bluuebunny/crossref_metadata_2025 huggingface dataset:
Oxidativestress‐Adirect bridge to central nervous system homeostatic dysfunction and Alzheimer's disease
Authors: Anwar Mai M.
Published: October 2021

Neurologists have highly observed a frequent increasing number of elderly patients with Alzheimer's disease (AD) without any relevant evidence of any genetic or known AD‐linked predisposing factors in the past few years. Those patients are characterized by continuous and irreversible neuron cells loss along with declined cognitive functions. Numerous studies have suggested that the exaggerated release of reactive oxygen species (ROS) within the brain may develop late‐onset neurodegenerative disorders, especially AD‐neuroinflammatory type. However, the central nervous system is vitally linked with whole‐brain chemical integrity and its related healthy state, the cascade by which ROS may result in AD's development has not been highly justified or even maintained. It is widely known that the brain consumes a vast amount of oxygen and is characterized by being rich in lipid polyunsaturated fatty acids content, explaining why it is a prone region to oxidative stress (OS) and ROS damage. The formed OS‐AD cytoskeletal protein aggregates can be considered a main predisposing factor for amyloid‐beta (Aβ) hallmarks precipitation. Herein, this review aims to provide a detailed information on how oxidative stress can play a pathogenic role in activating damage‐associated molecular patterns (DAMPs)–related toll‐like receptor‐4 inflammatory (TLR‐4) cascades resulting in the deposition of Aβ hallmarks in brain tissues ending with irreversible cognitive dysfunction. It also explains how microglia can be activated via ROS, which may significantly release several pro‐inflammatory cascades ending with general brain atrophy. Furthermore, different types of suggested antioxidant therapies will be discussed to combat AD‐related pathological disorders and hallmarks.
Examination of the binary system Al2O3‐ZrO2 by aero acoustic levitation melting
Authors: Niessen Jonas , Muehmer D. , Tonnesen T. , Telle R. , Gonzalez‐Julian J.
Published: November 2021

Al2O3‐ZrO2 composites exhibit excellent mechanical and high‐temperature properties. The solidification of various hypoeutectic compositions has been studied by means of aero‐acoustic levitation. A high‐speed camera recorded the crystallization, to the correlation of the video stills with the observed microstructures. Solidification takes place by formation of several nuclei and subsequent growth. Nuclei are formed in the supercooled melt, entailing to a fine‐grained, simultaneously solidified structure. The remaining melt between the growing nuclei is heated due to recalescence leading to primary precipitation of zirconia, followed by eutectic solidification. A consistent behavior is presented to explain the observed microstructures. Additionally, samples between 40 and 50 mol% ZrO2 exhibit lamellar areas, which exceed the initial zirconia composition. The observed microstructure strongly indicates the existence of a liquid miscibility gap.
Fluorescent Organohydrogel with Thermal‐Induced Color Change for Anti‐counterfeiting
Authors: Le Xiaoxia , Shang Hui , Gu Shirong , Yin Guangqiang , Shan Fuqing , Li Danyang , Chen Tao
Published: October 2021

Comprehensive Summary

Smart fluorescent patterns enable dynamic color variation under external stimuli, showing a much higher security level in the field of anti‐counterfeiting. However, there is still lacking of a simple and convenient way to achieve dynamic fluorescence changes. Herein, a fluorescent organohydrogel made up of a poly(N,N‐dimethylacrylamide‐co‐isopropylacrylamide) (p(DMA‐NIPAM)) hydrogel network and a poly(lauryl methacrylate) (PLMA) organogel network was fabricated via a two‐step interpenetrating technique. The former network bears naphthalimide moieties (DEAN, green fluorescent monomer) and the later contains 6‐acrylamidopicolinic acid (6APA, fluorescent ligand), leading to emitting green fluorescence. When Eu3+ was introduced and coordinated with 6APA, the organohydrogel displays red fluorescence, which can further emit yellow after applying thermal stimulus. Furthermore, by adjusting the proportion of comonomers, various organohydrogels can be obtained, which can be programmed and act as an effective platform for the encryption and decryption of secret information.
Proenkephalin and the risk of new‐onset heart failure: data from prevention of renal and vascular end‐stage disease
Authors: Emmens Johanna E. , ter Maaten Jozine M. , Brouwers Frank P. , Kieneker Lyanne M. , Damman Kevin , Hartmann Oliver , Schulte Janin , Bakker Stephan J. L. , de Boer Rudolf A. , Voors Adriaan A.
Published: October 2021

Background

Enkephalins of the opioid system exert several cardiorenal effects. Proenkephalin (PENK), a stable surrogate, is associated with heart failure (HF) development after myocardial infarction and worse cardiorenal function and prognosis in patients with HF. The association between plasma PENK concentrations and new‐onset HF in the general population remains to be established.

Hypothesis

We hypothesized that plasma PENK concentrations are associated with new‐onset HF in the general population.

Methods

We included 6677 participants from the prevention of renal and vascular end‐stage disease study and investigated determinants of PENK concentrations and their association with new‐onset HF (both reduced [HFrEF] and preserved ejection fraction [HFpEF]).

