bluuebunny/crossref_metadata_2025 huggingface dataset:
Al2C4H2 Isomers with the Planar Tetracoordinate Carbon (ptC)/Aluminum (ptAl)
Authors: Malhan Abdul Hamid , Sobinson Sony , Job Nisha , Shajan Shilpa , Mohanty Surya Prakash , Thimmakondu Venkatesan S. , Thirumoorthy Krishnan
Published: October 2022

Forty-one isomers of Al2C4H2 that lie within 50 kcal mol−1 are theoretically identified in this work using density functional theory. Among these, isomers 3 and 14 contain a planar tetracoordinate carbon (ptC) atom that lies at 3.3 and 16.9 kcal mol−1, respectively, and are above the global minimum geometry 1 at the ωB97XD/6-311++G(2d,2p) level of theory. The other ten isomers that also contain unique bonding features are isomers 4, 18, 20, 21, 22, 27, 28, 31, 34, and 40. Out of these isomers, 4, 18, 20, 22, 27, 28, and 34 contain planar tetracoordinate aluminum (ptAl) whereas isomers 31 and 40 contain both ptC and ptAl atoms. Chemical bonding characteristic features are thoroughly analyzed for all these eleven isomers with various bonding and topological quantum chemical tools, such as NBO, AdNDP, WBI, and ELF, except isomer 27 due to the observed elongated Al-Al bond length. The current results indicate that ptC isomer 3 is more stable than other isomers because electron delocalization is more prevalent and it also has double aromaticity as observed from the ELF, NICS, and AdNDP analysis. Further, the structural stability of these isomers is investigated through ab initio molecular dynamics (AIMD) simulation. Isomer 21 shows the planar pentacoordinate aluminum but it is observed as a kinetically unstable geometry from AIMD and, further, one could notice that it isomerizes to isomer 12.
Co-Expression of Pig IL-2 and Fusion Bovine Cathelicidin Gene by Recombinant Plasmids in Yeast and Their Promotion of Mouse Antibacterial Defense
Authors: Chen Jianlin , Peng Junjie , Ma Changjun , Zhang Linhan , Wu Xueyin , Wei Hong , Li Jianglin , Lü Xuebin , Gao Rong
Published: October 2022

In order to develop an effective and safe immunomodulator to enhance the antimicrobial bioactivity and immunity of animals against infectious bacterial diseases, a recombinant plasmid pGAPZαA-IL2-B co-expressing pig interleukin-2 (PIL-2) and fused bovine cathelicidin (FBC) genes were constructed using the 2A self-cleavage technique. After being expressed in Pichia pastoris strain SMD1168, the recombinant yeast was administered orally to 5-week-old female ICR mice. The control mice were similarly dosed with P. pastoris with a blank plasmid or FBC recombinant plasmid alone. At 28 days post-treatment, the mice were challenged intraperitoneally with virulent strains of either E. coli or S. aureus. Compared with the control groups, the mice that received recombinant yeast co-expressing PIL-2/FBC manifested significant increases in the number of leukocytes, CD4+ and CD8+ T cells, IgG, and the gene expressions of TLRs(TLR1,4,6,9), antimicrobial peptides(CRP4 and CRAMP) and cytokines (IL-2, 4, 6, 7, 12, 15, 23, IFN-γ, and TNF-α) in the blood. Furthermore, the treated mice displayed significantly higher survival than the other two control groups after the challenge. These results suggest that the antimicrobial activity and immunity of animals can be effectively enhanced by the in vivo co-expression of IL-2 and the FBS gene, which can facilitate the development of new immunopotentiation molecules to overcome the infection of antibiotic-resistant bacteria.
Immunosenescence, Inflammaging, and Lung Senescence in Asthma in the Elderly
Authors: Soma Tomoyuki , Nagata Makoto
Published: October 2022

Prevalence of asthma in older adults is growing along with increasing global life expectancy. Due to poor clinical consequences such as high mortality, advancement in understanding the pathophysiology of asthma in older patients has been sought to provide prompt treatment for them. Age-related alterations of functions in the immune system and lung parenchyma occur throughout life. Alterations with advancing age are promoted by various stimuli, including pathobionts, fungi, viruses, pollutants, and damage-associated molecular patterns derived from impaired cells, abandoned cell debris, and senescent cells. Age-related changes in the innate and adaptive immune response, termed immunosenescence, includes impairment of phagocytosis and antigen presentation, enhancement of proinflammatory mediator generation, and production of senescence-associated secretory phenotype. Immnunosenescence could promote inflammaging (chronic low-grade inflammation) and contribute to late-onset adult asthma and asthma in the elderly, along with age-related pulmonary disease, such as chronic obstructive pulmonary disease and pulmonary fibrosis, due to lung parenchyma senescence. Aged patients with asthma exhibit local and systemic type 2 and non-type 2 inflammation, associated with clinical manifestations. Here, we discuss immunosenescence’s contribution to the immune response and the combination of type 2 inflammation and inflammaging in asthma in the elderly and present an overview of age-related features in the immune system and lung structure.
Traumatic Brain Injury Leads to Alterations in Contusional Cortical miRNAs Involved in Dementia
Authors: Naseer Shahmir , Abelleira-Hervas Laura , Savani Dhwani , de Burgh Ross , Aleksynas Robertas , Donat Cornelius K. , Syed Nelofer , Sastre Magdalena
Published: October 2022

