron scattering results of ionic liquid containing polymer‐grafted Fe3O4 nanoparticles at higher particle concentrations. The diffusivity of imidazolium (HMIM+) cations of 1‐hexyl‐3‐methylimidazolium bis(trifluoromethylsulfonyl)imide (HMIM‐TFSI) in the presence of poly(methyl methacrylate)‐grafted Fe3O4 nanoparticles is discussed through the confinement. Analysis of the elastic incoherent structure factor revealed that the confinement radius decreased with the addition of grafted particles in HMIM‐TFSI/solvent mixture. We propose the confinement that is induced by the high concentration of grafted particles shrinks the HMIM‐TFSI restricted volume. We further conjecture that this enhanced diffusivity occurs as a result of the local ordering of cations within aggregates of poly(methyl methacrylate)‐grafted Fe3O4 nanoparticles.
Base‐Free Aerobic Oxidation of Furfuralcohols and Furfurals to Furancarboxylic Acids over Nitrogen‐Doped Carbon‐Supported AuPd Bowl‐Like Catalyst
Authors: Guan Wen , Zhang Yunlei , Yan Changhao , Chen Yao , Wei Yanan , Cao Yu , Wang Fang , Huo Pengwei
Published: June 2022

Upgrading furfuralcohols and furfurals to furancarboxylic acids is of great significance for high value‐added downstream chemicals synthesis and biomass conversion. Developing an efficient catalyst is the key to acquiring a completely sustainable process. Herein, nitrogen‐doped carbon‐supported bimetallic AuPd bowl‐like catalysts were synthesized. The surface wettability of nitrogen‐doped carbon was well adjusted by the nitrification process. Benefiting from the alloying effect of bimetallic AuPd catalyst and the formation of hydroxyl radical initiated by H2O dissociation on the hydrophilic surface of nitrated nitrogen‐doped carbon, base‐free aerobic oxidation of 5‐hydroxymethylfurfural (HMF) could produce the highest 2,5‐furandicarboxylic acid (FDCA) yield of 93.9 %. In‐situ infrared spectroscopy uncovered adsorption configuration of HMF, and the nitrated carbon surface was favorable for HMF and intermediates to enter the active sites, greatly promoting the catalytic oxidation process. Employing other furfuralcohols (furfuryl alcohol, furan‐2,5‐diyldimethanol, 2,5‐bishydroxymethylfuran) as well as furfural and 5‐methylfurfural as starting materials, 35.6–95.4 % yield of furancarboxylic acids (FDCA, 2‐furoic acid, 5‐methyl‐2‐furoic acid) were also obtained. Moreover, the developed catalysts could maintain excellent stability and activity after four successive runs. This deep insight into the role of bimetallic synergy and surface wettability provides a basis for the rational design of the highly efficient catalysts for the oxidation of furfuralcohols and furfurals and related reactions.
Nicotinamide‐N‐methyltransferase is a promising metabolic drug target for primary and metastatic clear cell renal cell carcinoma
Authors: Reustle Anna , Menig Lena‐Sophie , Leuthold Patrick , Hofmann Ute , Stühler Viktoria , Schmees Christian , Becker Michael , Haag Mathias , Klumpp Verena , Winter Stefan , Büttner Florian A. , Rausch Steffen , Hennenlotter Jörg , Fend Falko , Scharpf Marcus , Stenzl Arnulf , Bedke Jens , Schwab Matthias , Schaeffeler Elke
Published: June 2022

Background

The metabolic enzyme nicotinamide‐N‐methyltransferase (NNMT) is highly expressed in various cancer entities, suggesting tumour‐promoting functions. We systematically investigated NNMT expression and its metabolic interactions in clear cell renal cell carcinoma (ccRCC), a prominent RCC subtype with metabolic alterations, to elucidate its role as a drug target.