Results

Median PENK concentrations were 52.7 (45.1–61.9) pmol/L. Higher PENK concentrations were associated with poorer renal function and higher NT‐proBNP concentrations. The main determinants of higher PENK concentrations were lower estimated glomerular filtration rate (eGFR), lower urinary creatinine excretion, and lower body mass index (all p < .001). After a median 8.3 (7.8–8.8) years follow‐up, 221 participants developed HF; 127 HFrEF and 94 HFpEF. PENK concentrations were higher in subjects who developed HF compared with those who did not, 56.2 (45.2–67.6) versus 52.7 (45.1–61.6) pmol/L, respectively (p = .003). In competing‐risk analyses, higher PENK concentrations were associated with higher risk of new‐onset HF (hazard ratio [HR] = 2.09[1.47–2.97], p < .001), including both HFrEF (HR = 2.31[1.48–3.61], p < .001) and HFpEF (HR = 1.74[1.02–2.96], p = .042). These associations were, however, lost after adjustment for eGFR.

Conclusions

In the general population, higher PENK concentrations were associated with lower eGFR and higher NT‐proBNP concentrations. Higher PENK concentrations were not independently associated with new‐onset HFrEF and HFpEF and mainly confounded by eGFR.
Attributing the 2015/2016 Amazon basin drought to anthropogenic influence
Authors: Ribeiro G. G. , Anderson L. O. , Barretos N. J. C. , Abreu R. , Alves L. , Dong B. , Lott F. C. , Tett Simon F. B.
Published: October 2021

Droughts in the Amazon region have the potential to generate severe socio‐environmental impacts in addition to having the ability to interfere with the long‐term carbon cycle, thus affecting global climate. The 2015/2016 drought that occurred in this region, associated with an El Niño, was considered a record‐breaking event in terms of unprecedented warming and the largest extent of the drought affected areas. Anthropogenic influence on the probability and intensity of this drought was assessed using two ensembles of the Met Office's HadGEM3‐GA6 model. One ensemble was driven only with natural forcings and the other also included anthropogenic forcings. This analysis found that the intensity and probability of the 2015/2016 Amazon drought likely increased due to anthropogenic influence. The reliability of the model to represent the precipitation of the study area was assessed by comparing it with the Climate Hazards Group InfraRed Precipitation with Station data (CHIRPS) product (R2 = 0.81). Results indicate that anthropogenic forcings altered the drought intensity of 2015/2016 in the Amazon and increased the risk of this event by about four times with a confidence interval ranging from 2.7 to 4.7. We conclude that anthropogenic emissions threaten the functioning of the Amazon forest due to increased likelihood of extreme droughts.
Transdermal Photothermal Sterilization and Abscess Elimination Research of BSA‐CuS Nanoparticles in vivo
Authors: Zhao Yan , Zhao Jing‐Jing , Guo Jia‐Xin , Liu Shuang‐Qing , Li Yang , Wang Xiao‐Yi , Li Rong , Tang Hui‐Qin , Li Zhen‐Yu , Yang Hui‐Fen , Chen Bing
Published: November 2021

The treatment of subcutaneous abscess caused by drug‐resistant bacteria is facing great difficulties and receiving more attention. In this work, we employed BSA‐CuS nanoparticles as a photothermal reagent to apply photothermal therapy (PTT) to combat drug‐resistant bacteria in vitro and subcutaneous abscess in vivo. The BSA‐CuS nanoparticles were found to be stable and biocompatible without cytotoxicity toward NIH3T3 and 4T1 cells. In vitro experiments showed that three species of drug‐resistant pathogens, including Escherichia coli, Staphylococcus aureus, and Candida albicans, could be effectively sterilized under co‐incubation with BSA‐CuS nanoparticles and then irradiation with 1064 nm NIR laser via tissue penetration. BSA‐CuS nanoparticles together with 1064 nm NIR laser irradiation could also effectively diminish subcutaneous abscesses caused by drug‐resistant bacteria on mice under PTT and depth PTT without causing any serious side effects and organic damage in vivo.That is OK, thank you!
A scalable solver for a stochastic, hybrid cellular automaton model of personalized breast cancer therapy
Authors: Lai Xiaoran , Taskén Håkon A. , Mo Torgeir , Funke Simon W. , Frigessi Arnoldo , Rognes Marie E. , Köhn‐Luque Alvaro
Published: October 2021

Mathematical modeling and simulation is a promising approach to personalized cancer medicine. Yet, the complexity, heterogeneity and multi‐scale nature of cancer pose significant computational challenges. Coupling discrete cell‐based models with continuous models using hybrid cellular automata (CA) is a powerful approach for mimicking biological complexity and describing the dynamical exchange of information across different scales. However, when clinically relevant cancer portions are taken into account, such models become computationally very expensive. While efficient parallelization techniques for continuous models exist, their coupling with discrete models, particularly CA, necessitates more elaborate solutions. Building upon FEniCS, a popular and powerful scientific computing platform for solving partial differential equations, we developed parallel algorithms to link stochastic CA with differential equations (https://bitbucket.org/HTasken/cansim). The algorithms minimize the communication between processes that share CA neighborhood values while also allowing for reproducibility during stochastic updates. We demonstrated the potential of our solution on a complex hybrid cellular automaton model of breast cancer treated with combination chemotherapy. On a single‐core processor, we obtained nearly linear scaling with an increasing problem size, whereas weak parallel scaling showed moderate growth in solving time relative to increase in problem size. Finally, we applied the algorithm to a problem that is 500 times larger than previous work, allowing us to run personalized therapy simulations based on heterogeneous cell density and tumor perfusion conditions estimated from magnetic resonance imaging data on an unprecedented scale.
The Structured Process to Identify Fit‐For‐Purpose Data: A Data Feasibility Assessment Framework
Authors: Gatto Nicolle M. , Campbell Ulka B. , Rubinstein Emily , Jaksa Ashley , Mattox Pattra , Mo Jingping , Reynolds Robert F.
Published: October 2021

