bluuebunny/crossref_metadata_2025 huggingface dataset:
Succinylation Inhibits the Enzymatic Hydrolysis of the Extracellular Matrix Protein Fibrillin 1 and Promotes Gastric Cancer Progression
Authors: Wang Xingyun , Shi Xiao , Lu Hongcheng , Zhang Chen , Li Xiang , Zhang Tiancheng , Shen Jiajia , Wen Jianfei
Published: July 2022

Extracellular matrix (ECM) remodeling is crucial in the regulation of gastric cancer (GC) progression. This work aims to reveal novel posttranslational modifications and their relevant mechanisms in GC. In 3D matrix culture and animal models, it is found that fibrillin 1 (FBN1) expression is increased in advanced GC and has succinylation modification. The succinylation modification of FBN1 blocks its degradation by matrix metalloproteinases (MMPs). The long‐term accumulation and deposition of FBN1 enhance tumor progression by activating TGF‐β1 and intracellular PI3K/Akt pathway. The FBN1 succinylation site monoclonal antibody can effectively intervene the effect of succinylation modification and inhibit GC progression. FBN1 is specifically upregulated in the progression of GC compared with other tumors. In conclusion, FBN1 is widely present in the form of K672‐succinylated modifications in GC. Besides, the succinyl group of FBN1 blocks its binding to MMP2, inhibits its degradation by MMP2, and leads to the accumulation of FBN1, which poses a long‐term risk to the poor prognosis of GC.
Tuning the Size of Large Dense‐Core Vesicles and Quantal Neurotransmitter Release via Secretogranin II Liquid–Liquid Phase Separation
Authors: Lin Zhaohan , Li Yinglin , Hang Yuqi , Wang Changhe , Liu Bing , Li Jie , Yin Lili , Jiang Xiaohan , Du Xingyu , Qiao Zhongjun , Zhu Feipeng , Zhang Zhe , Zhang Quanfeng , Zhou Zhuan
Published: July 2022

Large dense‐core vesicles (LDCVs) are larger in volume than synaptic vesicles, and are filled with multiple neuropeptides, hormones, and neurotransmitters that participate in various physiological processes. However, little is known about the mechanism determining the size of LDCVs. Here, it is reported that secretogranin II (SgII), a vesicle matrix protein, contributes to LDCV size regulation through its liquid–liquid phase separation in neuroendocrine cells. First, SgII undergoes pH‐dependent polymerization and the polymerized SgII forms phase droplets with Ca2+ in vitro and in vivo. Further, the Ca2+‐induced SgII droplets recruit reconstituted bio‐lipids, mimicking the LDCVs biogenesis. In addition, SgII knockdown leads to significant decrease of the quantal neurotransmitter release by affecting LDCV size, which is differently rescued by SgII truncations with different degrees of phase separation. In conclusion, it is shown that SgII is a unique intravesicular matrix protein undergoing liquid–liquid phase separation, and present novel insights into how SgII determines LDCV size and the quantal neurotransmitter release.
Glutathione Pulse Therapy: Promote Spatiotemporal Delivery of Reduction‐Sensitive Nanoparticles at the “Cellular Level” and Synergize PD‐1 Blockade Therapy
Authors: Dong Songtao , Zhang Yuan , Guo Xiangnan , Zhang Chuang , Wang Zhaomeng , Yu Jiang , Liu Yubo , Li Chang , Hu Yuting , Sun Bingjun , Sun Mengchi , Zhang Haotian , Ouyang Defang , He Zhonggui , Wang Yongjun
Published: July 2022

Spatiotemporal delivery of nanoparticles (NPs) at the “cellular level” is critical for nanomedicine, which is expected to deliver as much cytotoxic drug into cancer cells as possible when NPs accumulate in tumors. However, macrophages and cancer‐associated fibroblasts (CAFs) that are present within tumors limit the efficiency of spatiotemporal delivery. To overcome this limitation, glutathion pulse therapy is designed to promote reduction‐sensitive Larotaxel (LTX) prodrug NPs to escape the phagocytosis of macrophages and penetrate through the stromal barrier established by CAFs in the murine triple negative breast cancer model. This therapy improves the penetration of NPs in tumor tissues as well as the accumulation of LTX in cancer cells, and remodels the immunosuppressive microenvironment to synergize PD‐1 blockade therapy. More importantly, a method is established that can directly observe the biodistribution of NPs between different cells in vivo to accurately quantify the target drugs accumulated in these cells, thereby advancing the spatiotemporal delivery research of NPs at the “cellular level.”
Smart Internal Bio‐Glues
Authors: Zhang Hengjie , Zhang Jianhua , Peng Xu , Li Zhan , Bai Wanjie , Wang Tianyou , Gu Zhipeng , Li Yiwen
Published: July 2022

Although smart bio‐glues have been well documented, the development of internal bio‐glues for non‐invasive or minimally invasive surgery is still met with profound challenges such as safety risk and the lack of deep tissue penetration stimuli for internal usage. Herein, a series of smart internal bio‐glues are developed via the integration of o‐nitrobenzene modified biopolymers with up‐conversion nanoparticles (UCNPs). Upon irradiation by near‐infrared (NIR) light, the prepared smart bio‐glues can undergo a gelation process, which may further induce strong adhesion between tissues under both dry and wet conditions based on multi‐interactions. Moreover, those NIR light‐responsive bio‐glues with deeper tissue penetration ability demonstrate good biocompatibility, excellent hemostatic performance, and the potent ability to accelerate wound healing for both external and internal wounds. This work provides new opportunities for minimally invasive surgery, especially in internal wound healing using smart and robust bio‐glues.
Restraining the Octahedron Collapse in Lithium and Manganese Rich NCM Cathode toward Suppressing Structure Transformation
Authors: Xu Zhou , Guo Xingzhong , Wang JunZhang , Yuan Yifei , Sun Qing , Tian Rui , Yang Hui , Lu Jun
Published: July 2022

