bluuebunny/crossref_metadata_2025 huggingface dataset:
Biodiversity and Bioprospecting of Fungal Endophytes from Houttuynia cordata Thunb. as a Potential Antibacterial and Anticancer Agent
Authors: Anshory Tamhid Hady , Sukmarini Linda , Fitria Annisa , Davi Setiawan Iwang , Wahyu Wardana Andika , Ilyas Muhammad , Pramisandi Amila , Triastuti Asih
Published: October 2024

Endophytic fungi are considered a new source of bioactive compounds that have important applications in agriculture and medicine. This study aims to investigate the biodiversity and potential of endophytic fungi isolated from Houttuynia cordata Thunb. as antimicrobials and anticancer agents. Out of ten isolated endophytes, four species have never been reported to be associated with H. cordata: Ceratobasidium sp., Cladosporium sp., Phomopsis sp., and Fusarium sp. The antibacterial activity assay revealed that the ethyl acetate extract of Ceratobasidium sp. HCS‐3 possessed most potent antibacterial activity against Escherichia coli and Staphylococcus aureus. In addition, its cytotoxic activity test showed the promising anticancer activity on lung cancer A549, osteosarcoma MG‐63, and cervical cancer HeLa cells with IC50 of 4.55±1.16, 32.14±2.78, and 1.54±0.66 ppm, respectively. Furthermore, metabolite profiling identified 66 compounds suggesting that benzoic acid, farnesol, and cyclopeptides may contribute to the antibacterial activity, while 4‐methoxycinnamic acid may have anticancer potential.
Antifungal Activity of Novel Isoindoline‐2‐Yl Putrescines as Potential Autophagy‐Activated Fungicide
Authors: Zhu Lisong , Huang Fengcheng , Wang Hongye , Zhao Yanjun , Luan Shaorong , Xiao Ciying , Huang Qingchun
Published: October 2024

The exacerbation of plant fungal diseases necessitates the development of new fungicides to prevent outbreaks. In this study, five novel isoindoline‐2‐yl putrescines (ISPs) were synthesized, and their synthetic procedures and gram‐scale preparation were explored. When tested at 50 μg mL−1, ISPs did not significantly inhibit mycelial growth on agar plates. However, at 100 μg mL−1, they demonstrated remarkable in vivo efficacy in mitigating Botrytis cinerea infection, especially ISP3 showed curative and protective activities of 91.9 % and 92.6 %, respectively. Moreover, ISP3 also effectively halted lesion expansion of gray mold, Sclerotic rot, and Fusarium scabs, while inducing excessive malformed top mycelial branches of B. cinerea and Sclerotinia sclerotiorum, suppressing sclerotia formation in S. sclerotiorum, and triggering autophagic vacuolization with numerous autophagosomes in the mycelia of these fungi. Molecular docking revealed that ISP3 effectively bound to the active site of BcAtg3, forming hydrogen bonds with Ser279, Gly343, Asp370, and Asp13, along with establishing a stable salt bridge with Asp13. Furthermore, ISP3 possessed favorable ADMET properties. These findings highlight ISP3 as a promising antifungal candidate through autophagy activation.
Three New Spirostan Glycosides from Dracaena Cochinchinensis with NO Production Inhibitory and Antimicrobial Activity
Authors: Hai Yen Pham , Thi Hai Yen Duong , Huu Tai Bui , Huy Hoang Nguyen , Thi Thanh Huong Phan , Anh Bang Ngo , Thi Dung Duong , Thi Trang Do , Anh Le Tuan , Van Kiem Phan
Published: October 2024

Three new spirostan glycosides, dracochinosides A–C (1–3), and four known steroidal glycosides (4–7) were isolated from the aerial parts of Dracaena cochinchinensis (Lour.) S.C.Chen. Their chemical structures were determined by the IR, HR‐ESI‐MS, 1D‐, and 2D‐NMR spectra. Compounds 1–3, 6 and 7 inhibited nitric oxide production in LPS activated RAW 264.7 cells with IC50 values ranging from 57.5 to 92.8 μM. In addition, all the isolated compounds exhibited at least one of seven tested microbial strains with the MIC values ranging from 0.016 to 0.128 mg/mL. This is the first report of compounds 5–7 from the genus Dracaena.
Convenient Partial Reduction of CO2 to a Useful C1 Building Block: Efficient Access to 13C‐Labelled N‐Heterocyclic Carbenes
Authors: Phillips Nicholas A. , Sapsford Joshua S. , Csókás Dániel , Kótai Bianka , Perez‐Tabarnero Ines , Díez‐González Silvia , Scott Daniel J. , Pápai Imre , Ashley Andrew E.
Published: October 2024

The selective, transition metal‐free hydrosilylation of CO2 to CH2(OSiEt3)2 has been achieved under mild conditions and in high isolated yields (up to 90%) by using Et3SiH and the simple, easily prepared borohydride catalyst Li+[HB(C6F5)3]−. The resulting CO2‐derived bis(silyl)acetal product—whose mechanism of formation has been interrogated through detailed computational and experimental studies—can be rapidly valorized through the facile synthesis of N‐heterocyclic carbenes, via their corresponding imidazolium salts. By using relatively inexpensive, isotopically enriched 13CO2 this protocol can be exploited to prepare NHC isotopologues that are selectively 13C labelled at the key, ligating C2 position. This provides an electronically responsive 13C NMR spectroscopic handle with dramatically enhanced sensitivity, which can directly benefit reactivity studies in both organo‐ and organometallic catalysis, where NHC use is ubiquitous.
Persistent Renal Dysfunction After Acute Kidney Injury Among STEMI Patients Undergoing Primary Coronary Intervention: Prevalence and Predictors
Authors: Frydman Shir , Freund Ophir , katash Haytham Abu , Rimbrot Daniel , Banai Shmuel , Shacham Yacov
Published: October 2024

Background

Acute kidney injury (AKI) is a common and serious complication of ST‐elevation myocardial infarction (STEMI). AKI and chronic kidney disease (CKD) are highly heterogeneous, leaving a wide gap between them. Therefore, the term acute kidney disease (AKD) was implemented, describing prolonged renal injury between 7 and 90 days. We aimed to evaluate the prevalence and predictors of AKD among STEMI patients.