To complement real‐world evidence (RWE) guidelines, the 2019 Structured Preapproval and Postapproval Comparative study design framework to generate valid and transparent real‐world Evidence (SPACE) framework elucidated a process for designing valid and transparent real‐world studies. As an extension to SPACE, here, we provide a structured framework for conducting feasibility assessments—a step‐by‐step guide to identify decision grade, fit‐for‐purpose data, which complements the United States Food and Drug Administration (FDA)’s framework for a RWE program. The process was informed by our collective experience conducting systematic feasibility assessments of existing data sources for pharmacoepidemiology studies to support regulatory decisions. Used with the SPACE framework, the Structured Process to Identify Fit‐For‐Purpose Data (SPIFD) provides a systematic process for conducting feasibility assessments to determine if a data source is fit for decision making, helping ensure justification and transparency throughout study development, from articulation of a specific and meaningful research question to identification of fit‐for‐purpose data and study design.
Precision Reimbursement for Precision Medicine: Using Real‐World Evidence to Evolve From Trial‐and‐Project to Track‐and‐Pay to Learn‐and‐Predict
Authors: Eichler Hans‐Georg , Trusheim Mark , Schwarzer‐Daum Brigitte , Larholt Kay , Zeitlinger Markus , Brunninger Martin , Sherman Michael , Strutton David , Hirsch Gigi
Published: October 2021

Basic scientists and drug developers are accelerating innovations toward the goal of precision medicine. Regulators create pathways for timely patient access to precision medicines, including individualized therapies. Healthcare payors acknowledge the need for change but downstream innovation for coverage and reimbursement is only haltingly occurring. Performance uncertainty, high price‐tags, payment timing, and actuarial risk issues associated with precision medicines present novel financial challenges for payors. With traditional drug reimbursement frameworks, payment is based on an assumed randomized controlled trial (RCT) projection of real‐world effectiveness, a “trial‐and‐project” strategy; the clinical benefit realized for patients is not usually ascertained ex post by collection of real‐world data (RWD). To mitigate financial risks resulting from clinical performance uncertainty, manufacturers and payors devised “track‐and‐pay” frameworks (i.e., the tracking of a pre‐agreed treatment outcome which is linked to financial consequences). Whereas some track‐and‐pay arrangements have been successful, inherent weaknesses include the potential for misalignment of incentives, the risk of channeling of patients, and a failure to use the RWD generated to enable continuous learning about treatments. “Precision reimbursement” (PR) intends to overcome inherent weaknesses of simple track‐and‐pay schemes. In combining the collection of RWD with advanced analytics (e.g., artificial intelligence and machine learning) to generate actionable real‐world evidence, with prospective alignment of incentives across all stakeholders (including providers and patients), and with pre‐agreed use and dissemination of information generated, PR becomes a “learn‐and‐predict” model of payment for performance. We here describe in detail the concept of PR and lay out the next steps to make it a reality.
A 10‐bit 1GSample/s hybrid digital‐to‐analog converter with a modified thermometer decoder in 65‐nm CMOS technology
Authors: Ghasemi Razieh , Karami Mohammad Azim
Published: October 2021

This paper proposes a new 10‐bit 1GS/s digital‐to‐analog converter (DAC). In the proposed DAC configuration, a beneficial combination of differential resistor ladder and current sources is utilized to attain a significant reduction of the number of unit current sources. Therefore, the suggested 10‐bit DAC is constructed based on only 21 current sources and 64 unit resistors, which results in a considerable decrease regarding the occupied area and power consumption. Also, a modified 4‐bit thermometer decoder using a low number of transistors, based on SET‐RST D flip‐flops (SR‐DFFs), is offered to drive the unit current sources synchronously. The proposed DAC is simulated in 65‐nm Complementary metal oxide semiconductor (CMOS) technology. The postlayout simulation results indicate the better integral nonlinearity (INL) and differential nonlinearity (DNL) parameters than 0.3 least significant bit (LSB) and 0.6 LSB, respectively. Based on achieved results, the proposed DAC consumes 9.31 mW using a single supply voltage of 1.2 V. Moreover, the spurious‐free dynamic range (SFDR) is above 57 dB over 600‐MHz Nyquist bandwidth, by considering 0.0134 mm2its occupied area.
Downregulation of Grem1 expression in the distal limb mesoderm is a necessary precondition for phalanx development
Authors: Lancman Joseph J. , Hasso Sean M. , Suzuki Takayuki , Kherdjemil Yacine , Kmita Marie , Ferris Andrea , Dong P. Duc S. , Ros Marian A. , Fallon John F.
Published: November 2021

Background

The phalanges are the final skeletal elements to form in the vertebrate limb and their identity is regulated by signaling at the phalanx forming region (PFR) located at the tip of the developing digit ray. Here, we seek to explore the relationship between PFR activity and phalanx morphogenesis, which define the most distal limb skeletal elements, and signals associated with termination of limb outgrowth.

Results

As Grem1 is extinguished in the distal chick limb mesoderm, the chondrogenesis marker Aggrecan is up‐regulated in the metatarsals and phalanges. Fate mapping confirms that subridge mesoderm cells contribute to the metatarsal and phalanges when subridge Grem1 is down‐regulated. Grem1 overexpression specifically blocks chick phalanx development by inhibiting PFR activity. PFR activity and digit development are also disrupted following overexpression of a Gli3 repressor, which results in Grem1 expression in the distal limb and downregulation of Bmpr1b.

