bluuebunny/crossref_metadata_2025 huggingface dataset:
The contribution of carbon budget to masting intervals in Veratrum album populations inhabiting different elevations
Authors: Ito Yohei , Kudo Gaku
Published: February 2024

Premise

Mast flowering/seeding is often more extreme in lower‐resource environments, such as alpine compared to lowland habitats. We studied a masting herb that had less extreme masting at higher elevations, and tested if this difference could be explained by higher photosynthetic productivity and/or lower reproductive investment at the higher‐elevation sites.

Methods

We examined the relationship between flowering intervals and carbon budget (i.e., the balance between reproductive investment and annual carbon fixation) in a masting herb, Veratrum album subsp. oxysepalum, across five lowland and six alpine populations in northern Japan. We evaluated the previous flowering histories of individual plants based on rhizome morphology and analyzed the masting patterns of individual populations. Total mass of the reproductive organs, as a proxy of reproductive investment, was compared between the lowland and alpine populations. Annual carbon fixation was estimated on the basis of photosynthetic capacity, total leaf area per plant, and seasonal transition of light availability.

Results

Interval between high‐flowering years was shorter and total reproductive investment was smaller in the alpine than in the lowland populations. Owing to its high photosynthetic capacity and continuous bright conditions, annual carbon fixation per plant was 1.5 times greater in alpine habitat than in lowland habitat. These results suggest that V. album alpine populations have shorter flowering intervals than lowland populations due to faster recovery from energy loss after reproduction.

Conclusions

Our study demonstrated that masting intervals in V. album populations can be explained by habitat‐specific carbon budget balances.
Visible–Light–Induced Phosphorylation Reaction of α‐Diazoesters with H‐Phosphine Oxides to Construct (Z)‐Phosphinic Hydrazones
Authors: Feng Yaping , Ding Hongyu , Liu Ruisheng , Wei Wei , Nan Guangming , Yi Dong
Published: February 2024

A convenient visible–light–promoted phosphorylation reaction of α‐diazoesters with H‐phosphine oxides for the preparation of (Z)‐phosphinic hydrazones has been explored. This reaction could be performed under mild conditions to afford a series of (Z)‐phosphinic hydrazones in moderate to good yields through photoisomerization of C=N bond.
Diet, Pace of Biological Aging, and Risk of Dementia in the Framingham Heart Study
Authors: Thomas Aline , Ryan Calen P. , Caspi Avshalom , Liu Zhonghua , Moffitt Terrie E. , Sugden Karen , Zhou Jiayi , Belsky Daniel W. , Gu Yian
Published: February 2024

Objective

People who eat healthier diets are less likely to develop dementia, but the biological mechanism of this protection is not well understood. We tested the hypothesis that healthy diet protects against dementia because it slows the pace of biological aging.

Methods

We analyzed Framingham Offspring Cohort data. We included participants ≥60 years‐old, free of dementia and having dietary, epigenetic, and follow‐up data. We assessed healthy diet as long‐term adherence to the Mediterranean‐Dash Intervention for Neurodegenerative Delay diet (MIND, over 4 visits spanning 1991–2008). We measured the pace of aging from blood DNA methylation data collected in 2005–2008 using the DunedinPACE epigenetic clock. Incident dementia and mortality were defined using study records compiled from 2005 to 2008 visit through 2018.

Results

Of n = 1,644 included participants (mean age 69.6, 54% female), n = 140 developed dementia and n = 471 died over 14 years of follow‐up. Greater MIND score was associated with slower DunedinPACE and reduced risks for dementia and mortality. Slower DunedinPACE was associated with reduced risks for dementia and mortality. In mediation analysis, slower DunedinPACE accounted for 27% of the diet‐dementia association and 57% of the diet‐mortality association.

Interpretation

Findings suggest that slower pace of aging mediates part of the relationship of healthy diet with reduced dementia risk. Monitoring pace of aging may inform dementia prevention. However, a large fraction of the diet‐dementia association remains unexplained and may reflect direct connections between diet and brain aging that do not overlap other organ systems. Investigation of brain‐specific mechanisms in well‐designed mediation studies is warranted. ANN NEUROL 2024;95:1069–1079
Diastereoselective Hydrogenation of Tetrasubstituted Olefins using a Heterogeneous Pt‐Ni Alloy Catalyst
Authors: Swann William A. , Yadav Anish , Colvin Nicholas B. , Freundl Nicole K. , Li Christina W.
Published: February 2024

Stereoselective hydrogenation of tetrasubstituted olefins is an attractive method to access compounds with two contiguous stereocenters. However, homogeneous catalysts for enantio‐ and diastereoselective hydrogenation exhibit low reactivity toward tetrasubstituted olefins due to steric crowding between the ligand scaffold and the substrate. Monometallic heterogeneous catalysts, on the other hand, provide accessible surface active sites for hindered olefins but exhibit unpredictable and inconsistent stereoinduction. In this work, we develop a Pt−Ni bimetallic alloy catalyst that can diastereoselectively hydrogenate unactivated, sterically‐bulky tetrasubstituted olefins, utilizing the more oxophilic Ni atoms to adsorb a hydroxyl directing group and direct facially‐selective hydrogen addition to the olefin via the Pt atoms. Structure‐activity studies on several Pt−Ni compositions underscore the importance of exposing a uniform PtNi alloy surface to achieve high diastereoselectivity and minimize side reactions. The optimized Pt−Ni/SiO2 catalyst exhibits good functional group tolerance and broad scope for tetrasubstituted olefins in a cyclopentene scaffold, generating cyclopentanol products with three contiguous stereocenters. The synthetic utility of the method is demonstrated in a four‐step synthesis of (1R,2S)‐(+)‐cis‐methyldihydrojasmonate with high yield and enantiopurity.
Mechanistic Understanding of Oxygen Activation on Bulk Au(111) Surface Using Tip‐Enhanced Raman Spectroscopy
Authors: Cai Zhen‐Feng , Tang Zi‐Xi , Zhang Yao , Kumar Naresh
Published: February 2024

