bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploiting trans‐Sulfinylation for the Synthesis of Diverse N‐Alkyl Sulfinamides via Decarboxylative Sulfinamidation
Authors: Andrews Jonathan A. , Woodger Russell G. , Palmer Christopher F. , Poole Darren L. , Willis Michael C.
Published: July 2024

Combining simple amines with the bench‐stable sulfinylamine Tr‐NSO allows in situ preparation of reactive alkyl sulfinylamines, which when combined with alkyl radicals generated by photocatalytic decarboxylation, provides N‐alkyl sulfinamides. The reactions are broad in scope and tolerate a wide variety of functional groups on both the acid and amine components. The sulfinamide products are used to prepare a selection of challenging S(VI) products. The method provides a convenient way to use reactive and unstable alkyl sulfinylamines.
Linearly Arranged Multi‐π‐Stacked Structure for Efficient Through‐Space Charge‐Transfer Emitters
Authors: Qu Yang‐Kun , Zhou Dong‐Ying , Zheng Qi , Zuo Peng , Che Zong‐Lu , Liao Liang‐Sheng , Jiang Zuo‐Quan
Published: July 2024

Noncovalent spatial interaction has become an intriguing and important tool for constructing optoelectronic molecules. In this study, we linearly attached three conjugated units in a multi π‐stacked manner by using just one trident bridge based on indeno[2,1‐b]fluorene. To achieve this structure, we improved the synthetic approach through double C−H activation, significantly simplifying the preparation process. Due to the proximity of the C10, C11, and C12 sites in indeno[2,1‐b]fluorene, we derived two novel donor|acceptor|donor (D|A|D) type molecules, 2DMB and 2DMFB, which exhibited closely packed intramolecular stacking, enabling efficient through‐space charge transfer. This molecular construction is particularly suitable for developing high‐performance thermally activated delayed fluorescence materials. With donor(s) and acceptor(s) constrained and separated within this spatially rigid structure, elevated radiative transition rates, and high photoluminescence quantum yields were achieved. Organic light‐emitting diodes incorporating 2DMB and 2DMFB demonstrated superior efficiency, achieving maximum external quantum efficiencies of 28.6 % and 16.2 %, respectively.
Synthesis and Comprehensive Studies of Be‐IV‐N2 (IV=Si, Ge): Solving the Mystery of Wurtzite‐Type Pmc21 Structures
Authors: Krach Georg , Witthaut Kristian , Steinadler Jennifer , Bräuniger Thomas , Milman Victor , Bayarjargal Lkhamsuren , Winkler Björn , Bykova Elena , Bykov Maxim , Schnick Wolfgang
Published: July 2024

The research for wurtzite‐type ternary nitride semiconductors containing earth abundant elements with a stoichiometry of 1 : 1 : 2 was focused on metals like Mg or Zn, so far. The vast majority of these Grimm–Sommerfeld analogue compounds crystallize in the β‐NaFeO2 structure, although a second arrangement in space group Pmc21 is predicted to be a viable alternative. Despite extensive theoretical and experimental studies, this structure has so far remained undiscovered. Herein, we report on BeGeN2 in a Pmc21 structure, synthesized from Be3N2 and Ge3N4 using a high‐pressure high‐temperature approach at 6 GPa and 800 °C. The compound was characterized by powder X‐ray diffraction (PXRD), solid state nuclear magnetic resonance (NMR), Raman and energy dispersive X‐ray (EDX) spectroscopy, temperature‐dependent PXRD, second harmonic generation (SHG) and UV/Vis measurements and in addition also compared to its lighter homologue BeSiN2 in all mentioned analytic techniques. The synthesis and investigation of both the first beryllium germanium nitride and the first ternary wurtzite‐type nitride crystallizing in space group Pmc21 open the door to a new field of research on wurtzite‐type related structures.
Preparation and performance of quaternary ammonium salt‐containing methacrylate copolymer‐based ultrafiltration membranes
Authors: Zhao Zihao , Xue Yunyun , Jiang Yani , Su Qianwei , Cui Ronglu , Yu Wenhan , Yang Wushang , Zhu Liheng , Fang Lifeng , Zhu Baoku
Published: July 2024

Ultrafiltration (UF) membranes with excellent dye removal and antibacterial activity are highly desired in dye wastewater treatment, and more importantly environmental protection puts high demands on polymeric membrane materials. In this work, three methacrylate copolymers containing quaternary ammonium salt were synthesized to cast UF membranes. The physicochemical property, structural evolution, dye separation, and antibacterial activity of as‐prepared membranes were systematically investigated. With increased content of the hydrophilic monomer allyl polypropylene glycol (APPG) in the feed, the wettability and positive charge of the resultant membranes were enhanced. Remarkably, the supporting layer of membranes changed from finger‐like pore structure to sponge‐like pore structure by increasing APPG content, and the sponge‐like membranes showed higher retention rates for dyes (99.78% for victoria blue B, 90.49% for methylene blue, and 97.43% for methyl blue) compared with the finger‐like membranes. Besides, the sponge‐like membranes exhibited high rejection for vctoria blue B (>99%) in dye/salt mixture and simultaneously low rejection for salts (<10%), indicating effective selective separation to dye/salt mixture, and also achieved easy regeneration. It was also found that increased hydrophilicity and positive charge endowed membranes with better antibacterial activity. This work will provide an alternative for dye/salt selective separation in dye effluent treatment.
The distribution and habitat characterization of the East Asian finless porpoise (Neophocaena asiaeorientalis sunameri) in coastal waters off Qingdao, China: Implications for management and conservation
Authors: Li Yongtao , Cheng Zhaolong , Zuo Tao , Niu Mingxiang , Chen Ruisheng , Wang Jun
Published: July 2024

The East Asian finless porpoise (Neophocaena asiaeorientalis sunameri) distributes in coastal waters across the western Pacific Ocean, ranging from the Taiwan Strait to northern China, Korea and Japan. Limited baseline data are available for this threatened species, including the coastal region of Qingdao, China, hindering the implementation of conservation management.