Methods

NNMT expression was assessed in primary ccRCC (n = 134), non‐tumour tissue and ccRCC‐derived metastases (n = 145) by microarray analysis and/or immunohistochemistry. Findings were validated in The Cancer Genome Atlas (kidney renal clear cell carcinoma [KIRC], n = 452) and by single‐cell analysis. Expression was correlated with clinicopathological data and survival. Metabolic alterations in NNMT‐depleted cells were assessed by nontargeted/targeted metabolomics and extracellular flux analysis. The NNMT inhibitor (NNMTi) alone and in combination with the inhibitor 2‐deoxy‐D‐glucose for glycolysis and BPTES (bis‐2‐(5‐phenylacetamido‐1,3,4‐thiadiazol‐2‐yl)ethyl‐sulfide) for glutamine metabolism was investigated in RCC cell lines (786‐O, A498) and in two 2D ccRCC‐derived primary cultures and three 3D ccRCC air–liquid interface models.

Results

NNMT protein was overexpressed in primary ccRCC (p = 1.32 × 10–16) and ccRCC‐derived metastases (p = 3.92 × 10–20), irrespective of metastatic location, versus non‐tumour tissue. Single‐cell data showed predominant NNMT expression in ccRCC and not in the tumour microenvironment. High NNMT expression in primary ccRCC correlated with worse survival in independent cohorts (primary RCC—hazard ratio [HR] = 4.3, 95% confidence interval [CI]: 1.5–12.4; KIRC—HR = 3.3, 95% CI: 2.0–5.4). NNMT depletion leads to intracellular glutamine accumulation, with negative effects on mitochondrial function and cell survival, while not affecting glycolysis or glutathione metabolism. At the gene level, NNMT‐depleted cells upregulate glycolysis, oxidative phosphorylation and apoptosis pathways. NNMTi alone or in combination with 2‐deoxy‐D‐glucose and BPTES resulted in inhibition of cell viability in ccRCC cell lines and primary tumour and metastasis‐derived models. In two out of three patient‐derived ccRCC air–liquid interface models, NNMTi treatment induced cytotoxicity.

Conclusions

Since efficient glutamine utilisation, which is essential for ccRCC tumours, depends on NNMT, small‐molecule NNMT inhibitors provide a novel therapeutic strategy for ccRCC and act as sensitizers for combination therapies.
Single‐cell RNA sequencing reveals the characteristics of cerebrospinal fluid tumour environment in breast cancer and lung cancer leptomeningeal metastases
Authors: Ruan Haoyu , Wang Zhe , Sun Ziwei , Wei Jia , Zhang Lei , Ju Huanyu , Wang Ting , Zhang Chao , Guan Ming , Pan Shiyang
Published: June 2022

Leptomeningeal metastases (LM) occur in patients with breast cancer (BC) and lung cancer (LC) showing exceptionally poor prognosis. The cerebrospinal fluid (CSF) tumour microenvironment (TME) of LM patients is not well defined at a single‐cell level. Based on the 10× genomics single‐cell RNA sequencing (scRNA‐seq) data from GEO database including five patient‐derived CSF samples of BC‐LM and LC‐LM, and four patient‐derived CSF samples of idiopathic intracranial hypertension (IIH) as controls, we analysed single‐cell transcriptome characteristics of CSF TME in LM patients compared to controls simultaneously and comprehensively. In addition, we performed 10× genomics scRNA‐seq on CSF cells derived from a BC‐LM patient to help generate a solid conclusion. The CSF macrophages in LM patients showing M2‐subtype signature and the emergence of regulatory T cells in LM confirmed the direction of tumour immunity toward immunosuppression. Then, the characteristics of CSF circulating tumour cells (CTCs) of breast cancer LM (BC‐LM) patients were classified into five molecular subtypes by PAM50 model. The communication between macrophages and five subtype‐specific CSF‐CTCs showed largest number of ligand‐receptor interactions. The five subtypes‐specific CSF‐CTCs showed great heterogeneities which were manifested in cell proliferation and cancer‐testis antigens expression. Gene regulatory networks (GRNs) analysis revealed that transcription factor SREBF2 was universally activated in the five subtypes‐specific CSF‐CTCs. Our results will provide inspiration on new directions of the mechanism research, diagnosis and therapy of LM.
Undifferentiated carcinoma with osteoclast‐like giant cells of pancreas on cytology: A case report with review of literature
Authors: Gupta Kanishk , Goyal Surbhi , Chaudhary Dimple , Sakhuja Puja , Narang Poonam , Nag Hirdaya Hulas
Published: June 2022

