bluuebunny/crossref_metadata_2025 huggingface dataset:
Reconstruction of an enigmatic Pennsylvanian cone reveals a relationship to Sphenophyllales
Authors: D'Antonio Michael P. , Hotton Carol L. , Smith Selena Y. , Crane Peter R. , Herrera Fabiany
Published: April 2024

Premise

We studied the 3D morphology of a small, well‐preserved cone from the Pennsylvanian Mazon Creek Lagerstätte to characterize its structure and determine its systematic affinity. Previously tentatively assigned to the enigmatic Tetraphyllostrobus, we show that it differs in key respects from that genus as described.

Methods

We systematically compared the new fossil with relevant Paleozoic cone genera and employed advanced imaging techniques, including scanning electron microscopy, Airyscan confocal super‐resolution microscopy, optical microscopy, and X‐ray microcomputed tomography to visualize and reconstruct the fossil cone in 3D.

Results

The analyses demonstrate unequivocally that the sporophylls of the new Mazon Creek cone are arranged in whorls of six and have characters typical of Sphenophyllales, including epidermal cells with undulatory margins and in situ spores assignable to Columinisporites. The combination of characters, including sporophyll arrangement, anatomy, and spore type, supports the establishment of Hexaphyllostrobus kostorhysii gen. et sp. nov. within Sphenophyllales. Furthermore, we show that Tetraphyllostrobus, although originally described as possessing smooth monolete spores, actually possesses Columinisporites‐type spores, indicating that it, too, was most likely a sphenophyll.

Conclusions

The recognition of Hexaphyllostrobus contributes to our knowledge of Pennsylvanian sphenophyll diversity, and in particular increases the number of species with in situ Columinisporites‐type spores. Attribution of Hexaphyllostrobus to Sphenophyllales calls into question current interpretations of Tetraphyllostrobus suggesting that future research on better‐preserved macrofossil material may demonstrate a sphenophyllalean relationship.
Albizzia chinensis (Osbeck) Merr extract YS ameliorates ethanol‐induced acute gastric ulcer injury in rats by regulating NRF2 signaling pathway
Authors: Tang Bo , Li Liangning , Yu Yuanzhi , Wang Guibin , Ma Shuanggang , Yu Shishan , Zhang Jianjun
Published: April 2024

Background

Around the world, there is a high incidence of gastric ulcers. YS, an extract from the Chinese herb Albizzia chinensis (Osbeck) Merr, has potential therapeutic applications for gastrointestinal diseases. Here we elucidated the protective effect and underlying mechanism of action of YS on gastric ulcer in rats injured by ethanol.

Methods

The ethanol‐induced gastric ulcer rat model was used to assess the protective effect of YS. A pathological examination of gastric tissue was performed by H&E staining. GES‐1 cells damaged by hydrogen peroxide were used to simulate oxidative damage in gastric mucosal epithelial cells. Endogenous NRF2 was knocked down using small interfering RNA. Immunoprecipitation was used to detect ubiquitination of NRF2. Co‐immunoprecipitation was used to detect the NRF2–Keap1 interaction.

Results

YS (10 and 30 mg/kg, i.g.) significantly reduced the ulcer index, decreased MDA level, and increased SOD and GSH levels in gastric tissues damaged by ethanol. YS promoted NRF2 translocation from cytoplasm to nucleus and enhanced the NQO1 and HO‐1 expression levels in injured rat gastric tissue. In addition, YS regulated NQO1 and HO‐1 via NRF2 in H2O2‐induced oxidative injured GES‐1 cells. Further studies on the underlying mechanism indicated that YS reduced the interaction between NRF2 and Keap1 and decreased ubiquitylation of NRF2, thereby increasing its stability and expression of downstream factors. NRF2 knockdown abolished the effect of YS on MDA and SOD in GES‐1 cells treated with H2O2.

Conclusion

YS reduced the NRF2–Keap1 interaction, promoting NRF2 translocation into the nucleus, which increasing the transcription and translation of NQO1 and HO‐1 and improved the antioxidant capacity of rat stomach.
Respiratory‐like movements during an apnea test
Authors: Kida Shinichi , Nagata Isao , Takei Tetsuhiro , Yoshizawa Kazuhiro , Suzuki Taketo , Yamada Hiroyuki , Nakayama Yusuke
Published: April 2024

Background

Despite the possible occurrence of spontaneous movements during an apnea test, respiratory‐like movements are rare.

Case Presentation

A 51‐year‐old man was transferred to our hospital when a sudden disturbance of consciousness developed into cardiac arrest. After spontaneous circulation returned, we diagnosed bilateral cerebellar hemorrhage. He remained comatose with dilated pupils, absent brainstem reflexes, spontaneous breathing, and electrocerebral activity. After being considered brain dead, his family opted for organ donation. The first legal brain death examination on day 5 was aborted because of respiratory‐like movements mimicking repetitive abdominal respiration during the apnea test. However, an enhanced magnetic resonance image of the head indicated no blood flow and somatosensory evoked potential testing revealed no brain‐derived potentials.

Conclusion

Respiratory‐like movements can occur during the apnea test in patients considered brain dead. Further research is required to understand this phenomenon.
Cortical Microhemorrhage Presentation of Small Vessel Primary Angiitis of the Central Nervous System
Authors: Guo Ai , Zhang Zhe , Dong Ge‐Hong , Su Lei , Gao Chenyang , Zhang Mengting , Shi Xiaoyu , Wang Huabing , Zhang Xinghu , Lu De‐Hong , Fu Ying , Jing Jing , Shi Fu‐Dong , Tian De‐Cai
Published: April 2024

Objective

Primary angiitis of the central nervous system (PACNS) is a rare vasculitis restricted to the brain, spinal cord, and leptomeninges. This study aimed to describe the imaging characteristics of patients with small vessel PACNS (SV‐PACNS) using 7 T magnetic resonance imaging (MRI).