Lithium and manganese rich nickel cobalt manganese oxide (LMRNCM), as an attractive high energy density cathode for advanced lithium‐ion batteries (LIBs), suffers from inevitable lattice oxygen release, irreversible transition metal (TM) ion migration, and interface side reactions at high charge cut‐off voltage. Herein, a facile and efficient surface strategy is proposed to stabilize the layered structure by regulating the chemical bond interaction between the polyacrylonitrile (PAN) binder and the LMRNCM particles. Due to the high retention of discharge specific capacity and average discharge voltage, the energy density retention of the PAN‐modified LMRNCM sample is up to 80.12% after 300 cycles at 100 mA g−1 current density, and the initial Coulombic efficiency and rate capacity are also improved simultaneously. Experimental and density functional theory evidence demonstrates that the exceptional performance is caused by the coordination bond interaction between the carbon‐nitrogen‐triple‐bond of PAN and the TM ion in the unstable transition metal oxygen octahedron. The interaction suppresses the irreversible migration of TM ions by increasing the energy barrier, and ensures that the PAN adheres to the LMRNCM particles tightly, which relieves electrolyte corrosion and enhances cohesiveness. This work exploits a modification strategy to stabilize the LMRNCM‐layered structure for high‐energy density LIB applications.
Elevated exposures to respirable crystalline silica among engineered stone fabrication workers in California, January 2019–February 2020
Authors: Surasi Krishna , Ballen Brittany , Weinberg Justine L. , Materna Barbara L. , Harrison Robert , Cummings Kristin J. , Heinzerling Amy
Published: July 2022

Background

Workers fabricating engineered stone face high risk for exposure to respirable crystalline silica (RCS) and subsequent development of silicosis. In response, the California Division of Occupational Safety and Health (Cal/OSHA) performed targeted enforcement inspections at engineered stone fabrication worksites. We investigated RCS exposures and employer adherence to Cal/OSHA's RCS and respiratory protection standards from these inspections to assess ongoing risk to stone fabrication workers.

Methods

We extracted employee personal air sampling results from Cal/OSHA inspection files and calculated RCS exposures. Standards require that employers continue monitoring employee RCS exposures and perform medical surveillance when exposures are at or above the action level (AL; 25 μg/m3); exposures above the permissible exposure limit (PEL; 50 μg/m3) are prohibited. We obtained RCS and respiratory protection standard violation citations from a federal database.

Results

We analyzed RCS exposures for 152 employees at 47 workplaces. Thirty‐eight (25%) employees had exposures above the PEL (median = 89.7 μg/m3; range = 50.7–670.7 μg/m3); 17 (11%) had exposures between the AL and PEL. Twenty‐four (51%) workplaces had ≥1 exposure above the PEL; 7 (15%) had ≥1 exposure between the AL and PEL. Thirty‐four (72%) workplaces were cited for ≥1 RCS standard violation. Twenty‐seven (57%) workplaces were cited for ≥1 respiratory protection standard violation.

Conclusions

Our investigation demonstrates widespread RCS overexposure among workers and numerous employer Cal/OSHA standard violation citations. More enforcement and educational efforts could improve employer compliance with Cal/OSHA standards and inform employers and employees of the risks for RCS exposure and strategies for reducing exposure.
Neurodevelopmental functioning in probands and non‐proband carriers of 22q11.2 microduplication
Authors: Drmic Irene E. , MacKinnon Modi Bonnie , McConnell Beth , Jilderda Sanne , Hoang Ny , Noor Abdul , Bassett Anne S. , Speevak Marsha , Stavropoulos Dimitri J. , Carter Melissa T.
Published: July 2022

Microduplication of the LCR22‐A to LCR22‐D region on chromosome 22q11.2 is a recurrent copy number variant found in clinical populations undergoing chromosomal microarray, and at lower frequency in controls. Often inherited, there is limited data on intellectual (IQ) and psychological functioning, particularly in those individuals ascertained through a family member rather than because of neurodevelopmental disorders. To investigate the range of cognitive‐behavioral phenotypes associated with 22q11.2 duplication, we studied both probands and their non‐proband carrier relatives. Twenty‐two individuals with 22q11.2 duplication (10 probands, 12 non‐proband carriers) were prospectively assessed with a battery of neuropsychological tests, physical examination, and medical record review. Assessment measures with standardized norms included IQ, academic, adaptive, psychiatric, behavioral, and social functioning. IQ and academic skills were within the average range, with a trend toward lower scores in probands versus non‐probands. Adaptive skills were within age expectations. Prevalence of attention deficits (probands only) and anxiety (both groups) was high compared with norms. The prevalence of autism spectrum disorder was relatively low (5% of total sample). Assessment of both probands and non‐probands with 22q11.2 duplication suggests that the phenotypic spectrum with respect to neurodevelopment overlaps significantly with the general population. IQ and academic abilities are in the average range for most of the individuals with 22q11.2 duplication in our study, regardless of ascertainment as a proband or non‐proband relative. Symptoms of attention deficit and anxiety were identified, which require further study. Results of this study further clarify the phenotype of individuals with 22q11.2 duplication, and provides important information for genetic counseling regarding this recurrent copy number variant.
In‐situ Synthesis of Ionic Liquids on B‐doped Mesoporous SiO2 Catalyst for Epoxide‐CO2 Cycloaddition
Authors: Ye Yifei , Chen Yanglin , Huang Junzhe , Sun Jianmin
Published: July 2022