Gaining mechanistic understanding of oxygen activation on metal surfaces is a topical area of research in surface science. However, direct investigation of on‐surface oxidation processes at the nanoscale and the empirical validation of oxygen activation pathways remain challenging for the conventional analytical tools. In this study, we applied tip‐enhanced Raman spectroscopy (TERS) to gain mechanistic insights into oxygen activation on bulk Au(111) surface. Specifically, oxidation of 4‐aminothiophenol (4‐ATP) to 4‐nitrothiophenol (4‐NTP) on Au(111) surface was investigated using hyperspectral TERS imaging. Nanoscale TERS images revealed a markedly higher oxidation efficiency in disordered 4‐ATP adlayers compared to the ordered adlayers signifying that the oxidation of 4‐ATP molecules proceeds via interaction with the on‐surface oxidative species. These results were further validated via direct oxidation of the 4‐ATP adlayers with H2O2 solution. Finally, TERS measurements of oxidized 4‐ATP adlayers in the presence of H2O18 provided the first empirical evidence for the generation of oxidative species on bulk Au(111) surface via water‐mediated activation of molecular oxygen. This study expands our mechanistic understanding of oxidation chemistry on bulk Au surface by elucidating the oxygen activation pathway.
Triazine Frameworks for the Photocatalytic Selective Oxidation of Toluene
Authors: Li Sizhe , Huber Niklas , Huang Wei , Wei Wenxin , Landfester Katharina , Ferguson Calum T. J. , Zhao Yan , Zhang Kai A. I.
Published: February 2024

Investigations into the selective oxidation of inert sp3 C−H bonds using polymer photocatalysts under mild conditions have been limited. Additionally, the structure‐activity relationship of photocatalysts often remains insufficiently explored. Here, a series of thiophene‐based covalent triazine frameworks (CTFs) are used for the efficient and selective oxidation of hydrocarbons to aldehydes or ketones under ambient aerobic conditions. Spectroscopic methods conducted in situ and density functional theory (DFT) calculations revealed that the sulfur atoms within the thiophene units play a pivotal role as oxidation sites due to the generation of photogenerated holes. The effect of photogenerated holes on photocatalytic toluene oxidation was investigated by varying the length of the spacer in a CTF donor‐acceptor based photocatalyst. Furthermore, the manipulation of reactive oxygen species was employed to enhance selectivity by weakening the peroxidative capacity. As an illustrative example, this study successfully demonstrated the synthesis of a precursor of the neurological drug AMG‐579 using a photocatalytic protocol.
Heteroatom‐Doped Ag25 Nanoclusters Encapsulated in Metal–Organic Frameworks for Photocatalytic Hydrogen Production
Authors: Wang He , Zhang Xiyuan , Zhang Wei , Zhou Meng , Jiang Hai‐Long
Published: February 2024

Atomically precise metal nanoclusters (NCs) with unique optical properties and abundant catalytic sites are promising in photocatalysis. However, their light‐induced instability and the difficulty of utilizing the photogenerated carriers for photocatalysis pose significant challenges. Here, MAg24 (M=Ag, Pd, Pt, and Au) NCs doped with diverse single heteroatoms have been encapsulated in a metal–organic framework (MOF), UiO‐66‐NH2, affording MAg24@UiO‐66‐NH2. Strikingly, compared with Ag25@UiO‐66‐NH2, the MAg24@UiO‐66‐NH2 doped with heteroatom exhibits much enhanced activity in photocatalytic hydrogen production, among which AuAg24@UiO‐66‐NH2 presents the best activity up to 3.6 mmol g−1 h−1, far superior to all other counterparts. Moreover, they display excellent photocatalytic recyclability and stability. X‐ray photoelectron spectroscopy and ultrafast transient absorption spectroscopy demonstrate that MAg24 NCs encapsulated into the MOF create a favorable charge transfer pathway, similar to a Z‐scheme heterojunction, when exposed to visible light. This promotes charge separation, along with optimized Ag electronic state, which are responsible for the superior activity in photocatalytic hydrogen production.
Discriminating the Active Ru Species Towards the Selective Generation of Singlet Oxygen from Peroxymonosulfate: Nanoparticles Surpass Single‐Atom Catalysts
Authors: Bi Guangyu , Ding Rongrong , Song Junsheng , Luo Mengjie , Zhang Haotian , Liu Meng , Huang Dahong , Mu Yang
Published: February 2024