Undifferentiated carcinoma with osteoclast‐like giant cells (UC‐OGC) is a rare malignant neoplasm accounting for <1% of pancreatic masses. Very few case reports and small series have described the cytomorphological features of this entity. We report a case of UC‐OGC arising in the pancreas presenting with liver metastasis in a 56‐year‐old man diagnosed by guided fine‐needle aspiration cytology (FNAC). A characteristic biphasic pattern comprising of malignant mononuclear cells with scattered bland giant cells were the hallmark features for cytological diagnosis. Our case along with review of cytology literature emphasize the utility of FNAC and the cell block in the diagnosis and management of this rare entity.
Transition Metal Scaffolds Used To Bring New‐to‐Nature Reactions into Biological Systems
Authors: Liu Yifei , Lai Ka Lun , Vong Kenward
Published: June 2022

As a means to develop new tools to manipulate biological systems, transition metals have been looked upon as an area of high potential due to the bioorthogonality of new‐to‐nature reactions. To facilitate their incorporation into complex biological systems, researchers have mainly focused on the development of metal catalyst complexes, protein scaffolds, and nanocarriers to protect and preserve the biocatalytic activity of transition metals. The intent of this review is to summarize these structural scaffolds, which has steadily allowed researchers to push transition metal usage not previously thought possible within bacteria, mammalian cells, and higher‐level organisms.
Structural Asymmetry and Chiroptical Activity of Chiral Antimony‐Halide Hybrids
Authors: Wang Zhiyu , Zhang Zixuan , Sung Herman H. Y. , Williams Ian D. , Lu Haipeng
Published: June 2022

Chiral metal‐halide hybrids have aroused widespread attention owing to their chemical and structural versatilities as well as unique optoelectronic and spin‐dependent properties. Several recent experiments have shown that organic chirality results in circularly polarized absorption and emission from the inorganic metal‐halide subcomponent; however, the exact structure chirality transfer mechanism and structure‐optical‐activity relation remain elusive. Here, we demonstrate how chiral organic cations lead to local structural asymmetry in a new series of chiral antimony‐halide hybrids, including zero‐dimensional edge‐shared (0D, A4Sb2X10, A=(R)‐(+)‐α‐methylbenzylammonium (R‐MBAH+) or (R)‐(−)‐1‐cyclohexylethylammonium (R‐CHEAH+), X=Br, I) and one‐dimensional corner‐shared (1D, A’2SbX5, A’=(R)‐(+)‐α‐ethylbenzylammonium (R‐EBAH+); X=Br, I). Structure analysis shows that organic ammoniums distort the antimony‐halide octahedra through asymmetric hydrogen bonding. The chiroptical activity is correlated with the exciton coupling strength, which can be tuned by the structural dimensionality. Our study unveils the molecular scale chirality transfer mechanism in these chiral metal‐halide hybrids.
Uncertainty and simulation‐based cost analyses for energy storage systems used in green buildings
Authors: Chadly Assia , Azar Elie , Mayyas Ahmad
Published: June 2022

