bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical description of dementia patients concerned by acetylcholinesterase inhibitor and other drugs in Dr. Soeharto Heerdjan Psychiatry Hospital
Authors: Syah Putra Muhammad Fahmi , Noor Nasruddin
Published: July 2022

Background: Dementia is a syndrome of brain damage caused by cognitive changes due to brain trauma or degenerative, while clinical symptoms in dementia have a variety of both cognitive impairments and non cognitive disorders so that appropriate management in the form of pharmacological interventions is needed.Objective: To determine the clinical symptoms of dementia patients and use of drug Acetylcholinesterase Inhibitor and other drugs as a treatment in the Dr. Suharto Heerdjan Psychiatric Hospital.Methods: Quantitative non-experimental or analytical research, and the determination of samples by consecutive sampling method, that is, all medical records that meet established inclusion and exclusion criteria are included in the study until the number of samples is met.Results: Obtained inclusion criteria of 96 medical records belonging to Dr. Soeharto Heerdjan Psychiatric Hospital patients. with gender of female and male, age presenile dementia (65 years) and senile dementia ( 65 years) were found. The classification is found in dementia patients including not classified dementia, Alzheimer's dementia, vascular dementia, ytt dementia, parkinson's dementia, and finally dementia ydk, for acetylcholinesterase drugs were founded using donepezil, rivastigmine, and galantamine. The symptoms are obtained with general symptoms of dementia, positive symptoms, and negative symptoms. Comorbid diseases include hypertension, paranoid schizophrenia, residual schizophrenia, tension type headache, anxiety disorders, recurrent depression, and depressive disorders. And other drugs include antipsychotics, antiparkinsonians, mood stabilizers, antidepressants, anxiolytics, anticonvulsants, analgesics, immunosuppressants, antihypertensive agents, vitamins, and N-Methyl-D-Aspartate.Conclusion: Dementia patients at Dr. Soeharto Heerdjan Psychiatric Hospital has the highest diagnosis of Alzheimer's dementia with the most clinical symptoms in sundowner symptoms and delusional symptoms with some of them having the most comorbid disease in the form of hypertension. As for management, drug use in the acetylcholinesterase group in the form of donepezil and other drugs such as antipsychotic drugs in the form of risperidone or olanzapin, and anti-hypertensive drugs in the form of captopril, amlodipine, and beta blockers are drugs that are often used in patients.
Penggunaan Obat Asma Pada Pasien Asma di Puskesmas Karang Rejo Tarakan
Authors: Yuansafikri Reysaharif , Permana Dharma
Published: July 2022

Latar belakangAsma adalah penyakit heterogen yang disebabkan pajanan alergen, ditandai dengan inflamasi jalan napas kronis dengan prevalensinya di Indonesia menurut Riset Kesehatan Dasar mencapai 4,5% dan untuk mengatasinya diperlukan obat – obat asma.TujuanPenelitian ini bertujuan untuk mengetahui penggunaan obat asma pada pasien asma di Puskesmas Karang Rejo Tarakan pada periode Januari – April 2017MetodeMetode penelitian yang dilakukan adalah deskriptif dengan mengumpulkan data sekunder dari rekam medik pasien asma memenuhi kriteria inklusi baru pertama kali mendapat terapi asma dengan data rekam medik yang lengkap.Hasil dan DiskusiJumlah pasien puskesmas sebanyak 26.947 dengan pasien yang memenuhi kriteria inklusi sebanyak  225 pasien terdiri dari laki – laki (56,8%) dan perempuan (43,2%) pada rentang usia terbanyak anak – anak usia 0-5 tahun (32,8%) dan usia 20-44 tahun (29,3%). Obat yang paling banyak digunakan adalah Salbutamol (42%) dan Dexsamethasone (21,2%). Monoterapi yang paling sering digunakan adalah Salbutamol (14,2%), kombinasi 2 obat yaitu Salbutamol dan Dexamethasone (27,1%), kombinasi 3 obat yaitu Salbutamol, Gliseril Guaiakolat, dan Dexsamethasone (13,7%), dan kombinasi 4 obat yaitu Salbutamol, Dexamethasone, Gliseril Guaiakolat dan Klorfeniramin Maleat (2,6%).KesimpulanSalbutamol merupakan obat utama dalam penanggulangan asma baik sebagai monoterapi, kombinasi 2 obat, kombinasi 3 obat, dan kombinasi 4 obat.
Tax legislation of Ukraine under the conditions of martial law
Authors:   West Ukrainian National University, KRYSOVATYY Andrij , VALIHURA Volodymyr ,   West Ukrainian National University
Published: July 2022