A series of functionalized ionic liquids (ILs) immobilized on B‐doped mesoporous SiO2 catalysts were fabricated for effectively converting CO2 into cyclic carbonates under metal‐absent and cocatalyst‐free conditions. Functionalized imidazolium ILs were in‐situ synthesized by Debus‐Rdziszewski imidazole reaction. Among the prepared catalysts, 5B−SiO2−NH2−3−I catalyst owing to the synergistic effects of nucleophile, Lewis acid‐base and hydroxyl hydrogen bond donors in the catalyst, presented the better catalytic activity for propylene epoxide to the product of propylene carbonate with 99% yield and selectivity at 110 °C and 2 MPa CO2. The catalyst also displayed moderate yield for various mono‐substituent epoxides. Besides, the gradual decline in the product yield during consecutive runs could be easily refreshed by aqueous acidic solution washing.
Environmentally Benign Transamidation Protocol for Weakly Nucleophilic Aromatic Amines with N‐Acyl‐2‐piperidinones: Catalyst‐, Additive‐, Base‐ and Solvent‐Free Condition
Authors: Rajan Ida Angel Priya Samuel , Subramani Muthuraman , Pushparathinam Gopinath , Rajendran Saravanakumar
Published: July 2022

Transamidation of weakly nucleophilic aromatic amines is achieved under melt conditions and in absence of catalyst, activating agent, base, and solvent. Chemoselectivity of the protocol is demonstrated with transamidation of aniline‐bearing protic carboxylic acid group and wide range of anilines. Broad applicability of the process is demonstrated with the synthesis of bioactive natural product amide, Avenanthranamide‐A. By‐product was isolated for re‐use in synthesis of starting amide, manifests atom economy, and sustainability of the protocol. Thus, our findings imply that the developed protocol is environmentally benign, operationally simple yet versatile for protection‐deprotection free synthesis of amides, peptides and amide‐based drugs.
Demographic changes in an Atlantic Forest primate community following a yellow fever outbreak
Authors: Possamai Carla B. , Rodrigues de Melo Fabiano , Mendes Sérgio Lucena , Strier Karen B.
Published: July 2022

We investigated demographic changes in three primate species (Alouatta guariba,Sapajus nigritus, andCallithrix flaviceps) at the Reserva Particular do Patrimônio Natural–Feliciano Miguel Abdala, Caratinga, Minas Gerais, Brazil, following a yellow fever outbreak (YFO) by comparing their population sizes before (2015) and after the outbreak (2017–2018), and by monitoring the size, composition, and reproductive status of groups from 2017 to 2021. Comparisons of pre‐ and post‐YFO census data indicate theA. guaribapopulation declined by 86.6%, from an estimated minimum of 522 individuals to 70 individuals. However, by October 2021, the population had grown to at least 86 individuals, with an adult sex ratio (N = 53) that was female‐biased (0.61). Eleven of the 13 groups being monitored systematically were reproductively active with high survivorship to 12 months of age.S. nigritusdeclined by 40%, from 377 to 226 individuals. The sex ratio of 33 adultS. nigritusis also female‐biased (0.71), and at least 8 of 15 groups being monitored are reproductively active.C. flavicepsdeclined by 80%, from 85 individuals to the 15–17 individuals observed from 2017 to 2021. The female‐biased adult sex ratio and presence of infants and juveniles in theA. guaribaandS. nigritusgroups are encouraging signs, but there is still great concern, especially forC. flaviceps.Continued monitoring of the demographics of these primates is needed as their persistence appears to still be at risk.
Dystrophinopathy Phenotypes and Modifying Factors in DMD Exon 45–55 Deletion
Authors: Poyatos‐García Javier , Martí Pilar , Liquori Alessandro , Muelas Nuria , Pitarch Inmaculada , Martinez‐Dolz Luis , Rodríguez Benjamin , Gonzalez‐Quereda Lidia , Damiá Maria , Aller Elena , Selva‐Gimenez Marta , Vilchez Roger , Diaz‐Manera Jordi , Alonso‐Pérez Jorge , Barcena José Eulalio , Jauregui Amaia , Gámez Josep , Aladrén Jesus Angel , Fernández Ariadna , Montolio Marisol , Azorin Inmaculada , Hervas David , Casasús Ana , Nieto Marisa , Gallano Pia , Sevilla Teresa , Vilchez Juan Jesus
Published: July 2022

Objective

Duchenne muscular dystrophy (DMD) exon 45–55 deletion (del45–55) has been postulated as a model that could treat up to 60% of DMD patients, but the associated clinical variability and complications require clarification. We aimed to understand the phenotypes and potential modifying factors of this dystrophinopathy subset.

Methods

This cross‐sectional, multicenter cohort study applied clinical and functional evaluation. Next generation sequencing was employed to identify intronic breakpoints and their impact on the Dp140 promotor, intronic long noncoding RNA, and regulatory splicing sequences. DMD modifiers (SPP1, LTBP4, ACTN3) and concomitant mutations were also assessed. Haplotypes were built using DMD single nucleotide polymorphisms. Dystrophin expression was evaluated via immunostaining, Western blotting, reverse transcription polymerase chain reaction (PCR), and droplet digital PCR in 9 muscle biopsies.

Results

The series comprised 57 subjects (23 index) expressing Becker phenotype (28%), isolated cardiopathy (19%), and asymptomatic features (53%). Cognitive impairment occurred in 90% of children. Patients were classified according to 10 distinct index‐case breakpoints; 4 of them were recurrent due to founder events. A specific breakpoint (D5) was associated with severity, but no significant effect was appreciated due to the changes in intronic sequences. All biopsies showed dystrophin expression of >67% and traces of alternative del45–57 transcript that were not deemed pathogenically relevant. Only the LTBP4 haplotype appeared associated the presence of cardiopathy among the explored extragenic factors.