Singlet oxygen (1O2) is an exceptional reactive oxygen species in advanced oxidation processes for environmental remediation. Despite single‐atom catalysts (SACs) representing the promising candidate for the selective generation of 1O2 from peroxymonosulfate (PMS), the necessity to meticulously regulate the coordination environment of metal centers poses a significant challenge in the precisely‐controlled synthetic method. Another dilemma to SACs is their high surface free energy, which results in an inherent tendency for the surface migration and aggregation of metal atoms. We here for the first time reported that Ru nanoparticles (NPs) synthesized by the facile pyrolysis method behave as robust Fenton‐like catalysts, outperforming Ru SACs, towards efficient activation of PMS to produce 1O2 with nearly 100 % selectivity, remarkably improving the degradation efficiency for target pollutants. Density functional theory calculations have unveiled that the boosted PMS activation can be attributed to two aspects: (i) enhanced adsorption of PMS molecules onto Ru NPs, and (ii) decreased energy barriers by offering adjacent sites for promoted dimerization of *O intermediates into adsorbed 1O2. This study deepens the current understanding of PMS chemistry, and sheds light on the design and optimization of Fenton‐like catalysts.
Hierarchically Responsive Alternating Nano‐Copolymers with Tailored Interparticle Bonds
Authors: He Huibin , Shen Xiaoxue , Yao Chongyang , Tao Jing , Chen Wenwen , Nie Zhihong , Wu Yue , Dai Liwei , Sang Yutao
Published: February 2024

Self‐assembly of inorganic nanoparticles (NPs) is an essential tool for constructing structured materials with a wide range of applications. However, achieving ordered assembly structures with externally programmable properties in binary NP systems remains challenging. In this work, we assemble binary inorganic NPs into hierarchically pH‐responsive alternating copolymer‐like nanostructures in an aqueous medium by engineering the interparticle electrostatic interactions. The polymer‐grafted NPs bearing opposite charges are viewed as nanoscale monomers (“nanomers”), and copolymerized into alternating nano‐copolymers (ANCPs) driven by the formation of interparticle “bonds” between nanomers. The resulting ANCPs exhibit reversibly responsive “bond” length (i.e., the distance between nanomers) in response to the variation of pH in a range of ~7–10, allowing precise control over the surface plasmon resonance of ANCPs. Moreover, specific interparticle “bonds” can break up at pH≥11, leading to the dis‐assembly of ANCPs into molecule‐like dimers and trimers. These dimeric and trimeric structures can reassemble to form ANCPs owing to the resuming of interparticle “bonds”, when the pH value of the solution changes from 11 to 7. The hierarchically responsive nanostructures may find applications in such as biosensing, optical waveguide, and electronic devices.
Portably and Visually Sensing Cytisine through Smartphone Scanning Based on a Post‐Modified Luminescence Center Strategy in Zinc‐Organic Frameworks
Authors: Li Xiang‐Shuai , Zhao Jian , Jiao Zhuo‐Hao , Zhao Xin‐Yuan , Hou Sheng‐Li , Zhao Bin
Published: February 2024

Cytisine (CTS) is a useful medicine for treating nervous disorders and smoking addiction, and exploring a convenient method to detect CTS is of great significance for long‐term/home medication to avoid the risk of poisoning, but it is full of challenges. Here, a modified metal–organic framework sensor Tb@Zn‐TDA‐80 with dual emission centers was prepared using a post‐modified luminescence center strategy. The obtained Tb@Zn‐TDA‐80 can serve as a CTS sensor with high sensitivity and selectivity. To achieve portable detection, Tb@Zn‐TDA‐80 was further fabricated as a membrane sensor, M−Tb@Zn‐TDA‐80, which displayed an obvious CTS‐responsive color change by simply dropping a CTS solution onto its surface. Benefiting from this unique functionality, M−Tb@Zn‐TDA‐80 successfully realized the visual detection and quantitative monitoring of CTS in the range of 5.26–52.6 mM by simply scanning the color with a smartphone. The results of nuclear magnetic resonance spectroscopy and theoretical computation illustrated that the high sensing efficiency of Tb@Zn‐TDA‐80 for CTS was attributed to the N−H⋅⋅⋅π and π⋅⋅⋅π interactions between the ligand and CTS. And luminescence quenching may result from the intramolecular charge transfer. This study provides a convenient method for ensuring long‐term medication safety at home.
Effect of Intrinsic Ferroelectric Phase Transition on Hydrogen Evolution Electrocatalysis
Authors: Wang Fengmei , Ju Lin , Wu Binglan , Li Shuhui , Peng Jian , Chen Yetao , Getaye Sendeku Marshet , Wang Kairui , Cai Yuchen , Yi Jun , Yang Ying , Wang Zhenxing , Sun Xiaoming
Published: February 2024

Heterogeneous electrocatalysis closely relies on the electronic structure of the catalytic materials. The ferroelectric‐to‐paraelectric phase transition of the materials also involves a change in the state of electrons that could impact the electrocatalytic activity, but such correlation remains unexplored. Here, we demonstrate experimentally and theoretically that the intrinsic electrocatalytic activity could be regulated as exampled by hydrogen evolution reaction catalysis over two‐dimensional ferroelectric CuInP2S6. The obvious discontinuity in the overpotential and apparent activation energy values for CuInP2S6 electrode are illustrated during the ferroelectric‐to‐paraelectric phase transition caused by copper displacement around Tc point (318 K), revealing the ferroelectro‐catalytic effect on thermodynamics and kinetics of electrocatalysis. When loading Pt single atom on the CuInP2S6, the paraelectric phase one showed an improved hydrogen evolution activity with smaller apparent activation energy over the ferroelectric phase counterpart. This is attributed to the copper hopping between two sulfur planes, which alternate between strong and weak H adsorption at the Pt sites to simultaneously promote H+ reactant adsorption and H2 product desorption.
Catechol‐Siderophore Mimics Convey Nucleic Acid Therapeutics into Bacteria
Authors: Pals Mathijs J. , Wijnberg Luuk , Yildiz Çağlar , Velema Willem A.
Published: February 2024