The Oceanographic characteristics were derived from on‐board measurements and satellite remote sensing, including depth, slope, sea surface temperature (SST), salinity and chlorophyll a (Chla) concentration. Kernel density estimation (KDE) was utilized to determine the extent of occurrence and core distribution of East Asian finless porpoises.

The surveys covered an area of 4532 km2, encompassing 7314 km of transect lines. The 95% KDE and 50% KDE for East Asian finless porpoises within the study site included 1987 and 297 km2, respectively. The 50% KDE revealed Laoshan Bay as the core distribution zone. Significant relationships were identified between distribution probability and three oceanographic variables: salinity, Chla concentration and distance to shore.

In this study, the Aoshan Bay Marine Park, which was designed with no prior knowledge of East Asian finless porpoise, shows partial overlap with the core distribution for this species. This demonstrates that MPAs (marine protected areas) that are not explicitly designated for marine mammals may not comprehensively address all their specific requirements, but the existence and conservation endeavours associated with the MPAs can still yield substantial positive outcomes for these species. 5. This study provides the inaugural comprehensive baseline data on the population distribution and habitat characteristics of the East Asian finless porpoise. It underscores the necessity for a robust data collection protocol spanning China, Japan and Korea to address the critical shortfall in baseline data and enhance conservation efforts.
Novel therapeutic strategies and drugs for idiopathic pulmonary fibrosis
Authors: Shi Zezhou , Zhou Min , Zhai Jingfang , Sun Jie , Wang Xiaojing
Published: July 2024

Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease of unknown etiology. Currently, drugs used to treat IPF in clinical practice exhibit severe side effects and limitations. To address these issues, this paper discusses the therapeutic effects of preclinical targeted drugs (such as STAT3 and TGF‐β/Smad pathway inhibitors, chitinase inhibitors, PI3K and phosphodiesterase inhibitors, etc.) and natural products on IPF. Through a summary of current research progress, it is found that natural products possess multitarget effects, stable therapeutic efficacy, low side effects, and nondrug dependence. Furthermore, we discuss the significant prospects of natural product molecules in combating fibrosis by influencing the immune system, expecting that current analytical data will aid in the development of new drugs or the investigation of active ingredients in natural products for potential IPF treatments in the future.
Synthesis, biological activities, and structure–activity relationships of Morita–Baylis–Hillman adducts: An update
Authors: Devi Nisha , Pathania Arun Singh , Singh Virender , Sharma Shubham
Published: July 2024

The Morita–Baylis–Hillman (MBH) reaction is a unique C–C bond‐forming technique for the generation of multifunctional allylic alcohols (MBH adducts) in a single operation. In recent years, these MBH adducts have emerged as a novel class of compounds with significant biological potential, including anticancer, anti‐leishmanial, antibacterial, antifungal, anti‐herbicidal effects and activity against Chagas disease, and so on. The aim of this review is to assimilate the literature findings from 2011 onwards related to the synthesis and biological potential of MBH adducts, with an emphasis on their structure–activity relationships (SAR). Although insight into the biological mechanisms of action for this recently identified pharmacophore is currently in its nascent stages, the mechanisms described so far are reviewed herein.
Control design of quadrotor aircraft based on improved integral backstepping sliding mode
Authors: Jinlong Zhang , Jianhong Wang , Ruchun Wen , Yongjun Ding , Xi Luo
Published: July 2024

An improved integral backstepping sliding mode control (IIBSMC) strategy is proposed to address the problems of long regulation time and poor disturbance resistance of integral backstepping control (IBC) for quadrotor aircraft. The IIBSMC method first introduces the integral term into the virtual variable on the basis of IBC, which makes the system respond faster, overshoot smaller and anti‐interference performance stronger. After that, combined with sliding mode control, the system is further processed to improve the control performance of the system. Finally, the quadrotor is controlled to achieve fixed‐point hovering and trajectory tracking, and the rotation and translation performance of the aircraft and the stability under external interference are improved. When the quadrotor aircraft is subjected to instantaneous interference, constant interference, sinusoidal interference, white noise interference, and complex interference, the simulation experiments of IBC, improved integral backstepping control (IIBC), integral backstepping sliding mode control (IBSMC), and IIBSMC are compared. It can be obviously found that the IIBSMC method has smaller system overshoot, faster recovery of the original equilibrium position, shorter adjustment time, and smaller error. When using the IIBSMC method to design the controller, the stability of the controller is theoretically proved by backstepping recursion. Finally, the simulation results show that the designed controller can better achieve fixed‐point hovering and trajectory tracking control well.
Recent development on nanomaterial‐based biosensors for identifying thyroid tumor biomarkers
Authors: Xu Kun , Wu XiaoLu
Published: July 2024