Conclusions

Based on expression and fate mapping studies, we propose that downregulation of Grem1 in the distal limb marks the transition from metatarsal to phalanx development. This suggests that downregulation of Grem1 in the distal limb mesoderm is necessary for phalanx development. Grem1 downregulation allows for full PFR activity and phalanx progenitor cell commitment to digit fate.
Revitalizing mouse diphyodontic dentition formation by inhibiting the sonic hedgehog signaling pathway
Authors: Mao Chuanqing , Lai Yongzhen , Liao Caiyu , Chen Jiangping , Hong Yuhang , Ren Chengyan , Wang Chengyong , Lu Meng , Chen Weihui
Published: November 2021

Background

Tooth regeneration depends on the longevity of the dental epithelial lamina. However, the exact mechanism of dental lamina regression has not yet been clarified. To explore the role of the Sonic hedgehog (Shh) signaling pathway in regression process of the rudimentary successional dental lamina (RSDL) in mice, we orally administered a single dose of a Shh signaling pathway inhibitor to pregnant mice between embryonic day 13.0 (E13.0) and E17.0.

Results

We observed that the Shh signaling pathway inhibitor effectively inhibited the expression of Shh signaling pathway components and revitalized RSDL during E15.0–E17.0 by promoting cell proliferation. In addition, mRNA‐seq, reverse transcription plus polymerase chain reaction (RT‐qPCR), and immunohistochemical analyses indicated that diphyodontic dentition formation might be related to FGF signal up‐regulation and the Sostdc1‐Wnt negative feedback loop.

Conclusions

Overall, our results indicated that the Shh signaling pathway may play an initial role in preventing further development of mouse RSDL in a time‐dependent manner.
Diabetic emergencies presenting during the COVID‐19 pandemic: A retrospective case analysis
Authors: Joseph Tobin , Crawley Eleanor , Qamar Sulmaaz , Zosmer Maya , Rayanagoudar Girish , Nethaji Chidambaram , Menon Ravi
Published: October 2021

Introduction

COVID‐19 has triggered a global pandemic and is an emerging situation. Diabetes has been associated with significant mortality in SARS and MERS‐COV infections. Patients with diabetes are at risk of COVID‐19 triggering diabetic emergencies due to known and unknown mechanisms. There is little evidence overviewing the clinical course of COVID‐19 patients who either present or have diabetic emergencies during their disease course.

Methods

We conducted a retrospective case analysis of all patients admitted to our hospital during the COVID‐19 pandemic. The inclusion criteria were all patients receiving treatment for COVID‐19 and either presenting with a diabetic emergency on admission or developing an emergency during their admission. Data collected for the study were all routinely collected data as part of the admission. We compared these data to nine patients with no COVID‐19.

Results

Thirty patients received treatment for a diabetic emergency, of which 21 also received treatment for COVID‐19. Significant differences were found between pH and bicarbonate on admission between RT‐PCR‐positive and both RT‐PCR‐negative and non‐COVID‐19 patients. Other results approaching significance include ALP and eGFR.

Discussion

Patients suffering from COVID‐19 and diabetes concurrently can suffer from profound metabolic disturbance, with a significant difference in inpatient mortality. However further, prospective detailed investigation into biochemical processes is needed to fully elucidate underlying mechanisms that affect these patients' outcomes.
Survival to intensive care unit discharge among in‐hospital cardiac arrest patients by applying audiovisual feedback device
Authors: Goharani Reza , Vahedian‐Azimi Amir , Pourhoseingholi Mohamad Amin , Amanpour Farzaneh , Rosano Giuseppe M.C. , Sahebkar Amirhossein
Published: October 2021

Aims

Survival rates after in‐hospital cardiac arrest remain very low. Although there is evidence that the use of audiovisual feedback devices can improve compression components, there are no data on patient survival. Therefore, we conducted this study to analyse the survival rate of patients with in‐hospital cardiac arrest after discharge from the intensive care unit.

Methods and results

This study was a secondary analysis of a prospective, randomized, controlled, parallel study of patients who received either standard manual chest compression or a real‐time feedback device. Parametric and semi‐parametric models were fitted to the data. Different survival time of length of stay was investigated by univariate and multiple analyses. Pearson's correlation between length of stay and hospital length of stay was obtained. A total of 900 patients with a mean survival time of 35 days were included. Intervention was associated with a higher length of stay. Relative time was significant in adjusted fitted log‐normal regression for intervention group, female gender, and cardiopulmonary resuscitation in the night shift. A positive correlation between length of stay and hospital length of stay was found.