Antibacterial resistance is a major threat for human health. There is a need for new antibacterials to stay ahead of constantly‐evolving resistant bacteria. Nucleic acid therapeutics hold promise as powerful antibiotics, but issues with their delivery hamper their applicability. Here, we exploit the siderophore‐mediated iron uptake pathway to efficiently transport antisense oligomers into bacteria. We appended a synthetic siderophore to antisense oligomers targeting the essential acpP gene in Escherichia coli. Siderophore‐conjugated PNA and PMO antisense oligomers displayed potent antibacterial properties. Conjugates bearing a minimal siderophore consisting of a mono‐catechol group showed equally effective. Targeting the lacZ transcript resulted in dose‐dependent decreased β‐galactosidase production, demonstrating selective protein downregulation. Applying this concept to Acinetobacter baumannii also showed concentration‐dependent growth inhibition. Whole‐genome sequencing of resistant mutants and competition experiments with the endogenous siderophore verified selective uptake through the siderophore‐mediated iron uptake pathway. Lastly, no toxicity towards mammalian cells was found. Collectively, we demonstrate for the first time that large nucleic acid therapeutics can be efficiently transported into bacteria using synthetic siderophore mimics.
Encephaloduroarteriosynangiosis Procedure: A Treatment Option for Patients With Moyamoya Disease
Authors: Karasin Beth , Boyce Marissa , Kleban Monica , Hancock Jonathan , Rizzo Gina , Hardinge Tara , Eskuchen Lauren , Watkinson Johanna , Gold Elizabeth
Published: February 2024

Moyamoya disease is a progressive cerebrovascular disorder for which there is no cure. It is characterized by narrowing of and occlusions in the blood vessels that supply the brain, which causes a fine vascular network to develop to serve as collateral pathways. Moyamoya disease can lead to a reduction of blood flow to the brain and increase the risk of stroke. Patients with moyamoya disease may present with ischemic or hemorrhagic complications. Treatment options may involve medical management or surgical revascularization (indirect, direct, or a combined approach). The encephaloduroarteriosynangiosis procedure is a form of indirect revascularization in which a portion of the superficial temporal artery is moved from the scalp to the brain surface. Regardless of the approach, the goal of revascularization is to improve blood flow to the affected area to prevent additional infarcts; the encephaloduroarteriosynangiosis procedure is a viable option to help prevent additional neurologic decline.
Clinical Issues — March 2024
Authors: Jones Emily
Published: February 2024

THIS MONTH

Exoskeleton use in the OR

Key words: exoskeleton, exosuit, ergonomics, musculoskeletal injury, fatigue and pain.

The Revised National Institute for Occupational Safety and Health Lifting Equation

Key words: ergonomic risk, Revised NIOSH Lifting Equation (RNLE), lifting index (LI), load, lifting task.

Surgical smoke safety during transurethral resection of the prostate procedures

Key words: surgical smoke, smoke evacuation, transurethral resection of the prostate (TURP), vaporization, resectoscope.

Preventing accidental dislodgement of tubes, drains, and catheters

Key words: patient transfer, dislodgement, catheters, tubes, drains.
Using disposable food packaging materials as printing, embedding, and sectioning media in the plant anatomy lab
Authors: Angeles Guillermo , Madero‐Vega Carolina
Published: February 2024

Premise

During the COVID‐19 pandemic lockdown, all laboratory work was suspended, and we were obliged to work from home, causing delays in our research. As the disruption to supply chains made it difficult to obtain our regular lab supplies, we were obliged to search for substitutes. We became familiar with a plastic material known as biaxially oriented polypropylene (BOPP) that is widely used in the food industry for wrapping or storing fruits, vegetables, and meat. BOPP is easily dissolved in organic solvents such as xylenes, acetone, or thinner, but these reagents are very toxic, flammable, and can cause nausea in some users. After testing several alternatives, we found a polyurethane remover that proved to be an effective and relatively harmless BOPP solvent.

Methods and Results

By dissolving thin slices of BOPP in a polyurethane solvent, we obtained a clean fluid that we used to obtain leaf surface prints that could be mounted on microscope slides with a coverslip. This fluid produced excellent bark and wood sections and can be used to obtain wood or charcoal surface prints. Our attempts to use it as a mounting medium were unsuccessful.

Conclusions

BOPP dissolved in a polyurethane remover is a handy, versatile resource for plant microtechniques. In addition to its economic advantages, it is useful in terms of reducing plastic pollution.
A Computational Perspective on the Reactivity of π‐spacers in Self‐Immolative Elimination Reactions
Authors: Padula Daniele
Published: February 2024

The controlled release of chemicals, especially in drug delivery, is crucial, often employing “self–immolative” spacers to enhance reliability. These spacers separate the payload from the protecting group, ensuring a more controlled release. Over the years, design rules have been proposed to improve the elimination process's reaction rate by modifying spacers with electron–donating groups or reducing their aromaticity. The spacer design is critical for determining the range of functional groups released during this process. This study explores various strategies from the literature aimed at improving release rates, focusing on the electronic nature of the spacer, its aromaticity, the electronic nature of its substituents, and the leaving groups involved in the elimination reaction. Through computational analysis, I investigate activation free energies by identifying transition states for model reactions. My calculations align qualitatively with experimental results, demonstrating the feasibility and reliability of computationally pre–screening model self–immolative eliminations. This approach allows proposing optimal combinations of spacer and leaving group for achieving the highest possible release rate.
Stimuli‐triggered Self‐Assembly of Gold Nanoparticles: Recent Advances in Fabrication and Biomedical Applications
Authors: Zhao Yan , Cui Chaoxiang , Fan Guohua , Shi Haibin
Published: February 2024