Methods

This retrospective observational study included 2940 consecutive patients admitted with STEMI between 2008 and 2022. Renal function was assessed upon admission and routinely thereafter. Renal outcomes were evaluated according to KDIGO criteria, with AKD defined as persistent renal injury of between 7 and 90 days.

Results

Two hundred and fifty‐two subjects with STEMI and AKI were included; of them, 117 (46%) developed AKD. Among baseline CKD patients, higher rates of AKD were observed (60% vs. 46%). KDIGO index ≥ 2 was an independent predictor for AKD in in subjects without baseline CKD (AOR 2.63, 95% CI 1.07−6.53). In subjects with baseline CKD, older age and higher creatinine were independent predictors for AKD. Subjects with AKD had a higher 1‐year mortality rate (HR 3.39, 95% CI 1.71−6.72, p < 0.01). This trend was mainly driven by the CKD subpopulation where higher mortality rates for AKD on CKD were observed (HR 5.26, 95% CI 1.83−15.1, p < 0.01).

Conclusion

AKD is common among STEMI patients with AKI. The presence of CKD and higher KDIGO stage should prompt strict monitoring for early diagnosis, treatment, and prevention of renal function deterioration.
Effect of asymptomatic intervertebral flexion patterns on lumbar disc pressure: A finite element analysis study
Authors: Nematimoez Mehdi , Haddas Ram , Breen Alexander
Published: October 2024

Movement patterns may be a factor for manipulating the lumbar load, although little information is yet available in the literature about the relationship between this variable and intervertebral disc pressure (IDP). A finite element model of the lumbar spine (49‐year‐old asymptomatic female) was used to simulate intervertebral movements (L2–L5) of 127 asymptomatic participants. The data from participants that at least completed a simulation of lumbar vertebral movement during the first 53% of a movement cycle (flexion phase) were used for further analyses. Then, for each vertebral angular motion curve with constant spatial peaks, different temporal patterns were simulated in two stages: (1) in lumbar pattern exchange (LPE), each vertebral angle was simulated by the corresponding vertebrae of other participants data; (2) in vertebral pattern exchange (VPE), vertebral angles were simulated by each other. The k‐mean algorithm was used to cluster two groups of variables; peak and cumulative IDP, in both stages of simulations (i.e., LPE and VPE). In the second stage of the simulation (VPE), Kendall's tau was utilized to consider the relationship between different temporal patterns and IDPs for each individual lumbar level. Cluster analyses showed that the temporal movement pattern did not exhibit any effect on the peak IDP while the cumulative IDP changed significantly for some patterns. Earlier involvement in lumbar motion at any level led to higher IDP in the majority of simulations. There is therefore a possibility of manipulating lumbar IDP by changing the temporal pattern with the same ROM, in which optimal distribution of the loads among lumbar levels may be applied as preventive or treatment interventions. Evaluating load benefits, such as load, on biomechanically relevant lumbar levels, dynamically measured by quantitative fluoroscopy, may help inform interventional exercises.
Activating Invasion and Metastasis in Small Cell Lung Cancer: Role of the Tumour Immune Microenvironment and Mechanisms of Vasculogenesis, Epithelial‐Mesenchymal Transition, Cell Migration, and Organ Tropism
Authors: He Carl
Published: October 2024

Background

Small cell lung cancer (SCLC) harbours the most aggressive phenotype of all lung cancers to correlate with its bleak prognosis. The aggression of SCLC is partially attributable to its strong metastatic tendencies. The biological processes facilitating the metastasis in SCLC are still poorly understood and garnering a deeper understanding of these processes may enable the exploration of additional targets against this cancer hallmark in the treatment of SCLC.

Recent Findings

This narrative review will discuss the proposed molecular mechanisms by which the cancer hallmark of activating invasion and metastasis is featured in SCLC through important steps of the metastatic pathway, and address the various molecular targets that may be considered for therapeutic intervention. The tumour immune microenvironment plays an important role in facilitating immunotherapy resistance, whilst the poor infiltration of natural killer cells in particular fosters a pro‐metastatic environment in SCLC. SCLC vasculogenesis is achieved through VEGF expression and vascular mimicry, and epithelial‐mesenchymal transition is facilitated by the expression of the transcriptional repressors of E‐cadherin, the suppression of the Notch signalling pathway and tumour heterogeneity. Nuclear factor I/B, selectin and B1 integrin hold important roles in SCLC migration, whilst various molecular markers are expressed by SCLC to assist organ‐specific homing during metastasis. The review will also discuss a recent article observing miR‐1 mRNA upregulation as a potential therapeutic option in targeting the metastatic activity of SCLC.