Introduction. The full-scale war launched by the Russian Federation against Ukraine on February 24, 2022 immediately had a negative impact on all areas of society. The situation that has developed required urgent measures of the state in terms of regulating the issues of ensuring the provision of minimum public services and business support, including the anti-crisis tax regulation. Problem Statement. In response to the challenges, the Verkhovna Rada of Ukraine adopted a number of laws that eased the tax burden, eliminated the tax consequences of various support operations for the Armed Forces of Ukraine and persons affected by the consequences of the war. At the same time, the adopted innovations liberalized the tax system of Ukraine and endangered its fiscal security. Purpose. Critical expert analysis of tax legislation innovations adopted during the period of martial law and the formation of proposals for its adjustment in the conditions of war and post-war recovery. Methods. The following general scientific and special methods were used in the research process: logical analysis, synthesis, expert evaluation, description, comparison, theoretical generalization and abstract-logical. Results. Most of the adopted norms of tax legislation in the conditions of martial law do not contain financial and economic justification, were adopted on the basis of subjective judgments and did not have a regulatory effect. Instead, the martial law tax reform significantly reduced the fiscal function of taxes and created the conditions for abuse by dishonest taxpayers. Conclusions. The way out of the economic crisis caused by the war requires systemic state regulation. And tax instruments should play an important role in this system. At the same time, anti-crisis tax regulation must take into account a number of factors, among which the key factors are the fiscal needs of the state, the formation of a favorable business environment, the standards of tax compliance prescribed in the directives of the EU Council, and the military situation in the country. Further anti-crisis tax regulation in Ukraine is proposed to be considered under two scenarios: favorable (quick end of hostilities and transition to post-war recovery); negative (prolonged military actions of the aggressor country and the transition to the frozen conflict phase). Proposals for improvement of tax legislation based on the above scenarios have been formulated.
Potential benefits of tanniferous forages in integrative crop-livestock agroecosystems
Authors: Clemensen Andrea , Halvorson Jonathan J. , Christensen Rachael , Kronberg Scott L.
Published: July 2022

Integrating livestock into cropping systems may enhance ecosystem services while still providing efficient food production. Including tanniferous forages in crop-livestock systems could further enhance ecosystem services. Interest in phytochemicals, such as tannins, has increased over the past several decades, and research continues to reveal the potential benefits of tannins in agricultural systems. However, research evaluating the influence of tanniferous forages in integrative crop-livestock systems is limited. We discuss how tannins influence soil microbial dynamics and nutrient cycling, the function of tannins in forages, and the role tannins have in improving the health of foraging animals. We speculate on potential advantages for human health from consumption of animal-based foods from animals that consumed tanniferous forages or supplemental plant materials. Expanding our knowledge and integration of phytochemicals in muti-faceted agroecosystem research and utilizing their influence in agriculture system dynamics may be an effective tool to enhance agroecological sustainability.
Differences in Linear Epitopes of Ara h 9 Recognition in Peanut Allergic and Tolerant, Peach Allergic Patients
Authors: Sánchez-Ruano L. , Fernández-Lozano C. , Ferrer M. , Gómez F. , de la Hoz B. , Martínez-Botas J. , Goikoetxea M. J.
Published: July 2022

Background

Peanut-allergic patients from the Mediterranean region are predominantly sensitized to the lipid transfer protein (LTP) Ara h 9, and the peach LTP Pru p 3 seems to be the primary sensitizer. However, LTP sensitization in peanut allergy is not a predictive marker for clinically relevant symptoms.

Objective

We aimed to identify sequential epitopes of IgE and IgG4 from Pru p 3 and Ara h 9 in peach-allergic patients sensitized to peanuts. We also sought to determine the differences in IgE and IgG4 binding between patients who had developed peanut allergy and those tolerating peanuts.

Methods

A total of 46 peach-allergic patients sensitized to peanuts were selected. A total of 35 patients were allergic to peanuts (peanut-allergic group) and 11 were tolerant to peanuts (peanut-tolerant group). We measured sIgE and sIgG4 in peanut, peach, and their recombinant allergen (Ara h 1, Ara h 2, Ara h 3, Ara h 8, and Ara h 9) with fluorescence enzyme immunoassay. We examined the IgE and IgG4 binding to sequential epitopes using a peptide microarray corresponding to linear sequences of the LTPs Ara h 9 and Pru p 3 with a library of overlapping peptides with a length of 20 amino acids (aa) and an offset of 3 aa.

Results

The frequency and the intensity of IgE recognition of Ara h 9 and Pru p 3 peptides were higher in the peanut-tolerant group than in the peanut-allergic group. We found four Ara h 9 peptides (p4, p14, p21, and p25) and four Pru p 3 peptides (p1, p3, p21, and p24) with a significantly elevated IgE recognition in peanut-tolerant patients. Only one peptide of Ara h 9 (p4) recognized by IgG4 was significantly elevated in the peanut-tolerant group. The IgG4/IgE ratio of Ara h 9 peptide 4 was significantly higher in peanut-tolerant patients than in peanut-allergic patients, while no significant differences were observed in the IgG4/IgE ratio of this peptide in Pru p 3.

Conclusion

Although we found significant differences in IgE and IgG4 recognition of Ara h 9 and Pru p 3 between peanut-tolerant and peanut-allergic patients (all of whom were allergic to peach), polyclonal IgE peptide recognition of both LTPs was observed in peach-allergic patients tolerating peanuts. However, the IgG4 blocking antibodies against Ara h 9 peptide 4 could provide an explanation for the absence of clinical reactivity in peanut-tolerant peach-allergic patients. Further studies are needed to validate the usefulness of IgG4 antibodies against Ara h 9 peptide 4 for peanut allergy diagnosis.
Prediction of protein secondary structure based on an improved channel attention and multiscale convolution module
Authors: Jin Xin , Guo Lin , Jiang Qian , Wu Nan , Yao Shaowen
Published: July 2022