Interpretation

We confirmed that del45–55 segregates a high proportion of benign phenotypes, severe cases, and isolated cardiac and cognitive presentations. Although some influence of the intronic breakpoint position and the LTBP4 modifier may exist, the pathomechanisms responsible for the phenotypic variability remain largely unresolved. ANN NEUROL 2022;92:793–806
Association between Human Blood Metabolome and the Risk of Alzheimer's Disease
Authors: Sun Lulu , Guo Daoxia , Jia Yiming , Shi Mengyao , Yang Pinni , Wang Yu , Liu Fanghua , Chen Guo‐Chong , Zhang Yonghong , Zhu Zhengbao
Published: July 2022

Objective

Alzheimer's disease (AD) is the most common degenerative neurological disorder with limited therapeutic options. Therefore, it is particularly important to explore the potential biomarkers implicated in the occurrence and progression of AD prior to clinical testing.

Methods

We selected 119 unique blood metabolites from 3 metabolome genome‐wide association studies (GWASs) with 147,827 European participants. Summary data about AD were obtained from a GWAS meta‐analysis with 63,926 European individuals from the International Genomics of Alzheimer's Project. MR analyses were performed to assess the associations of blood metabolites with AD, and a phenome‐wide MR analysis was further applied to ascertain the potential on‐target side effects of metabolite interventions.

Results

Four metabolites were identified as causal mediators for AD, including epiandrosterone sulfate (odds ratio [OR] per SD increase: 0.60; 95% confidence interval [CI]: 0.51–0.71; p = 6.14 × 10−9), 5alpha‐androstan‐3beta‐17beta‐diol disulfate (OR per SD increase: 0.69; 95% CI: 0.57–0.84; p = 1.98 × 10−4), sphingomyelin (OR per SD increase: 2.53; 95% CI: 1.78–3.59; p = 2.10 × 10−7), and glutamine (OR per SD increase: 0.83; 95% CI: 0.77–0.89; p = 2.09 × 10−6). Phenome‐wide MR analysis showed that epiandrosterone sulfate, 5alpha‐androstan‐3beta‐17beta‐diol disulfate and sphingomyelin mediated the risk of multiple diseases, and glutamine had beneficial effects on the risk of 4 diseases.

Interpretation

Genetically predicted increased epiandrosterone sulfate, 5alpha‐androstan‐3beta‐17beta‐diol disulfate, and glutamine might be associated with a decreased risk of AD, while sphingomyelin was associated with an increased risk. Side‐effect profiles were characterized to help inform drug target prioritization, and glutamine might be a promising target for the prevention and treatment of AD with no predicted detrimental side effects. ANN NEUROL 2022;92:756–767
Theoretical calculations for new coumarin Schiff base complexes as candidates for in vitro and in silico biological applications
Authors: Abdel‐Kader Nora S. , Moustafa Hussein , El‐Ansary Aida L. , Farghaly Aya M.
Published: July 2022

The Schiff base (Sb) formed by the condensation of 8‐acetyl‐7‐hydroxy‐4‐methyl coumarin and sulfaclozine was used for the preparation of [Cu2(CH3COO)3(Sb)(H2O)] (Cu2‐Sb) and [Pd2(OH)3(Sb)(H2O)]·2H2O (Pd2‐Sb) complexes. Also, the mixed ligand zinc complex, [(Sb)Zn(Cipro)]·4H2O, (Sb‐Zn‐Cipro) was prepared from (Sb) and ciprofloxacin. Many tools of analysis as elemental and spectral studies, in addition to thermogravimetry (TG), molar conductance, magnetic moment, X‐ray diffraction (XRD), energy dispersive X‐ray (EDX), scanning electron microscope (SEM), and electron spin resonance (ESR) measurements, were used to prove the complexes' composition. The morphology studies confirm the nanostructure of copper and palladium complexes. At the B3LYP/GENECP level, the optimal structure of the complexes was estimated using the 6‐31G++(d, p) basis set for C, H, N, S, and O atoms and the Los Alamos National Laboratory double zeta (LANL2DZ) basis set for metal atoms. A distorted square planar geometry is presumed for (Pd2‐Sb), and distorted tetrahedral geometry is presumed for (Cu2‐Sb) and (Sb‐Zn‐Cipro). The in vitro examination of the antimicrobial activity of the complexes was performed. The cytotoxic effects of the (Pd2‐Sb) and (Sb‐Zn‐Cipro) against MCF‐7 (breast cancer) and HCT‐116 (colon cancer) cell lines were achieved in vitro. The results showed that (Sb‐Zn‐Cipro) has the best biological activity. In view of this, the in silico binding mode of (Sb‐Zn‐Cipro) complex with Escherichia coli (KAS I‐PDB ID‐1FJ4), Staphylococcus aureus tyrosyl‐tRNA synthetase (PDB id: 1JIJ), yeast‐specific serine/threonine protein phosphatase (PPZ1) of Candida albicans (PDB ID: 5JPE), breast cancer mutant oxidoreductase (PDB ID: 3HB5), and colon cancer human cyclin‐dependent kinase 2; CDK2 (PDB ID: 6GUE) was performed using molecular docking.
Influence of chloride and sulfate solution on the long‐term durability of modified rubberized concrete
Authors: Kumar Rahul , Verma Manvendra , Dev Nirendra , Lamba Nitin
Published: July 2022