Methods

This ongoing prospective observational cohort study included patients who met the Calabrese and Mallek criteria and underwent 7 T MRI scan. The MRI protocol includes T1‐weighted magnetization‐prepared rapid gradient echo imaging, T2 star weighted imaging, and susceptibility‐weighted imaging. Two experienced readers independently reviewed the neuroimages. Clinical data were extracted from the electronic patient records. The findings were then applied to a cohort of patients with large vessel central nervous system (CNS) vasculitis.

Results

We included 21 patients with SV‐PACNS from December 2021 to November 2023. Of these, 12 (57.14%) had cerebral cortical microhemorrhages with atrophy. The pattern with microhemorrhages was described in detail based on the gradient echo sequence, leading to the identification of what we have termed the “coral‐like sign.” The onset age of patients with coral‐like sign (33.83 ± 9.93 years) appeared younger than that of patients without coral‐like sign (42.11 ± 14.18 years) (P = 0.131). Furthermore, the cerebral lesions in patients with cortical microhemorrhagic SV‐PACNS showed greater propensity toward bilateral lesions (P = 0.03). The coral‐like sign was not observed in patients with large vessel CNS vasculitis.

Interpretation

The key characteristics of the coral‐like sign represent cerebral cortical diffuse microhemorrhages with atrophy, which may be an important MRI pattern of SV‐PACNS. ANN NEUROL 2024;96:194–203
A Universal Self‐Propagating Synthesis of Aluminum‐Based Oxyhalide Solid‐State Electrolytes
Authors: Zhang Simeng , Xu Yang , Wu Han , Pang Tianlu , Zhang Nian , Zhao Changtai , Yue Junyi , Fu Jiamin , Xia Shengjie , Zhu Xiangzhen , Wang Guanzhi , Duan Hui , Xiao Biwei , Mei Tao , Liang Jianwen , Sun Xueliang , Li Xiaona
Published: April 2024

Inorganic solid‐state electrolytes (SSEs) play a vital role in high‐energy all‐solid‐state batteries (ASSBs). However, the current method of SSE preparation usually involves high‐energy mechanical ball milling and/or a high‐temperature annealing process, which is not suitable for practical application. Here, a facile strategy is developed to realize the scalable synthesis of cost‐effective aluminum‐based oxyhalide SSEs, which involves a self‐propagating method by the exothermic reaction of the raw materials. This strategy enables the synthesis of various aluminum‐based oxyhalide SSEs with tunable components and high ionic conductivities (over 10−3 S cm−1 at 25 °C) for different cations (Li+, Na+, Ag+). It is elucidated that the amorphous matrix, which mainly consists of various oxidized chloroaluminate species that provide numerous sites for smooth ion migration, is actually the key factor for the achieved high conductivities. Benefit from their easy synthesis, low cost, and low weight, the aluminum‐based oxyhalide SSEs synthesized by our approach could further promote practical application of high‐energy‐density ASSBs.
Planar Tetranuclear Uranium Hydride Cluster Supported by ansa‐Bis(cyclopentadienyl) Ligands
Authors: Li Kai , del Rosal Iker , Zhao Yue , Maron Laurent , Zhu Congqing
Published: April 2024

Polynuclear metal hydride clusters play important roles in various catalytic processes, with most of the reported polynuclear metal hydride clusters adopting a polyhedral three‐dimensional structure. Herein, we report the first example of a planar tetranuclear uranium hydride cluster [(CpCMe2CMe2Cp)U]4(μ2‐H)4(μ3‐H)4 (U4H8). It was synthesized by reacting an ansa‐bis(cyclopentadienyl) ligand‐supported uranium chloride precursor [(CpCMe2CMe2Cp)U]3(μ2‐Cl)3(μ3‐Cl)2 with NaHBEt3. The presence of hydrides in U4H8 was confirmed by NMR spectroscopy and its reactivity with phenol and carbon tetrachloride. DFT calculations also facilitated the determination of the hydrides’ positions in U4H8, featuring four bridging μ2‐H ligands and four face‐capping μ3‐H ligands, with the four U centers arranged in a rhombic geometry. The U4H8 represents not only the first example of planar polynuclear actinide metal hydride cluster but also the uranium hydride cluster with the highest nuclearity reported to date.
Design of Solid Polycationic Electrolyte to Enable Durable Chloride‐Ion Batteries
Authors: Yang Xu , Fu Zhiqiang , Han Ran , Lei Yaojie , Wang Shijian , Zhao Xin , Meng Yuefeng , Liu Hao , Zhou Dong , Aurbach Doron , Wang Guoxiu
Published: April 2024

The high energy density and cost‐effectiveness of chloride‐ion batteries (CIBs) make them promising alternatives to lithium‐ion batteries. However, the development of CIBs is greatly restricted by the lack of compatible electrolytes to support cost‐effective anodes. Herein, we present a rationally designed solid polycationic electrolyte (SPE) to enable room‐temperature chloride‐ion batteries utilizing aluminum (Al) metal as an anode. This SPE endows the CIB configuration with improved air stability and safety (i.e. free of flammability and liquid leakage). A high ionic conductivity (1.3×10−2 S cm−1 at 25 °C) has been achieved by the well‐tailored coordination structure of the SPE. Meanwhile, the solid polycationic electrolyte ensures stable electrodes|electrolyte interfaces, which effectively inhibit the growth of dendrites on the Al anodes and degradation of the FeOCl cathodes. The Al|SPE|FeOCl chloride‐ion batteries showcased a high discharge capacity around 250 mAh g−1 (based on the cathodes) and extended lifespan. Our electrolyte design opens a new avenue for developing low‐cost chloride‐ion batteries.
Revealing Na+‐coordination induced Failure Mechanism of Metal Sulfide Anode for Sodium Ion Batteries
Authors: Fu Yuchen , Sun Jun , Zhang Yunsheng , Qu Wei , Wang Weichao , Yao Meng , Zhang Yun , Wang Qian , Tang Yongfu
Published: April 2024