Prediction of the protein secondary structure is a key issue in protein science. Protein secondary structure prediction (PSSP) aims to construct a function that can map the amino acid sequence into the secondary structure so that the protein secondary structure can be obtained according to the amino acid sequence. Driven by deep learning, the prediction accuracy of the protein secondary structure has been greatly improved in recent years. To explore a new technique of PSSP, this study introduces the concept of an adversarial game into the prediction of the secondary structure, and a conditional generative adversarial network (GAN)-based prediction model is proposed. We introduce a new multiscale convolution module and an improved channel attention (ICA) module into the generator to generate the secondary structure, and then a discriminator is designed to conflict with the generator to learn the complicated features of proteins. Then, we propose a PSSP method based on the proposed multiscale convolution module and ICA module. The experimental results indicate that the conditional GAN-based protein secondary structure prediction (CGAN-PSSP) model is workable and worthy of further study because of the strong feature-learning ability of adversarial learning.
Transfer mechanism of cell-free synthesized membrane proteins into mammalian cells
Authors: Umbach Simon , Levin Roman , Neumann Sebastian , Steinmetzer Torsten , Dötsch Volker , Bernhard Frank
Published: July 2022

Nanodiscs are emerging to serve as transfer vectors for the insertion of recombinant membrane proteins into membranes of living cells. In combination with cell-free expression technologies, this novel process opens new perspectives to analyze the effects of even problematic targets such as toxic, hard-to-express, or artificially modified membrane proteins in complex cellular environments of different cell lines. Furthermore, transferred cells must not be genetically engineered and primary cell lines or cancer cells could be implemented as well. We have systematically analyzed the basic parameters of the nanotransfer approach and compared the transfer efficiencies from nanodiscs with that from Salipro particles. The transfer of five membrane proteins was analyzed: the prokaryotic proton pump proteorhodopsin, the human class A family G-protein coupled receptors for endothelin type B, prostacyclin, free fatty acids type 2, and the orphan GPRC5B receptor as a class C family member. The membrane proteins were cell-free synthesized with a detergent-free strategy by their cotranslational insertion into preformed nanoparticles containing defined lipid environments. The purified membrane protein/nanoparticles were then incubated with mammalian cells. We demonstrate that nanodiscs disassemble and only lipids and membrane proteins, not the scaffold protein, are transferred into cell membranes. The process is detectable within minutes, independent of the nanoparticle lipid composition, and the transfer efficiency directly correlates with the membrane protein concentration in the transfer mixture and with the incubation time. Transferred membrane proteins insert in both orientations, N-terminus in and N-terminus out, in the cell membrane, and the ratio can be modulated by engineering. The viability of cells is not notably affected by the transfer procedure, and transferred membrane proteins stay detectable in the cell membrane for up to 3 days. Transferred G-protein coupled receptors retained their functionality in the cell environment as shown by ligand binding, induction of internalization, and specific protein interactions. In comparison to transfection, the cellular membrane protein concentration is better controllable and more uniformly distributed within the analyzed cell population. A further notable difference to transfection is the accumulation of transferred membrane proteins in clusters, presumably determined by microdomain structures in the cell membranes.
Role of chitosan in titanium coatings. trends and new generations of coatings
Authors: López-Valverde Nansi , Aragoneses Javier , López-Valverde Antonio , Rodríguez Cinthia , Macedo de Sousa Bruno , Aragoneses Juan Manuel
Published: July 2022

Survival studies of dental implants currently reach high figures. However, considering that the recipients are middle-aged individuals with associated pathologies, research is focused on achieving bioactive surfaces that ensure osseointegration. Chitosan is a biocompatible, degradable polysaccharide with antimicrobial and anti-inflammatory properties, capable of inducing increased growth and fixation of osteoblasts around chitosan-coated titanium. Certain chemical modifications to its structure have been shown to enhance its antibacterial activity and osteoinductive properties and it is generally believed that chitosan-coated dental implants may have enhanced osseointegration capabilities and are likely to become a commercial option in the future. Our review provided an overview of the current concepts and theories of osseointegration and current titanium dental implant surfaces and coatings, with a special focus on the in vivo investigation of chitosan-coated implants and a current perspective on the future of titanium dental implant coatings.
A Structured Scaffold Featuring Biomimetic Heterogeneous Architecture for the Regeneration of Critical-Size Bone Defects
Authors: Wang Lingjun , Mao Jiannan , Cai Feng , Tang Jincheng , Xi Kun , Feng Yu , Xu Yichang , Liang Xiao , Gu Yong , Chen Liang
Published: July 2022

The regeneration of critical-size bone defects on long bones has remained a significant challenge because of the complex anatomical structure and vascular network. In such circumstances, current biomaterial forms with homogeneous structure and function can hardly satisfy the need for both osteogenesis and angiogenesis. In the current study, a heterogeneous biomimetic structured scaffold was constructed with the help of a 3D printed mold to simultaneously mimic the outer/inner periosteum and intermediate bone matrix of a natural long bone. Because of the reinforcement via modified mesoporous bioactive glass nanoparticles (MBGNs), enhanced structural stability and adequate osteogenic capacity could be achieved for the intermediate layer of this scaffold. Conversely, GelMA incorporated with VEGF-loaded liposome exhibiting controlled release of the angiogenic factor was applied to the inner and outer layers of the scaffold. The resulting heterogeneous structured scaffold was shown to successfully guide bone regeneration and restoration of the natural bone anatomic structure, rendering it a promising candidate for future orthopedic clinical studies.
Asymmetric stem-loop–mediated isothermal amplification of nucleic acids for DNA diagnostic assays by simple modification of canonical PCR primers
Authors: Mao Rui , Wu Xinyao , Miao Qing , Cai Ting
Published: July 2022