Limited investigations are available on the influence of chloride and sulfate solutions on pozzolana‐based cement rubberized concrete after crumb rubber treatment. Mechanical and durability characteristics of rubberized concrete are assessed and compared to conventional concrete. Five contents of crumb rubber (10%–30% at 5% of increment) are utilized for partially replacing fine aggregate in concrete. The optimum amount of crumb rubber in concrete is revealed at a replacement level of 15%. The specimens remained in the crystalline form after being immersed in NaCl (sodium chloride), Na2SO4 (sodium sulfate), and MgSO4 (magnesium sulfate) solution, according to structural analyses by XRD (X‐ray diffraction). When rubberized concrete is submerged in both sulfate solutions with the same concentrations and for the same amount of time, the specimens immersed in Na2SO4 solution lose less weight and compressive strength than specimens submerged in MgSO4 solution. The losses in compressive strength of conventional concrete are 1.86%, 3.57%, and 4.82% when immersed in NaCl, Na2SO4, and MgSO4 solution. However, the losses are 1.67%, 2.79%, and 3.16% in rubberized concrete only at 24 weeks. Pozzolana‐based cement and after crumb rubber treatment, the rubberized concrete can resist chloride and sulfate solutions for a long duration.
Self‐healing and chemical resistance polyurethane elastomers based on 2‐ureido‐4[1H]pyrimidinone
Authors: Fu Wenyu , Mei Huifeng , Zhang Zhijia , Wang Qiang , Li Rui , Zhang Songsong , Wang Guojun , Wei Hao , Zhang Chenyuan , Lin Cunguo , Wang Lei
Published: July 2022

Self‐healing polyurethane elastomers allow increasing the life cycle, adapting to the circular economy, thus reducing the generation of waste. In this work, ureido‐4[1H]‐pyrimidinone (UPy) compounds was used to construct on supramolecular polymer. The self‐healing polyurethane elastomers were successfully prepared by supramolecular polymer based on UPy via a simple blending way. The self‐healing performance of the polyurethane elastomers with UPy were investigated by the scratch test and the cut‐off test, respectively. The scratch of the self‐healing polyurethane elastomer (PU‐15UPy) was totally healed in 1 h at 35°C. The tensile strength and the elongation at break of PU‐15UPy were 0.81 MPa and 563.8%. After the cut‐off test, the healing efficiencies of tensile strength were 63.8% (0.51 MPa) and 85.2% (0.69 MPa) after healing for 10 h at 35 and 80°C, respectively. The healing efficiency of tensile strength reached the value of 90.1% (0.73 MPa) after healing for 24 h at 80°C. The chemical resistance of the self‐healing polyurethane elastomers was tested by immersion in water, NaCl solution (3%), HCl solution (5%), NaOH solution (5%), and diesel, respectively. The mass loss of self‐healing polyurethane elastomers were all less than 2% after immersed in these solutions for 1 month, indicating the excellent chemical resistance performance of PU‐15UPy.
Hydrophobic transition of soluble polymer aerogel composites
Authors: He Hao , Liu Qiang , Gao Bing‐Bing , Zhang Shui‐Dong , Chen Hong‐Bing
Published: July 2022

In order to overcome the hydrophilic problem of aerogels based on soluble polymer, the transition of aerogel composites from hydrophilic to hydrophobic was achieved by grafting 1H, 1H, 2H, 2H‐Perfluorodecyltrimethoxysilane (FAS). Simply immersing in FAS ethanol solution and then ambient drying, this method is universal and efficient, we successfully achieved the soluble polymer aerogels hydrophobic transition. Taking polyvinyl alcohol (PVOH)/SiO2 as an example, the changes of structure and properties of aerogels before and after modification were characterized in detail. It was proved that FAS was successfully grafted and ethanol evaporation had little effect on the microstructure of aerogel. The resulting aerogels possess very good hydrophobicity, with water contact angle of up to 147.5° (3 wt.% FAS). The aerogel exhibits good stability in maintaining hydrophobicity in a harsh environment, such as in extreme pH and temperature. We introduced a universal method for hydrophobic modification, which is of great significance for the practical application of aerogels.
Assessing treatability with simulated lake drawdown: Quantifying drought‐driven turbidity in source water
Authors: Hannoun Deena , Belding Jeffrey , Tietjen Todd , Devaney Robert
Published: July 2022

The Colorado River Basin is experiencing a significant drought that began in 2000. As water supplies are projected to continue declining, water managers are concerned with the ongoing treatability of Lake Mead water, which provides 90% of the source water for the Las Vegas Valley, and is a crucial link to downstream source water. The drinking water intake currently draws high‐quality, low‐turbidity water; however, turbidity is projected to increase. This study assesses treatability by quantifying projected turbidity of source water withdrawn from a drinking water intake in Lake Mead, Nevada. The water quality modeling results provide projections for Lake Mead water turbidities in the case of extreme drawdown and provide guidance for treatment staff. The underlying process incorporated existing water quality data and identified potential problems, yielding a template for hydrodynamic and water quality modeling that utilities can take advantage of to plan for future changes in source water quality.
Synthesis and characterization of N‐rich fluorescent bio‐dots as a reporter in the design of dual‐labeled FRET probe for TaqMan PCR: A feasibility study
Authors: Imani Mahsa , Mohajeri Nasrin , Rastegar Mojgan , Zarghami Nosratollah
Published: July 2022

DNA‐based analytical techniques have provided an advantageous sensing assay in the realm of biotechnology. Bio‐inspired fluorescent nanodots are a novel type of biological staining agents with excellent optical properties widely used for cellular imaging and diagnostics. In the present research, we successfully synthesized bio‐dots with excellent optical properties and high‐quantum yield from DNA sodium salt through the hydrothermal method. We conjugated the bio‐dots with 3' Eclipse Dark Quencher (Eclipse)‐labeled single‐strand oligodeoxyribonucleotide according to carbodiimide chemistry, to design a fluorescence resonance energy transfer (FRET) probe. The results confirmed the prosperous synthesis and surface functionalization of the bio‐dot. Analysis of size, zeta potential, and FTIR spectroscopy verified successful bioconjugation of the bio‐dots with probes. UV‐visibility analysis and fluorescence intensity profile of the bio‐dot and bio‐dot@probes represented a concentration‐dependent quenching of fluorescent signal of bio‐dot by Eclipse after probe conjugation. The results demonstrated that TaqMan PCR was not feasible using the designed bio‐dot@probes. Our results indicated that bio‐dot can be used as an efficient fluorescent tag in the design of fluorescently labeled oligonucleotides with high biocompatibility and optical features.
Exosomes: Biogenesis, targeting, characterization and their potential as "Plug & Play" vaccine platforms
Authors: Dyball Laura E , Smales C. Mark
Published: July 2022