The incidence of thyroid tumors has been increasing yearly over the past decade, making it the fourth highest tumor in women. This places various biological burdens on those affected. Currently, thyroid tumors are primarily diagnosed using percutaneous fine needle aspiration and ultrasound. However, these methods are complex, expensive, and less accurate, and they may fail to detect some thyroid nodules. As an alternative, researchers are focusing on blood‐based biomarkers in addition to the traditional diagnostic methods, assisted predominantly by nanomaterials. Early identification of thyroid cancer is crucial as it is highly treatable. Various sensing systems have been developed using nanomaterial‐mediated approaches to enhance the detection system. Nanomaterials are effectively applied in biosensors for surface functionalization and are conjugated with biomolecules to improve the interaction with the target analyte. This review discusses nanomaterial‐assisted thyroid tumor detection, with a special focus on nanomaterial‐based biosensors.
Targeting protein condensation in cGAS‐STING signaling pathway
Authors: Li Yajie , Zhao Dongbo , Chen Dahua , Sun Qinmiao
Published: July 2024

The cGAS‐STING signaling pathway plays a pivotal role in sensing cytosolic DNA and initiating innate immune responses against various threats, with disruptions in this pathway being associated with numerous immune‐related disorders. Therefore, precise regulation of the cGAS‐STING signaling is crucial to ensure appropriate immune responses. Recent research, including ours, underscores the importance of protein condensation in driving the activation and maintenance of innate immune signaling within the cGAS‐STING pathway. Consequently, targeting condensation processes in this pathway presents a promising approach for modulating the cGAS‐STING signaling and potentially managing associated disorders. In this review, we provide an overview of recent studies elucidating the role and regulatory mechanism of protein condensation in the cGAS‐STING signaling pathway while emphasizing its pathological implications. Additionally, we explore the potential of understanding and manipulating condensation dynamics to develop novel strategies for mitigating cGAS‐STING‐related disorders in the future.
Disease‐specific health‐related quality of life trajectories up to 15 years after curative treatment for esophageal cancer—a prospective cohort study
Authors: Cheng Zhao , Johar Asif , Lagergren Jesper , Schandl Anna , Lagergren Pernilla
Published: July 2024

Background

The presence of distinct long‐term disease‐specific HRQL trajectories after curative treatment for esophageal cancer and factors associated with such trajectories are unclear.

Materials and Methods

This population‐based and longitudinal cohort study included 425 esophageal cancer patients who underwent curative treatment, including esophagectomy, in Sweden in 2001–2005 and were followed up until 2020, that is, 15‐year follow‐up. The outcomes were 10 disease‐specific HRQL symptoms, measured by the well‐validated EORTC QLQ‐OES18 questionnaire at 6 months (n = 402 patients), and 3 (n = 178), 5 (n = 141), 10 (n = 92), and 15 years (n = 52) after treatment. HRQL symptoms were examined for distinct trajectories by growth mixture models. Weighted logistic regression models provided odds ratios (OR) with 95% confidence intervals (95% CI) for nine factors in relation to HRQL trajectories: age, sex, education, proxy baseline HRQL, comorbidity, tumor histology, chemo(radio)therapy, pathological tumor stage, and postoperative complications.

Results

Distinct HRQL trajectories were identified for each of the 10 disease‐specific symptoms. HRQL trajectories with more symptoms tended to persist or alleviate over time, while trajectories with fewer symptoms were more stable. Eating difficulty had three trajectories: persistently less, persistently moderate, and persistently more symptoms. The OR of having a persistently more eating difficulty trajectory was decreased for adenocarcinoma histology (OR = 0.44, 95% CI 0.21–0.95), and increased for pathological tumor stage III‐IV (OR = 2.19, 95% CI 0.99–4.82) and 30‐day postoperative complications (OR = 2.54, 95% CI 1.26–5.12).

Conclusion

Distinct trajectories with long‐term persistent or deteriorating disease‐specific HRQL symptoms were identified after esophageal cancer treatment. Tumor histology, tumor stage, and postoperative complications may facilitate detection of high‐risk patients for unwanted trajectories.
Photoactivated Anticancer Activity of Cobalt(III) Complexes with Naturally Occurring Flavonoids Chrysin and Silibinin
Authors: Dutta Jyotirmoy , Bera Arpan , Upadhyay Aarti , Yadav Ashish Kumar , Banerjee Samya , Sarkar Tukki , Hussain Akhtar
Published: July 2024

Photoactive metal complexes of bioessential transition metal ions with natural chelators are gaining interest as photocytotoxic agents for cancer photodynamic therapy (PDT). We report six new cobalt(III) complexes with a mixed‐ligand formulation [Co(B)2(L)](ClO4)2 (Co1–Co6), where B represents a N,N‐donor α‐diimine ligand, namely, phenanthroline (phen; Co1, Co2), dipyrido[3,2‐d:2’,3’‐f]quinoxaline (dpq; Co3, Co4), and dipyrido[3,2‐a:2’,3’‐c]phenazine (dppz; Co5, Co6), and L is the monoanionic form of the naturally occurring flavonoids chrysin (chry; Co1, Co3, Co5) and silibinin (sili; Co2, Co4, Co6). Complexes displayed a d‐d absorption band within 500–700 nm and exhibited excellent dark and photostability in solution. Cytotoxicity studies indicated significant activity of Co5 and Co6 against cervical (HeLa) and lung (A549) cancer cells under visible light (400–700 nm) irradiation giving low micromolar IC50 values (2.3–3.4 μM, phototoxicity index~15–30). The complexes demonstrated notably low toxicity against normal HPL1D lung epithelial cells. Flow cytometry assay revealed an apoptotic mode of cell damage triggered by the complexes when irradiated. ROS generation assay indicated the involvement of singlet oxygen species in the cell death mechanism when irradiated with light. Overall, complexes Co5 and Co6 with coordinated dipyridophenazine and flavonoid ligands are potential candidates for cancer PDT applications.
High‐molecular‐weight glutenin subunit profiles of eastern US soft winter wheat desirable for making soft‐bite white salted noodles
Authors: Ma Fengyun , Baik Byung‐Kee
Published: July 2024

Background and Objectives

High‐molecular‐weight glutenin subunits (HMW‐GSs) composition has a significant influence on wheat gluten strength and product quality. Flour protein content and gluten strength required for making soft‐bite white salted noodles (WSNs) are well established, whereas the association of HMW‐GS composition with WSN quality is poorly understood. Eastern US soft winter (ESW) wheat varieties carrying diverse HMW‐GS profiles were evaluated for protein characteristics and WSN‐making quality and compared to those of commercial noodle flours (CNFs) to identify HMW‐GSs desirable for making noodles.