There is compelling evidence that head injury is a significant environmental risk factor for Alzheimer’s disease (AD) and that a history of traumatic brain injury (TBI) accelerates the onset of AD. Amyloid-β plaques and tau aggregates have been observed in the post-mortem brains of TBI patients; however, the mechanisms leading to AD neuropathology in TBI are still unknown. In this study, we hypothesized that focal TBI induces changes in miRNA expression in and around affected areas, resulting in the altered expression of genes involved in neurodegeneration and AD pathology. For this purpose, we performed a miRNA array in extracts from rats subjected to experimental TBI, using the controlled cortical impact (CCI) model. In and around the contusion, we observed alterations of miRNAs associated with dementia/AD, compared to the contralateral side. Specifically, the expression of miR-9 was significantly upregulated, while miR-29b, miR-34a, miR-106b, miR-181a and miR-107 were downregulated. Via qPCR, we confirmed these results in an additional group of injured rats when compared to naïve animals. Interestingly, the changes in those miRNAs were concomitant with alterations in the gene expression of mRNAs involved in amyloid generation and tau pathology, such as β-APP cleaving enzyme (BACE1) and Glycogen synthase-3-β (GSK3β). In addition increased levels of neuroinflammatory markers (TNF-α), glial activation, neuronal loss, and tau phosphorylation were observed in pericontusional areas. Therefore, our results suggest that the secondary injury cascade in TBI affects miRNAs regulating the expression of genes involved in AD dementia.
Clinical Significance and Immune Infiltration Analyses of the Cuproptosis-Related Human Copper Proteome in Gastric Cancer
Authors: Tang Xiaohuan , Guo Ting , Wu Xiaolong , Gan Xuejun , Wang Yiding , Jia Fangzhou , Zhang Yan , Xing Xiaofang , Gao Xiangyu , Li Ziyu
Published: October 2022

Background: The human copper Cu proteome, also termed Cu-binding proteins (CBP), is responsible for transporting “free” Cu to the cell that is related to cuproptosis. However, their role in gastric cancer (GC) has not been reported. Methods: RNA expression data of 946 GC patients were collected. A series of machine learning and bioinformatic approaches were combined to build a CBP signature to predict survival and immune microenvironment and guide the priority treatment. Immunohistochemistry and multicolor immunofluorescence (mIF) in 1076 resection slides were used to verify immune features. Results: A CBP signature was constructed using the machine learning method from TCGA that classifies cases as CBP_low and CBP_high groups. Multivariable Cox analysis confirmed that the CBP signature was an independent prognostic factor in the training and validation cohorts. Additionally, GC patients with low CBPscores showed an increase in anti-tumor immune microenvironment, which was further verified by mIF in pathological resections following immunotherapy. Importantly, patients with low CBPscores had higher levels of TMB/MSI and responded well to immunotherapy. Conclusions: We conducted the first and comprehensive CBP analysis of GC patients and established a clinically feasible CBP signature for predicting survival and response to treatment, which will be helpful for guiding personalized medicine.
Plasma Fatty Acid Composition Is Associated with Histological Findings of Nonalcoholic Steatohepatitis
Authors: Miyake Teruki , Furukawa Shinya , Matsuura Bunzo , Yoshida Osamu , Miyazaki Masumi , Shiomi Akihito , Kanzaki Sayaka , Nakaguchi Hironobu , Sunago Kotaro , Nakamura Yoshiko , Imai Yusuke , Watanabe Takao , Yamamoto Yasunori , Koizumi Yohei , Tokumoto Yoshio , Hirooka Masashi , Kumagi Teru , Abe Masanori , Hiasa Yoichi
Published: October 2022

The relationship between advanced nonalcoholic steatohepatitis (NASH) and plasma fatty acid composition remains unknown. We aimed to examine the plasma fatty acid composition in biopsy-confirmed nonalcoholic fatty liver disease (NAFLD) and evaluate the relationship between histological findings and fatty acid composition. Overall, 235 patients (134 women) with NAFLD were enrolled. Comprehensive blood chemistry tests and histological examinations of liver samples were conducted. Multivariate analyses adjusted for age, sex, body mass index, alanine aminotransferase, hemoglobin A1c, creatinine, total cholesterol, triglyceride, and NAFLD Activity Score values showed that lower levels of arachidic, behenic, α-linolenic, eicosatetraenoic, docosapentaenoic, and docosahexaenoic acids and higher levels of mead acid were associated with fibrosis stage 3–4. Furthermore, higher lauric acid, myristic acid, and palmitic acid levels and monounsaturated fatty acids such as palmitoleic acid and oleic acid were significantly associated with high NAS in analyses adjusted for the same factors and fibrosis stage. The plasma fatty acid composition was associated with the histological evidence of NASH. Increased synthesis of fatty acids is associated with NASH; insufficient intake of n-3 essential fatty acids and reduced elongation of fatty acids are associated with fibrosis in NASH. These features may help clinicians to understand and treat advanced NASH cases.
In Vivo Analysis of the Dynamic Motion Stability Characteristics of Geese’s Neck
Authors: Wang Jiajia , Sun Haoxuan , Jia Wenfeng , Zhang Fu , Qian Zhihui , Cui Xiahua , Ren Lei , Ren Luquan
Published: October 2022