Nucleic acid–based assays have been adopted as mainstream tools for clinical diagnostics, food safety, and environment monitoring with the merits of accuracy, rapidity, and sensitivity. Loop-mediated isothermal amplification (LAMP) is a well-established method to rapidly identify nucleic acids and has gained recognition and been developed for clinical applications in resource-limited areas. However, the needs for specifically designed primer sets and non-specific amplification hinder the development of LAMP-based nucleic acid tests. Here, a promoted method, termed asymmetric stem-loop–mediated isothermal amplification (ASLAMP) by simple modification of canonical PCR primers, was developed to attempt to overcome those drawbacks. The two primers in the ASLAMP reaction can be easily obtained by adding a stem-loop sequence part to one PCR primer at 5′-ends to get the folding primer (FP), then adding the same primer to the counter canonical PCR primer at 5′-ends to get the turn-back primer (TP). The ASLAMP method was demonstrated in detecting the H1N1 gene fragment with merits of simple primer design, short target sequence, and high amplification efficiency. In addition, the ASLAMP method showed similar efficacy compared with LAMP targeting at the same H1N1 gene sequence. Furthermore, Shigella detection monitored by real-time fluorescence and endpoint colorimetric approaches were taken as examples for evaluation of the practical application of the ASLAMP method, both offered 100% sensitivity and specificity. In conclusion, the novel ASLAMP method with simplicity of primer design, low requirement of equipment, efficiency, and rapidity has exhibited its great prospect for establishment of DNA isothermal amplification in point of care application.
Development of in situ bioprinting: A mini review
Authors: MacAdam Aidan , Chaudry Emaan , McTiernan Christopher D. , Cortes David , Suuronen Erik J. , Alarcon Emilio I.
Published: July 2022

Bioprinting has rapidly progressed over the past decade. One branch of bioprinting known as in situ bioprinting has benefitted considerably from innovations in biofabrication. Unlike ex situ bioprinting, in situ bioprinting allows for biomaterials to be printed directly into or onto the target tissue/organ, eliminating the need to transfer pre-made three-dimensional constructs. In this mini-review, recent progress on in situ bioprinting, including bioink composition, in situ crosslinking strategies, and bioprinter functionality are examined. Future directions of in situ bioprinting are also discussed including the use of minimally invasive bioprinters to print tissues within the body.
Recent advances in PLGA micro/nanoparticle delivery systems as novel therapeutic approach for drug-resistant tuberculosis
Authors: Shao Liqun , Shen Shu , Liu Huan
Published: July 2022

Tuberculosis is a severe infectious disease caused by Mycobacterium tuberculosis and is a significant public health concern globally. The World Health Organization (WHO) recommends a combination regimen of several drugs, such as rifampicin (RIF), isoniazid (INH), pyrazinamide (PZA), and ethambutol (ETB), to treat tuberculosis. However, these drugs have low plasma concentrations after oral administration and require multiple high doses, which may lead to the occurrence and development of drug-resistant tuberculosis. Micro/Nanotechnology drug delivery systems have considerable potential in treating drug-resistant tuberculosis, allowing the sustained release of the drug and delivery of the drug to a specific target. These system properties could improve drug bioavailability, reduce the dose and frequency of administration, and solve the problem of non-adherence to the prescribed therapy. This study systematically reviewed the recent advances in PLGA micro/nanoparticle delivery systems as a novel therapeutic approach for drug-resistant tuberculosis.
Combining Metabolic Engineering and Multiplexed Screening Methods for 3-Hydroxypropionic Acid Production in Pichia pastoris
Authors: Fina Albert , Heux Stephanie , Albiol Joan , Ferrer Pau
Published: July 2022

Production of 3-hydroxypropionic acid (3-HP) in Pichia pastoris (syn. Komagataella phaffii) via the malonyl-CoA pathway has been recently demonstrated using glycerol as a carbon source, but the reported metrics were not commercially relevant. The flux through the heterologous pathway from malonyl-CoA to 3-HP was hypothesized as the main bottleneck. In the present study, different metabolic engineering approaches have been combined to improve the productivity of the original 3-HP producing strains. To do so, an additional copy of the gene encoding for the potential rate-limiting step of the pathway, i.e., the C-terminal domain of the malonyl-CoA reductase, was introduced. In addition, a variant of the endogenous acetyl-CoA carboxylase (ACC1S1132A) was overexpressed with the aim to increase the delivery of malonyl-CoA. Furthermore, the genes encoding for the pyruvate decarboxylase, aldehyde dehydrogenase and acetyl-CoA synthase, respectively, were overexpressed to enhance conversion of pyruvate into cytosolic acetyl-CoA, and the main gene responsible for the production of the by-product D-arabitol was deleted. Three different screening conditions were used to classify the performance of the different strains: 24-deep-well plates batch cultures, small-scale cultures in falcon tubes using FeedBeads® (i.e., slow release of glycerol over time), and mini bioreactor batch cultures. The best two strains from the FeedBeads® screening, PpHP8 and PpHP18, were tested in bioreactor fed-batch cultures using a pre-fixed exponentially increasing feeding rate. The strain PpHP18 produced up to 37.05 g L−1 of 3-HP at 0.712 g L−1 h−1 with a final product yield on glycerol of 0.194 Cmol−1 in fed-batch cultures. Remarkably, PpHP18 did not rank among the 2-top producer strains in small scale batch cultivations in deep-well plates and mini bioreactors, highlighting the importance of multiplexed screening conditions for adequate assessment of metabolic engineering strategies. These results represent a 50% increase in the product yield and final concentration, as well as over 30% increase in volumetric productivity compared to the previously obtained metrics for P. pastoris. Overall, the combination of glycerol as carbon source and a metabolically engineered P. pastoris strain resulted in the highest 3-HP concentration and productivity reported so far in yeast.
Effect of biochar on antibiotics and antibiotic resistance genes variations during co-composting of pig manure and corn straw
Authors: Tong Zhenye , Liu Fenwu , Tian Yu , Zhang Jingzhi , Liu Hui , Duan Jiaze , Bi Wenlong , Qin Junmei , Xu Shaozu
Published: July 2022