Findings

Subunit 2* showed associations with low cooking yield and high hardness of cooked WSN. ESW wheat varieties carrying subunits 2 + 121 produced WSN with higher cooking loss, and lower hardness and tensile force than those carrying subunits 5 + 10, 2 + 12, or 2 + 10. The 1BL/1RS translocation exhibited an association with increased adhesiveness of WSN.

Conclusions

ESW wheat varieties carrying one of three HMW‐GS profiles, (2*, 7* + 8, 5 + 10), (2*, 7 + 9, 5 + 10) or (2*, 13 + 16, 2 + 12), produced WSN of comparable quality to those prepared from CNFs.

Significance and Novelty

The determination of HMW‐GS composition would be an effective tool for the identification and development of ESW wheat varieties possessing protein characteristics suitable for making WSN.
Surgical management of high‐grade vesicoureteral reflux in an 18‐month‐old female with a solitary kidney: A case report from a resource‐limited setting
Authors: Nhungo Charles John , Mwakalukwa Kelvin Richard , Wambura Erasto Phares , Kibona Herry Godfrey , Mushi Fransia Arda , Msangi Nimwindael Stephen , Maro Isaack Mlatie , Kimu Njiku Marko , Nyongole Obadia Venance , Mkony Charles A.
Published: July 2024

Key Clinical Message

Conservative nonsurgical therapy ensures that the resolution is nearly 80% for vesicoureteral reflux grades I and II and 30%–50% for vesicoureteral reflux grades III and V within 4–5 years of follow‐up. Open surgical reimplantation of ureters of grades IV and V is a highly successful procedure, with reported correction rates ranging from 95% to 99% regardless of the severity of vesicoureteral reflux.

Patients with vesicoureteral reflux present with a wide range of severity. With an incidence of approximately 1%, vesicoureteral reflux is a relatively common urological abnormality in children. Postnatal diagnosis of vesicoureteral reflux is typically made following a diagnosis of a urinary tract infection and less frequently following family screening. Voiding cystourethrograms remain the gold standard for diagnosing vesicoureteral reflux. To preserve the kidney and prevent the need for potential renal replacement therapy, infants with a single kidney require significantly more assessments and prompt decision‐making. Surgical correction is advised for patients with vesicoureteral reflux grades IV and V, while vesicoureteral reflux grades I, II, and III are managed conservatively.
Ulcerative colitis associated mononeuritis multiplex in 75‐year‐old patient: Rare case report
Authors: Pourbagherian Omid , Jafarpour Mehdi , Tahsini Sepideh , Eftekharsadat Amir Taher , Javid Maryam
Published: July 2024

Key Clinical Message

Inflammatory bowel disease (IBD) refers to a collection of chronic, idiopathic inflammatory/autoimmune disorders of the gastrointestinal tract characterized by relapsing and remitting episodes. In this case report, we will report a patient who has encountered ulcerative colitis related to mononeuritis multiplex as a rare clinical scenario. A 75‐year‐old male patient, with a prior medical history including long‐standing hypertension, recurring episodes of peripheral joint arthritis, leg skin lesions reminiscent of erythema nodosum, and persistent chronic diarrhea over the past 2 years, was recently hospitalized at the rheumatology department of Imam Reza Hospital in Tabriz. Throughout the patient's hospital stay, a series of diagnostic assessments were conducted, encompassing procedures such as colonoscopy, electromyography and nerve conduction studies, echocardiography, renal ultrasonography, and standard hematological analyses. The patient underwent the following treatment regimen, which resulted in a significant improvement in his condition.
Three Design Strategies for Improving the Thermal Stability of Lithium‐Ion Batteries
Authors: Mukai Kazuhiko
Published: July 2024

Today's information and communication technologies heavily rely on lithium‐ion batteries (LIBs), which were commercialized by Sony in 1991. However, owing to their self‐contained nature, the thermal runaway that leads to rupture or explosion hinders their safe, worry‐free utilization in electric vehicles (EVs) and stationary energy storage systems (SESSs). This contribution introduces three design strategies for improving the thermal stability of LIBs: i) replacing materials for a smaller change in enthalpy, ii) optimizing the solid electrolyte interphase film, and iii) stabilizing the crystal lattice. These strategies could pave the way to satisfying the heretofore competing needs for LIBs to have both high energy density and high thermal stability, enabling further widespread applications to EVs and SESSs.
Fluorescence of Aggregated Aromatic Peptides for Studying the Kinetics of Aggregation and Hardening of Amyloid‐like Structures
Authors: Diaferia Carlo , Gallo Enrico , Cimmino Luca , Laurenzi Valentina , De Marco Agostino , Morelli Giancarlo , Stornaiuolo Mariano , Accardo Antonella
Published: July 2024