Conclusions

Implementation of feedback device improved survival and length of stay. Cardiopulmonary resuscitation performance during the night shift decreased the survival time, which could be due to the inexperienced staff available outside working hours.
Stereoselective Synthesis of 1,2‐cis‐Glycosyl Sulfones and Their Application in One‐Pot Julia Olefination for the Synthesis of exo‐Glycals
Authors: Oka Natsuhisa , Suzuki Kanna , Mori Ayumi , Ando Kaori
Published: October 2021

Glycosyl sulfones are important intermediates in the synthesis of various sugar derivatives. However, their 1,2‐cis‐isomers have not been extensively studied because of lower availability. Herein, we report the highly stereoselective synthesis of heteroaryl‐substituted 1,2‐cis‐glycosyl sulfones via glycosylation of heteroarylthiols and subsequent oxidation by magnesium monoperphthalate. One‐pot Julia olefination using these 1,2‐cis‐glycosyl sulfones was also studied. It furnished thermodynamically less stable (E)‐exo‐glycals with E/Z selectivity of up to 91 : 9.
A flow‐through microfluidic chip for continuous dielectrophoretic separation of viable and non‐viable human T‐cells
Authors: Mustafa Adil , Pedone Elisa , Marucci Lucia , Moschou Despina , Lorenzo Mirella Di
Published: October 2021

Effective methods for rapid sorting of cells according to their viability are critical in T cells based therapies to prevent any risk to patients. In this context, we present a novel microfluidic device that continuously separates viable and non‐viable T‐cells according to their dielectric properties. A dielectrophoresis (DEP) force is generated by an array of castellated microelectrodes embedded into a microfluidic channel with a single inlet and two outlets; cells subjected to positive DEP forces are drawn toward the electrodes array and leave from the top outlet, those subjected to negative DEP forces are repelled away from the electrodes and leave from the bottom outlet. Computational fluid dynamics is used to predict the device separation efficacy, according to the applied alternative current (AC) frequency, at which the cells move from/to a negative/positive DEP region and the ionic strength of the suspension medium. The model is used to support the design of the operational conditions, confirming a separation efficiency, in terms of purity, of 96% under an applied AC frequency of 1.5 × 106 Hz and a flow rate of 20 μl/h. This work represents the first example of effective continuous sorting of viable and non‐viable human T‐cells in a single‐inlet microfluidic chip, paving the way for lab‐on‐a‐chip applications at the point of need.
Infantile‐onset myoclonic developmental and epileptic encephalopathy: A new RARS2 phenotype
Authors: de Valles‐Ibáñez Guillem , Hildebrand Michael S. , Bahlo Melanie , King Chontelle , Coleman Matthew , Green Timothy E. , Goldsmith John , Davis Suzanne , Gill Deepak , Mandelstam Simone , Scheffer Ingrid E. , Sadleir Lynette G.
Published: October 2021

Recessive variants in RARS2, a nuclear gene encoding a mitochondrial protein, were initially reported in pontocerebellar hypoplasia. Subsequently, a recessive RARS2 early‐infantile (<12 weeks) developmental and epileptic encephalopathy was described with hypoglycaemia and lactic acidosis. Here, we describe two unrelated patients with a novel RARS2 phenotype and reanalyse the published RARS2 epilepsy phenotypes and variants. Our novel cases had infantile‐onset myoclonic developmental and epileptic encephalopathy, presenting with a progressive movement disorder from 9 months on a background of normal development. Development plateaued and regressed thereafter, with mild to profound impairment. Multiple drug‐resistant generalized and focal seizures occurred with episodes of non‐convulsive status epilepticus. Seizure types included absence, atonic, myoclonic, and focal seizures. Electroencephalograms showed diffuse slowing, multifocal, and generalised spike‐wave activity, activated by sleep. Both patients had compound heterozygous RARS2 variants with likely impact on splicing and transcription. Remarkably, of the now 52 RARS2 variants reported in 54 patients, our reanalysis found that 44 (85%) have been shown to or are predicted to affect splicing or gene expression leading to protein truncation or nonsense‐mediated decay. We expand the RARS2 phenotypic spectrum to include infantile encephalopathy and suggest this gene is enriched for pathogenic variants that disrupt splicing.
Changes in the vegetation cover of transgressive dune fields: A case study in Cape Woolamai, Victoria
Authors: Gao Jinjuan , Kennedy David M. , Konlechner Teresa M. , McSweeney Sarah , Chiaradia Andre , McGuirk Marita
Published: November 2021

Changes in vegetation cover and dune mobility of Woolamai dune fields on the southeast coast of Australia were quantified based on a time series of aerial imagery (1939 to 2020). Results showed that the dune fields have shifted from nearly all bare sand (with <5% vegetation cover) to a new quasi‐equilibrium state, being almost fully stabilized by vegetation (>80%) from 1939 to 2020. Three temporal stages of vegetation change were identified, namely: (I) early expansion over 1939–1975; (II) rapid growth from 1976 to 2010; and (III) recent ‘quasi‐equilibrium’ state in 2010–2020. In stage I, complex impacts of climate and human activities co‐existed with uncertainty of the dominant factor. In this early stage, vegetation growth was constrained to the low and sheltered areas, indicating the influence of topography. Rapid vegetation growth took place in 1976–2010 (stage II), during which a re‐vegetation programme combined with favourable climate conditions promoted vegetation growth. In the last decade (stage III), vegetation might have reached a new quasi‐equilibrium when the vegetation almost reached a maximum. The slight loss of vegetation could be attributed to weed control and an unfavourable climate for growth (drier and windier) in Woolamai dune fields.