The goose’s neck is an excellent stabilizing organ with its graceful neck curves and flexible movements. However, the stabilizing mechanism of the goose’s neck remains unclear. This study adopts a dynamic in vivo experimental method to obtain continuous and accurate stable motion characteristics of the goose’s cervical vertebra. Firstly, the results showed that when the body of a goose was separately moved back and forth along the Y direction (front and back) and Z direction (up and down), the goose’s neck can significantly stabilize the head. Then, because of the limitation of the X-ray imaging area, the three-dimensional intervertebral rotational displacements for vertebrae C4–C8 were obtained, and the role that these five segments play in the stabilization of the bird’s neck was analyzed. This study reveals that the largest range of the adjacent vertebral rotational movement is around the X-axis, the second is around the Y-axis, and the smallest is around the Z-axis. This kinematic feature is accord with the kinematic feature of the saddle joint, which allows the flexion/around X-axis and lateral bending/around Y-axis, and prevents axial rotation/around Z-axis.
Progress in the Development of Detection Strategies Based on Olfactory and Gustatory Biomimetic Biosensors
Authors: Chen Yating , Du Liping , Tian Yulan , Zhu Ping , Liu Shuge , Liang Dongxin , Liu Yage , Wang Miaomiao , Chen Wei , Wu Chunsheng
Published: October 2022

The biomimetic olfactory and gustatory biosensing devices have broad applications in many fields, such as industry, security, and biomedicine. The development of these biosensors was inspired by the organization of biological olfactory and gustatory systems. In this review, we summarized the most recent advances in the development of detection strategies for chemical sensing based on olfactory and gustatory biomimetic biosensors. First, sensing mechanisms and principles of olfaction and gustation are briefly introduced. Then, different biomimetic sensing detection strategies are outlined based on different sensing devices functionalized with various molecular and cellular components originating from natural olfactory and gustatory systems. Thereafter, various biomimetic olfactory and gustatory biosensors are introduced in detail by classifying and summarizing the detection strategies based on different sensing devices. Finally, the future directions and challenges of biomimetic biosensing development are proposed and discussed.
Omicron BA.2.75 Subvariant of SARS-CoV-2 Is Expected to Have the Greatest Infectivity Compared with the Competing BA.2 and BA.5, Due to Most Negative Gibbs Energy of Binding
Authors: Popovic Marko
Published: October 2022

Omicron BA.2.75 may become the next globally dominant strain of COVID-19 in 2022. The BA.2.75 sub-variant has acquired more mutations (9) in spike protein and other genes of SARS-CoV-2 than any other variant. Thus, its chemical composition and thermodynamic properties have changed compared with earlier variants. In this paper, the Gibbs energy of the binding and antigen-receptor binding rate was reported for the BA.2.75 variant. Gibbs energy of the binding of the Omicron BA.2.75 variant is more negative than that of the competing variants BA.2 and BA.5.
Experimental Study on Seismic Behavior of Precast Bolt-Connected Steel-Members End-Embedded Concrete (PBSEC) Beam-Column Connections
Authors: Wang Zhun , Feng De-Cheng , Wu Gang
Published: October 2022

With the rapid development and research of precast concrete frame structures, it is not difficult to find that the structural form and seismic performance of dry-connected precast joints have always been the focus of research. Since this type of structural system is complex, the construction is inconvenient in practical application, and many additional parts need to be installed, this paper develops a kind of precast bolt-connected steel-members end-embedded concrete (PBSEC) beam-column connection to solve the shortcomings of the current dry-connected precast joints. There is no wet work in the assembly process, and all-dry construction and assembly methods are used. There is no need to pour concrete and support formwork, which significantly improves construction efficiency compared to wet and cast-in-situ connections. Low cyclic reversed loading tests were conducted to obtain test data, such as failure mode, hysteresis curve, skeleton curve, stiffness, ductility, and deformation capacity of the precast concrete joint. The failure mode of the PBSEC joints is the buckling failure of the connecting steel plate, leading to a perfect seismic capacity and collapse resistance of the structure. The hysteresis curves of the PBSEC joints are bow-shaped and full in shape, showing high energy dissipation capacity. The bearing capacity of the joints begins to rise rapidly at the initial loading stage and then decreases slowly after reaching the peak, which is an ideal shape. By summarizing the average peak load, strength degradation coefficient, loop energy per cycle, loop energy per level, and cumulative energy damping coefficient, it is found that the joint using 10 mm thick Q235 steel can obtain the most suitable failure mode and obtain the best energy dissipation performance. When the strength of the steel plate material increases, the energy dissipation performance of the joint drops.
A Technique for Optimizing the Sequences Yielding under Load of Concentrically-Braced Steel Frames
Authors: Li Bin , Wang Zhan , Fan Yanjing , Pan Jianrong , Wang Peng , Zhou Zhenfeng
Published: October 2022

Concentrically-braced steel framing is widely used in tall buildings. Designing with adequate but not excessive seismic resistance is a challenge because of the limited experience of seismic failure and the huge variety of components used. A quantitative method for defining an acceptable range of component parameters is proposed and tested using published experimental data and finite element modeling. The method involves the structural yield mechanism control method of the steel concentrically-braced frame. It is proposed by inequality iteration of different structural components’ bearing capacities. It generates acceptable ranges for the parameters defining the properties of the columns, beams, and braces. The test results show that concentrically-braced steel frames designed within the recommended ranges will have the desired sequence of component yielding. The sequence is, however, highly sensitive to components’ parameter values. In practical engineering stochastic variability in the parameters must be considered.
Influence of Project Governance on Opportunistic Behavior: Taking a Dynamic Perspective
Authors: Han Wenjing , Yin Yilin
Published: October 2022