Metal sulfide (MS) is regarded as a promising candidate of the anode materials for sodium‐ion battery (SIB) with ideal capacity and low cost, yet still suffers from the inferior cycling stability and voltage degradation. Herein, the coordination relationship between the discharge product Na2S with the Na+ (NaPF6) in the electrolyte, is revealed as the root cause for the cycling failure of MS. Na+‐coordination effect assistants the dissolution of Na2S, further delocalizing Na2S from the reaction interface under the function of electric field, which leads to the solo oxidation of the discharge product element metal without the participation of Na2S. Besides, the higher highest occupied molecular orbital of Na2S suggest the facilitated Na2S solo oxidation to produce sodium polysulfides (NaPSs). Based on these, lowering the Na+ concentration of the electrolyte is proposed as a potential improvement strategy to change the coordination environment of Na2S, suppressing the side reactions of the solo‐oxidation of element metal and Na2S. Consequently, the enhanced conversion reaction reversibility and prolonged cycle life are achieved. This work renders in‐depth perception of failure mechanism and inspiration for realizing advanced conversion‐type anode.
Insights into E. coli Cyclopropane Fatty Acid Synthase (CFAS) Towards Enantioselective Carbene Free Biocatalytic Cyclopropanation.
Authors: Omar Iman , Crotti Michele , Li Chuhan , Pisak Krisztina , Czemerys Blazej , Ferla Salvatore , van Noord Aster , Paul Caroline E. , Karu Kersti , Ozbalci Cagakan , Eggert Ulrike , Lloyd Richard , Barry Sarah M. , Castagnolo Daniele
Published: April 2024

Cyclopropane fatty acid synthases (CFAS) are a class of S‐adenosylmethionine (SAM) dependent methyltransferase enzymes able to catalyse the cyclopropanation of unsaturated phospholipids. Since CFAS enzymes employ SAM as a methylene source to cyclopropanate alkene substrates, they have the potential to be mild and more sustainable biocatalysts for cyclopropanation transformations than current carbene‐based approaches. This work describes the characterisation of E. coli CFAS (ecCFAS) and its exploitation in the stereoselective biocatalytic synthesis of cyclopropyl lipids. ecCFAS was found to convert phosphatidylglycerol (PG) to methyl dihydrosterculate 1 with up to 58 % conversion and 73 % ee and the absolute configuration (9S,10R) was established. Substrate tolerance of ecCFAS was found to be correlated with the electronic properties of phospholipid headgroups and for the first time ecCFAS was found to catalyse cyclopropanation of both phospholipid chains to form dicyclopropanated products. In addition, mutagenesis and in silico experiments were carried out to identify the enzyme residues with key roles in catalysis and to provide structural insights into the lipid substrate preference of ecCFAS. Finally, the biocatalytic synthesis of methyl dihydrosterculate 1 and its deuterated analogue was also accomplished combining recombinant ecCFAS with the SAM regenerating AtHMT enzyme in the presence of CH3I and CD3I respectively.
An iridium‐based phosphorescence probe for HClO/ClO− detection and application of recognizing exogenous/endogenous HClO/ClO− in cells
Authors: Xu Sha , Ju Qikai , Li Zhijian , Mao Xueting , Chen Shuaihua , Pu Shouzhi , Zhang Daobin
Published: April 2024

Hypochlorous acid (HClO) and its ionic form (ClO−), as important components of reactive oxygen species, were produced mainly in mitochondria and participated in various biological processes, and they abnormal level could cause various diseases and threaten human health. Hence, a “turn‐on” phosphorescent probe Ir‐DAMN based on Ir (III) complex was synthesized to monitor HClO/ClO− in DMF/PBS solution and living cells. Due to isomerization of C=N bond, probe Ir‐DAMN exhibited very weak phosphorescence initially, which displayed obvious phosphorescent enhancement at 620 nm after upon addition with ClO−. Confocal bioimaging experiments implied that probe Ir‐DAMN possessed good cell membrane permeability, specific localization of mitochondria and could achieve detection of exogenous and endogenous HClO/ClO− in the living cells.
Motor difficulties in 16p11.2 copy number variation
Authors: Jutla Amandeep , Harvey Loraine , Veenstra‐VanderWeele Jeremy , Chung Wendy K.
Published: April 2024

The rare genetic variants 16p11.2 duplication and 16p11.2 deletion have opposing effects on brain structure and function, yet are associated with broadly similar clinical phenotypes that include autism, intellectual impairment, psychiatric illness, and motor difficulties. In recent years, studies have identified subtle distinctions between the phenotypic effects of 16p11.2 duplication and 16p11.2 deletion with respect to patterns of autism, intellectual impairment, and psychiatric illness. However, although divergent phenotypic findings in some motor domains have been reported, no study has yet made a comprehensive comparison of motor difficulties between 16p11.2 deletion and 16p11.2 duplication carriers to elucidate points of convergence and divergence. We sought to make such a comparison in a group of 133 16p11.2 deletion carriers, 122 duplication carriers, and 388 familial controls, hypothesizing that motor impairment would overall be greater in deletion than duplication carriers. In a series of regression models, we found that 16p11.2 deletion status tended to predict greater impairment along indices of gross motor function, but less impairment along indices of fine motor function. These findings point to a potential pattern of performance difficulties that could be investigated in future studies. Elucidating motor differences between 16p11.2 duplication and 16p11.2 deletion carriers may help in understanding the complex effect of 16p11.2 copy number variation and other rare genetic causes of autism.
Evaluation of Botox treatment in patients with chronic scrotal pain: Protocol for a randomized double‐blinded control trial
Authors: Schiellerup Nicolai Skov , Kobberø Hanne , Andersen Karin , Poulsen Charlotte Aaberg , Poulsen Mads Hvid
Published: April 2024

Background

Chronic scrotal pain is a common condition with a prevalence of 2.5–4.8% in male outpatients. Up to 40% of these patients report depressive symptoms and many feel isolated. Minimal invasive treatment is lacking, while spermatic cord injections of Botox® (BTX) have been proposed to offer long‐term pain relief.