Exosomes are typically characterized as spherical extracellular vesicles less than 150 nm in diameter that have been released into the extracellular environment via fusion of multivesicular bodies (MVBs) to the plasma membrane. Exosomes play a key role in cell‐cell communication, vary widely in their composition and potential cargo, and are reportedly involved in processes as diverse as angiogenesis, apoptosis, antigen presentation, inflammation, receptor‐mediated endocytosis, cell proliferation, and differentiation, and cell‐signaling. Exosomes can also act as biomarkers of health and disease and have enormous potential use as therapeutic agents. Despite this, the understanding of how exosome biogenesis can be utilized to generate exosomes carrying specific targets for particular therapeutic uses, their manufacture, detailed analytical characterization, and methods of application are yet to be fully harnessed. In this review, the author describes the current understanding of these areas of exosome biology from a biotechnology and bioprocessing aspect, but also highlight the challenges that remain to be overcome to fully harness the power of exosomes as therapeutic agents, with a particular focus on their use and application as vaccine platforms.
Recent developments in cell shipping methods
Authors: Heydarzadeh Shabnam , Kheradmand Kia Sima , Boroomand Seti , Hedayati Mehdi
Published: July 2022

As opposed to remarkable advances in the cell therapy industry, research reveal inexplicable difficulties associated with preserving and post‐thawing cell death. Post cryopreservation apoptosis is a common occurrence that has attracted the attention of scientists to use apoptosis inhibitors. Transporting cells without compromising their survival and function is crucial for any experimental cell‐based therapy. Preservation of cells allows the safe transportation of cells between distances and improves quality control testing in clinical and research applications. The vitality of transported cells is used to evaluate the efficacy of transportation strategies. For many decades, the conventional global methods of cell transfer were not only expensive but also challenging and had adverse effects. The first determination of some projects is optimizing cell survival after cryopreservation. The new generation of cryopreservation science wishes to find appropriate and alternative methods for cell transportation to ship viable cells at an ambient temperature without dry ice or in media‐filled flasks. The diversity of cell therapies demands new cell shipping methodologies and cryoprotectants. In this review, we tried to summarize novel improved cryopreservation methods and alternatives to cryopreservation with safe and viable cell shipping at ambient temperature, including dry preservation, hypothermic preservation, gel‐based methods, encapsulation methods, fibrin microbeads, and osmolyte solution compositions.
Screening of small molecular biomarker candidates using untargeted metabolomics strategy in peripheral blood from rats with neuroinflammatory injury induced by whole‐brain irradiation
Authors: Meng Xianshuang , Bai Hua , Ma Qiang , Zhang Peng , Ma Hong , Deng Yulin
Published: July 2022

Neuroinflammatory injury is one of the typical brain injuries after the body is exposed to radiation. It is mainly characterized by the release of inflammatory factors by activated microglia and peripherally invading lymphocytes. To provide early warning for nerve injury and early diagnosis of neurodegenerative diseases, it is of great significance to explore the biomarker candidates of neuroinflammatory injury. This study focused on the screening of small molecular biomarker candidates in peripheral blood from rats with neuroinflammatory injury induced by whole‐brain irradiation. The rats were exposed to 0, 10, 10 × 3, and 30 Gy of cobalt‐60 γ‐rays. Serum was collected on the 30th day after exposure and analyzed using reversed‐phase liquid chromatography and hydrophilic interaction liquid chromatography coupled with high‐resolution mass spectrometry based on untargeted metabolomics. Biomarker candidates were investigated by comparing the 0‐Gy group and three irradiation groups using univariate statistical analysis, principal component analysis, and orthogonal partial least squares discriminant analysis. Eleven biomarker candidates were putatively identified, and four major altered metabolic pathways were found. The screened small molecular biomarker candidates could be used as a useful supplement to traditional biomacromolecule markers and may be valuable for radiation protection, target therapy of inflammatory injury, and discovery of new target drugs for the prevention and cure of related neurodegenerative diseases.
Advanced Strategies of Enzyme Activity Regulation for Biomedical Applications
Authors: Chen Zihan , Zhao Yu , Liu Yang
Published: July 2022

Enzymes are important macromolecular biocatalysts that accelerate chemical and biochemical reactions in living organisms. Most human diseases are related to alterations in enzyme activity. Moreover, enzymes are potential therapeutic tools for treating different diseases, such as cancer, infections, and cardiovascular and cerebrovascular diseases. Precise remote enzyme activity regulation provides new opportunities to combat diseases. This review summarizes recent advances in the field of enzyme activity regulation, including reversible and irreversible regulation. It also discusses the mechanisms and approaches for on‐demand control of these activities. Furthermore, a range of stimulus‐responsive inhibitors, polymers, and nanoparticles for regulating enzyme activity and their prospective biomedical applications are summarized. Finally, the current challenges and future perspectives on enzyme activity regulation are discussed.
Regulation of immune cell metabolism in health and disease: Special focus on T and B cell subsets
Authors: Chakraborty Sayan , Khamaru Poulomi , Bhattacharyya Arindam
Published: July 2022