The importance of project governance in curbing opportunistic behavior (OB) has been clearly established in the project literature. Although contract governance and trust are considered critical factors that explain project governance, there is a lack of understanding regarding their interplay at various stages of project development. The current study takes a dynamic perspective and breaks down contract governance into contract completeness (CC) and contract enforcement (CE), while differentiating ex-ante trust from ex-post trust. As such, the current study takes a dynamic perspective and the Grossman-Hart-Moore (GHM) model, which aims to investigate how each of the two facets of contract governance and trust intertwine during the management of construction projects as well as their effects on OB. We undertook a questionnaire survey of individuals involved in 342 construction projects in China, and our research results show that, first of all, governance mechanisms at different stages have different inhibitory effects on OB. Taking contract-signing as the boundary, the governance effect of a contract is gradually enhanced, while the governance effect of trust is gradually reduced. Second, ex-ante trust is more important than ex-post trust: the former moderates not only the relationship between CE and OB, but also the influence of CC on OB. Finally, a contract that is overly complete is not conducive to precluding OB, as such completeness can give the contract parties a sense of security that is guaranteed. The current study not only garners insights into project governance research but also provides implications for architectural practitioners in deploying resources that relate to governance mechanisms.
Analysis of Spatio-Temporal Characteristics and Trend Forecast of Building Industry VOCs Emissions in China
Authors: Dai Hongbin , Huang Guangqiu , Wang Jingjing , Zeng Huibin
Published: October 2022

Emissions of volatile organic compounds (VOCs) from the building industry in China are increasing. Predicting future trends in China’s building industry VOCs will help the implementation of China’s construction VOCs emission reduction policy. The aim of this study is to combine Granger causality analysis, Ridge regression, GM(1,N), and categorical boosting (CatBoost) methods for the analysis of factors influencing and trend prediction of VOCs emissions from building industry in China. Firstly, the spatial and temporal characteristics of building industry VOCs emissions in China were calculated, based on building industry VOCs emissions data from 2006 to 2020 for each province and city in China. Secondly, Granger causality tests and STIRPAT models were used to examine the influencing factors of construction VOCs, combined with ridge regression to estimate the elasticity coefficients of the influencing factors and feature screening, which were used as input features for prediction. Finally, a combination of the improved GM(1,N) model and the CatBoost model was used to predict and compare the results with those of the GM(1,N) model, the support vector regression model (SVR), the random forest (RF), and the CatBoost model. The results show that the combined model with improved GM(1,N) and CatBoost has better prediction accuracy than the other models. China’s building industry VOCs emissions are increasing year on year and are not expected to reach their peak by 2030. The size of the population, the number of people employed in the building industry, and the area of housing floor space under construction are important influencing factors that affect VOCs emissions from building industry in China. Based on the predicted results for the different scenario settings, building industry VOCs emissions are lower in the short term for the baseline scenario and in the long term for the high-speed scenario.
Sentinel Lymph Node Gene Expression Signature Predicts Recurrence-Free Survival in Cutaneous Melanoma
Authors: Karapetyan Lilit , Gooding William , Li Aofei , Yang Xi , Knight Andrew , Abushukair Hassan M. , Vargas De Stefano Danielle , Sander Cindy , Karunamurthy Arivarasan , Panelli Monica , Storkus Walter J. , Tarhini Ahmad A. , Kirkwood John M.
Published: October 2022

We sought to develop a sentinel lymph node gene expression signature score predictive of disease recurrence in patients with cutaneous melanoma. Gene expression profiling was performed on SLN biopsies using U133A 2.0 Affymetrix gene chips. The top 25 genes associated with recurrence-free survival (RFS) were selected and a penalized regression function was used to select 12 genes with a non-zero coefficient. A proportional hazards regression model was used to evaluate the association between clinical covariates, gene signature score, and RFS. Among the 45 patients evaluated, 23 (51%) had a positive SLN. Twenty-one (46.7%) patients developed disease recurrence. For the top 25 differentially expressed genes (DEG), 12 non-zero penalized coefficients were estimated (CLGN, C1QTNF3, ADORA3, ARHGAP8, DCTN1, ASPSCR1, CHRFAM7A, ZNF223, PDE6G, CXCL3, HEXIM1, HLA-DRB). This 12-gene signature score was significantly associated with RFS (p < 0.0001) and produced a bootstrap C index of 0.888. In univariate analysis, Breslow thickness, presence of primary tumor ulceration, SLN positivity were each significantly associated with RFS. After simultaneously adjusting for these prognostic factors in relation to the gene signature, the 12-gene score remained a significant independent predictor for RFS (p < 0.0001). This SLN 12-gene signature risk score is associated with melanoma recurrence regardless of SLN status and may be used as a prognostic factor for RFS.
A North-West London Experience of the Impact of Treatment Related Toxicity on Clinical Outcomes of Elderly Patients with Germ Cell Tumors
Authors: Sharma Anand , Morrison Laura , Milic Marina , Ghose Aruni , Gogbashian Andrew , Vasdev Nikhil , Agarwal Samita , Pullar Ben , Rustin Gordon
Published: October 2022