Study Design

This research protocol comprises a prospective multicentre, randomized, double‐blinded clinical trial drawing patients from other urological departments in the region of Southern Denmark.

End Points

The primary end point will be reduction in pain evaluated by visual analogue score for pain at 3 months. Secondary end point will be length of effect of BTX injections along with changes in quality of life.

Patients and Methods

The study will include 50 patients for randomization to either spermatic cord block with 100 IE BTX or sterile saline. All patients will prior to randomization undergo physical examination and will be asked to fulfil multiple questionnaires regarding pain and impact in daily life, that is, (1) visual analogue score for pain, (2) quality of life (EQ‐5D‐5L), (3) Chronic Prostatitis Symptom Index (NIH‐CPSI), (4) ICD‐10 depression questionnaire (MDI), (5) Likert global assessment scale, and (6) International Index of Erectile Function questionnaire. Physical examination and fulfilment of the questionnaires will be repeated multiple times throughout the study period of 12 weeks. After this time point, patients will be unblinded, and the control arm will be given the opportunity of cross‐over.
Multivariate data analysis of process parameters affecting the growth and productivity of stable Chinese hamster ovary cell pools expressing SARS‐CoV‐2 spike protein as vaccine antigen in early process development
Authors: Reyes Sebastian‐Juan , Lemire Lucas , Molina Raul‐Santiago , Roy Marjolaine , L'Ecuyer‐Coelho Helene , Martynova Yuliya , Cass Brian , Voyer Robert , Durocher Yves , Henry Olivier , Pham Phuong Lan
Published: April 2024

The recent COVID‐19 pandemic revealed an urgent need to develop robust cell culture platforms which can react rapidly to respond to this kind of global health issue. Chinese hamster ovary (CHO) stable pools can be a vital alternative to quickly provide gram amounts of recombinant proteins required for early‐phase clinical assays. In this study, we analyze early process development data of recombinant trimeric spike protein Cumate‐inducible manufacturing platform utilizing CHO stable pool as a preferred production host across three different stirred‐tank bioreactor scales (0.75, 1, and 10 L). The impact of cell passage number as an indicator of cell age, methionine sulfoximine (MSX) concentration as a selection pressure, and cell seeding density was investigated using stable pools expressing three variants of concern. Multivariate data analysis with principal component analysis and batch‐wise unfolding technique was applied to evaluate the effect of critical process parameters on production variability and a random forest (RF) model was developed to forecast protein production. In order to further improve process understanding, the RF model was analyzed with Shapley value dependency plots so as to determine what ranges of variables were most associated with increased protein production. Increasing longevity, controlling lactate build‐up, and altering pH deadband are considered promising approaches to improve overall culture outcomes. The results also demonstrated that these pools are in general stable expressing similar level of spike proteins up to cell passage 11 (~31 cell generations). This enables to expand enough cells required to seed large volume of 200–2000 L bioreactor.
α‐Hederin induces paraptosis by targeting GPCRs to activate Ca2+/MAPK signaling pathway in colorectal cancer
Authors: Rao Xiwu , Li Ziwen , Zhang Qinchang , Lai Yueyang , Liu Jianrong , Li Liu , Cheng Haibo , Shen Weixing , Sun Dongdong
Published: April 2024

Background

Non‐apoptotic cell death is presently emerging as a potential direction to overcome the apoptosis resistance of cancer cells. In the current study, a natural plant agent α‐hederin (α‐hed) induces caspase‐independent paraptotic modes of cell death.

Purpose

The present study is aimed to investigate the role of α‐hed induces paraptosis and the associated mechanism of it.

Methods

The cell proliferation was detected by CCK‐8. The cytoplasm organelles were observed under electron microscope. Calcium (Ca2+) level was detected by flow cytometry. Swiss Target Prediction tool analyzed the potential molecule targets of α‐hed. Molecular docking methods were used to evaluate binding abilities of α‐hed with targets. The expressions of genes and proteins were analyzed by RT‐qPCR, western blotting, immunofluorescence, and immunohistochemistry. Xenograft models in nude mice were established to evaluate the anticancer effects in vivo.

Results

α‐hed exerted significant cytotoxicity against a panel of CRC cell lines by inhibiting proliferation. Besides, it induced cytoplasmic vacuolation in all CRC cells. Electron microscopy images showed the aberrant dilation of endoplasmic reticulum and mitochondria. Both mRNA and protein expressions of Alg‐2 interacting proteinX (Alix), the marker of paraptosis, were inhibited by α‐hed. Besides, both Swiss prediction and molecular docking showed that the structure of α‐hed could tightly target to GPCRs. GPCRs were reported to activate the phospholipase C (PLC)‐β3/ inositol 1,4,5‐trisphosphate receptor (IP3R)/ Ca2+/ protein kinase C alpha (PKCα) pathway, and we then found all proteins and mRNA expressions of PLCβ3, IP3R, and PKCα were increased by α‐hed. After blocking the GPCR signaling, α‐hed could not elevate Ca2+ level and showed less CRC cell cytotoxicity. MAPK cascade is the symbol of paraptosis, and we then demonstrated that α‐hed activated MAPK cascade by elevating Ca2+ flux. Since non‐apoptotic cell death is presently emerging as a potential direction to overcome chemo‐drug resistance, we then found α‐hed also induced paraptosis in 5‐fluorouracil‐resistant (5‐FU‐R) CRC cells, and it reduced the growth of 5‐FU‐R CRC xenografts.