Conclusion

Treatment of SCLC remains a clinical challenge due to its recalcitrant and aggressive nature. Amongst the many hallmarks used by SCLC to enable its aggressive behaviour, that of its ability to invade surrounding tissue and metastasise is particularly notable and understanding the molecular mechanisms in SCLC metastasis can identify therapeutic targets to attenuate SCLC aggression and improve mortality.
Cytokine Release Syndrome Associated With Immune‐Modulating Chemotherapy: Potential Mitigating Role of Intravenous Omega‐3 Fatty Acid Triglycerides
Authors: Driscoll David F. , Bistrian Bruce R.
Published: October 2024

Background

Patient susceptibility to cytokine release syndrome (CRS) resulting from immune‐modulating chemotherapy has profound implications for clinical outcome. This is particularly true for patients receiving CAR T‐cell therapy. First‐line pharmacotherapy for CRS includes the administration of the IL‐6 receptor‐binding monoclonal antibody tocilizumab, or tocilizumab and corticosteroids. Other agents, such as siltuximab, anakinra, and dasatinab are also being explored for refractory cases of CRS. This review summarizes the potential role of omega‐3 fatty acids, that is, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) at ameliorating CRS in cancer patients receiving immune‐modulating chemotherapy, and is compared with current treatment strategies to reduce the severity of the inflammatory response.

Recent Findings

Selective blockade of specific proinflammatory mediators (e.g., IL‐6) is effective, but carries a significant risk of serious opportunistic infections. In contrast, omega‐3 fatty acids affect multiple triggers underlying the inflammatory response (i.e., prostaglandins, leukotrienes, transcription factors, and specialized proresolving molecules), and its major limitation is avoidance of hypertriglyceridemia, which can be managed by reducing the rate of intravenous administration. This discussion proposes a novel approach by continuous infusion of omega‐3 fatty acids to modulate the intensity of the severe systemic inflammatory response from CRS. The purpose of this review is to highlight the potential clinical benefits of a specialized omega‐3 fatty acids dosage form to mitigate the severity of CRS as a hypothetical alternative to current treatment.

Conclusion

Optimizing the formulation, for example, enriched fish oil that meets drug concentration standards for EPA and DHA, a continuous infusion rate, reductions in long‐chain saturated fatty acids concentrations, and addition of medium‐chain triglycerides to improve EPA + DHA utilization and physical stability are key pharmaceutical factors. This may result in a safer and more effective option than targeted abrogation of cytokines and consequent risks of adverse drug reactions, but will require formal study in randomized control trials in humans.
Factors Determining the Selectivity of NO Reduction Catalyzed by Copper‐Vanadium Oxide Cluster Anions Cu2VO3−5−
Authors: Wang Si‐Dun , Liu Yi , Ma Tong‐Mei , Li Xiao‐Na , He Sheng‐Gui
Published: October 2024

Catalytic NO reduction by CO is imperative to satisfy the increasingly rigorous emission regulations. Identifying the structural characteristic of crucial intermediate that governs the selectivity of NO reduction is pivotal to having a fundamental understanding on real‐life catalysis. Herein, benefiting from the state‐of‐the‐art mass spectrometry, we demonstrated experimentally that the Cu2VO3–5− clusters can mediate the catalysis of NO reduction by CO, and two competitive channels to generate N2O and N2 can co‐exist. Quantum‐chemical calculations were performed to rationalize this selectivity. The formation of the ONNO unit on the Cu2 dimer was demonstrated to be a precursor from which two pathways of NO reduction start to emerge. In the pathway of N2O generation, only the Cu2 dimer was oxidized and the VO3 moiety functions as a “support”, while both moieties have to contribute to anchor oxygen atoms from the ONNO unit and then N2 can be generated. This finding displays a clear picture to elucidate how and why the involvement of VO3 “support” can regulate the selectivity of NO reduction.
Temporal Directionality Between Symptoms During Treatment of Depressed Inpatients: A Dynamic Time Warp Network Analysis
Authors: Cocx‐Swiebel Daphne A. , van Son Gabrielle , Scheper Anita , Stuivenga Mirella , Sabbe Bernard , Hebbrecht Kaat , Giltay Erik J.
Published: October 2024

Background

Depression is generally perceived from the perspective of the common‐cause disease model. However, the network perspective assumes mutual influence of individual symptoms and stresses the importance of investigating symptom dynamics. Gaining a better understanding of symptom dynamics within individuals might contribute to more effective treatments.

Methods

Current exploratory longitudinal research studied the associations and directionality between 43 symptoms from the generic questionnaire Symptom Questionnaire‐48 (SQ‐48) using dynamic time warp (DTW) analyses, in which trajectories with similar time‐dependent patterns can be identified. Data from individuals were analysed first, yielding distance matrices for all symptom trajectories, after which the data were aggregated.

Results

The 148 included patients were all admitted for the treatment of their clinical depression. Undirected DTW analyses of three patients with longer time series but otherwise randomly chosen showed large variability among individuals. Group‐level undirected DTW analyses showed numerous significant edges between symptoms, largely clustering symptoms according to the eight pre‐existing subscales of the SQ‐48. Group‐level directed DTW analyses showed five symptoms with significant outstrength: ‘hopeless’, ‘restless’, ‘down/depressed’, ‘feeling tense’ and ‘no enjoyment’, meaning that change in these key symptoms preceded change in other symptoms.

Limitations

The 43 included symptoms of the SQ‐48 primarily focus on internalizing problems in severely depressed inpatients, potentially limiting generalizability.