Pig manure is a reservoir of antibiotics and antibiotic resistance genes (ARGs). The effect of biochar on the variations in physicochemical properties, bacterial communities, antibiotics, ARGs, and mobile genetic elements (MGEs) of compost product during co-composting of pig manure and corn straw have been investigated in this study. Compared with the control treatment (CK), biochar addition accelerated the increase in pile temperature and prolonged the high temperature period (>55°C) for 2 days. Under biochar influence, organic matter degradation, NH4+-N conversion and NO3−-N production was accelerated, and dissolved total organic carbon (DOC) and dissolved total nitrogen (DTN) utilization by microorganisms were enhanced. Biochar addition altered the microbial community and promoted the vital activity of Actinobacteria in the later composting stage. The antibiotics removal efficiency (except danofloxacin and enrofloxacin) was accelerated in the early composting stage (1–14 days) by biochar addition, the pile temperature had a positive effect on antibiotics removal, and the total antibiotics removal efficiency in CK and CK+Biochar treatments was 69.58% and 78.67% at the end of the composting process, respectively. The absolute abundance of most of the ARGs in the CK+Biochar treatment was lower than that in the CK treatment during composting, and the ARGs removal mainly occurred in the early (1–14 days) and later (28–50 days) stages. Biochar addition reduced the absolute abundance of MGEs (intI1, intI2) in the compost product, and most of the ARGs had a significant positive correlation with MGEs. Network analysis and redundancy analysis showed that ARGs and MGEs occurred in various host bacteria (Firmicutes, Actinobacteria, Bacteroidetes, Proteobacteria, and Halanaerobiaeota), and that DTN and NH4+-N are the main factors regulating the changes in bacterial communities, antibiotics, ARGs, and MGEs during composting. Moreover, MGEs contributed the most to the variation in ARGs. In summary, biochar addition during composting accelerated antibiotics removal and inhibited accumulation and transmission of ARGs. The results of this study could provide theoretical and technical support for biochar application for antibiotics and ARGs removal during livestock and poultry manure composting.
Effect of expanded polytetrafluoroethylene thickness on paclitaxel release and edge stenosis in stent graft
Authors: Zhu Qing , Ye Ping , Niu Haifeng , Chang Zhaohua
Published: July 2022

Stent grafts have been widely used to treat lower extremity arterial stenosis or occlusion. However, there are major issues with edge stenosis and loss of patency over time. Paclitaxel-coated stent grafts have been proven to be effective in preventing edge stenosis, but the insufficient amounts of paclitaxel released may limit the effectiveness of drug-eluting stent grafts. In this study, we examined whether paclitaxel-coated expanded polytetrafluoroethylene (ePTFE) stent graft thickness influences paclitaxel release properties and inhibits edge stenosis. Low-, medium-, and high-thickness paclitaxel-coated stent grafts were prepared by varying the thickness of inner and outer ePTFE layers. Surface morphologies of the stent grafts were analyzed using a scanning electron microscope. The stent grafts were then implanted in the iliac arteries of 20 healthy swine. Twelve pigs were used to assess edge stenosis, and digital subtraction angiography was performed at day 30 (n = 4), 90 (n = 4), and 180 (n = 4). Histological evaluation of the treated arteries was also performed. Eight pigs were used for pharmacokinetic analysis, and the treated arteries were obtained at day 1 (n = 2), 30 (n = 2), 90 (n = 2) and 180 (n = 2). Scanning electron microscopy confirmed that the mean pore size of the stent grafts decreased with increasing thickness. The results of angiographic and histological evaluation demonstrated that low-thickness ePTFE-stent grafts resulted in edge stenosis and apparent intimal hyperplasia at 180 days, whereas for medium-thickness ePTFE-stent grafts, no obvious edge stenosis and intimal hyperplasia was noted in the similar time period. The results of pharmacokinetic evaluation showed that at 180 days, the paclitaxel concentration of treated arteries of the medium group was 36 ± 53 ng/g, while concentrations in the low group was not detectable. Stent grafts with increased ePTFE thickness appear to allow for more delayed release of paclitaxel compared to low-thickness ePTFEs.
Surface polydopamine modification of bone defect repair materials: Characteristics and applications
Authors: Du Jianhang , Zhou Ying , Bao Xiaogang , Kang Zhanrong , Huang Jianming , Xu Guohua , Yi Chengqing , Li Dejian
Published: July 2022