Conclusions

Collectively, our findings proved α‐hed as a promising candidate for inducing non‐apoptotic cell death, paraptosis. It may overcome the resistance of apoptotic‐based chemo‐resistance in CRC.
Synthesis of Novel 4‐Acyloxy‐2′‐Bromo‐6′‐Chloropodophyllotoxin Derivatives Displaying Significant Insecticidal Activity Against Mythimna Separata
Authors: Tian Yuee , Ma Shiyue , Liu Yibo , Li Yan , Chen Genqiang , Che Zhiping
Published: April 2024

In order to explore novel natural product‐based insecticidal agent, two important intermediates (2 and 3) and 4‐acyloxy‐2′‐bromo‐6′‐chloropodophyllotoxin derivatives (4 a–f and 5 a–f) were designed and prepared, and their structures were confirmed by 1H‐NMR, 13C NMR, HRMS, ESI‐MS, optical rotation and melting point (mp). The stereochemical configuration of compound 4 b was unambiguously confirmed by single‐crystal X‐ray diffraction. Moreover, we evaluated the insecticidal activity of target compounds 4 a–f and 5 a–f against a serious agricultural pest of Mythimna separata by using the leaf‐dipping method. Among all tested compounds, compounds 4 d, 5 d and 5 f exhibited stronger insecticidal activity with a final mortality rate exceeding 60 %. Especially compound 5 d exhibited the best insecticidal activity, with a final mortality rate of 74.1 %. It has been proven that introducing bromine or chlorine atoms at the C‐2′, C‐2′ and C‐6′ positions of the E ring of podophyllotoxin can produce more potent compounds. In addition, the configuration of the C‐4 position is important for insecticidal activity, and 4β‐configuration is optimal. This will pave the way for further design, structural modification, and development of derivatives of podophyllotoxin as insecticidal agents.
Navigating challenges in diagnosing acquired hemophilia A: A case report from Syria
Authors: Nayouf Oubai , Laflouf Miriam , Hamdan Ibrahim , Alghazawi Ibrahim , Aldairi Omar , Sulaiman Ameen
Published: April 2024

Key clinical message

Acquired hemophilia A is a rare bleeding disorder. Rapid diagnosis with prolonged aPTT and low FVIII, and immediate use of bypassing agents and steroids are crucial for better outcomes, highlighting the importance of early recognition and management.
Prenatal discovery of a testicular mass: A rare silver lining to timely management of giant congenital inguinal hernia
Authors: Bin Vissotsak , Bin Sakviseth
Published: April 2024

Key Clinical Message

Prenatal diagnosis of inguinal hernia is significant for preparing postnatal management to ensure timely surgical interventions. Early recognition through physical examination after birth is easy and vital to confirm the post‐natal diagnosis.
Organo‐Soluble Colloidal MoS2 Quantum Dots (QDs) as an Efficient Photocatalyst for α‐Amino Phosphonate Synthesis
Authors: Kayal Abir , De Mrinmoy
Published: April 2024

α‐Amino phosphonates are bio‐isosteres of amino acids and have numerous biochemical activities. While they are generally prepared via carbon–phosphorus bond formation using a plethora of methods but using recyclable photo‐catalysts and readily accessible amine and phosphites are not commonly used in synthesis. Herein, we used organo‐soluble MoS2 Quantum Dots (QDs) as an exceptionally efficient nano‐photocatalyst for the synthesis of α‐amino phosphonates. Our approach emphasizes on photocatalysis within organic media, providing a facile and effective method for conducting these intricate organic conversions under mild conditions. This straightforward process harnesses the power of molecular oxygen (O2) as an oxidizing agent. To elaborate, our method is intricately guided by the inherent capability of MoS2 QDs to enter an excited state upon absorption of blue light. This excited state bears appropriate potential energy to initiate the formation of reactive iminium ion species from N‐phenyl benzylamine, thus driving the desired product formation. Mechanistic analysis has also unveiled the pivotal role of MoS2 QDs in generating reactive superoxide radicals from O2 through single electron transfer (SET), underscoring their significance in the process. Remarkably, this photocatalytic transformation furnishes a diverse array of functionalized products, expanding its applicability and potential implications in various contexts.
Rational design of diamond through microstructure engineering: From synthesis to applications
Authors: Ku Yalun , Huang Wentao , Li Xing , Wan Li , Zhang Kuikui , Yan Longbin , Guo Ying , Cheng Shaobo , Shan Chongxin
Published: April 2024

Diamond possesses excellent thermal conductivity and tunable bandgap. Currently, the high‐pressure, high‐temperature, and chemical vapor deposition methods are the most promising strategies for the commercial‐scale production of synthetic diamond. Although diamond has been extensively employed in jewelry and cutting/grinding tasks, the realization of its high‐end applications through microstructure engineering has long been sought. Herein, we discuss the microstructures encountered in diamond and further concentrate on cutting‐edge investigations utilizing electron microscopy techniques to illuminate the transition mechanism between graphite and diamond during the synthesis and device constructions. The impacts of distinct microstructures on the electrical applications of diamond, especially the photoelectrical, electrical, and thermal properties, are elaborated. The recently reported elastic and plastic deformations revealed through in situ microscopy techniques are also summarized. Finally, the limitations, perspectives, and corresponding solutions are proposed.
Studying Cation Exchange in {Cr7Co} Pseudorotaxanes: Preparatory Studies for Making Hybrid Molecular Machines
Authors: Bennett Tom S. , Geue Niklas , Timco Grigore A. , Whitehead George F. S. , Vitorica‐Yrezabal Inigo J. , Barran Perdita E. , McInnes Eric J. L. , Winpenny Richard E. P.
Published: April 2024