Energy storage systems (ESS) provide buildings with the ability to store electricity generated from renewable energy sources (eg, solar photovoltaics), increasing building operational flexibility and reliability. Previous studies on ESS in buildings often make assumptions about key input parameters (eg, installation factor, roundtrip efficiency, etc.) being fixed, overlooking potential performance risks due to uncertainty or variations in these parameters. The goal of this paper is to quantify the impact of uncertainty in technical and financial parameters on the economic performance of Li‐ion batteries (LIB), proton‐exchange membranes reversible fuel cells (PEM RFC), and reversible solid oxide cells (RSOC). The analysis is conducted on three medium‐sized office buildings located in three different climate zones of the United States: 2B (Phoenix, AZ), 3B‐Coast (Los Angeles, CA), and 4C (Seattle, WA). Two metrics are used to evaluate the economic viability of the selected technologies, namely the levelized cost of electricity (LCOE) and the levelized cost of energy storage (LCOS). While the results of the LCOE and LCOS differed in value between those cities, the cost breakdown for LCOS in all locations shows that capital cost is the biggest cost contributor, followed by electricity cost. A Monte‐Carlo simulation was also conducted to assess the impact of uncertainty in input parameters on the LCOS model. The simulation results allowed us to generate probable ranges and probability tables for the LCOS.
Myricetin ameliorated prediabetes via immunomodulation and gut microbiota interaction
Authors: Yang Li , Gao Yongchao , Gong Jupeng , Wang Hui , Farag Mohamed A. , Simal‐Gandara Jesus , Zhao Yonghua , Nie Shaoping , Xiao Jianbo
Published: June 2022

The global prevalence of prediabetes is on the rise, and it is of value to manage prediabetes and predisposal to diabetes at an early stage. Myricetin is a natural polyhydroxyflavonoid, found in planta with several health benefits. This study aimed to evaluate the effects of myricetin on prediabetes. In vitro assay indicated that the cell viability, endocytosis and phagocytosis of macrophages were inhibited in RAW 264.7 cells under high glucose (HG) levels, concurrent with an increase in reactive oxygen species level. Administration of myricetin at a dose of 10 μM, restored the immunosuppressive effects mediated by HG. Moreover, the viability of Jurkat cells was also inhibited concurrent with inhibition of interleukin‐2 (IL‐2) and interferon‐gamma (IFN‐γ) expression levels versus increase PD‐1 after treated with myricetin at the dose of 10 μM. In a prediabetic mouse model fed with high fat diet, increase in body weight, fat mass, fasting blood glucose, Triglyceride (TG), total cholesterol (TC) and low‐density lipoprotein cholesterol (LDL‐C) were observed. Flow cytometry analysis revealed a significant decrease in CD8+ T cells in the spleen and blood, whereas the expression of PD‐1 on CD3+, CD4+, and CD8+ T cells in the spleen and lymph was significantly elevated. Administration of myricetin showed a potential hypoglycemic and lipid‐lowering effect in both prevention and treatment, in addition to restoration of innate and adaptive immune immunity in mice and confirmed by the in vitro immunomodulation effect. In addition, 16S rRNA showed that myricetin ameliorated prediabetes may be related to decrease in the relative abundance of Acetatifactor, Blautia, Intestinimonas, Anaerotruncus, and Peptococcus.
Reclaimed and Up‐Cycled Cathodes for Lithium‐Ion Batteries
Authors: Gastol Dominika , Marshall Jean , Cooper Elizabeth , Mitchell Claire , Burnett David , Song Tengfei , Sommerville Roberto , Middleton Bethany , Crozier Mickey , Smith Robert , Haig Sam , McElroy Con Robert , van Dijk Nick , Croft Paul , Goodship Vannessa , Kendrick Emma
Published: June 2022