Bone defects are a common challenge for clinical orthopedic surgeons. The existing bone defect repair materials are difficult to achieve satisfactory osseointegration between the material and the bone. Therefore, it is increasingly important to find effective methods to improve the integration of the materials with the bone and thus facilitate bone defect repair. Researchers have found that polydopamine (PDA) has a structure and properties similar to the adhesive proteins secreted by mussels in nature, with good biocompatibility, bioactivity, hydrophilicity, bio-adhesion and thermal stability. PDA is therefore expected to be used as a surface modification material for bone repair materials to improve the bonding of bone repair materials to the bone surface. This paper reviews research related to PDA-modified bone repair materials and looks at their future applications.
Ice-Water Phase Change Studies in Plastic and Non-Plastic Silts
Authors: Bheemasetti Tejo V. , Tohm Calvin , Lingwall Bret N.
Published: July 2022

This article presents experimental results and analysis of change in freezing characteristics of clays and silts with change in pH and moisture content in the pore structures. The plastic and non-plastic silts and clays in the cold regions undergo significant changes in thermal properties causing non-equilibrium thermal conditions which can lead to frost-heave, thaw-weakening, thawing-induced landslides, and mass wasting events. In geotechnical engineering, particularly in cold regions, a soil’s thermal properties play a large role in the design, functionality, and longevity of an earthen structure. The thermal properties of the soil will also govern the porous media phase changes influencing thermal hysteresis and heat capacity in soils. These variables will change with seasonal freeze–thaw cycles, which can lead to changes in a soil’s structure, fabric, density, moisture content, and strength over time. With global warming causing the temperatures to gradually rise over time, the rapidly varying seasonal freeze–thaw cycles are now becoming an issue in areas where the designs have relied heavily on the permafrost. This research study investigates the fundamental changes to freezing and thawing characteristics of plastic and non-plastic silts with changes in frost penetration rates (cooling rate); moisture content (liquid limit, plastic limit, and optimum moisture content); pH (2–7); and soil type with different percentages of fines content and specific surface area.
Computational Metabolomics Reveals the Potential Mechanism of Matrine Mediated Metabolic Network Against Hepatocellular Carcinoma
Authors: Wang Kexin , Ye Xiangmin , Yin Chuanhui , Ren Qing , Chen Yupeng , Qin Xuemei , Duan Chuanzhi , Lu Aiping , Gao Li , Guan Daogang
Published: July 2022

Hepatocellular carcinoma (HCC) is a complex issue in cancer treatment in the world at present. Matrine is the main active ingredient isolated from Sophora flavescens air and possesses excellent antitumor effects in HCC. However, the specific underlying mechanisms, especially the possible relationships between the anti-HCC effect of matrine and the related metabolic network of HCC, are not yet clear and need further clarification. In this study, an integrative metabolomic-based bioinformatics algorithm was designed to explore the underlying mechanism of matrine on HCC by regulating the metabolic network. Cell clone formation, invasion, and adhesion assay were utilized in HCC cells to evaluate the anti-HCC effect of matrine. A cell metabolomics approach based on LC-MS was used to obtain the differential metabolites and metabolic pathways regulated by matrine. The maximum activity contribution score model was developed and applied to calculate high contribution target genes of matrine, which could regulate a metabolic network based on the coexpression matrix of matrine-regulated metabolic genes and targets. Matrine significantly repressed the clone formation and invasion, enhanced cell–cell adhesion, and hampered cell matrix adhesion in SMMC-7721 cells. Metabolomics results suggested that matrine markedly regulated the abnormal metabolic network of HCC by regulating the level of choline, creatine, valine, spermidine, 4-oxoproline, D-(+)-maltose, L-(−)-methionine, L-phenylalanine, L-pyroglutamic acid, and pyridoxine, which are involved in D-glutamine and D-glutamate metabolism, glycine, serine and threonine metabolism, arginine and proline metabolism, etc. Our proposed metabolomic-based bioinformatics algorithm showed that the regulating metabolic networks of matrine exhibit anti-HCC effects through acting on MMP7, ABCC1, PTGS1, etc. At last, MMP7 and its related target β-catenin were validated. Together, the metabolomic-based bioinformatics algorithm reveals the effects of the regulating metabolic networks of matrine in treating HCC relying on the unique characteristics of the multitargets and multipathways of traditional Chinese medicine.
The transcription factor LEF1 interacts with NFIX and switches isoforms during adult hippocampal neural stem cell quiescence
Authors: García-Corzo Laura , Calatayud-Baselga Isabel , Casares-Crespo Lucía , Mora-Martínez Carlos , Julián Escribano-Saiz Juan , Hortigüela Rafael , Asenjo-Martínez Andrea , Jordán-Pla Antonio , Ercoli Stefano , Flames Nuria , López-Alonso Victoria , Vilar Marçal , Mira Helena
Published: July 2022