In the design of dynamic supramolecular systems used in molecular machines, it is important to understand the binding preferences between the macrocycle and stations along the thread. Here, we apply 1H NMR spectroscopy to investigate the relative stabilities of a series of linear alkylammonium templated pseudorotaxanes with the general formula [H2NRR’][Cr7CoF8(O2CCH2tBu)16] by exchanging the cation in solution. Our results show that the pseudorotaxanes are able to exchange threads via a dissociative mechanism. The position of equilibrium is dependent upon the ammonium cation and solvent used. Short chain primary ammonium cations are shown to be far less favourable macrocycle stations than secondary ammonium cations. Collision‐induced dissociation mass spectrometry (CID‐MS) has been used to look at disassembly of the pseudorotaxanes in a solvent‐free environment and stability trends compared to those in acetone‐d6. The energy needed to induce 50 % of the precursor ion loss (E50) is used and shows a similar trend to the equilibria measured by NMR. The relative stabilities of these hybrid inorganic‐organic pseudo‐rotaxanes are different to those of host‐guest compounds involving crown ethers and this may be valuable for the design of molecular machines.
Redox Behaviour and Redox Potentials of Dyes in Aqueous Buffers and Protic Ionic Liquids
Authors: Smith Lachlan O. , Thatcher Kathryn M. , Henderson‐Walshe Oscar J. , Crittenden Deborah L.
Published: April 2024

Organic dyes hold promise as inexpensive electrochemically‐active building blocks for new renewable energy technologies such as redox‐flow batteries and dye‐sensitised solar cells, especially if they display high oxidation and/or low reduction potentials in cheap, non‐flammable solvents such as water or protic ionic liquids. Systematic computational and experimental characterisation of a representative selection of acidic and basic dyes in buffered aqueous solutions and propylammonium formate confirm that quinoid‐type mechanisms impart electrochemical reversibility for the majority of systems investigated, including quinones, fused tricyclic heteroaromatics, indigo carmine and some aromatic nitrogenous species. Conversely, systems that generate longlived radical intermediates – arylmethanes, hydroquinones at high pH, azocyclic systems – tend to display irreversible electrochemistry, likely undergoing ring‐opening, dimerisation and/or disproportionation reactions.
Electronic Control of Polyproline II Helix Stability via the Identity of Acyl Capping Groups: the Pivaloyl Group Particularly Promotes PPII
Authors: Bhatt Megh R. , Zondlo Neal J.
Published: April 2024

The type II polyproline helix (PPII) is a fundamental secondary structure of proteins, important in globular proteins, in intrinsically disordered proteins, and at protein‐protein interfaces. PPII is stabilized in part by n→π* interactions between consecutive carbonyls, via electron delocalization between an electron‐donor carbonyl lone pair (n) and an electron‐acceptor carbonyl (π*) on the subsequent residue. We previously demonstrated that changes to the electronic properties of the acyl donor can predictably modulate the strength of n→π* interactions, with data from model compounds, in solution in chloroform, in the solid state, and computationally. Herein, we examined whether the electronic properties of acyl capping groups could modulate the stability of PPII in peptides in water. In X−PPGY‐NH2 peptides (X=10 acyl capping groups), the effect of acyl group identity on PPII was quantified by circular dichroism and NMR spectroscopy. Electron‐rich acyl groups promoted PPII relative to the standard acetyl (Ac−) group, with the pivaloyl and iso‐butyryl groups most significantly increasing PPII. In contrast, acyl derivatives with electron‐withdrawing substituents and the formyl group relatively disfavored PPII. Similar results, though lesser in magnitude, were also observed in X−APPGY‐NH2 peptides, indicating that the capping group can impact PPII conformation at both proline and non‐proline residues. The pivaloyl group was particularly favorable in promoting PPII. The effects of acyl capping groups were further analyzed in X–DfpPGY‐NH2 and X−ADfpPGY‐NH2 peptides, Dfp=4,4‐difluoroproline. Data on these peptides indicated that acyl groups induced order Piv‐ > Ac‐ > For‐. These results suggest that greater consideration should be given to the identity of acyl capping groups in inducing structure in peptides.
Asymmetric catalysis by chiral FLPs: A computational mini‐review
Authors: Patra Shanti Gopal
Published: April 2024

Steric hindrance in Lewis acid (LA) and Lewis base (LB) obstruct the Lewis acid–base adduct formation, and the pair was termed as frustrated Lewis pair (FLP). In the past 16 years, the field of enantioselective catalysis by chiral FLPs has been slowly growing. It was shown that chiral LAs are significant as they are involved in the hydrogen transfer (HT) step to the imine, resulting in enantioselectivity. After H2 activation, the borohydride can exist in a number of plausible conformations and their stability is governed by the presence of noncovalent interaction through C–H····π and π····π interactions. However, LBs are not ideal for asymmetric induction as they compete with the imine substrate as a counter LB. Further, the proton transfer from chiral LB to the imine does not induce any chirality as chirality develops in the HT step. However, intramolecular FLPs with chiral scaffold are very efficient as they possess an optimum distance between LA and LB, which facilitates the H2 activation but precludes the adduct formation of the small molecules substrate with the LA component. This mini‐review summarizes computational investigation involving chiral LA and LB, and discusses intramolecular FLPs in the enantioselective catalysis.
Pd‐Catalyzed Dienylation of Propargylic Esters Enabling Highly Stereoselective Synthesis of Danishefsky‐Type Trisubstituted Dienes
Authors: Zhou Chen , Dai Mengfu , Yin Xiaoyu , Zhang Mingyue , Gu Weijin , Chen Liang‐An
Published: April 2024