Background/Aim: The occurrence of germ cell tumour (GCT) in the elderly is rare, with scarce data available. The aim of this study was to understand the clinical outcomes of patients with GCT in patients aged > 45 years. Materials and Methods: A retrospective study was conducted in a large tertiary cancer centre in north-west London. Between 1 January 2003 and 31 March 2022, 108 cases of GCT in men aged > 45 years were identified and treated at the Mount Vernon Cancer Centre. The median age at diagnosis was 54 years (range = 45–70 years). Results: The 5-year survival rate of all patients was 96%, and the toxicity profile was similar to the younger age group. Conclusion: Older patients with GCT are able to tolerate chemotherapy; however, care must be taken to prevent life-threatening complications using appropriate dose modification.
Characterizing and Targeting Genes Regulated by Transcription Factor MYBL2 in Lung Adenocarcinoma Cells
Authors: Lee Yuri , Wu Zexun , Yang Seolyn , Schreiner Shannon M. , Gonzalez-Smith Leonardo D. , Rhie Suhn K.
Published: October 2022

Overexpression of MYBL2 is associated with poor survival of lung adenocarcinoma patients, but the molecular mechanism by which it regulates transcription and carcinogenesis has not yet been elucidated. In this study, we performed ChIP-seq using an MYBL2-targeted antibody and discovered that MYBL2 primarily binds to the promoters of highly expressed genes in lung adenocarcinoma cells. Using a knockdown experiment of MYBL2 and global transcriptome profiling, we identified that over a thousand genes are dysregulated by MYBL2, and MYBL2 acts as a transcriptional activator in lung adenocarcinoma cells. Moreover, we revealed that the binding sites of FOXM1 are largely shared with MYBL2 binding sites, and genes involved in cell cycle phase transitions are regulated by these transcription factors. We furthermore investigated the effect of a previously reported FOXM1 inhibitor, FDI-6, in lung adenocarcinoma cells. We demonstrated that FDI-6 decreases the proliferation of lung adenocarcinoma cells and inhibits the activities of FOXM1 as well as MYBL2. Moreover, we found that genes involved in cell death and cell cycle are inhibited by FDI-6. Overall, our findings suggest that MYBL2 and FOXM1 activate cell cycle genes together, acting as oncogenic transcription factors in lung adenocarcinoma cells, and they are potential treatment targets for the disease.
Electromotive Enhanced Drug Administration in Oncology: Principles, Evidence, Current and Emerging Applications
Authors: Min Jolene Wong Si , Saeed Nidda , Coene Annelies , Adriaens Mieke , Ceelen Wim
Published: October 2022

Local-regional administration of cytotoxic drugs is an important adjunct to systemic chemotherapy amongst cancer patients. It allows for targeted delivery of agents at high concentration to target sites while minimizing systemic side effects. Despite the pharmacokinetic advantages of the local–regional approach, drug transport into tumor nodules remains limited due to the biophysical properties of these tissues. Electromotive enhanced drug administration (EMDA) represents a potential solution to overcome challenges in local drug transport by applying electric currents. Through electrokinetic phenomena of electromigration, electroosmosis and electroporation, electric currents have been shown to improve drug penetration and distribution in a wide variety of clinical applications. Amongst patients with non-muscular invasive bladder cancer (NMIBC) and basal and squamous cell skin cancers, EMDA has been successfully adopted and proven efficacious in several pre-clinical and clinical studies. Its application in ophthalmological and other conditions has also been explored. This review provides an overview of the underlying principles and factors that govern EMDA and discusses its application in cancer patients. We also discuss novel EMDA approaches in pre-clinical studies and explore future opportunities of developments in this field.
Sensitization of Patient-Derived Colorectal Cancer Organoids to Photon and Proton Radiation by Targeting DNA Damage Response Mechanisms
Authors: Pape Kristin , Lößner Anna J. , William Doreen , Czempiel Tabea , Beyreuther Elke , Klimova Anna , Lehmann Claudia , Schmäche Tim , Merker Sebastian R. , Naumann Max , Ada Anne-Marlen , Baenke Franziska , Seidlitz Therese , Bütof Rebecca , Dietrich Antje , Krause Mechthild , Weitz Jürgen , Klink Barbara , von Neubeck Cläre , Stange Daniel E.
Published: October 2022

Pathological complete response (pCR) has been correlated with overall survival in several cancer entities including colorectal cancer. Novel total neoadjuvant treatment (TNT) in rectal cancer has achieved pathological complete response in one-third of the patients. To define better treatment options for nonresponding patients, we used patient-derived organoids (PDOs) as avatars of the patient’s tumor to apply both photon- and proton-based irradiation as well as single and combined chemo(radio)therapeutic treatments. While response to photon and proton therapy was similar, PDOs revealed heterogeneous responses to irradiation and different chemotherapeutic drugs. Radiotherapeutic response of the PDOs was significantly correlated with their ability to repair irradiation-induced DNA damage. The classical combination of 5-FU and irradiation could not sensitize radioresistant tumor cells. Ataxia-telangiectasia mutated (ATM) kinase was activated upon radiation, and by inhibition of this central sensor of DNA damage, radioresistant PDOs were resensitized. The study underlined the capability of PDOs to define nonresponders to irradiation and could delineate therapeutic approaches for radioresistant patients.
Risk Factors Associated with Pancreatic Cancer in the UK Biobank Cohort
Authors: Ke Te-Min , Lophatananon Artitaya , Muir Kenneth R.
Published: October 2022