Conclusions

DTW networks provided us with five key symptoms based on the dynamics of symptom scores. Future studies could explore whether process‐based therapy targeted at symptoms with high outstrength might result in more effectivity as part of personalized treatment.
Assessing Patient Satisfaction With Metacognitive Training (MCT) for Psychosis: A Systematic Review of Randomized Clinical Trials
Authors: Acuña Vanessa , Cavieres Álvaro , Arancibia Marcelo , Escobar Camila , Moritz Steffen , Gaweda Lukasz , Lamarca María , Berna Fabrice , König Caroline , Ochoa Susana
Published: October 2024

Objectives

Metacognitive training (MCT) for psychosis is a group intervention that combines cognitive‐behavioural therapy and psychoeducation. It has proven efficacy in reducing psychotic symptoms and correcting cognitive biases implicated in the development and maintenance of psychotic symptoms. However, other outcomes, such as patient satisfaction with the intervention, have not been well studied despite their importance for adherence and overall success. A systematic review of randomized clinical trials was conducted to assess satisfaction with MCT among adults with psychotic spectrum disorders.

Methods

The search was conducted in Ovid Embase, Ovid MEDLINE, PsycINFO and Cochrane Central Register of Controlled Trials (CENTRAL). PRISMA guidelines and the Cochrane Risk of Bias Tool were followed, and certainty of evidence was ascertained using the Grading of Recommendations Assessment, Development and Evaluation framework. The study is registered with PROSPERO (CRD42023418097).

Results

Patient satisfaction was considered the primary outcome in 3 of the 10 studies reviewed. Four studies compared MCT with other psychosocial interventions (a newspaper discussion group, cognitive remediation and supportive therapy), two of which found significantly higher satisfaction with MCT. A high percentage of all patients found MCT comprehensible and considered it an important part of their treatment; they would recommend the training to others and found the group setting advantageous. Most participants expressed high subjective satisfaction or acceptance of MCT.

Conclusions

The authors found evidence that MCT may be associated with high levels of satisfaction in clinical trials whose main objective is to assess patient satisfaction, but more research is needed to consolidate the findings, especially for the extended version of MCT.
Pathway‐Based Similarity Measurement to Quantify Transcriptomics Similarity Between Human Tissues and Preclinical Models
Authors: Parekh Paarth , Sherfey Jason , Alaybeyoglu Begum , Cirit Murat
Published: October 2024

Accurate clinical translation of preclinical research remains challenging, primarily due to species‐specific differences and disease and patient heterogeneity. An important recent advancement has been development of microphysiological systems that consist of multiple human cell types that recapitulate key characteristics of their respective human systems, allowing essential physiologic processes to be accurately assessed during drug development. However, an unmet need remains regarding a quantitative method to evaluate the similarity between diverse sample types for various contexts of use (CoU)‐specific pathways. To address this gap, this study describes the development of pathway‐based similarity measurement (PBSM), which leverages RNA‐seq data and pathway‐based information to assess the human relevance of preclinical models for specific CoU. PBSM offers a quantitative method to compare the transcriptomic similarity of preclinical models to human tissues, shown here as proof of concept for liver and cardiac tissues, enabling improved model selection and validation. Thus, PBSM can successfully support CoU selection for preclinical models, assess the impact of different gene sets on similarity calculations, and differentiate among various in vitro and in vivo models. PBSM has the potential to reduce the translational gap in drug development by allowing quantitative evaluation of the similarity of preclinical models to human tissues, facilitating model selection, and improving understanding of context‐specific applications. PBSM can serve as a foundation for enhancing the physiological relevance of in vitro models and supporting the development of more effective therapeutic interventions.
Luminescent Pentacene‐Loaded Carbon Nanodots with Red‐Light Triggered Photothermal and Photosensitizing Properties
Authors: Forte Giuseppe , Consoli Grazia M. L. , Ferreri Loredana , Maugeri Ludovica , Foti Alice , Satriano Cristina , Fangano Giorgia , Petralia Salvatore
Published: October 2024

The development of multifunctional nanosystems for photo‐induced hyperthermia and photodynamic effect is a challenging topic in the research of advanced materials for application in biomedical field. Here, we report red‐luminescent carbon‐nanodots (CDs‐PNM/PTC) derived from entrapment of pentacene (PTC) in nanodots prepared from poly(N‐isopropylacrylamide) polymer (CDs‐PNM) by an easy and reagent‐free method. The CD‐PNM/PTC nanosystem was characterized by different techniques (UV‐Vis spectrophotometry, fluorescence, NMR, AFM). Molecular modelling investigations were performed to unveil stability, structures and energy of the CD‐PNM/PTC supramolecular adducts at 298 K and 315 K. The nanosized CDs‐PNM/PTC exhibited excellent water‐dispersibility, good photothermal conversion efficiency and photosensitizing effect at 680 nm. No significant toxicity and eukaryotic cell uptake are features that open to potential applications in photothermal‐photodynamic treatments.
Antecedents and consequences of environmental, social, and governance: A bibliometric analysis based on the Web of Science database
Authors: Liu Manzhi , Lu Jia , Zhao Chen , Luo Jie , Liu Qiyao , Wang Hui , Fang Shuting , Yang Yaxin
Published: October 2024

Since the concept of environmental, social, and governance (ESG) was introduced in 2004, countries worldwide have been promoting sustainable ESG principles. Based on reviewing the literature in the field of ESG between 2006 and 2023, this paper analyses the concept of ESG, its theoretical perspectives and its research areas, and then systematically constructs a detailed architectural map of the development history of ESG and its impact. By sorting out the current status of cooperation and hot topics in the ESG literature, this paper comprehensively explores the latest progress of research in the field of ESG. The study finds that (1) the concept of ESG has been gradually integrated into corporate research and investment frameworks; (2) more than half of the research focus (58.55%) is on the field of business economics; (3) the most common keywords in the ESG literature include. “corporate social responsibility”, “impact”, “performance.”
Enhanced Methanol Electrooxidation and Supercapacitive Performance via Compositional Engineering of Colloidal Ni‐Co Alloying Nanoparticles
Authors: Li Junshan , Ma Yi , Yu Jing , Li Luming , Yang Honghui , Gu Wei , Shi Jiao , Wang Jun , Zhu Yongfa
Published: October 2024