The capability of amyloid‐like peptide fibers to emit intrinsic‐fluorescence enables the study of their formation, stability and hardening through time‐resolved fluorescence analysis, without the need for additional intercalating dyes. This approach allows the monitoring of amyloid‐like peptides aggregation kinetics using minimal sample volumes, and the simultaneous testing of numerous experimental conditions and analytes, offering rapid and reproducible results. The analytical procedure applied to the aromatic hexapeptide F6, alone or derivatized with PEG (polyethylene glycol) moiety of different lengths, suggests that aggregation into large anisotropic structures negatively correlates with initial monomer concentration and relies on the presence of charged N‐ and C‐termini. PEGylation reduces the extent of aggregates hardening, possibly by retaining water, and overall impacts the final structural properties of the aggregates.
Nano in the classroom – innovative experiments on the topic of nanochemistry in secondary education and the school laboratory setting Nan_OS
Authors: Becker Daniel , Kreienhop Nils , Otte Lars , Beeken Marco
Published: July 2024

Selbstreinigende Oberflächen, Nanocarrier in der Medizin oder Photokatalysatoren für die Gewässerreinigung. Die Nanochemie nimmt immer mehr Platz in der Forschung, aber auch in unserem Alltag ein. In diesem Zuge wurde 2022 die Neueinführung des Themenfelds Nanochemie in die Anforderungen an die Allgemeine Hochschulreife und somit in die Lehrpläne einiger Bundesländer, unter anderem Niedersachen, beschlossen. Aus diesem Anlass wurde das Schülerlabor‐Setting Nan_OS für den außerschulischen Lernstandort GreenLab_OS für die gymnasiale Oberstufe entwickelt. Auf Grundlage der im Kerncurriculum für die Sekundarstufe II des Landes Niedersachsen festgesetzten Kompetenzen erhalten die Schülerinnen und Schüler einen Einblick in die Eigenschaften, Anwendung, Chancen sowie Risiken der Nanochemie. Es sollen verschiedene Phänomene, die auf die spezifischen Eigenschaften von Nanopartikeln zurückzuführen sind, didaktisch reduziert vermittelt werden. Die Schülerinnen und Schüler untersuchen im Schülerlabor‐Setting spezifische Eigenschaften, wie das hohe Oberflächen‐zu‐Volumen‐Verhältnis, die anregbare Fluoreszenz von kohlenstoffhaltigen Carbon Quantum Dots und die daraus resultierenden Anwendungsmöglichkeiten von Nanostrukturen sowie Nanopartikel. Zusätzlich setzen sich die Schülerinnen und Schüler im Schülerlabor‐Setting mit der Synthese von Nanopartikeln auseinander. Im Sinne der Bewertungskompetenz erarbeiten und bewerten die Schülerinnen und Schüler materialgestützt die möglichen Chancen und Risiken der Nanochemie, Nanotechnologie und Nanopartikeln. In diesem Artikel wird zunächst ein Einblick in die Geschichte der Nanotechnologie gegeben, um anschließend die grundlegende Einbettung von Nan_OS vorzustellen. Abschließend werden drei innovative Experimente aus dem Setting erläutert, die auch für den Regelunterricht der Sekundarstufe II geeignet sind.
Barriers confronting smallholder cassava farmers in the adoption and utilization of climate‐smart agriculture in the Afigya Kwabre South District, Ghana
Authors: Baffour‐Ata Frank , Boakye Louisa , Acquah Lordina Ekua , Brown Samuel Boamah , Kafui John Dagadu , Marfo Austin Appiah , Acheampong Prince , Wheagar Salome
Published: July 2024

Climate‐smart agriculture (CSA) is key to addressing climate change threats faced by smallholder farmers in Ghana. Nonetheless, evidence of the barriers challenging smallholder farmers in the implementation of CSA practices remains limited in Ghana. This study, therefore, investigated the barriers opposing smallholder cassava farmers in implementing CSA practices in the Afigya Kwabre South District, Ghana. The study used descriptive statistics and content analysis to analyze primary data collected through 200 household surveys and 10 key informant interviews from four selected communities (Aboabogya, Aduamoa, Aduman Old Town, and Aduman New Town) in the district. Results revealed that the smallholder cassava farmers implemented key CSA practices including mulching (89%), mixed farming (86%), crop diversification (84%), and crop rotation (81%) to build their resilience in food systems. Furthermore, the results showed that the critical enablers to the farmers’ utilization of CSA practices were access to weather and climate services (82%), a secured land tenure system (75%), and knowledge of the effects of climate change (68%). Also, the results indicated that the key barriers challenging smallholder cassava farmers in the implementation of CSA practices were inadequate technological assistance (91%), the incidence of pests and diseases (90%), and a lack of knowledge and understanding of CSA (90%). We recommend that smallholder cassava farmers adopt improved varieties of cassava that are resistant to pests and diseases, drought tolerant, high yielding, and possessing desirable quality traits. Smallholder cassava farmers can also participate in contract farming schemes that link them to agribusinesses that can offer them access to quality inputs, credit, training, and guaranteed markets for their produce.
Genoarchitectural Definition of the Adult Mouse Mesocortical Ring: A Contribution to Cortical Ring Theory
Authors: Puelles Luis , Alonso Antonia , García‐Calero Elena
Published: July 2024