Evidence on pancreatic cancer (PaCa) risk factors from large population-based cohort studies is limited. This study investigated the PaCa risk factors and the population attributable fraction (PAF) of modifiable risk factors in the UK Biobank cohort. The UK Biobank is a prospective cohort consisting of 502,413 participants with a mean follow-up time of 8.2 years. A binomial generalized linear regression model was used to calculate relative risks for PaCa risk factors. PAF was calculated to estimate the proportional reduction in PaCa if modifiable risk factors were to be eliminated. A total of 728 (0.14%) PaCa incident cases and 412,922 (82.19%) non-PaCa controls were analyzed. The non-modifiable risk factors included age and gender. The modifiable risk factors were cigarette smoking, overweight and obesity, increased waist circumstance, abdominal obesity, Diabetic Mellitus (DM), and pancreatitis history. The PAF suggested that eliminating smoking and obesity can contribute around a 16% reduction in PaCa cases while avoiding abdominal obesity can eliminate PaCa cases by 22%. Preventing pancreatitis and DM could potentially reduce PaCa cases by 1% and 6%, respectively. This study has identified modifiable and non-modifiable PaCa risk factors in the UK population. The PAF of modifiable risk factors can be applied to inform PaCa prevention programs.
CYP153A71 from Alcanivorax dieselolei: Oxidation beyond Monoterminal Hydroxylation of n-Alkanes
Authors: Jacobs Cheri Louise , do Aido-Machado Rodolpho , Tolmie Carmien , Smit Martha Sophia , Opperman Diederik Johannes
Published: October 2022

Selective oxyfunctionalization of non-activated C–H bonds remains a major challenge in synthetic chemistry. The biocatalytic hydroxylation of non-activated C–H bonds by cytochrome P450 monooxygenases (CYPs), however, offers catalysis with high regio- and stereoselectivity using molecular oxygen. CYP153s are a class of CYPs known for their selective terminal hydroxylation of n-alkanes and microorganisms, such as the bacterium Alcanivorax dieselolei, have evolved extensive enzymatic pathways for the oxyfunctionalization of various lengths of n-alkanes, including a CYP153 to yield medium-chain 1-alkanols. In this study, we report the characterization of the terminal alkane hydroxylase from A. dieselolei (CYP153A71) for the oxyfunctionalization of medium-chain n-alkanes in comparison to the well-known CYP153A6 and CYP153A13. Although the expected 1-alkanols are produced, CYP153A71 readily converts the 1-alkanols to the corresponding aldehydes, fatty acids, as well as α,ω-diols. CYP153A71 is also shown to readily hydroxylate medium-chain fatty acids. The X-ray crystal structure of CYP153A71 bound to octanoic acid is solved, yielding an insight into not only the regioselectivity, but also the binding orientation of the substrate, which can be used in future studies to evolve CYP153A71 for improved oxidations beyond terminal n-alkane hydroxylation.
Identifying Candidate Circulating RNA Markers for Coronary Artery Disease by Deep RNA-Sequencing in Human Plasma
Authors: Ward Zoe , Schmeier Sebastian , Pearson John , Cameron Vicky A , Frampton Chris M , Troughton Richard W , Doughty Rob N , Richards A. Mark , Pilbrow Anna P
Published: October 2022

Advances in RNA sequencing (RNA-Seq) have facilitated transcriptomic analysis of plasma for the discovery of new diagnostic and prognostic markers for disease. We aimed to develop a short-read RNA-Seq protocol to detect mRNAs, long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) in plasma for the discovery of novel markers for coronary artery disease (CAD) and heart failure (HF). Circulating cell-free RNA from 59 patients with stable CAD (half of whom developed HF within 3 years) and 30 controls was sequenced to a median depth of 108 paired reads per sample. We identified fragments from 3986 messenger RNAs (mRNAs), 164 long non-coding RNAs (lncRNAs), 405 putative novel lncRNAs and 227 circular RNAs in plasma. Circulating levels of 160 mRNAs, 10 lncRNAs and 2 putative novel lncRNAs were altered in patients compared with controls (absolute fold change >1.2, p < 0.01 adjusted for multiple comparisons). The most differentially abundant transcripts were enriched in mRNAs encoded by the mitochondrial genome. We did not detect any differences in the plasma RNA profile between patients who developed HF compared with those who did not. In summary, we show that mRNAs, lncRNAs and circular RNAs can be reliably detected in plasma by deep RNA-Seq. Multiple coding and non-coding transcripts were altered in association with CAD, including several mitochondrial mRNAs, which may indicate underlying myocardial ischaemia and oxidative stress. If validated, circulating levels of these transcripts could potentially be used to help identify asymptomatic individuals with established CAD prior to an acute coronary event.
Uterine Artery Pseudoaneurysm after an Uncomplicated Vaginal Delivery: A Case Report
Authors: Böckenhoff Paul , Kupczyk Patrick , Lindner Kira , Strizek Brigitte , Gembruch Ulrich
Published: October 2022

Uterine artery pseudoaneurysm (UAP) is a rare and potentially life-threatening vascular anomaly caused by inadequate sealing of a ruptured wall of a uterine artery. It mainly occurs after a traumatic lesion and can lead to delayed postpartum hemorrhage. We report a rare case of UAP after an uncomplicated vaginal delivery in a patient with a history of deep-infiltrating endometriosis. Selective coil embolization was successfully performed. UAPs should always be considered in cases of unexplained abdominal pain after surgery or childbirth with or without vaginal bleeding.
Effect of Storage Conditions on the Physicochemical Characteristics of Bilayer Edible Films Based on Iron Yam–Pea Starch Blend and Corn Zein
Authors: Song Xiaoyong
Published: October 2022