Metabolism is a dynamic process and keeps changing from time to time according to the demand of a particular cell to meet its bio‐energetic requirement. Different immune cells rely on distinct metabolic programs which allow the cell to balance its requirements for energy, molecular biosynthesis, and effector activity. In the aspect of infection and cancer immunology, effector T and B cells get exhausted and help tumor cells to evade immunosurveillance. On the other hand, T cells become hyperresponsive in the scenario of autoimmune diseases. In this article, we have explored the uniqueness and distinct metabolic features of key CD4+ T and B helper cell subsets, CD4+ T, B regulatory cell subsets and CD8+ T cells regarding health and disease. Th1 cells rely on glycolysis and glutaminolysis; inhibition of these metabolic pathways promotes Th1 cells in Treg population. However, Th2 cells are also dependent on glycolysis but an abundance of lactate within TME shifts their metabolic dependency to fatty acid metabolism. Th17 cells depend on HIF‐1α mediated glycolysis, ablation of HIF‐1α reduces Th17 cells but enhance Treg population. In contrast to effector T cells which are largely dependent on glycolysis for their differentiation and function, Treg cells mainly rely on FAO for their function. Therefore, it is of utmost importance to understand the metabolic fates of immune cells and how it facilitates their differentiation and function for different disease models. Targeting metabolic pathways to restore the functionality of immune cells in diseased conditions can lead to potent therapeutic measures.
Transcatheter vacuum‐assisted left‐sided mass extraction with the AngioVac system
Authors: Qintar Mohammed , Wang Dee Dee , Lee James , Villablanca Pedro , Eng Marvin H. , Frisoli Tiberio , O'Neill Brian P. , O'Neill William W.
Published: July 2022

Objectives

To study the safety and efficacy of AngioVac for left‐sided transcatheter vacuum‐assisted mass extraction (TVME).

Background

The AngioVac system is approved for right‐sided TVME and has emerged as an effective and safe alternative for open surgical treatment. The use of the AngioVac device for aspiration of left‐sided TVME has been limited.

Methods

Consecutive patients from two Michigan centers who underwent left‐sided TVME were included. Data on patient demographics, procedural information, in‐hospital and follow‐up events were collected through electronic medical records review. Technical success was defined as aspirating of 70%–100% of the material.

Results

Ten patients (mean age 58.3 [±17.3] years, 50% male) were included. Indications for TMVE were in large for recurrent embolic events. All patients underwent bilateral cerebro‐embolic protection using the Sentinel device. The total mean procedure time was 192.5 (±47.5) min of which the meantime for active aspiration (bypass time) was 9.3 (±4.2) min. The circuit configuration was: arteriovenous (AV) in four cases and arterioarterial (AA) in six cases. Successful aspiration was achieved in 80% of cases. No complications were reported (range follow‐up 1–16 months).

Conclusions

Our small case series demonstrates the feasibility and safety of the AngioVac system in left‐sided mass extraction. Larger trials are needed to further demonstrate its effectiveness and safety and potentially apply for on‐label use.
Particle Generation with Liquid Carbon Dioxide Emulsions
Authors: Lauscher Clara , Schaldach Gerhard , Thommes Markus
Published: July 2022

Spray drying is a common technique for particle generation. However, due to limitations in the droplet size, the production of solid submicron particles using conventional atomizers has proven to be challenging. With the aim of overcoming this limitation, the generation and expansion of emulsions of an aqueous solution and liquid carbon dioxide with a subsequent drying step was investigated. Potassium chloride concentrations in the solution between 0.1 and 10 wt. % and mass loads of the aqueous disperse phase between 0.01 and 0.09 were used in order to study their impact on the droplet and particle size. For the lowest potassium chloride concentration, median particle diameters in the submicron size range were measured for all mass loads of the disperse phase.
Photochromic Fentanyl Derivatives for Controlled μ‐Opioid Receptor Activation
Authors: Lahmy Ranit , Hübner Harald , Schmidt Maximilian F. , Lachmann Daniel , Gmeiner Peter , König Burkhard
Published: July 2022

Photoswitchable ligands as biological tools provide an opportunity to explore the kinetics and dynamics of the clinically relevant μ‐opioid receptor. These ligands can potentially activate or deactivate the receptor when desired by using light. Spatial and temporal control of biological activity allows for application in a diverse range of biological investigations. Photoswitchable ligands have been developed in this work, modelled on the known agonist fentanyl, with the aim of expanding the current “toolbox” of fentanyl photoswitchable ligands. In doing so, ligands have been developed that change geometry (isomerize) upon exposure to light, with varying photophysical and biochemical properties. This variation in properties could be valuable in further studying the functional significance of the μ‐opioid receptor.
A case of psoriasiform drug eruption caused by temozolomide
Authors: Oguro Tokuko , Nakajima Kimiko , Aoki Natsuko , Yamamoto Mayuko , Sano Shigetoshi
Published: July 2022

Psoriasiform drug eruption is defined as condition similar to psoriasis triggered by drug administration, including de novo development of psoriasis or exacerbation of pre‐existing psoriasis. Herein, we describe a 52‐year‐old Japanese woman, who developed disseminated psoriasiform lesions following administration of temozolomide, a remedy for glioblastoma, although cutaneous adverse events by this drug was very rare. In addition, we assume that altered inflammatory signals associated with psoriasis, such as activation of signal transducer and activator of transcription 3 (STAT3), might be involved in the underlying pathomechanism of drug eruption caused by temozolomide.
Targeted parallel DNA sequencing detects circulating tumor‐associated variants of the mitochondrial and nuclear genomes in patients with neuroblastoma
Authors: Riehl Lara , Mulaw Medhanie , Kneer Katharina , Beer Meinhard , Beer Ambros , Barth Thomas F. , Benes Vladimir , Schulte Johannes , Fischer Matthias , Debatin Klaus‐Michael , Beltinger Christian
Published: July 2022

Background

The utility for liquid biopsy of tumor‐associated circulating single‐nucleotide variants, as opposed to mutations, of the mitochondrial (mt) and nuclear genomes in neuroblastoma (NB) is unknown.

Procedure

Variants of the mt and nuclear genomes from tumor, blood cells, and consecutive plasma samples of five patients with metastatic NB that relapsed or progressed were analyzed. Targeted parallel sequencing results of the mt genome, and of the coding region of 139 nuclear genes and 22 miRNAs implicated in NB, were correlated with clinical imaging and laboratory data.