Gold nanoparticles have been widely used in engineering, material chemistry, and biomedical applications owing to their ease of synthesis and functionalization, localized surface plasmon resonance (LSPR), great chemical stability, excellent biocompatibility, tunable optical and electronic property. In recent years, the decoration and modification of gold nanoparticles with small molecules, ligands, surfactants, peptides, DNA/RNA, and proteins have been systematically studied. In this review, we summarize the recent approaches on stimuli‐triggered self‐assembly of gold nanoparticles and introduce the breakthrough of gold nanoparticles in disease diagnosis and treatment. Finally, we discuss the current challenge and future prospective of stimuli‐responsive gold nanoparticles for biomedical applications.
Interdependencies in Electrode Manufacturing: A Comprehensive Study Based on Design Augmentation and Explainable Machine Learning
Authors: Haghi Sajedeh , Chen Yao , Molzberger Annika , Daub Rüdiger
Published: February 2024

Electrode manufacturing, as the core of battery cell production, is a complex process chain with a large number of interrelated parameters. An in‐depth understanding of the processes, their relevant parameters, and the resulting effects on intermediate and final product properties can accelerate the transition toward quality‐oriented, efficient battery cell production. Given the complexity of the process chain, data‐driven models have emerged as promising solutions for analyzing the existing interdependencies. The accuracy and effectiveness of these models significantly depend on the quality and comprehensiveness of the underlying data. With a low‐quality dataset, there is an increased risk of drawing inaccurate conclusions or generating misleading results. This article aimed to demonstrate a use case for the evaluation and enhancement of historical datasets to provide a statistically robust foundation for the development of machine learning models. The study was based on pilot‐scale anode manufacturing and covered variations in the coating, drying, and calendering processes. The key intermediate product and process parameters were used to predict two primary target variables: adhesion strength and discharge capacity at different C‐rates. To gain a better understanding of the analyzed interdependencies, explainable machine learning methods were adopted.
Epistemic misalignments in microbiome research
Authors: Boem Federico , Suárez Javier
Published: February 2024

We argue that microbiome research should be more reflective on the methods that it relies on to build its datasets due to the danger of facing a methodological problem which we call “epistemic misalignment.” An epistemic misalignment occurs when the method used to answer specific scientific questions does not track justified answers, due to the material constraints imposed by the very method. For example, relying on 16S rRNA to answer questions about the function of the microbiome generates epistemic misalignments, due to the different temporal scales that 16S rRNA provides information about and the temporal scales that are required to know about the functionality of some microorganisms. We show how some of these exist in contemporary microbiome science and urge microbiome scientists to take some measures to avoid them, as they may question the credibility of the field as a whole.
Nonparametric analysis of delayed treatment effects using single‐crossing constraints
Authors: Henderson Nicholas C. , Nam Kijoeng , Feng Dai
Published: February 2024

Clinical trials involving novel immuno‐oncology therapies frequently exhibit survival profiles which violate the proportional hazards assumption due to a delay in treatment effect, and, in such settings, the survival curves in the two treatment arms may have a crossing before the two curves eventually separate. To flexibly model such scenarios, we describe a nonparametric approach for estimating the treatment arm‐specific survival functions which constrains these two survival functions to cross at most once without making any additional assumptions about how the survival curves are related. A main advantage of our approach is that it provides an estimate of a crossing time if such a crossing exists, and, moreover, our method generates interpretable measures of treatment benefit including crossing‐conditional survival probabilities and crossing‐conditional estimates of restricted residual mean life. Our estimates of these measures may be used together with efficacy measures from a primary analysis to provide further insight into differences in survival across treatment arms. We demonstrate the use and effectiveness of our approach with a large simulation study and an analysis of reconstructed outcomes from a recent combination therapy trial.
An evaluation of training components necessary to teach staff members to conduct an intensive pediatric feeding intervention
Authors: Clark Ronald J. , Wilder David A.
Published: February 2024

In applied behavior analysis, parents or other caregivers are often trained to implement an intervention after the intervention has been demonstrated effective when implemented by professionals. However, training novice staff members to conduct specific behavioral interventions has received less attention. This is particularly true in the context of training staff to implement interventions to treat food refusal. In the current study, we implemented three levels of training to evaluate the level of intensity required to train staff members (i.e., behavior technicians, Registered Behavior Technicians®, and Board‐Certified Behavior Analysts®) to implement a feeding protocol with a role play partner. Only one participant met the mastery criteria following the first training phase, which included written instructions and video modeling. Following 72 h of exposure to the instructional materials, we provided participants an opportunity to ask clarifying questions about the procedure (second training phase). Only one participant met mastery in this phase. Three other participants required in vivo feedback and modeling (third training phase) to master the protocol. We discuss clinical implications and future research directions.
Engineering cannabinoid production in Saccharomyces cerevisiae
Authors: Schmidt Christina , Aras Marco , Kayser Oliver
Published: February 2024