As electric vehicles become more widely used, there is a higher demand for lithium‐ion batteries (LIBs) and hence a greater incentive to find better ways to recycle these at their end‐of‐life (EOL). This work focuses on the process of reclamation and re‐use of cathode material from LIBs. Black mass containing mixed LiMn2O4 and Ni0.8Co0.15Al0.05O2 from a Nissan Leaf pouch cell are recovered via two different recycling routes, shredding or disassembly. The waste material stream purity is compared for both processes, less aluminium and copper impurities are present in the disassembled waste stream. The reclaimed black mass is further treated to reclaim the transition metals in a salt solution, Ni, Mn, Co ratios are adjusted in order to synthesize an upcycled cathode, LiNi0.6Mn0.2Co0.2O2 via a co‐precipitation method. The two reclamation processes (disassembly and shredding) are evaluated based on the purity of the reclaimed material, the performance of the remanufactured cell, and the energy required for the complete process. The electrochemical performance of recycled material is comparable to that of as‐manufactured cathode material, indicating no detrimental effect of purified recycled transition metal content. This research represents an important step toward scalable approaches to the recycling of EOL cathode material in LIBs.
Biostratigraphy, palaeoecology, and palaeobiogeography of the Middle–Late Eocene ostracods, north‐west Fayoum area, Egypt
Authors: El Baz Sherif M. , Wanas Hamdalla A. , Abou Awad Heba Allah , Assal Ehab M.
Published: June 2022

The present study focuses principally on the late Middle Eocene–early Late Eocene ostracods from two successions (Garet Umm Rigl section and Qasr El Sagha sections), in the northwestern portion of Fayoum area, Egypt. Stratigraphically, the studied successions are classified into three formations (from base to top), the Gehannam, Birket Qarun, and Qasr El Sagha (Temple Member). The recorded ostracod assemblage contains 33 species belonging to 20 genera and 9 families. According to their stratigraphic ranges, three local biozones are recognized, Asymmetricythere yousefi–Loxoconcha pseudopunctatella, Reticulina heluanensis–Leguminocythereis sadeki, and Trachyleberis nodosus nodosulcatus–Ruggeria (Keijella) glabella. The comparison of the proposed biozones with their equivalents inside Egypt denotes a Middle–Late Eocene age for the studied sections. Based on the character of investigated ostracods, three ecozones are distinguished. An inner–outer neritic environment is suggested for the first ecozone, inner‐middle neritic conditions for the second, while shallow water conditions are proposed for the third ecozone. In addition, this paper represents an attempt to detect the palaeobiogeographic provinces of Eocene ostracods by means of multivariate analyses (principle component analysis, Q‐mode cluster analysis and similarity index). These analyses are applied on a matrix composed of some selected Eocene species from 10 regions located at the southern Tethys and western Africa. The results identify three distinctive provinces, North Africa (Algeria, Tunisia, Libya, and Egypt), the Middle East (Jordan and Israel) and West Africa (Senegal, Togo, Ivory Coast and Nigeria). The distinctive affinities between these provinces suggests ostracod migration along the southern Tethys during the Eocene age.
Multiproxy analysis constraining climatic control over the Cenozoic depositional history of Kachchh, Western India
Authors: Chaudhuri Swagata , De Shuvabrata , Srivastava Hema , Chattopadhyay Koustav , Bhaumik Ajoy K.
Published: June 2022

A well‐developed 86 m‐thick Cenozoic sedimentary succession in the Matanomadh area, western Kachchh, was studied to assess the stratigraphic positions of different units, ascertain depositional environments, and the degree of climatic controls over time depositional processes. Age‐diagnostic nannoplankton species Cyclicargolithus floridanus (46.29–12.1 Ma), Reticulofenestra dictyoda (53–30.8 Ma), Reticulofenestra minuta (50.5–2.59 Ma) and foraminiferal species, for example, Orbulinoides beckmanni (41–39.5 Ma) found across studied units envisage the stratigraphic age and palaeoenvironment. CaO with strong negative elemental correlation, binary/ternary discriminant tectonic and depositional regimes cross‐plot from units indicate the biogenic origin of limestones and shales were formed in typical passive, marginal, shallow littoral settings with plausible detritus influx from Deccan basaltic provenance. Total organic carbon with TE‐REE respectively connotes a sedimentation process in a nearly consistent open shallow marine, locally transient semi‐restricted marginal basin in a tropical‐equatorial region. Furthermore, principal component analysis (PCA) of weathering indices based on elemental abundance and X‐ray diffraction data of clays deterministically suggest with empirical relation between humid tropical climate‐induced weathering and fluctuant terrestrial influx. Palaeoredox indices with biological data demonstrate localized redox‐stratified conditions. However, coherent signatures of the global events such as Eocene Thermal Maximum‐2, Middle Eocene Climatic Optimum, and Mid Miocene Climatic Optimum can be traced and validated by synthesizing geochemical data for direct/indirect estimation of sediment routing, rainfall (αAlMg and αAlCa) and climate proxies (PCA), productivity indices (Babio, Cubio and Nibio), and localized periodic oxic‐dysoxic environment (V/Cr, U/Th, Ni/Co) from core samples.
Exploration of energy‐based volumetric heating on ferrothermal porous convection: Effects of MFD viscosity and boundary conditions
Authors: Savitha Lakkanna , Nanjundappa Chikkanalluru Erappa , Shivakumara Inapura Siddagangaiah
Published: June 2022