Stem cells in adult mammalian tissues are held in a reversible resting state, known as quiescence, for prolonged periods of time. Recent studies have greatly increased our understanding of the epigenetic and transcriptional landscapes that underlie stem cell quiescence. However, the transcription factor code that actively maintains the quiescence program remains poorly defined. Similarly, alternative splicing events affecting transcription factors in stem cell quiescence have been overlooked. Here we show that the transcription factor T-cell factor/lymphoid enhancer factor LEF1, a central player in canonical β-catenin-dependent Wnt signalling, undergoes alternative splicing and switches isoforms in quiescent neural stem cells. We found that active β-catenin and its partner LEF1 accumulated in quiescent hippocampal neural stem and progenitor cell (Q-NSPC) cultures. Accordingly, Q-NSPCs showed enhanced TCF/LEF1-driven transcription and a basal Wnt activity that conferred a functional advantage to the cultured cells in a Wnt-dependent assay. At a mechanistic level, we found a fine regulation of Lef1 gene expression. The coordinate upregulation of Lef1 transcription and retention of alternative spliced exon 6 (E6) led to the accumulation of a full-length protein isoform (LEF1-FL) that displayed increased stability in the quiescent state. Prospectively isolated GLAST + cells from the postnatal hippocampus also underwent E6 retention at the time quiescence is established in vivo. Interestingly, LEF1 motif was enriched in quiescence-associated enhancers of genes upregulated in Q-NSPCs and quiescence-related NFIX transcription factor motifs flanked the LEF1 binding sites. We further show that LEF1 interacts with NFIX and identify putative LEF1/NFIX targets. Together, our results uncover an unexpected role for LEF1 in gene regulation in quiescent NSPCs, and highlight alternative splicing as a post-transcriptional regulatory mechanism in the transition from stem cell activation to quiescence.
Single-Cell Transcriptomics of Proliferative Phase Endometrium: Systems Analysis of Cell–Cell Communication Network Using CellChat
Authors: Fang Zishui , Tian Yao , Sui Cong , Guo Yaxin , Hu Xinyao , Lai Youhua , Liao Zhiqi , Li Jie , Feng Guihai , Jin Lei , Qian Kun
Published: July 2022

The endometrium thickness increases by which endometrial angiogenesis occurs in parallel with the rapid growth of endometrium during the proliferative phase, which is orchestrated by complex cell–cell interactions and cytokine networks. However, the intercellular communication has not been fully delineated. In the present work, we studied the cell–cell interactome among cells of human proliferative phase endometrium using single-cell transcriptomics. The transcriptomes of 33,240 primary endometrial cells were profiled at single-cell resolution. CellChat was used to infer the cell–cell interactome by assessing the gene expression of receptor–ligand pairs across cell types. In total, nine cell types and 88 functionally related signaling pathways were found. Among them, growth factors and angiogenic factor signaling pathways, including EGF, FGF, IGF, PDGF, TGFb, VEGF, ANGPT, and ANGPTL that are highly associated with endometrial growth, were further analyzed and verified. The results showed that stromal cells and proliferating stromal cells represented cell–cell interaction hubs with a large number of EGF, PDGF incoming signals, and FGF outgoing signals. Endothelial cells exhibited cell–cell interaction hubs with a plenty of VEGF, TGFb incoming signals, and ANGPT outgoing signals. Unciliated epithelial cells, ciliated epithelial cells, and macrophages exhibited cell–cell interaction hubs with substantial EGF outgoing signals. Ciliated epithelial cells represented cell–cell interaction hubs with a large number of IGF and TGFb incoming signals. Smooth muscle cells represented lots of PDGF incoming signals and ANGPT and ANGPTL outgoing signals. This study deconvoluted complex intercellular communications at the single-cell level and predicted meaningful biological discoveries, which deepened the understanding of communications among endometrial cells.
Reconstruction of the Global Polarity of an Early Spider Embryo by Single-Cell and Single-Nucleus Transcriptome Analysis
Authors: Akiyama-Oda Yasuko , Akaiwa Takanori , Oda Hiroki
Published: July 2022

Patterning along an axis of polarity is a fundamental step in the development of a multicellular animal embryo. In the cellular field of an early spider embryo, Hedgehog signaling operates to specify a “fuzzy” French-flag-like pattern along the primary axis, which is related to the future anterior–posterior (A–P) axis. However, details regarding the generation and development of a diversity of cell states based on the embryo polarity are not known. To address this issue, we applied single-cell RNA sequencing to the early spider embryo consisting of approximately 2,000 cells. Our results confirmed that this technique successfully detected 3 cell populations corresponding to the germ layers and some transient cell states. We showed that the data from dissociated cells had sufficient information for reconstruction of a correct global A–P polarity of the presumptive ectoderm, without clear segregation of specific cell states. This outcome is explained by the varied but differentially overlapping expression of Hedgehog-signal target genes and newly identified marker genes. We also showed that the data resources generated by the transcriptome analysis are applicable to a genome-wide search for genes whose expression is spatially regulated, based on the detection of pattern similarity. Furthermore, we performed single-nucleus RNA sequencing, which was more powerful in detecting emerging cell states. The single-cell and single-nucleus transcriptome techniques will help investigate the pattern-forming processes in the spider model system in an unbiased, comprehensive manner. We provided web-based resources of these transcriptome datasets for future studies of pattern formation and cell differentiation.
Recent advances in targeting protein kinases and pseudokinases in cancer biology
Authors: Riegel Kristina , Vijayarangakannan Parthiban , Kechagioglou Petros , Bogucka Katarzyna , Rajalingam Krishnaraj
Published: July 2022