This study showed that variations in vegetation cover and dune mobility through time are not simply linked to a single factor but depend on the occurrence of multiple factors (e.g. topography, climate and human activities) that promote stability, or alternatively, mobility of the dune system. This research contributes to expanding our understanding of the complexity of the bio‐geomorphologic dynamics in dune fields. It also provides detailed observational evidence for the historical trajectory of vegetation expansion from the bare dune fields to a fully stabilized state, which can be used to verify and refine models for other similar dune sites.
Recombinant lactic acid bacteria as promising vectors for mucosal vaccination
Authors: Qiao Nan , Du Guangsheng , Zhong Xiaofang , Sun Xun
Published: October 2021

Lactic acid bacteria (LAB), a diverse family of gram‐positive bacteria, has been proven effective in delivering varieties of therapeutic and prophylactic molecules such as antigens and cytokines. Featuring the properties of acid‐resistant, high uptake into Peyer's patches, and superior capacity for inducing secretory IgA antibodies, LAB have good potential to be used as vaccine vectors for mucosal vaccination. Mucosal immunization enables both mucosal and systemic immune responses, which are critical for resisting pathogens that invade the host through the mucosal surfaces. With the development of genetic engineering, LAB strains, primarily Lactococcus and Lactobacillus have been exploited to express a range of heterologous antigens. Numerous studies have demonstrated that LAB mucosal vaccines can stimulate all arms of the immune system to provide adequate protection against pathogen infections. Additionally, several LAB‐based human papillomavirus vaccines have entered the clinical trial studies, which suggest the great promise of LAB vaccines for new interventions in mucosal transport diseases. Herein, we will discuss the factors that influence the immunogenicity of LAB vaccines, including LAB strains, the location of antigens, and administration routes, and focus on the current strategies that have been reported for optimizing LAB vaccines.
Rationally designed modular drug delivery platform based on intracellular peptide self‐assembly
Authors: An Hong‐Wei , Mamuti Muhetaerjiang , Wang Xiaofeng , Yao Haodong , Wang Man‐Di , Zhao Lina , Li Li‐Li
Published: October 2021

Modulated molecular design‐based intracellular self‐assembly strategy has showed great potentiality in drug delivery, due to its assembling nature‐resulted optimized drug biodistribution and metabolism. The modular designing concept endows the delivery system multiple functions, such as, selectivity and universality to improve the pharmacokinetics of loaded drugs. However, the accurate controlling of the self‐assembling process in desired site to achieve optimal drug delivery is posed great challenges toward rational molecular design. Here, we fabricated a modulated drug‐delivery system (MDS) through intracellular peptide self‐assembly to realize effective drug delivery. MDS was designed based on modulated molecular designing strategy which contains five functional motifs and effectively transformed into fibrous nanostructures inside target cells by caspase3/7 hydrolysis directed in situ self‐assembly. The experimental studies and molecular simulations were carried out to evaluate the successful construction and delivering efficacy of MDS. According to the experimental results and molecular simulation analysis, the percentage of solvent‐exposed surface area of assembling modular (KLVFFAE), as well as its non‐covalent interaction between four other modules synergeticly decide the solubility of molecules. The weak intramolecular forces of the peptide back bone, such as, hydrogen bond, as well as multivalent interactions of the side chains such as, salt bridge and hydrophobic interaction both contribute to the self‐assembly of the molecules. The significant structural difference between delivering molecules optimize the system to adapt hydrophilic and hydrophobic drugs. Finally, the predicted drug delivery molecule specifically recognizes targeted cancer cell lines and self‐assembles to form fibers intracellularly, resulting in prolonged drug retention and accumulation. The regular prediction and rational molecular design will benefit the further construction and optimization of modulated drug delivery platform.
Impacts of the COVID‐19 pandemic on vegetable production systems and livelihoods: Smallholder farmer experiences in Burkina Faso
Authors: Middendorf B. Jan , Traoré Hamidou , Middendorf Gerad , Jha Prakash K. , Yonli Djibril , Palé Siébou , Prasad P.V. Vara
Published: November 2021

At the onset of COVID‐19, researchers quickly recognized the need for research on the consequences of the pandemic for agricultural and food systems, both in terms of immediate impacts on access to inputs and labor, disruptions in transportation and markets, and the longer‐term implications on crop productivity, income, and livelihoods. Vegetable production and supply chains are particularly vulnerable due to the perishable nature of the products and labor‐intensive production practices. The purpose of this study was to understand the impacts of COVID‐19 on vegetable production in Burkina Faso in terms of both the biophysical aspects such as yields and access to inputs and socioeconomic aspects such as access to labor, markets, and social services. A survey was developed to better understand smallholder farmer experiences regarding the impacts of COVID‐19 on their vegetable production systems and social well‐being. The survey was administered (between August and October 2020) with smallholder farmers (n= 605) in 13 administrative regions covering all agroecological zones of Burkina Faso. The survey results clearly show impacts of COVID‐19 on vegetable systems, including a reduction in access to inputs, a reduction in yields, a loss of income, reduced access to local and urban markets, reduced access to transportation, and an increase in post‐harvest loss. Market access, distribution, and disruptions were a major shock to the system. Results also showed an increase in women's labor in the household, and for youth, an increase in unemployment, job loss, and concerns of poverty. Finally, food security and social supports were highlighted as major issues for resilience and livelihoods. The results from this survey should be helpful to policymakers and researchers to develop policies and strategies to minimize the negative impacts of this ongoing pandemic on the agri‐food systems and support smallholder farmers to overcome stress caused by COVID‐19.
Cordyceps militaris extract induces apoptosis and pyroptosis via caspase‐3/PARP/GSDME pathways in A549 cell line
Authors: Hu Zixuan , Lai Yijing , Ma Chaoya , Zuo Lina , Xiao Guanlin , Gao Haili , Xie Biyuan , Huang Xuejun , Gan Haining , Huang Dane , Yao Nan , Feng Baoguo , Ru JieXia , Chen Yuxing , Cai Dake
Published: October 2021