Among renewable energy technologies, particular attention is paid to electrochemically transforming methanol into valuable formate and storing energy into supercapacitors. In this study, we detailed a simple colloidal‐based protocol for synthesizing a series of alloy nanoparticles with tuned Ni/Co atomic ratios, thereby optimizing their electrochemical performance. With the addition of 1 M methanol in 1 M KOH, the optimized composition was able to electrochemically produce formate at 0.149 mmol cm−2 h−1 with a Faradaic efficiency up to 95.1 % at 0.6 V versus Hg/HgO within a 22 h testing period. In 1 M KOH solution without methanol, the supercapacitive performance was achieved at a specific capacitance of over 1500 F g−1, and outstanding cycling stability with only approximately 20 % decay after continuous 10000 charging‐discharging cycles. These results underscore that the prepared Ni−Co alloy nanoparticles serve as multi‐functional electrodes for electrochemical energy conversion and storage, particularly in the MOR and supercapacitors applications.
Hydrogen‐Bond‐Assisted Electrocatalytic Semi‐Oxidation of 5‐Hydroxymethylfurfural into 2,5‐Diformylfuran by Operando Dissociated N‐Oxyl Mediator
Authors: Yin Ying , Lv Ximeng , Lv Zhuoran , Fang Lei , Fan Tao , Wang Man , Chen Ziyang , Lyu Naixin , Gou Gaozhang , Zhang Lijuan , Zheng Gengfeng , Li Liangchun
Published: October 2024

The conversion of 5‐hydroxymethylfurfural (HMF) to 2,5‐diformylfuran (DFF) is a promising approach for enhancing biomass utilization. Nevertheless, traditional methods using noble metal catalysts face challenges due to high costs and poor selectivity towards DFF. Herein, we developed a novel catalytic electrode integrating N‐hydroxyphthalimide (NHPI) into a metal‐organic framework on a hydrophilic carbon cloth. This design significantly enhances the selective adsorption of HMF due to stronger hydrogen‐bond interaction between the electrode's hydrophilic surface and the C(sp3)−OH group in HMF compared to the C(sp2)=O in DFF. Additionally, the electro‐driven dissociation of the NHPI‐linker generates stabilized N‐Oxyl radicals that promote selective semi‐oxidation of HMF under neutral conditions. As a result, this approach achieves a high yield rate of 138.2 mol molcat−1 h−1 with a selectivity of 96.7 % for the HMF‐to‐DFF conversion. This work introduces a novel strategy for designing catalytic electrodes with stabilized N‐Oxyl radicals, and offers a promising method for electrocatalytic DFF synthesis, leveraging hydrogen‐bond interaction between electrode surface and HMF.
State‐of‐the‐Art Light‐Driven Hydrogen Generation from Formic Acid and Utilization in Enzymatic Hydrogenations
Authors: Peng Yong , Sakoleva Thaleia , Rockstroh Nils , Bartling Stephan , Schoenmakers Pierre , Lim Guiyeoul , Wei Duo , Bayer Thomas , Dörr Mark , Böttcher Dominique , Lauterbach Lars , Junge Henrik , Bornscheuer Uwe T. , Beller Matthias
Published: October 2024

A concept of combining photocatalytically generated hydrogen with green enzymatic reductions is demonstrated. The developed photocatalytic formic acid (FA) dehydrogenation setup based on Pt(x)@TiO2 shows stable hydrogen generation activity, which is two orders of magnitude higher than reported values of state‐of‐the‐art systems. Mechanistic studies confirm that hydrogen generation proceeds via a photocatalytic pathway, which is entirely different from purely thermal reaction mechanisms previously reported. The viability of the presented approach is demonstrated by the synthesis of value‐added compounds 3‐phenylpropanal and (2R, 5S)‐dihydrocarvone at ambient pressure and room temperature, which should be applicable for many other hydrogenation processes, e. g., for the preparation of flavours and fragrance compounds, as well as pharmaceuticals.
Research on Cascaded On‐Board DC/DC Converter Based on Three‐Phase Interleaved LLC
Authors: Zhou Kai , Zheng Xu , Liu Yang
Published: October 2024

The on‐board DC/DC converter proposed in this research consists of a Buck converter and a three‐phase interleaved LLC resonant converter. This paper analyzes the average current and output current ripple characteristics of the rear‐stage converter in addition to explaining the topology and working principles of the front‐stage Buck converter and the rear‐stage three‐phase interleaved LLC resonant converter. To establish a single‐phase fundamental equivalent circuit for the rear‐stage converter, apply the fundamental wave analysis method, and it is essential for comprehending the impact of relevant system parameters on voltage gain characteristics and resonant operating regions. Conducting research on the two‐stage on‐board DC/DC converter's control strategy involves establishing small‐signal circuit models for both front and rear stage converters, derivation of parameters for double closed‐loop control, and determination of the control strategy employing phase‐shifted current sharing for the rear‐stage converter in cases where significant tolerance exists in resonant components. The simulation for a two‐stage on‐board DC/DC converter results indicates that under various conditions of resonant component tolerance, the converter is capable of achieving balanced phase currents and demonstrates minimal output current ripple prior to capacitor filtering. A 1.5‐kW experimental prototype has been fabricated, and the experimental findings indicate that the output voltage remains stable at 13.8 V despite fluctuations in input voltage. The highest efficiency of the prototype is about 96.27%, and the utilization of phase‐shifting current balancing control results in a notable reduction in output current ripple. This provides more evidence that the design of a two‐stage on‐board DC/DC converter is correct.
Developing messenger RNA biomarkers: A workflow to characterise and identify transcript target sequences unaffected by alternative splicing for reproducible gene transcript quantification by reverse transcriptase quantitative polymerase chain reaction
Authors: Padhi Bhaja Krushna , Pelletier Guillaume
Published: October 2024