Edible iron yam–pea starch-based bilayer films with a water and oil proof layer of corn zein were prepared by casting method and stored under normal temperature (25 °C; relative humidity (RH): 43%, 54%, 65%), refrigeration (4 °C) and freezing (−17 °C) for 150 days. The mechanical properties, scanning electron microscope (SEM) micrographs, oxygen and water vapor permeability, color, transmittance, haze, water content were systematically evaluated after 0, 30, 60, 90, 120 and 150 days. The transmittance, haze, and water content of bilayer films changed greatly within 150 days, which indirectly indicated the changes of the internal microstructure of the film matrix. The results were further verified by SEM analysis. Water and oxygen resistance gradually become worse. At 25 °C and 54% RH, the barrier performances were relatively strong. Films had relatively good tensile strength at normal temperature and high humidity, and relatively good elongation at break at low temperature and high humidity. SEM observation showed that there was no interlayer separation during storage. The internal network structure disappeared and reappeared again. The changes of internal microstructure also verified the changes of barrier and mechanical properties of bilayer films.
The Predictive Significance of Prognostic Nutritional Index and Serum Albumin/Globulin Ratio on the Overall Survival of Penile Cancer Patients Undergoing Penectomy
Authors: Song Wei-Jie , Li Ni-Chujie , Gao Jun , Xu Zhi-Peng , Liu Jian-Ye , Long Zhi , He Le-Ye
Published: October 2022

Objective: To assess the value of using the prognostic nutritional index (PNI) and serum albumin/globulin ratio (AGR) in predicting the overall survival (OS) of patients with penile cancer (PC) undergoing penectomy. Materials and methods: A retrospective analysis of 123 patients who were admitted to our hospital due to PC from April 2010 to September 2021 and who underwent penectomy were included in the study. The optimal cut-off value of the PNI and AGR was determined by receiver operating characteristic curve analysis. Kaplan–Meier analysis and the Cox proportional hazard model were used to evaluate the correlation between the PNI, AGR, and OS in patients with PC. Results: A total of 16 of the 123 patients died during the follow-up period, and the median follow-up time was 58.0 months. The best cut-off values of the PNI and AGR were set to 49.03 (95% confidence interval 0.705–0.888, Youden index = 0.517, sensitivity = 57.9%, specificity = 93.7%, p < 0.001) and 1.28 (95% confidence interval 0.610–0.860, Youden index = 0.404, sensitivity = 84.1%, specificity = 56.2%, p = 0.003). The Kaplan–Meier analysis showed that the OS of the patients in the high PNI group and the high AGR group was significantly higher than that of the patients in the low PNI group and the low AGR group (p < 0.001). The univariable analysis showed that the aCCI, the clinical N stage, the pathological stage, and the PNI, AGR, SII, and PLR are all predictors of OS in patients with PC (p < 0.05). The multivariable analysis showed that the PNI (risk rate [HR] = 0.091; 95% CI: 0.010–0.853; p = 0.036) and the AGR (risk rate [HR] = 0.171; 95% CI: 0.043–0.680; p = 0.012) are independent prognostic factors for predicting OS in patients with PC undergoing penectomy. Conclusions: Both the PNI score and the serum AGR are independent prognostic factors for predicting OS in patients with PC undergoing penectomy.
The First-Named Fossil Ostrich: A Revision of Struthio asiaticus, from the Siwaliks of India
Authors: Buffetaut Eric
Published: October 2022

The first fossil ostrich to have been named, by Milne-Edwards in 1869–1871, was Struthio asiaticus, a taxon based on a specimen collected by Colonel Colvin in the Siwaliks of India, consisting of associated postcranial elements (vertebrae, forelimb elements, a fragmentary tarsometatarsus and first phalanx of the third toe). Although it was described as least twice in some detail in the 19th century, the specimen has since then been interpreted in conflicting ways. A revision of the type material and its history shows that it came in all likelihood from the Siwaliks of present-day India, not Pakistan. The exact locality is unknown and the stratigraphic position of the specimen is uncertain (the frequent attribution to the Dhok Pathan Formation is not based on solid evidence). Contrary to what has sometimes been claimed, Struthio asiaticus was neither a small nor an especially large ostrich. It was apparently comparable in size with the modern S. camelus, but had slightly more robust cervical vertebrae and carpal bones. It seems to have been relatively short-toed. Because of the incompleteness of the material and uncertainties about its geological age, it is difficult to assess the place of Struthio asiaticus in the evolutionary history of the ostriches. Reports of Struthio asiaticus from Africa and north-eastern Asia are based on misinterpretations and should be discarded.
Genome-Wide Characterization and Identification of the YABBY Gene Family in Mango (Mangifera indica)
Authors: Xia Yuqi , Luo Ruixiong , Sun Ruiqing , Yang Nan , Pu Jinji , Gao Aiping , Zhang He
Published: October 2022