Data mining was performed at the databases of the Allen Institute for Brain Science (RRID:SCR_017001) searching for genes expressed selectively throughout the adult mouse mesocortex (transitional cortex ring predicted within the concentric ring theory of mammalian cortical structure, in contrast with central isocortex [ICx] and peripheral allocortex). We aimed to explore a shared molecular profile selective of all or most mesocortex areas. This approach checks and corroborates the precision of other previous definitory criteria, such as poor myelination and high kainate receptor level. Another aim was to examine which cortical areas properly belong to mesocortex. A total of 34 positive adult selective marker genes of mesocortex were identified, jointly with 12 negative selective markers, making a total of 46 markers. All of them identify the same set of cortical areas surrounding the molecularly different ICx as well as excluding adjacent allocortex. Four representative mesocortex markers—Crym, Lypd1, Cdh13, and Smoc2—are amply illustrated, jointly with complementary material including myelin basic protein, to check myelination, and Rorb, to check layer 4 presence. The retrosplenial (ReSp) area, long held to be mesocortical, does not share any of the 46 markers of mesocortex and instead expresses Nr4a2 and Tshz2, selective parahippocampal allocortex markers. Moreover, it is not hypomyelinic and lacks a Rorb‐positive layer 4, aspects generally present in mesocortex. Exclusion of the ReSp area from the mesocortex ring reveals the latter to be closed at this locus instead by two adjacent areas previously thought to be associative visual ICx (reidentified here molecularly as postsplenial and parasplenial mesocortex areas). The concepts of ICx, mesocortex, and parahippocampal allocortex are thus subtly modified by substantial molecular evidence.
The Neural Representation of Binaural Sound Localization Cues Across Different Subregions of the Chicken's Inferior Colliculus
Authors: Aralla Roberta , Pauley Claire , Köppl Christine
Published: July 2024

The sound localization behavior of the nocturnally hunting barn owl and its underlying neural computations is a textbook example of neuroethology. Differences in sound timing and level at the two ears are integrated in a series of well‐characterized steps, from brainstem to inferior colliculus (IC), resulting in a topographical neural representation of auditory space. It remains an important question of brain evolution: How is this specialized case derived from a more plesiomorphic pattern? The present study is the first to match physiology and anatomical subregions in the non‐owl avian IC. Single‐unit responses in the chicken IC were tested for selectivity to different frequencies and to the binaural difference cues. Their anatomical origin was reconstructed with the help of electrolytic lesions and immunohistochemical identification of different subregions of the IC, based on previous characterizations in owl and chicken. In contrast to barn owl, there was no distinct differentiation of responses in the different subregions. We found neural topographies for both binaural cues but no evidence for a coherent representation of auditory space. The results are consistent with previous work in pigeon IC and chicken higher‐order midbrain and suggest a plesiomorphic condition of multisensory integration in the midbrain that is dominated by lateral panoramic vision.
Vibrational Features of Oxyamines: A Comparative Study of N,N‐Diethylhydroxylamine and N,N‐Diethylacetyloxyamine
Authors: Pizzano Emanuele , Baroncelli Filippo , Melandri Sonia , Evangelisti Luca , Ricci Marcello , Mazzacurati Marzia , Pori Matteo , Torreggiani Armida , Maris Assimo
Published: July 2024

The ability of oxyamines to undergo homolytic cleavage of the O−C bond, leading to the formation of stable radicals, is widely used in polymerization processes and to prevent oxidative stress in materials. We present a mid and near‐infrared spectroscopy study on two model compounds, N,N‐diethylhydroxyloxyamine (C4H11NO) and its acetyl derivative N,N‐diethylacetyloxyamine (C6H13NO2) in the liquid phase. The analysis of the spectra is based on a complete exploration of the conformational space, coupled to harmonic and anharmonic calculations performed using the generalized second‐order vibrational perturbation theory (GVPT2) formalism at the B3LYP−D3(BJ)/Def2‐TZVP level of calculation and potential energy distribution analysis. In the most stable species out of 25, the three amine chains present an all‐anti arrangement, with the carbonyl oxygen atom pointing towards the nitrogen lone pair. The simulated spectra are in overall good agreement with the experimental ones, and suitable for the assignment of the main observed bands. Furthermore, similarities and divergences between the two molecules are discussed.
Real‐World Evidence to Support EU Regulatory Decision Making—Results From a Pilot of Regulatory Use Cases
Authors: Prilla Stefanie , Groeneveld Sophie , Pacurariu Alexandra , Restrepo‐Méndez María Clara , Verpillat Patrice , Torre Carla , Gartner Christian , Mol Peter G. M. , Naumann‐Winter Frauke , Breen Kieran C. , Gault Nathalie , Gross‐Martirosyan Liana , Benchetrit Sylvie , Aylward Brian , Stoyanova‐Beninska Violeta , O'Donovan Maura , Straus Sabine , Kjaer Jesper , Arlett Peter
Published: July 2024

Studies using real‐world data (RWD) can complement evidence from clinical trials and fill evidence gaps during different stages of a medicine's lifecycle. This review presents the experience resulting from the European Medicines Agency (EMA) pilot to generate RWE to support evaluations by EU regulators and down‐stream decision makers from September 2021 to February 2023. A total of 61 research topics were identified for RWE generation during this period, covering a wide range of research questions, primarily generating evidence on medicines safety (22, 36%), followed by questions on the design and feasibility of clinical trials (11, 18%), drug utilization (10, 16%), clinical management (10, 16%), and disease epidemiology. A significant number of questions were related to the pediatric population and/or rare diseases. A total of 27 regulatory‐led RWD studies have been conducted. Most studies were descriptive and aimed at estimating incidence and prevalence rates of clinical outcomes including adverse events or to evaluate medicines utilization. The review highlights key learnings to guide further efforts to enable the use and establish the value of real‐world evidence (RWE) for regulatory decisions. For instance, there is a need to access additional fit‐for‐purpose and representative data, and to explore further means to provide timely evidence that meets regulatory timelines. The need for early interactions and close collaboration with study requesters, e.g., from the Agency's scientific Committees, to better understand the research question is equally important. Finally, the review provides our perspective on the way forward to maximize the potential of regulatory‐led RWE generation.
Dosing Strategies and Quantitative Clinical Pharmacology for Bispecific T‐Cell Engagers Development in Oncology
Authors: Elmeliegy Mohamed , Chen Joseph , Dontabhaktuni Aruna , Gaudy Allison , Kapitanov Georgi I. , Li Junyi , Mim Sabiha R. , Sharma Sharad , Sun Qin , Ait‐Oudhia Sihem
Published: July 2024