Most eukaryotic genes generate multiple messenger RNA (mRNA) transcript variants by alternative splicing. The incomplete annotation of gene transcripts in genomic databases can result in improper primer design, adversely affecting the reliability of gene expression measurements by reverse transcriptase quantitative polymerase chain reaction (RT‐qPCR). Hence, we present a workflow combining bioinformatics analyses, to select two to three evolutionarily conserved constitutive exons in rats, mice and humans as target sequences for PCR primer design, with experimental RT‐PCR amplification and amplicon sequencing to confirm the expression and identity of gene transcript targets. The application of this workflow to the characterization of neurodevelopmental biomarker genes identified an unannotated exon in the rat Map2 gene, illustrating the importance of target sequence validation for the development of translational mRNA biomarkers for toxicological and biomedical studies.
Ganaxolone Therapy After Preterm Birth Restores Cerebellar Oligodendrocyte Maturation and Myelination in Guinea Pigs
Authors: Pavy Carlton L. , Shaw Julia C. , Dyson Rebecca M. , Palliser Hannah K. , Moloney Roisin A. , Sixtus Ryan P. , Berry Mary J. , Hirst Jonathan J.
Published: October 2024

The postnatal environment is challenging for the preterm neonate with exposure to hypoxic and excitotoxic events, amplified by premature loss of placentally derived neurosteroids. Between preterm birth and term equivalent age (TEA), cerebellar development continues despite these challenges. We hypothesize that neurosteroid replacement therapy during this time will support optimal cerebellar development. Guinea pig sows delivered at term (∼69 days gestation) or were induced to deliver preterm (∼62 days), with preterm pups receiving ganaxolone or vehicle until TEA. Postnatal assessments comprised salivary cortisol (corrected postnatal age [CPA] 0, 7, 38), behavioral analysis (CPA7, 38), and tissue collection (CPA0 and CPA40). Neurodevelopmental markers (MBP, Olig2, and NeuN) were assessed in the cerebellum by immunohistochemistry, whereas RT‐PCR was utilized to investigate key inhibitory/excitatory pathways and oligodendrocyte lineage markers. Following preterm birth, there was evidence of a hyperactive phenotype, increased salivary cortisol concentrations, and impaired myelination and oligodendrocyte maturation at the protein level. mRNA expressions of key inhibitory/excitatory pathways and myelin stability were also altered following preterm birth. Importantly, we showed that neurosteroid replacement therapy returns cerebellar development and behavior toward a term‐like phenotype. Therefore, ganaxolone may reduce the vulnerability of the cerebellum to postnatal challenges arising from preterm birth.
Safety and efficacy of up to 60 h of iv istaroxime in pre‐cardiogenic shock patients: Design of the SEISMiC trial
Authors: Biegus Jan , Mebazaa Alexander , Metra Marco , Pagnesi Matteo , Chioncel Ovidiu , Davison Beth , Filippatos Gerasimos , Tycińska Agnieszka , Novosadova Maria , Gulati Gaurav , Barros Marianela , Diaz Maria Luz , Guardia Carlos , Zymliński Robert , Gajewski Piotr , Ponikowski Piotr , Simmons Phillip , Simonson Steven , Cotter Gad
Published: October 2024

Aims

Cardiogenic shock (CS) is linked to high morbidity and mortality rates, posing a challenge for clinicians. Interventions to improve tissue perfusion and blood pressure are crucial to prevent further deterioration. Unfortunately, current inotropes, which act through adrenergic receptor stimulation, are associated with malignant arrhythmias and poorer outcomes. Due to its unique mechanism of action, istaroxime should improve haemodynamics without adrenergic overactivation. The SEISMiC study is designed to examine the safety and efficacy (haemodynamic effect) of istaroxime administrated in pre‐CS patients.

Methods and Results

The SEISMiC study is a multinational, multicentre, randomized, double‐blind, placebo‐controlled safety and efficacy study with two parts (A and B). The study enrols patients hospitalized for decompensated heart failure (pre‐CS, not related to myocardial ischaemia) with persistent hypotension [systolic blood pressure (SBP) 70–100 mmHg for at least 2 h] and clinically confirmed congestion, NT‐proBNP ≥1400 pg/mL, and LVEF≤40%. Subjects must not have taken intravenous (iv) vasopressors, inotropes or digoxin in the past 6 h. Eligible patients are randomized to receive IV infusion of istaroxime (different doses and regimens in Parts A and B) or placebo for up to 60 h. Central haemodynamics, ECG Holter monitoring, cardiac ultrasound and biomarkers are recorded at predefined time points during the trial. The study's primary efficacy endpoint is the SBP area under the curve from baseline curve from baseline to 6 and 24 h in the combined SEISMiC Parts A and B population. Key secondary efficacy endpoints include haemodynamic, laboratory and clinical measures in SEISMiC B alone in the combined SEISMiC A and B studies.