Kinases still remain the most favorable members of the druggable genome, and there are an increasing number of kinase inhibitors approved by the FDA to treat a variety of cancers. Here, we summarize recent developments in targeting kinases and pseudokinases with some examples. Targeting the cell cycle machinery garnered significant clinical success, however, a large section of the kinome remains understudied. We also review recent developments in the understanding of pseudokinases and discuss approaches on how to effectively target in cancer.
Transcriptome Dynamics in the Developing Larynx, Trachea, and Esophagus
Authors: Wendt Kristy D. , Brown Jared , Lungova Vlasta , Mohad Vidisha , Kendziorski Christina , Thibeault Susan L.
Published: July 2022

The larynx, trachea, and esophagus share origin and proximity during embryonic development. Clinical and experimental evidence support the existence of neurophysiological, structural, and functional interdependencies before birth. This investigation provides the first comprehensive transcriptional profile of all three organs during embryonic organogenesis, where differential gene expression gradually assembles the identity and complexity of these proximal organs from a shared origin in the anterior foregut. By applying bulk RNA sequencing and gene network analysis of differentially expressed genes (DEGs) within and across developing embryonic mouse larynx, esophagus, and trachea, we identified co-expressed modules of genes enriched for key biological processes. Organ-specific temporal patterns of gene activity corresponding to gene modules within and across shared tissues during embryonic development (E10.5-E18.5) are described, and the laryngeal transcriptome during vocal fold development and maturation from birth to adulthood is characterized in the context of laryngeal organogenesis. The findings of this study provide new insights into interrelated gene sets governing the organogenesis of this tripartite organ system within the aerodigestive tract. They are relevant to multiple families of disorders defined by cardiocraniofacial syndromes.
The regulation of skin homeostasis, repair and the pathogenesis of skin diseases by spatiotemporal activation of epidermal mTOR signaling
Authors: Wang Juan , Cui Baiping , Chen Zhongjian , Ding Xiaolei
Published: July 2022

The epidermis, the outmost layer of the skin, is a stratified squamous epithelium that protects the body from the external world. The epidermis and its appendages need constantly renew themselves and replace the damaged tissues caused by environmental assaults. The mechanistic target of rapamycin (mTOR) signaling is a central controller of cell growth and metabolism that plays a critical role in development, homeostasis and diseases. Recent findings suggest that mTOR signaling is activated in a spatiotemporal and context-dependent manner in the epidermis, coordinating diverse skin homeostatic processes. Dysregulation of mTOR signaling underlies the pathogenesis of skin diseases, including psoriasis and skin cancer. In this review, we discuss the role of epidermal mTOR signaling activity and function in skin, with a focus on skin barrier formation, hair regeneration, wound repair, as well as skin pathological disorders. We propose that fine-tuned control of mTOR signaling is essential for epidermal structural and functional integrity.
Connexin Mutants Cause Cataracts Through Deposition of Apatite
Authors: Minogue Peter J. , Sommer Andre J. , Williams James C. , Bledsoe Sharon B. , Beyer Eric C. , Berthoud Viviana M.
Published: July 2022

Cataracts are lens opacities that are among the most common causes of blindness. It is commonly believed that cataracts develop through the accumulation of damage to lens proteins. However, recent evidence suggests that cataracts can result from calcium ion accumulation and the precipitation of calcium-containing salts. To test for the presence of precipitates and to identify their components, we studied the lenses of mice that develop cataracts due to mutations of connexin46 and connexin50. Micro-computed tomography showed the presence of radio-dense mineral in the mutant lenses, but not in wild-type lenses. Three-dimensional reconstructions of the scans showed that the distribution of the radio-dense mineral closely paralleled the location and morphology of the cataracts. The mutant lens homogenates also contained insoluble particles that stained with Alizarin red (a dye that stains Ca2+ deposits). Using attenuated total internal reflection micro–Fourier transform infrared spectroscopy, we identified the mineral as calcium phosphate in the form of apatite. Taken together, these data support the novel paradigm that cataracts are formed through pathological mineralization within the lens.
Focus on the tumor microenvironment: A seedbed for neuroendocrine prostate cancer
Authors: Zhou Hengfeng , He Qiangrong , Li Chao , Alsharafi Bassam Lutf Mohammed , Deng Liang , Long Zhi , Gan Yu
Published: July 2022

The tumor microenvironment (TME) is a microecology consisting of tumor and mesenchymal cells and extracellular matrices. The TME plays important regulatory roles in tumor proliferation, invasion, metastasis, and differentiation. Neuroendocrine differentiation (NED) is a mechanism by which castration resistance develops in advanced prostate cancer (PCa). NED is induced after androgen deprivation therapy and neuroendocrine prostate cancer (NEPC) is established finally. NEPC has poor prognosis and short overall survival and is a major cause of death in patients with PCa. Both the cellular and non-cellular components of the TME regulate and induce NEPC formation through various pathways. Insights into the roles of the TME in NEPC evolution, growth, and progression have increased over the past few years. These novel insights will help refine the NEPC formation model and lay the foundation for the discovery of new NEPC therapies targeting the TME.
Flash functional group-tolerant biaryl-synthesis based on integration of lithiation, zincation and negishi coupling in flow
Authors: Ashikari Yosuke , Guan Kaiteng , Nagaki Aiichiro
Published: July 2022

We achieved an integration of a lithiation of aryl bromides, a zincation of thus-generated aryllithiums, and a Negishi coupling of the arylzinc with an aryl halide in one flow. Taking advantages of flow microreactors, biaryls bearing a wide range of functional groups, especially biaryls bearing multiple electrophilic-functionalities were synthesized.