Bispecific T‐cell Engagers (TCEs) are promising anti‐cancer treatments that bind to both the CD3 receptors on T cells and an antigen on the surface of tumor cells, creating an immune synapse, leading to killing of malignant tumor cells. These novel therapies have unique development challenges, with specific safety risks of cytokine release syndrome. These on‐target adverse events fortunately can be mitigated and deconvoluted from efficacy via innovative dosing strategies, making clinical pharmacology key in the development of these therapies. This review assesses dose selection and the role of quantitative clinical pharmacology in the development of the first eight approved TCEs. Model informed drug development (MIDD) strategies can be used at every stage to guide TCE development. Mechanistic modeling approaches allow for (1) efficacious yet safe first‐in‐human dose selection as compared with in vitro minimum anticipated biological effect level (MABEL) approach; (2) rapid escalation and reducing number of patients with subtherapeutic doses through model‐based adaptive design; (3) virtual testing of different step‐up dosing regimens that may not be feasible to be evaluated in the clinic; and (4) selection and justification of the optimal clinical step‐up and full treatment doses. As the knowledge base around TCEs continues to grow, the relevance and utilization of MIDD strategies for supporting the development and dose optimization of these molecules are expected to advance, optimizing the benefit–risk profile for cancer patients.
In Situ Monitoring of Crystallinity of FeSe2 Thin Films During Thermal Annealing and the Annealing Effects on the Structural, Optical and Dielectric Properties
Authors: Gaabour Laila H. , Qasrawi Atef Fayez , Alharbi Seham R.
Published: July 2024

Herein stacked layers of iron selenide (FeSe2) thin films are deposited by the physical evaporation technique and thermally annealed. An in situ monitoring of the crystallinity during the annealing process has shown that the crystallinity is reached at 100 °C. The crystallinity of the films that preferred the orthorhombic phase is enhanced with increasing annealing temperature. Evidences about the improved crystallinity are presented by the increased crystallite and grain sizes, decreased microstrain values, decreased stacking faults, and decreased defect densities with increasing annealing temperature. Optical investigations have shown impressive effect of the annealing process on the optical reflectance, optical contrast, and light absorbability. Namely, respective improvement percentages exceeding 170%, 64%, and 140% is achieved near E≈2 eV for samples annealed at 200 °C for 20 min. Both direct and indirect optical transitions are dominant in the film. In addition the annealing increased the dielectric constant in the spectral range of 1.17–4.20 eV. Maximum dielectric enhancement by 214% is reached near ≈2.10 eV. Moreover, the annealing process increases the optical conductivity and drift mobility of the FeSe2 films. The improvement in the crystallinity that resulted in enhanced optical properties makes the thermally annealed FeSe2 films promising for optoelectronic technology applications.
Oxidative Cleavage of α‐O‐4, β‐O‐4, and 4‐O‐5 Linkages in Lignin Model Compounds Over P, N Co‐Doped Carbon Catalyst: A Metal‐Free Approach
Authors: Chauhan Arzoo , Rajendra Kanchan Dipika , Banerjee Arghya , Srivastava Rajendra
Published: July 2024

Developing efficient metal‐free catalysts for lignin valorization is essential but challenging. In this study, a cost‐effective strategy is employed to synthesize a P, N co‐doped carbon catalyst through hydrothermal and carbonization processes. This catalyst effectively cleaved α‐O‐4, β‐O‐4, and 4‐O‐5 lignin linkages, as demonstrated with model compounds. Various catalysts were prepared at different carbonization temperatures and thoroughly characterized using techniques such as XRD, RAMAN, FTIR, XPS, NH3‐TPD, and HRTEM. Attributed to higher acidity, the P5NC‐500 catalyst exhibited the best catalytic activity, employing H2O2 as the oxidant in water. Additionally, this metal‐free technique efficiently converted simulated lignin bio‐oil, containing all three linkages, into valuable monomers. Density Functional Theory calculations provided insight into the reaction mechanism, suggesting substrate and oxidant activation by P−O−H sites in the P5NC‐500, and by N−C−O−H in the CN catalyst. Moreover, the catalyst′s recyclability and water utilization enhance its environmental compatibility, offering a highly sustainable approach to lignin valorization with potential applications in various industries.
N‐acetyltransferase 10 facilitates tumorigenesis of diffuse large B‐cell lymphoma by regulating AMPK/mTOR signalling through N4‐acetylcytidine modification of SLC30A9
Authors: Ding Mengfei , Yu Zhuoya , Lu Tiange , Hu Shunfeng , Zhou Xiangxiang , Wang Xin
Published: July 2024

Background

Accumulating studies suggested that posttranscriptional modifications exert a vital role in the tumorigenesis of diffuse large B‐cell lymphoma (DLBCL). N4‐acetylcytidine (ac4C) modification, catalyzed by the N‐acetyltransferase 10 (NAT10), was a novel type of chemical modification that improves translation efficiency and mRNA stability.