Conclusions

The study results will contribute to our understanding of the role of istaroxime in pre‐CS patients and potentially provide insight into the drug's haemodynamic effects and safety in this population.
Processing of Angelica (Angelica sylvestris L.) into a functional jam with addition of carob and cinnamon extracts: Evaluation of sensorial, physicochemical, and nutritional characteristics and in vitro bioaccessibility of phenolics
Authors: Koç Alibaşoğlu Elif , Acoğlu Çelik Büşra , Ceylan Fatma Duygu , Özoğlu Özüm , Bekar Ertürk , Çapanoğlu Esra , Tamer Canan Ece , Korukluoğlu Mihriban , Çopur Ömer Utku , Yolci Ömeroğlu Perihan
Published: October 2024

A traditional Angelica jam has been produced from stems of Angelica sylvestris L. growing at the foot of Mount Uludag in Bursa for many years. The aim of this study was to develop new functional formulations of Angelica jam by adding carob and cinnamon extracts, and to evaluate the effect of jam processing and the extracts' addition on the sensory attributes, physicochemical and nutritional characteristics of Angelica jams as well as in vitro bioavailability of phenolics. The main physicochemical properties of the jams including total water‐soluble dry matter (Brix value), pH, invert sugar content, total dietary fiber content, and 5‐(hydroxymethyl) furfural (HMF) ranged between 71.80–72.70 °Bx, 3.65–3.91, 39.30%–49.60%, 0.70–0.90 g/100 g, and 91.00–105.50 mg/kg, respectively. The most abundant minerals were potassium (K), calcium (Ca), magnesium (Mg), phosphorus (P), and iron (Fe) within a concentration range of 80.49–388.67 mg/kg, 111.10–135.00 mg/kg, 24.00–43.28 mg/kg, 7.57–28.06 mg/kg, and 0.52–1.14 mg/kg, respectively. Sensory analysis revealed that general acceptability of Angelica jams in a 9‐point hedonic scale was above 7. The highest antioxidant capacity values of Angelica jam and its functional forms fortified with carob and cinnamon extracts were obtained as 96.68 ± 11.30 mg TE/100 g DM, 248.49 ± 17.78 mg TE/100 g DM, and 193.11 ± 16.06 mg TE/100 g DM, respectively, with the ABTS (2,2′‐azino‐bis‐3‐ethylbenzothiazoline‐6‐sulfonic acid) method. It was observed that the main phenolic compound of the jams was caffeic acid. Depending on the type of extract added into the formulations, trans‐cinnamic acid and gallic acid (GA) became predominant phenolics. Total antioxidant capacity (TAC) of Angelica sylvestris stem decreased by 72%–85% with the heat treatment applied during jam processing. While total phenolic content (TPC) and total antioxidant capacity (measured by the DPPH (1,1‐diphenyl‐2‐picrylhydrazyl) method) increased as a result of intestinal digestion of the jam, it was observed that bioaccessibility of most of the phenolic compounds decreased after intestinal digestion of the jams.
Encapsulation of Curcumin With Persian Gum and Its Application to the Production of Functional Yogurt: Physicochemical, Antioxidant, Sensory Properties, and Starter Bacteria Survival Study
Authors: Taghadosi Maziar , Bolandi Marzieh , Baghaei Homa
Published: October 2024

This study aimed to evaluate the ability of Persian gum to encapsulate curcumin and enhance its stability in dairy products. Given the increasing interest in functional foods, this study investigated the incorporation of nanocapsules containing curcumin (CLN) into functional stirred yogurt (CLN‐Y). CLN was prepared with Persian gum (PG) at different levels and included in the yogurt formula (CLN‐Y1%, CLN‐Y2%, and CLN‐Y3%). The physicochemical properties, rheological characteristics, antioxidant activity (AA), survival of starter bacteria, and sensory properties of the yogurt were evaluated over a 21‐day storage period at 4°C. The results showed that CLN significantly improved AA (reduction of 7.31% in the control vs. 1.85% in CLN‐Y3%), viscosity, hardness, and water holding capacity (reduction of 2.27% in control vs. 1.14% in CLN‐Y3%), while reducing syneresis (an increase of 10.87% in control vs. 3.16% in CLN‐Y3%) during storage (p < 0.05). CLN concentration directly affected AA. Although CLN‐Y exhibited a yellowish color and lower light intensity than the control, the samples were well accepted during storage. Increasing CLN levels led to decreased taste, color, and overall acceptance scores, and a 3% concentration is recommended for yogurt formulation due to its potential to improve yogurt quality, provide antioxidant benefits, maintain probiotic viability, and achieve high consumer acceptance during storage.
The cumulative impact of clinical risk on brain networks and associations with executive function impairments in adolescents with congenital heart disease
Authors: Ehrler Melanie , Speckert Anna , Kretschmar Oliver , Tuura O'Gorman Ruth , Latal Beatrice , Jakab Andras
Published: October 2024