Phytocannabinoids are natural products with highly interesting pharmacological properties mainly produced by plants. The production of cannabinoids in a heterologous host system has gained interest in recent years as a promising alternative to production from plant material. However, the systems reported so far do not achieve industrially relevant titers, highlighting the need for alternative systems. Here, we show the production of the cannabinoids cannabigerolic acid and cannabigerol from glucose and hexanoic acid in a heterologous yeast system using the aromatic prenyltransferase NphB from Streptomyces sp. strain CL190. The production was significantly increased by introducing a fusion protein consisting of ERG20WW and NphB. Furthermore, we improved the production of the precursor olivetolic acid to a titer of 56 mg L−1. The implementation of the cannabinoid synthase genes enabled the production of Δ9‐tetrahydrocannabinolic acid, cannabidiolic acid as well as cannabichromenic acid, where the heterologous biosynthesis of cannabichromenic acid in a yeast system was demonstrated for the first time. In addition, we found that the product spectrum of the cannabinoid synthases localized to the vacuoles of the yeast cells was highly dependent on extracellular pH, allowing for easy manipulation. Finally, using a fed‐batch approach, we showed cannabigerolic acid and olivetolic acid titers of up to 18.2 mg L−1 and 117 mg L−1, respectively.
Implications of carbon catabolite repression for Aspergillus‐based cell factories: A review
Authors: Wang Zhen‐Dong , Wang Bao‐Teng , Jin Long , Ruan Hong‐Hua , Jin Feng‐Jie
Published: February 2024

Carbon catabolite repression (CCR) is a global regulatory mechanism that allows organisms to preferentially utilize a preferred carbon source (usually glucose) by suppressing the expression of genes associated with the utilization of nonpreferred carbon sources. Aspergillus is a large genus of filamentous fungi, some species of which have been used as microbial cell factories for the production of organic acids, industrial enzymes, pharmaceuticals, and other fermented products due to their safety, substrate convenience, and well‐established post‐translational modifications. Many recent studies have verified that CCR‐related genetic alterations can boost the yield of various carbohydrate‐active enzymes (CAZymes), even under CCR conditions. Based on these findings, we emphasize that appropriate regulation of the CCR pathway, especially the expression of the key transcription factor CreA gene, has great potential for further expanding the application of Aspergillus cell factories to develop strains for industrial CAZymes production. Further, the genetically modified CCR strains (chassis hosts) can also be used for the production of other useful natural products and recombinant proteins, among others. We here review the regulatory mechanisms of CCR in Aspergillus and its direct application in enzyme production, as well as its potential application in organic acid and pharmaceutical production to illustrate the effects of CCR on Aspergillus cell factories.
Biosynthesis of the antioxidant γ‐glutamyl‐cysteine with engineered Yarrowia lipolytica
Authors: Do Diem , Guruk Mümine , Kus‐Liśkiewicz Małgorzata , Damblon Christian , Arguelles‐Arias Anthony , Erten Huseyin , Fickers Patrick
Published: February 2024

The dipeptide γ‐glutamylcysteine (γ‐GC), the first intermediate of glutathione (GSH) synthesis, is considered as a promising drug to reduce or prevent plethora of age‐related disorders such as Alzheimer and Parkinson diseases. The unusual γ‐linkage between the two constitutive amino acids, namely cysteine and glutamate, renders its chemical synthesis particularly challenging. Herein, we report on the metabolic engineering of the non‐conventional yeast Yarrowia lipolytica for efficient γ‐GC synthesis. The yeast was first converted into a γ‐GC producer by disruption of gene GSH2 encoding GSH synthase and by constitutive expression of GSH1 encoding glutamylcysteine ligase. Subsequently genes involved in cysteine and glutamate anabolism, namely MET4, CYSE, CYSF, and GDH1 were overexpressed with the aim to increase their intracellular availability. With such a strategy, a γ‐GC titer of 464 nmol mg−1 protein (93 mg gDCW−1) was obtained within 24 h of cell growth.
The choice of ultra‐low attachment plates impacts primary human and primary canine hepatocyte spheroid formation, phenotypes, and function
Authors: Xing Chen , Kemas Aurino , Mickols Evgeniya , Klein Kathrin , Artursson Per , Lauschke Volker M.
Published: February 2024

Organotypic three‐dimensional liver spheroid cultures in which hepatic cells retain their molecular phenotype and functionality have emerged as powerful tools for preclinical drug development. In recent years a multitude of culture systems have been developed; however, a thorough side‐by‐side benchmarking of the different methods is lacking. Here, we compared the performance of ten different 96‐ and 384‐well microplate types to support spheroid formation and long‐term culture. Specifically, we evaluated differences in spheroid formation kinetics, viability, functionality, expression patterns, and their utility for hepatotoxicity assessments using primary human hepatocytes (PHH) and primary canine hepatocytes (PCH). All 96‐well plates enabled formation of PHH liver spheroids, albeit with differences between plates in spheroid size, geometry, and reproducibility. Performance of different 384‐wells was less consistent. Only 6/10 microplates supported the formation of PCH aggregates. Interestingly, even if PCH aggregates in these six microplates were more loosely packed than PHH spheroids, they maintained their function and were compatible with long‐term pharmacological and toxicological assays. Overall, Corning and Biofloat plates showed the best performance in the formation of both human and canine liver spheroids with highest viability, most physiologically relevant phenotypes, superior CYP activity and lowest coefficient of variation in toxicity assays. The presented data constitutes a valuable resource that demonstrates the impacts of current ultra‐low attachment plates on liver spheroid metrics and can guide evidence‐based plate selection. Combined, these results have important implications for the cross‐comparison of different studies and can facilitate the standardization and reproducibility of three‐dimensional liver culture experiments.
Innovative translational platforms for rapid developing clinical vaccines against COVID‐19 and other infectious disease
Authors: Wang Ning , Wang Ting
Published: February 2024