Comprehensive Summary

The stereochemical synthesis of highly substituted Danishefsky‐type dienes remains unsolved in organic chemistry. We describe a simple and efficient approach for the stereoselective synthesis of Danishefsky‐type trisubstituted dienes from readily available propargylic esters via Pd‐catalyzed dienylation reaction through the key intermediate metallacyclobutene in a regio‐, chemo‐ and stereoselective fashion. This method facilitates a broad range of challenging trisubstituted dienes with a high level of stereocontrol. The synthetic utilities of oxygenated trisubstituted dienes have been demonstrated by the downstream chemistry, which notably undergoes Diels‐Alder reaction with a variety of electron‐deficient dienophiles to furnish multisubstituted cyclohexenes in good yields with excellent stereoselectivity.
Metal‐Organic Framework Nanozyme Enabling Dual‐Functional Photo‐Induced Charge Transfer and Biomimetic Precipitation for Advanced Organic Photoelectrochemical Transistor Bioanalysis
Authors: Xu Ke‐Xin , Yuan Cheng , Lou Hao , Chen Feng‐Zao , Zhang Ling , Chen Guangxu , Han De‐Man , Zhao Wei‐Wei
Published: April 2024

Comprehensive Summary

We report herein the first observation of MOF nanozyme enabling dual‐functional photo‐induced charge transfer and biomimetic precipitation for advanced organic photoelectrochemical transistor (OPECT) bioanalysis. Specifically, Fe/Co‐MIL‐88, serving simultaneously as the semiconductor and nanozyme, was explored as a dual‐functional gating module in OPECT. Upon light illumination, it could accelerate the charge transfer of the photogate to produce enhanced photo‐induced voltage. Meanwhile, its catalytic property could efficiently produce biomimetic precipitation to block the nanopores in Fe/Co‐MIL‐88 and thus alter the device characteristics. The generic bioanalytical potential of such a rationale was then demonstrated with an aptasensing assisted by magnetic separation. This work represents the first exploration of biomimetic precipitation from MOF nanozymes for generic OPECT bioanalysis, it is expected to attract more interest in various nanozymes for novel optoelectronic bioanalytics.
Chiral Lewis Base/Achiral Acid Co‐Catalyzed Atroposelective Sulfenylation of Pyrrole Derivatives: Construction of C—N Axially Chiral Sulfides
Authors: Yang Qin , Luo Hui‐Yun , Zhu Deng , Zhang Xin‐Yu , Ke Hua , Chen Zhi‐Min
Published: April 2024

Comprehensive Summary

Chiral BINAM‐derived selenide/achiral acid co‐catalyzed atroposelective electrophilic sulfenylation of pyrrole derivatives has been realized for the first time. A variety of C—N axially chiral sulfur‐containing pyrrole derivatives were readily obtained in moderate to good yields with moderate to excellent enantioselectivities. This catalytic system involves sequential desymmetrization and kinetic resolution.
Comparison of programmed death‐ligand 1 expression in adenocarcinoma and squamous cell carcinoma of the cervix in paraffin blocks of patients with cervical cancer
Authors: Hosseini Maryam Sadat , Shafizadeh Fatemeh , Bahremani Mohammad Hashemi , Farzaneh Farah , Ashrafganjoei Tahereh , Arab Maliheh , Talayeh Maryam , Jafari Fatemeh , Abdshah Alireza
Published: April 2024

Aims

Cervical cancer (CC) is a common malignancy in women, predominantly caused by human papillomavirus. The most subtypes are adenocarcinomas (AC) and squamous cell carcinomas (SCC), which show various features and treatment responses. Programmed death‐ligand 1 (PD‐L1) and programmed cell death protein 1 (PD‐1) as Immune checkpoint molecules, play a role in immune evasion. We investigated PD‐L1 expression in AC and SCC of the cervix and explored its link to clinical characteristics.

Methods and results

The present cross‐sectional research was done between 2016 and 2022 on samples in Shahid Beheshti University of Medical Sciences‐affiliated hospitals in Iran. Histological tissue samples of CCs (16 AC and 48 SCC) were assessed, and clinical information was obtained by reviewing their medical documents. PD‐L1 expression was evaluated by immunohistochemistry and we used the combined positive score. SCC cases showed a higher (not significant) PD‐L1 expression. The PD‐L1 expression and clinical characteristics were not significantly correlated in both subgroups.

Conclusion

Although SCC cases exhibited higher PD‐L1 expression, this difference was non‐significant. More investigations should highlight the role of PD‐L1 in CC and the potential benefits of immunotherapy.
Carbon‐Rich Plasma‐Deposited Silicon Oxycarbonitride Films Derived from 4‐(Trimethylsilyl)morpholine as a Novel Single‐Source Precursor
Authors: Ermakova Evgeniya , Tsyrendorzhieva Irina , Mareev Alexander , Pavlov Dmitry , Maslova Olga , Shayapov Vladimir , Maksimovskiy Eugene , Yushina Irina , Kosinova Marina
Published: April 2024

4‐(trimethylsilyl)morpholine O(CH2CH2)2NSi(CH3)3 (TMSM) was investigated as a single‐source precursor for SiCNO films synthesis. Optical emission spectroscopy of plasma generated from TMSM/He, TMSM/H2, and TMSM/NH3 gas mixtures revealed the presence of N2, CH, H, CN, and CO species. The last two are suggested to be responsible for the lowering of carbon concentration in the films in comparison with the precursor. The refractive index ranged from 1.5 to 2.0, and bandgap varied from 2.0 to 4.6 eV, which pointed that some of the films can be used as antireflective coatings in silicon photovoltaic cell technologies and dielectric layers in electronic devices.
Aβ oligomers peak in early stages of Alzheimer's disease preceding tau pathology
Authors: Blömeke Lara , Rehn Fabian , Kraemer‐Schulien Victoria , Kutzsche Janine , Pils Marlene , Bujnicki Tuyen , Lewczuk Piotr , Kornhuber Johannes , Freiesleben Silka D. , Schneider Luisa‐Sophie , Preis Lukas , Priller Josef , Spruth Eike J. , Altenstein Slawek , Lohse Andrea , Schneider Anja , Fliessbach Klaus , Wiltfang Jens , Hansen Niels , Rostamzadeh Ayda , Düzel Emrah , Glanz Wenzel , Incesoy Enise I. , Butryn Michaela , Buerger Katharina , Janowitz Daniel , Ewers Michael , Perneczky Robert , Rauchmann Boris‐Stephan , Teipel Stefan , Kilimann Ingo , Goerss Doreen , Laske Christoph , Munk Matthias H. , Sanzenbacher Carolin , Spottke Annika , Roy‐Kluth Nina , Heneka Michael T. , Brosseron Frederic , Wagner Michael , Wolfsgruber Steffen , Kleineidam Luca , Stark Melina , Schmid Matthias , Jessen Frank , Bannach Oliver , Willbold Dieter , Peters Oliver
Published: April 2024