Methods

GEO databases and clinical samples were used to explore the expression and clinical value of NAT10 in DLBCL. CRISPER/Cas9‐mediated knockout of NAT10 was performed to determine the biological functions of NAT10 in DLBCL. RNA sequencing, acetylated RNA immunoprecipitation sequencing (acRIP‐seq), LC‐MS/MS, RNA immunoprecipitation (RIP)‐qPCR and RNA stability assays were performed to explore the mechanism by which NAT10 contributed to DLBCL progression.

Results

Here, we demonstrated that NAT10‐mediated ac4C modification regulated the occurrence and progression of DLBCL. Dysregulated N‐acetyltransferases expression was found in DLBCL samples. High expression of NAT10 was associated with poor prognosis of DLBCL patients. Deletion of NAT10 expression inhibited cell proliferation and induced G0/G1 phase arrest. Furthermore, knockout of NAT10 increased the sensitivity of DLBCL cells to ibrutinib. AcRIP‐seq identified solute carrier family 30 member 9 (SLC30A9) as a downstream target of NAT10 in DLBCL. NAT10 regulated the mRNA stability of SLC30A9 in an ac4C‐dependent manner. Genetic silencing of SLC30A9 suppressed DLBCL cell growth via regulating the activation of AMP‐activated protein kinase (AMPK) pathway.

Conclusion

Collectively, these findings highlighted the essential role of ac4C RNA modification mediated by NAT10 in DLBCL, and provided insights into novel epigenetic‐based therapeutic strategies.
Multi‐omics analysis reveals drivers of loss of β‐cell function after newly diagnosed autoimmune type 1 diabetes: An INNODIA multicenter study
Authors: Armenteros Jose Juan Almagro , Brorsson Caroline , Johansen Christian Holm , Banasik Karina , Mazzoni Gianluca , Moulder Robert , Hirvonen Karoliina , Suomi Tomi , Rasool Omid , Bruggraber Sylvaine F. A. , Marcovecchio M. Loredana , Hendricks Emile , Al‐Sari Naba , Mattila Ismo , Legido‐Quigley Cristina , Suvitaival Tommi , Chmura Piotr J. , Knip Mikael , Schulte Anke M. , Lee Jeong Heon , Sebastiani Guido , Grieco Giuseppina Emanuela , Elo Laura L. , Kaur Simranjeet , Pociot Flemming , Dotta Francesco , Tree Tim , Lahesmaa Riitta , Overbergh Lut , Mathieu Chantal , Peakman Mark , Brunak Søren ,   the INNODIA investigators
Published: July 2024

Aims

Heterogeneity in the rate of β‐cell loss in newly diagnosed type 1 diabetes patients is poorly understood and creates a barrier to designing and interpreting disease‐modifying clinical trials. Integrative analyses of baseline multi‐omics data obtained after the diagnosis of type 1 diabetes may provide mechanistic insight into the diverse rates of disease progression after type 1 diabetes diagnosis.

Methods

We collected samples in a pan‐European consortium that enabled the concerted analysis of five different omics modalities in data from 97 newly diagnosed patients. In this study, we used Multi‐Omics Factor Analysis to identify molecular signatures correlating with post‐diagnosis decline in β‐cell mass measured as fasting C‐peptide.

Results

Two molecular signatures were significantly correlated with fasting C‐peptide levels. One signature showed a correlation to neutrophil degranulation, cytokine signalling, lymphoid and non‐lymphoid cell interactions and G‐protein coupled receptor signalling events that were inversely associated with a rapid decline in β‐cell function. The second signature was related to translation and viral infection was inversely associated with change in β‐cell function. In addition, the immunomics data revealed a Natural Killer cell signature associated with rapid β‐cell decline.

Conclusions

Features that differ between individuals with slow and rapid decline in β‐cell mass could be valuable in staging and prediction of the rate of disease progression and thus enable smarter (shorter and smaller) trial designs for disease modifying therapies as well as offering biomarkers of therapeutic effect.
A fine‐scale examination of parturition timing in temperate ungulates
Authors: Turnley Matthew T. , Hughes Tabitha A. , Larsen Randy T. , Hersey Kent R. , Broadway Matthew S. , Chitwood M. Colter , Fairbanks W. Sue , Lonsinger Robert C. , McMillan Brock R.
Published: July 2024

Parturition timing has long been a topic of interest in ungulate research. However, few studies have examined parturition timing at fine scale (e.g., <1 day). Predator activity and environmental conditions can vary considerably with diel timing, which may result in selective pressure for parturition to occur during diel times that maximize the likelihood of neonate survival. We monitored parturition events and early‐life survival of elk (Cervus canadensis) and mule deer (Odocoileus hemionus) in Utah, USA to better understand diel timing of parturition in temperate ungulates. Diel timing of parturition was moderately synchronous among conspecifics and influenced by environmental variables on the date of parturition. For elk, parturition events were most common during the morning crepuscular period and generally occurred later (i.e., closer to 12:00) when a relatively large proportion of the moon was illuminated. For mule deer, parturition events were most common during the diurnal period and generally occurred later (i.e., closer to 15:00) on cold, wet dates. Diel timing of parturition did not influence neonate survival, but larger datasets may be required to verify the apparent lack of influence. Although additional work could evaluate alternative variables that might affect parturition timing, our data provide an improved and finer scale understanding of reproductive ecology and phenology in ungulates.