Patients with congenital heart disease (CHD) demonstrate altered structural brain network connectivity. However, there is large variability between reported results and little information is available to identify those patients at highest risk for brain alterations. Thus, we aimed to investigate if network connectivity measures were associated with the individual patient's cumulative load of clinical risk factors and with family‐environmental factors in a cohort of adolescents with CHD. Further, we investigated associations with executive function impairments. In 53 adolescents with CHD who underwent open‐heart surgery during infancy, and 75 healthy controls, diffusion magnetic resonance imaging and neuropsychological assessment was conducted at a mean age of 13.2 ± 1.3 years. Structural connectomes were constructed using constrained spherical deconvolution tractography. Graph theory and network‐based statistics were applied to investigate network connectivity measures. A cumulative clinical risk (CCR) score was built by summing up binary risk factors (neonatal, cardiac, neurologic) based on clinically relevant thresholds. The role of family‐environmental factors (parental education, parental mental health, and family function) was investigated. An age‐adjusted executive function summary score was built from nine neuropsychological tests. While network integration and segregation were preserved in adolescents with CHD, they showed lower edge strength in a dense subnetwork. A higher CCR score was associated with lower network segregation, edge strength, and executive function performance. Edge strength was particularly reduced in a subnetwork including inter‐frontal and fronto‐parietal‐thalamic connections. There was no association with family‐environmental factors. Poorer executive functioning was associated with lower network integration and segregation. We demonstrated evidence for alterations of network connectivity strength in adolescents with CHD — particularly in those patients who face a cumulative exposure to multiple clinical risk factors over time. Quantifying the cumulative load of risk early in life may help to better predict trajectories of brain development in order to identify and support the most vulnerable patients as early as possible.
Combined inhibition of CTPS1 and ATR is a metabolic vulnerability in p53‐deficient myeloma cells
Authors: Durand Romane , Bellanger Céline , Descamps Géraldine , Dousset Christelle , Maïga Sophie , Derrien Jennifer , Thirouard Laura , Bouard Louise , Asnagli Hélène , Beer Philip , Parker Andrew , Gomez‐Bougie Patricia , Devilder Marie‐Claire , Moreau Philippe , Touzeau Cyrille , Moreau‐Aubry Agnès , Chiron David , Pellat‐Deceunynck Catherine
Published: October 2024

In multiple myeloma, as in B‐cell malignancies, mono‐ and especially bi‐allelic TP53 gene inactivation is a high‐risk factor for treatment resistance, and there are currently no therapies specifically targeting p53 deficiency. In this study, we evaluated if the loss of cell cycle control in p53‐deficient myeloma cells would confer a metabolically actionable vulnerability. We show that CTP synthase 1 (CTPS1), which encodes a CTP synthesis rate‐limiting enzyme essential for DNA and RNA synthesis in lymphoid cells, is overexpressed in samples from myeloma patients displaying a high proliferation rate (high MKI67 expression) or a low p53 score (synonymous with TP53 deletion and/or mutation). This overexpression of CTPS1 was associated with reduced survival in two cohorts. Using scRNA‐seq analysis in 24 patient samples, we further demonstrate that myeloma cells in the S or G2/M phase display high CTPS1 expression. Pharmacological inhibition of CTPS1 by STP‐B induced cell cycle arrest in early S phase in isogenic NCI‐H929 or XG7 TP53+/+, TP53−/−, and TP53R175H/R175H cells and in a TP53−/R123STOP patient sample. The functional annotation of transcriptional changes in 10 STP‐B‐treated myeloma cell lines revealed a decrease in protein translation and confirmed the blockade of cells into the S phase. The pharmacological inhibition of ATR, which governs the intrinsic S/G2 checkpoint, in STP‐B‐induced S‐phase arrested cells synergistically induced cell death in TP53+/+, TP53−/−, and TP53R175H/R175H isogenic cell lines (Bliss score >15). This combination induced replicative stress and caspase‐mediated cell death and was highly effective in resistant/refractory patient samples with TP53 deletion and/or mutation and in TP53−/− NCI‐H929 xenografted NOD‐scid IL2Rgamma mice. Our in vitro, ex vivo, and in vivo data provide the rationale for combined CTPS1 and ATR inhibition for the treatment of p53‐deficient patients.
Adult Neurogenesis and the Initiation of Social Aggression in Male Mice
Authors: Tsuda Mumeko C. , Akoh‐Arrey Talia , Mercurio Jeffrey C. , Rucker Ariana , Airey Megan L. , Jacobs Hannah , Lukasz Daria , Wang Lijing , Cameron Heather A.
Published: October 2024

The hippocampus is important for social behavior and exhibits unusual structural plasticity in the form of continued production of new granule neurons throughout adulthood, but it is unclear how adult neurogenesis contributes to social interactions. In the present study, we suppressed neurogenesis using a pharmacogenetic mouse model and examined social investigation and aggression in adult male mice to investigate the role of hippocampal adult‐born neurons in the expression of aggressive behavior. In simultaneous choice tests with stimulus mice placed in corrals, mice with complete suppression of adult neurogenesis in adulthood (TK mice) exhibited normal social investigation behaviors, indicating that new neurons are not required for social interest, social memory, or detection of and response to social olfactory signals. However, mice with suppressed neurogenesis displayed decreased offensive and defensive aggression in a resident‐intruder paradigm, and less resistance in a social dominance test, relative to neurogenesis‐intact controls, when paired with weight and strain‐matched (CD‐1) mice. During aggression tests, TK mice were frequently attacked by the CD‐1 intruder mice, which never occurred with WTs, and normal CD‐1 male mice investigated TK mice less than controls when corralled in the social investigation test. Importantly, TK mice showed normal aggression toward prey (crickets) and smaller, nonaggressive (olfactory bulbectomized) C57BL/6J intruders, suggesting that mice lacking adult neurogenesis do not avoid aggressive social interactions if they are much larger than their opponent and will clearly win. Taken together, our findings show that adult hippocampal neurogenesis plays an important role in the instigation of intermale aggression, possibly by weighting a cost–benefit analysis against confrontation in cases where the outcome of the fight is not clear.