A vaccine is a biological preparation that contains the antigen capable of stimulating the immune system to form the defense against pathogens. Vaccine development often confronts big challenges, including time/energy‐consuming, low efficacy, lag to pathogen emergence and mutation, and even safety concern. However, these seem now mostly conquerable through constructing the advanced translational platforms that can make innovative vaccines, sometimes, potentiated with a distinct multifunctional VADS (vaccine adjuvant delivery system), as evidenced by the development of various vaccines against the covid‐19 pandemic at warp speed. Particularly, several covid‐19 vaccines, such as the viral‐vectored vaccines, mRNA vaccines and DNA vaccines, regarded as the innovative ones that are rapidly made via the high technology‐based translational platforms. These products have manifested powerful efficacy while showing no unacceptable safety profile in clinics, allowing them to be approved for massive vaccination at also warp speed. Now, the proprietary translational platforms integrated with the state‐of‐the‐art biotechnologies, and even the artificial intelligence (AI), represent an efficient mode for rapid making innovative clinical vaccines against infections, thus increasingly attracting interests of vaccine research and development. Herein, the advanced translational platforms for making innovative vaccines, together with their design principles and immunostimulatory efficacies, are comprehensively elaborated.
Recent advances in mRNA‐based vaccine for cancer therapy; bench to bedside
Authors: Kenoosh Hadeel Ahmed , Pallathadka Harikumar , Hjazi Ahmed , Al‐Dhalimy Aiman Mohammed Baqir , Zearah Sajad Ali , Ghildiyal Pallavi , Al‐Mashhadani Zuhair I. , Mustafa Yasser Fakri , Hizam Manar Mohammed , Elawady Ahmed
Published: February 2024

The messenger RNA (mRNA) vaccines have progressed from a theoretical concept to a clinical reality over the last few decades. Compared to conventional vaccination methods, these vaccines have a number of benefits, such as substantial potency, rapid growth, inexpensive production, and safe administration. Nevertheless, their usefulness was restricted up to now due to worries about the erratic and ineffective circulation of mRNA in vivo. Thankfully, these worries have largely been allayed by recent technological developments, which have led to the creation of multiple mRNA vaccination platforms for cancer and viral infections. The mRNA vaccines have been demonstrated as a powerful alternative to traditional conventional vaccines because of their high potency, safety and efficacy, capacity for rapid clinical development, and potential for rapid, low‐cost manufacturing. The paper will examine the present status of mRNA vaccine technology and suggest future paths for the advancement and application of this exciting vaccine platform as a common therapeutic choice.
Achieving 78.2 % Faraday Efficiency for Electrochemical Ammonia Production Via Covalent Modification of CNTs with B4C
Authors: Li Tian , Li Huajing , Wang Jialu , Zhang Meng , Zhang Yijun , Li Ting , Shen Lihua , Bi Jiantao , Li Yuangang
Published: February 2024

Electrochemical reduction of N2 to NH3 provides an alternative to the Haber‐Bosch process for sustainable NH3 production driven by renewable electricity. Here, we reported carbon nanotubes (CNTs) covalently modified with boron carbide (B4C) as a nonmetallic catalyst for efficient electrochemical nitrogen reduction reaction (NRR) under ambient conditions. The structure of the catalyst was characterized by transmission electron microscopy (TEM), X‐ray diffraction (XRD), elemental mapping, X‐ray photoelectron spectroscopy (XPS) and Raman spectroscopy. The catalyst held a superior selectivity for NRR with high Faraday efficiency of 78.2 % accompanying with NH3 yield rate of 14.0 μg mg−1cat. h−1 under the condition of 0.1 M Na2SO4 and −0.6 V vs. RHE. Electrochemical experiments including cyclic voltammetry, electrochemical impedance spectroscopy and Tafel polarization curves were performed to explain the best electrochemical properties of B4C/CNTs among the samples. This work demonstrates that the strategy of covalent modification plays an important role to improve the selectivity of electrochemical NRR catalyst, thus allowing the reactions to proceed more efficiently.
Spin‐Flip via Subtle Electronic Perturbation in Axially Ligated Diiron(III) Porphyrin Dimer
Authors: Chakraborty Paulami , Ghosh Niva , Awasthi Nidhi , Rath Sankar Prasad
Published: February 2024