INTRODUCTION

Soluble amyloid beta (Aβ) oligomers have been suggested as initiating Aβ related neuropathologic change in Alzheimer's disease (AD) but their quantitative distribution and chronological sequence within the AD continuum remain unclear.

METHODS

A total of 526 participants in early clinical stages of AD and controls from a longitudinal cohort were neurobiologically classified for amyloid and tau pathology applying the AT(N) system. Aβ and tau oligomers in the quantified cerebrospinal fluid (CSF) were measured using surface‐based fluorescence intensity distribution analysis (sFIDA) technology.

RESULTS

Across groups, highest Aβ oligomer levels were found in A+ with subjective cognitive decline and mild cognitive impairment. Aβ oligomers were significantly higher in A+T− compared to A−T− and A+T+. APOE ε4 allele carriers showed significantly higher Aβ oligomer levels. No differences in tau oligomers were detected.

DISCUSSION

The accumulation of Aβ oligomers in the CSF peaks early within the AD continuum, preceding tau pathology. Disease‐modifying treatments targeting Aβ oligomers might have the highest therapeutic effect in these disease stages.

Highlights

Using surface‐based fluorescence intensity distribution analysis (sFIDA) technology, we quantified Aβ oligomers in cerebrospinal fluid (CSF) samples of the DZNE‐Longitudinal Cognitive Impairment and Dementia (DELCODE) cohort

Aβ oligomers were significantly elevated in mild cognitive impairment (MCI)

Amyloid‐positive subjects in the subjective cognitive decline (SCD) group increased compared to the amyloid‐negative control group

Interestingly, levels of Aβ oligomers decrease at advanced stages of the disease (A+T+), which might be explained by altered clearing mechanisms
Cardiac sympathetic nerve activity trends after renal denervation in heart failure with preserved ejection fraction
Authors: Shiraki Tatsuya , Mizuno Hiroya , Kishi Takuya , Asakura Masanori , Asanoi Hidetsugu , Yasumura Yoshio , Sakata Yasushi
Published: April 2024

This case report describes the application of ultrasound renal denervation (uRDN) using the Paradise System in a patient with heart failure with preserved ejection fraction. Initially, the cardiac sympathetic nerve activity of the patient exhibited a late heart/mediastinum (H/M) ratio of 2.00 and a washout rate of 66.0% by cardiac iodine‐123 metaiodobenzylguanidine (123I‐MIBG) scintigraphy. Subsequently, the patient underwent transfemoral uRDN targeting the left, right upper, and right lower renal arteries. At the 6 month follow‐up, no significant change was observed in 123I‐MIBG findings; however, the estimated stressed blood volume (eSBV) decreased from 1722 to 1029 mL/70 kg. At 18 months, 123I‐MIBG findings improved, with the late H/M ratio reaching 2.76 and the washout rate decreasing to 43.1%. This case report highlights the potential of uRDN in reducing eSBV within 6 months and subsequently improving cardiac sympathetic nerve activity at the 18 month follow‐up.
Stoichiometric and Catalytic Reduction of Carbon Dioxide by a Sterically Encumbered Amidinato Magnesium Hydride
Authors: Huadsai Wimonsiri , Vendier Laure , Görls Helmar , Magna Lionel , Bontemps Sébastien , Westerhausen Matthias
Published: April 2024

A sterically encumbered dinuclear amidinato magnesium hydride 3 with bridging hydrido ligands was synthesized from the metalation of the corresponding amidine 1 with dibutylmagnesium and subsequent treatment with phenylsilane. This complex reacts stoichiometrically with 1 atm of carbon dioxide at room temperature in tetrahydrofuran (THF) to the corresponding bis(thf) adduct of the dinuclear formate complex 4‐2 thf with bridging formate anions. This complex is stable in THF at 60 °C for more than 16 hours but decomposes into the amidine 1 upon removal of ligated thf ligands. Complex 3 efficiently catalyzes the reduction of carbon dioxide with 9‐BBN, yielding bis(boryl)acetal (R2BO)2CH2, and with silanes H4‐nSiPhn (n=1, 2, and 3). The bis(silyl)acetal is quantitatively accessible for Ph3SiH (n=3) whereas during the reduction of CO2 with hydrogen‐richer silanes (n=1, 2) siloxanes form and methane evolves.
Selenosulfones, a Meetup of Chalcogens: A Journey Into Their Recent Chemistry
Authors: Bagnoli Luana , Rosati Ornelio , Marini Francesca , Santi Claudio , Sancineto Luca
Published: April 2024

A mini review focused on the chemistry of selenosulfones reported since 2019 is here presented. Initially, methods aimed to the preparation of such moiety are discussed. Successively 1,2‐, 1,3‐, 1,4‐ and 1,7‐addition reactions to C−C single and multiple bonds are illustrated. The forth chapter focuses on electrophilic aromatic substitutions. The fifth chapter deals with C−H functionalizations while the sixth one shows the reactions with aryl diazonium salts or its precursors. The radical coupling with redox active reagents, is the subject of section seventh. Selenosulfones challenged in nucleophilic substitutions and in reactions with phosphorus‐containing compounds are shown in chapter eight and nine followed by the conclusions and perspectives section.