Results

All tumors harbored multiple somatic mt and nuclear single nucleotide variants with low allelic frequency, most of them not detected in the circulation. In one patient a tumor‐associated mt somatic variant was detected in the plasma before and during progressive disease. In a second patient a circulating nuclear tumor‐associated DNA variant heralded clinical relapse. In all patients somatic mt and nuclear variants not evident in the tumor biopsy at time of diagnosis were found circulating at varying timepoints. This suggests either tumor heterogeneity, evolution of tumor variants or a confounding contribution of normal tissues to somatic variants in patient plasma. The number and allelic frequency of the circulating variants did not reflect the clinical course of the tumors. Mutational signatures of mt and nuclear somatic variants differed. They varied between patients and were detected in the circulation without mirroring the patients' course.

Conclusions

In this limited cohort of NB patients clinically informative tumor‐associated mt and nuclear circulating variants were detected by targeted parallel sequencing in a minority of patients.
A Randomized Thorough QT Study of Apomorphine Sublingual Film in Patients With Parkinson's Disease
Authors: Stocchi Fabrizio , Peckham Elizabeth L. , De Pandis Maria Francesca , Sciarappa Ken , Kleiman Robert , Agbo Felix , Olanow C. Warren , Blum David , Navia Bradford
Published: July 2022

A randomized thorough QT study was conducted to assess the effects of apomorphine sublingual film (SL‐APO) on corrected QT interval (QTc) and other cardiac conduction parameters in patients with Parkinson's disease (PD) and “OFF” episodes. Patients were titrated to an SL‐APO dose that resulted in FULL “ON,” followed by up to two additional doses (maximum 60 mg), then randomized at the highest tolerated dose to a treatment sequence of SL‐APO, placebo, and moxifloxacin (400 mg, positive control) in a three‐way crossover design. Changes from baseline in time‐matched, placebo‐adjusted Fridericia‐corrected QTc interval (ΔΔQTcF) and Bazett‐corrected QTc interval (ΔΔQTcB) were analyzed from postdose electrocardiograms. Forty patients were randomized and received single doses of study treatments. Upper limits of 90% confidence intervals (CIs) for ΔΔQTcF of SL‐APO were below the 10‐millisecond regulatory threshold at all prespecified timepoints, demonstrating no clinically significant effect on QTcF. Lower limits of 90% CIs for ΔΔQTcF of moxifloxacin exceeded the 5‐millisecond regulatory threshold at all timepoints up to 3 hours, confirming assay sensitivity. SL‐APO had no clinically meaningful effects on QTcB, PR/QRS intervals, heart rate, or electrocardiogram‐derived morphology (EudraCT identifier: 2016‐001762‐29; ClinicalTrials.gov identifier: NCT03187301).
Intrusion detection system based firefly algorithm‐random forest for cloud computing
Authors: Moharamkhani Elaheh , Yahyaei Feriz Hendi Mohammad , Bandar Eisa , Izadkhasti Amir , Sirwan Raza Rzgar
Published: July 2022

Cloud computing is an active environment for accessing shared resources. Security in this environment, is one of the most important issues and concerns. An intrusion detection system is used to provide security and privacy. The intrusion detection system distinguishes between attacks and normal activities and prevents attacks on the cloud environment and notifies managers and cloud providers by creating alerts. Intrusion detection systems are usually implemented with different solutions. In this article, we present an intrusion detection system based on firefly algorithm and random forest algorithm that has the ability to detect intrusion with high accuracy in cloud computing, the results of model testing and evaluation, efficient and appropriate indicates the existence of the proposed method.
Genetic improvement of soybeans in Brazil: South and Midwest regions
Authors: Milioli Anderson Simionato , Meira Daniela , Panho Maiara Cecília , Madella Laura Alexandra , Woyann Leomar Guilherme , Todeschini Matheus Henrique , Zdziarski Andrei Daniel , Ramos Campagnolli Otávio , Menegazzi Caroline Patrícia , Colonelli Lucas Leite , Fernandes Rogê Afonso Tolentino , Melo Carlos Lásaro Pereira de , Fernandes de Oliveira Marcelo , Bertagnolli Paulo Fernando , Arias Carlos Alberto Arrabal , Giasson Nizio Fernando , Matsumoto Marcos Norio , Quiroga Marcos , Rossi Silva Raphael , Bertan Ivandro , Capelin Marcio Andrei , Matei Gilvani , Benin Giovani
Published: July 2022

Soybean [Glycine max (L.) Merril] is one of the main crops produced worldwide, and on‐farm yields have increased considerably in the last decades in Brazil. We evaluated the genetic gain for agronomic, phenological, and end‐use quality traits in 29 cultivars in the South Region, and in 38 cultivars in the Midwest Region in Brazil, released from 1966 to 2011. Field trials were conducted in Macroregions 1, 2, and 4, in 2016–2017, 2017–2018, and 2018–2019 crop seasons. The best linear unbiased predictors (BLUP) of the cultivars were obtained for each trait using a linear model. The BLUPs were regressed with the year of release using linear and quadratic regression models. The rates of genetic gain for seed yield ranged from 11.98 to 15.31 kg ha–1 yr–1 (0.33 to 0.42% yr–1) in the South Region, and from 13.58 to 21.84 kg ha–1 yr–1 (0.47 to 0.77% yr–1) in the Midwest Region. New cultivars presented taller plants and more seed oil content, oil and protein yield, and lower seed weight, days to flowering, days to maturity, and seed protein content than old cultivars in the South Region, although with differences between the Macroregions. In the Midwest Region, new cultivars showed higher seed oil content, oil and protein yield, and lower bottom pod height and seed protein content than old cultivars. Our results showed that breeding programs have been efficient to improve soybean yield and other traits across the years, without yield plateaus in sight.