The impact of energy‐based volumetric internal heating and magnetic field‐dependent (MFD) viscosity on the onset of ferrothermal porous convection for different types of boundary conditions is investigated. The lower and upper boundaries are considered to be either rigid or stress‐free. The lower boundary is insulating, while at the upper boundary a Robin type of thermal condition is applied. Besides this, a general type of boundary conditions is invoked on the magnetic potential. The stability eigenvalue problem is solved numerically using the Galerkin‐type of weighted residuals technique with the Rayleigh number, as the eigenvalue. The results obtained for different boundary combinations are found to be qualitatively similar though not quantitatively. The effect of Biot number, MFD viscosity, and porous parameters is to hinder, while the influence of internal heat source strength, magnetic number, and the nonlinearity of fluid magnetization is to advance the onset of convection. The rigid and conducting boundaries offer a more stabilizing influence on the onset when compared to stress‐free and insulating boundaries. The convection cells get contracted the most when the boundaries are rigid and also when the upper boundary is conducting. The results delineated under the limiting cases are found to be in good agreement with those available in the literature.
Design and synthesis of benzimidazole derivatives as antimycobacterial agents
Authors: Sindhu Gagandeep , Kholiya Rohit , Kidwai Saqib , Singh Padam , Singh Ramandeep , Rawat Diwan S.
Published: June 2022

A series of 2,5‐disubstituted benzimidazole derivatives was synthesized with the aim to identify compounds with potent anti‐TB activity. All the compounds were screened in vitro against cultured Mycobacterium tuberculosis H37Rv strain and found to be exhibiting MIC99 values in the range of 0.195–100 µM. Out of 43 synthesized compounds, two compounds 11h and 13e showed better anti‐TB activity than the reference drug isoniazid.
Effects of gadodiamide and gadoteric acid on lung tissue: A comparative study
Authors: Beyazal Çeliker Fatma , Tümkaya Levent , Suzan Zehra T. , Topcu Atilla , Mercantepe Tolga , Çinar Seda , Yazici Zihni A. , Yılmaz Adnan
Published: June 2022

We set out to investigate the effects of gadodiamide and gadoteric acid, used for magnetic resonance imaging, on the lungs. In this study, 32 male Sprague Dawley rats were used. These were allocated into four groups; The first group (control) was untreated. The second group received isotonic saline on the first and fourth days of the week for 5 weeks. Following the same schedule, the third and fourth groups received a total of 2 mg/kg gadodiamide and gadoteric acid, respectively, in place of saline. The alveolar Wall thickness was evaluated. Gadodiamide and gadoteric acid significantly increased the numbers of collagen‐3 and caspase‐3 positive cells in the lung tissue (p < 0.05). In addition, these two substances increased the alveolar Wall thickness (p < 0.05). Furthermore, they increased the levels of malondialdehyde and glutathione (p < 0.05). This study demonstrates that both linear and macrocyclic contrast agents are toxic for the lungs in rats.