Spin state switching in the metal center is a crucial phenomenon in many enzymatic reactions in biology. The spin state alteration, a critical step in cytochrome P450 catalysis, is driven most likely through a weak perturbation upon substrate binding in the enzyme, which is still not well clarified. In the current work, the spin state transition of iron(III) from high to intermediate via an admixed state is observed upon a subtle electronic perturbation to the sulphonate moieties coordinated axially to a diiron(III)porphyrin dimer. While electron‐donating substituents stabilize the high‐spin state of iron(III), strongly electron‐withdrawing groups stabilize an intermediate‐spin state, whereas the moderate electron‐withdrawing nature of axial ligands resulted in an admixed state. Confirmation of the molecular structures and their spin states have been made utilizing single‐crystal X‐ray structure analysis, Mössbauer, magnetic, EPR, and 1H NMR spectroscopic investigations. The position of the signals of the porphyrin macrocycle in the paramagnetic 1H NMR is found to be very characteristic of the spin state of the iron center in solution. The Curie plot for the pure high‐spin complexes shows the signals′ temperature dependency in line with the Curie law. Conversely, the pure intermediate‐spin state of iron exhibits an anti‐Curie temperature dependence, whereas the admixed‐spin state of iron displays significant curvature of the lines in the Curie plot. An extensive DFT analysis displays a linear dependence between the energy difference between d
and d
orbital versus Fe−Npor distance for the complexes reported here. Furthermore, a strong linear correlation between the Fe−O distance and the spin density over the oxygen atom, as well as the Fe−Npor distance for the complexes, has been observed. Thus, a slight electronic perturbation at the axial ligand of the diheme resulted in a large change in the electronic structures with a spin‐flip. This is at par with the metalloenzymes, which employ minute perturbations around the periphery of the active sites, leading to spin state transitions.
Optimization of received signal strength in visible light communication using the combination of heuristic algorithms
Authors: Pandarinathan Suganya , Jeyachitra R. K.
Published: February 2024

LEDs are a prominent technique for a pervasive communication system using visible light communication (VLC), since LED includes long life expectancy, fast switching, and being visible light and is less expensive, which is safe for the human body, though still many technical problems presented to be addressed, especially in an indoor environment. Due to this, the major aim of this task is to afford a hybridized optimization algorithm that is highly suitable for enabling the signal to noise ratio (SNR) and received signal strength (RSS) maximization in VLC. Here, the coordinate of each point of the receiver photo detector in the VLC system is tuned by the new hybridized algorithm. The fusion of two optimization algorithms like Deer Hunting Optimization Algorithm (DHOA) and Dragonfly Algorithm (DA) termed as Fitness‐oriented Dragonfly‐based DHOA (FD‐DHOA) is used to attain the objective concerning the RSS or received power and SNR. The proposed model tries to attain maximum RSS and SNR at the receiver instead of calculating it at every angle. Moreover, the experimental analysis proves that the developed model validates the orientation that generates an optimum RSS and SNR value at the receiver.
Mexidol, Cytoflavin, and succinic acid derivatives as antihypoxic, anti‐ischemic metabolic modulators, and ergogenic aids in athletes and consideration of their potential as performance enhancing drugs
Authors: Jędrejko Karol , Catlin Oliver , Stewart Timothy , Muszyńska Bożena
Published: February 2024

Emoxypine (ethylmethylhydroxypyridine) is a synthetic derivative of vitamin B6. Emoxypine succinate is a registered drug in Russia and Ukraine under various trade names including Mexidol, Mexicor, and Armadin Long. Mexidol demonstrates antihypoxic and anti‐ischemic effects and also modulates metabolism. The use of Mexidol by Russian athletes has been confirmed in the past. Current use by athletes is unknown as this drug is not monitored or included in drug testing protocol. Metabotropic and antihypoxic effects of Mexidol were compared to the effects of meldonium or trimetazidine, both of which are included on the World Anti‐Doping Agency (WADA) Prohibited List in category S4.4. Metabolic Modulators. The conjugation of emoxypine with succinate elevates the therapeutic effectiveness of the Mexidol formulation as succinic acid itself has important impacts to consider despite being a common food additive and drug excipient. Other succinic acid salts like ammonium succinate, found as dietary supplement, have been patented as performance enhancers. Available research on healthy subjects suggests that combinations of selected 3‐substituted pyridine derivatives with succinate including Mexidol and a related drug Cytoflavin can enhance the performance of athletes. Cytoflavin is a multi‐component formula containing meglumine sodium succinate, nicotinamide (vitamin B3), inosine (riboxin), and riboflavin. Other related succinate‐based drugs include Remaxol, Reamberin, and Cogitum. Mexidol and Cytoflavin and related substances exhibit similar biological effects as drugs on the WADA Prohibited List, and if they are used for performance enhancement by athletes, they could be worthy of consideration as prohibited substances in sport.
A meso‐damage‐based constitutive model for yellow sandstone under dry–wet cycles
Authors: Qin Zhe , Zhang Runchang , Mao Weizheng , Han Jihuan , Li Zhiwen , Zhang Sunhao
Published: February 2024

The mechanical properties of rocks weaken under dry–wet cycles. This weakening may significantly modify the safety reserve of underground caverns or reservoir bank slopes. However, meso‐damage has not been carefully studied based on micromechanical observations and analyses. Therefore, in this study, meso‐damage of a yellow sandstone is investigated and a meso‐damage‐based constitutive model for dry–wet cycles is proposed. First, computed tomography scanning and uniaxial compression tests were conducted on yellow sandstones under different dry–wet cycles. Second, the evolution of rock mesostructures and the damage mechanism subjected to dry–wet cycles were simulated using the discrete element method with Particle Flow Code in 2 Dimensions (PFC2D) software. Third, a constitutive model was proposed based on the meso‐statistical theory and damage mechanics. Finally, this constitutive model was verified with the experimental results to check its prediction capability. It is found that the radius and number of pore throats in the sandstone increase gradually with the number of dry–wet cycles, and the pore structure connectivity is also improved. The contact force of sandstone interparticle cementation decreases approximately linearly and the continuity of the particle contact network is continuously broken. The meso‐deformation and strength parameters show similar declining patterns to the modulus of elasticity and peak strength of the rock sample, respectively. This meso‐damage‐based constitutive model can describe well the rock deformation in the initial pressure density stage and the damage stage under the coupling effect of dry–wet cycles and loads.