Cordyceps militaris (CM) is traditionally used as dietary therapy for lung cancer patients in China. CM extract (CME) is hydrosoluble fraction of CM and extensively investigated. Caspase‐3‐involved cell death is considered as its major anticancer mechanism but inconclusive. Therefore, we explore its caspase‐3‐dependent programmed cell death nature (apoptosis and pyroptosis) and validate its caspase‐3‐dependent property in loss‐of‐function experiment. Component profile of CME is detected by High Performance Liquid Chromatography‐ quadrupole time‐of‐flight mass spectrometry (HPLC‐qTOF). Results show that CME causes pyroptosis‐featured cell bubbling and cell lysis and inhibits cell proliferation in A549 cell. CME induces chromatin condensing and makes PI+/annexin V+ staining in bubbling cells, indicating genotoxicity, apoptosis, and pyroptosis cell death are caused by CME. High concentration of CME (200 μg/ml) exerts G2/M and G0 cell cycles arresting and suppresses P53‐downstream proliferative proteins, including P53, P21, CDC25B, CyclinB1, Bcl‐2, and BCL2 associated agonist of cell death (BAD), but 1–100 μg/ml of CME show less effect on proteins above. Correspondingly, caspase‐3 activity and caspase‐3 downstream proteins including pyroptotic effector gasdermin‐E (GSDME) and apoptotic marker cleaved‐poly‐ADP‐ribose polymerase (PARP) are significantly promoted by CME. Moreover, regarding membrane pore formation in pyroptotic cell, expression of membrane GSDME (GSDME antibody conjugated with PE‐Cy7 for detection in flow cytometry) is remarkably increased by CME treatment. By contrast, other pyroptosis‐related proteins such as P2X7, NLRP3, GSDMD, and Caspase‐1 are not affected after CME treatment. Additionally, TET2 is unexpectedly raised by CME. In present of caspase‐3 inhibitor Ac‐DEVD‐CHO (Ac‐DC), CME‐induced cytotoxicity, cell bubbling, and genotoxicity are reduced, and CME‐induced upregulation of apoptosis (cleaved‐PARP‐1) and pyroptosis (GSDME‐NT) proteins are reversed. Lastly, 22 components are identified in HPLC‐qTOF experiment, and they are classified into trophism, neoadjuvant component, cytotoxic component, and cancer deterioration promoter according to previous references. Conclusively, CME causes caspase‐3‐dependent apoptosis and pyroptosis in A549 through caspase‐3/PARP and caspase‐3/GSDME pathways, and it provides basic insight into clinic application of CME for cancer patients.
Costing Analysis of Scalable Carbon‐Based Perovskite Modules Using Bottom Up Technique
Authors: Kajal Priyanka , Verma Bhupesh , Vadaga Satya Gangadhara Rao , Powar Satvasheel
Published: November 2021

In recent years, perovskite solar cells (PSCs) have achieved a remarkable power conversion efficiency of 25.5%, indicating that they are a promising alternative to dominant Si photovoltaic (PV) technology. This technology is expected to solve the world's energy demand with minimal investment and very low CO2 emissions. The market has shown a lot of interest in PSCs technology. A technoeconomic analysis is a useful tool for tracking manufacturing costs and forecasting whether technology will eventually achieve market‐driven prices. A technoeconomic analysis of a 100 MW carbon‐based perovskite solar module (CPSM) factory located in India is presented in this paper. Two CPSMs architectures—high‐temperature processed CPSMs (Module A) and low‐temperature processed CPSM's (Module B)—are expected to offer minimum sustainable prices (MSPs) of $ 0.21 W‐1 and $ 0.15 W‐1. On the basis of MSP, the levelized cost of energy (LCOE) is calculated to be 3.40 ¢ kWh‐1 for module A and 3.02 ¢ kWh‐1 for module B, with a 10‐year module lifetime assumption. The same modules with a 25‐year lifespan have LCOEs of 1.66 and 1.47 ¢ kWh‐1, respectively. These estimates are comparable to market dominant crystalline silicon solar modules, and they are also favorable for utilizing perovskite solar cell technology.
Contribution of the multi‐echo approach in accelerated functional magnetic resonance imaging multiband acquisition
Authors: Kovářová Anežka , Gajdoš Martin , Rektor Ivan , Mikl Michal
Published: October 2021

We wanted to verify the effect of combining multi‐echo (ME) functional magnetic resonance imaging (fMRI) with slice acceleration in simultaneous multi‐slice acquisition. The aim was to shed light on the benefits of multiple echoes for various acquisition settings, especially for levels of slice acceleration and flip angle. Whole‐brain ME fMRI data were obtained from 26 healthy volunteers (using three echoes; seven runs with slice acceleration 1, 4, 6, and 8; and two different flip angles for each of the first three acceleration factors) and processed as single‐echo (SE) data and ME data based on optimal combinations weighted by the contrast‐to‐noise ratio. Global metrics (temporal signal‐to‐noise ratio, signal‐to‐noise separation, number of active voxels, etc.) and local characteristics in regions of interest were used to evaluate SE and ME data. ME results outperformed SE results in all runs; the differences became more apparent for higher acceleration, where a significant decrease in data quality is observed. ME fMRI can improve the observed data quality metrics over SE fMRI for a wide range of accelerated fMRI acquisitions.
Breviscapine alleviates NASH by inhibiting TGF‐β‐activated kinase 1‐dependent signaling
Authors: Lan Tian , Jiang Shuo , Zhang Jing , Weng Qiqing , Yu Yang , Li Haonan , Tian Song , Ding Xin , Hu Sha , Yang Yiqi , Wang Weixuan , Wang Lexun , Luo Duosheng , Xiao Xue , Piao Shenghua , Zhu Qing , Rong Xianglu , Guo Jiao
Published: October 2021