YABBY is a specific transcription factor gene family in plants. It has the typical N-terminal C2C2-type zinc-finger domain and the C-terminal YABBY conservative structure domain, which play an important role in the development of the leaves and floral organs. The YABBY gene family directs leaf polarity in mango, playing an important role in maintaining species specificity. In this study, a total of seven YABBY genes were identified in the mango (Mangifera indica) genome. The seven YABBY family members possessed both typical C2C2 and YABBY domains. A phylogenetic tree was constructed based on the amino acid sequences of the 42 YABBY proteins of mango, Arabidopsis, apple, grape, and peach. The phylogenetic tree indicated that the members of the mango YABBY family could be divided into three subfamilies, including CRC, YAB5, and YAB3. Quantitative real-time PCR showed that the transcription levels of the MiYABBYs were significantly different under biotic and abiotic stresses. The transcription level of MiYABBY7 was significantly down-regulated at 0–72 h after Xanthomonas campestris pv. mangiferaeindicae infection, methyl jasmonate and salicylic acid stresses. The MiYABBY1 transcription level was significantly down-regulated at 0–72 h after Colletotrichum gloeosporioides infection. MiYABBYs were expressed specifically in different leaves and fruit, and MiYABBY6 was significantly up-regulated during leaf and fruit development. However, MiYABBY5 showed a contrary transcriptional pattern during leaf and fruit development. This is first report on the mango YABBY gene family at the genome-wide level. These results will be beneficial for understanding the biological functions and molecular mechanisms of YABBY genes.
Hyperspectral Inversion of Soil Carbon and Nutrient Contents in the Yellow River Delta Wetland
Authors: Nie Leichao , Dou Zhiguo , Cui Lijuan , Tang Xiying , Zhai Xiajie , Zhao Xinsheng , Lei Yinru , Li Jing , Wang Jinzhi , Li Wei
Published: October 2022

Hyperspectral inversion techniques can facilitate soil quality monitoring and evaluation. In this study, the Yellow River Delta Wetland Nature Reserve was used as the study area. By measuring and analyzing soil samples under different vegetation types and collecting soil reflectance spectra, the relationships between vegetation types, soil depth, and the changes in soil total carbon (TC), total nitrogen (TN), and total phosphorus (TP) contents were assessed. The spectral data set was changed by spectral first derivative processing and division of the sample set according to vegetation type. The correlation between soil carbon, nitrogen, and phosphorus contents, and soil spectra was also analyzed, sensitive bands were selected, and the partial least-squares (PLS) method, support vector machine (SVM) method, and random forest (RF) model were used to establish the inversion model based on the characteristic bands. The optimal combination of spectral transformation, sample set partitioning, and inversion model was explored. The results showed significant differences (p < 0.05) in soil TC, TN, and TP contents under reed and saline alkali poncho vegetation, but not between soil element contents under different stratifications of the same plant species. The first derivative reflectance had higher correlation coefficients with soil TC, TN, and TP contents compared with the original reflectance, while the sensitive bands and quantities of the three elements differed. The division of the sample sets according to vegetation type and the first derivative treatment can improve the prediction accuracy of the model. The best combination of sample set plus FD plus RF for TC, TN, and TP in reed soil and sample set plus FD plus SVM for TC, TN, and TP in saline alkali pine soil provides technical support to further improve the prediction accuracy of TC, TN, and TP in wetland soil.
A Systematic Review of Architectural Design Collaboration in Immersive Virtual Environments
Authors: Yu Rongrong , Gu Ning , Lee Gun , Khan Ayaz
Published: October 2022

Emerging applications of immersive virtual technologies are providing architects and designers with powerful interactive environments for virtual design collaboration, which has been particularly beneficial since 2020 while the architecture, engineering and construction (AEC) industry has experienced an acceleration of remote working. However, there is currently a lack of critical understanding about both the theoretical and technical development of immersive virtual environments (ImVE) for supporting architectural design collaboration. This paper reviewed recent research (since 2010) relating to the topic in a systematic literature review (SLR). Through the four steps of identification, screening, eligibility check, and inclusion of the eligible articles, in total, 29 journal articles were reviewed and discussed from 3 aspects: ImVE in the AEC industry, ImVE for supporting virtual collaboration, and applications of ImVE to support design collaboration. The results of this review suggest that future research and technology development are needed in the following areas: (1) ImVE support for design collaboration, particularly at the early design stage; (2) cognitive research about design collaboration in ImVE, toward the adoption of more innovative and comprehensive methodologies; (3) further enhancements to ImVE technologies to incorporate more needed advanced design features.
Application of CRISPR/Cas Systems in the Nucleic Acid Detection of Infectious Diseases
Authors: Li Junwei , Wang Yuexia , Wang Bin , Lou Juan , Ni Peng , Jin Yuefei , Chen Shuaiyin , Duan Guangcai , Zhang Rongguang
Published: October 2022

The CRISPR/Cas system is a protective adaptive immune system against attacks from foreign mobile genetic elements. Since the discovery of the excellent target-specific sequence recognition ability of the CRISPR/Cas system, the CRISPR/Cas system has shown excellent performance in the development of pathogen nucleic-acid-detection technology. In combination with various biosensing technologies, researchers have made many rapid, convenient, and feasible innovations in pathogen nucleic-acid-detection technology. With an in-depth understanding and development of the CRISPR/Cas system, it is no longer limited to CRISPR/Cas9, CRISPR/Cas12, and other systems that had been widely used in the past; other CRISPR/Cas families are designed for nucleic acid detection. We summarized the application of CRISPR/Cas-related technology in infectious-disease detection and its development in SARS-CoV-2 detection.