Background and Aims

NAFLD is a key component of metabolic syndrome, ranging from nonalcoholic fatty liver to NASH, and is now becoming the leading cause of cirrhosis and HCC worldwide. However, due to the complex and unclear pathophysiological mechanism, there are no specific approved agents for treating NASH. Breviscapine, a natural flavonoid prescription drug isolated from the traditional Chinese herb Erigeron breviscapus, exhibits a wide range of pharmacological properties, including effects on metabolism. However, the anti‐NASH efficacy and mechanisms of breviscapine have not yet been characterized.

Approach and Results

We evaluated the effects of breviscapine on the development of hepatic steatosis, inflammation, and fibrosis in vivo and in vitro under metabolic stress. Breviscapine treatment significantly reduced lipid accumulation, inflammatory cell infiltration, liver injury, and fibrosis in mice fed a high‐fat diet, a high‐fat/high‐cholesterol diet, or a methionine‐ and choline‐deficient diet. In addition, breviscapine attenuated lipid accumulation, inflammation, and lipotoxicity in hepatocytes undergoing metabolic stress. RNA‐sequencing and multiomics analyses further indicated that the key mechanism linking the anti‐NASH effects of breviscapine was inhibition of TGF‐β‐activated kinase 1 (TAK1) phosphorylation and the subsequent mitogen‐activated protein kinase signaling cascade. Treatment with the TAK1 inhibitor 5Z‐7‐oxozeaenol abrogated breviscapine‐mediated hepatoprotection under metabolic stress. Molecular docking illustrated that breviscapine directly bound to TAK1.

Conclusion

Breviscapine prevents metabolic stress–induced NASH progression through direct inhibition of TAK1 signaling. Breviscapine might be a therapeutic candidate for the treatment of NASH.
Impact of Platelet Count on Perioperative Bleeding in Patients With Cirrhosis Undergoing Surgical Treatments of Liver Cancer
Authors: Ronca Vincenzo , Barabino Matteo , Santambrogio Roberto , Opocher Enrico , Hodson James , Bertolini Emanuela , Birocchi Simone , Piccolo Gaetano , Battezzati PierMaria , Cattaneo Marco , Podda Gian Marco
Published: October 2021

In patients with cirrhosis with severe thrombocytopenia (platelet count [PC] <50 × 109/L) and undergoing invasive procedures, it is common clinical practice to increase the PC with platelet transfusions or thrombopoietin receptor agonists to reduce the risk of major periprocedural bleeding. The aim of our study was to investigate the association between native PC and perioperative bleeding in patients with cirrhosis undergoing surgical procedures for the treatment of hepatocellular carcinoma (HCC). We retrospectively evaluated 996 patients with cirrhosis between 1996 and 2018 who underwent surgical treatments of HCC by liver resection (LR) or radiofrequency ablation (RFA) without prophylactic platelet transfusions. Patients were allocated to the following three groups based on PC: high (>100 × 109/L), intermediate (51‐100 × 109/L), and low (≤50 × 109/L). PC was also analyzed as a continuous covariate on multivariable analysis. The primary endpoint was major perioperative bleeding. The overall event rate of major perioperative bleeding was 8.9% and was not found to differ significantly between the high, intermediate, and low platelet groups (8.1% vs. 10.2% vs. 10.8%, P = 0.48). On multivariable analysis, greater age, aspartate aminotransferase, lower hemoglobin, and treatment with LR (vs. RFA) were found to be significant independent predictors of major perioperative bleeding, with associations with disease etiology and year of surgery also observed. After adjusting for these factors, the association between PC and major perioperative bleeding remained nonsignificant. Conclusion: Major perioperative bleeding was not significantly associated with PC in patients with cirrhosis undergoing surgical treatment of HCC, even when their PC was <50 × 109/L. With the limit of a retrospective analysis, our data do not support the recommendation of increasing PC in patients with severe thrombocytopenia in order to decrease their perioperative bleeding risk.
Numerical solution for natural convection flow near a vertical porous plate having convective boundary condition with nonlinear thermal radiation
Authors: Jha Basant K. , Samaila Gabriel
Published: October 2021

This article presents the theoretical study of the effects of suction/injection and nonlinear thermal radiation on boundary layer flow near a vertical porous plate. The importance of the convective boundary condition as regards the heat transfer rate is taken into account. The coupled nonlinear boundary layer equations are translated into a set of ordinary differential equations via a similarity transformation. The consequences of the active parameters like the suction parameter, injection parameter, convective heat transfer parameter, nonlinear thermal radiation parameters, and Grashof number dictating the flow transport are examined. The numerical result obtained shows that with suction/injection, the heat transfer rate could be increased with nonlinear thermal radiation parameter augment whereas decays with the convective heat transfer parameter and Grashof number. In the presence of suction/injection, the wall shear stress generally increases with nonlinear thermal radiation parameter, convective heat transfer parameter, and Grashof number. The suction has an increasing effect on Nusselt number and shear stress whereas a decreasing effect on Nusselt number and skin friction is seen with injection augment. The nonlinear thermal radiation is an increasing function of the temperature gradient far away from the plate whereas a decreasing function near the porous plate.