bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhancing the biosynthesis of riboflavin in the recombinant Escherichia coli BL21 strain by metabolic engineering
Authors: Fu Bing , Ying Junhui , Chen Qingwei , Zhang Qili , Lu Jiajie , Zhu Zhiwen , Yu Ping
Published: January 2023

In this study, to construct the riboflavin-producing strain R1, five key genes, ribA, ribB, ribC, ribD, and ribE, were cloned and ligated to generate the plasmid pET-AE, which was overexpressed in Escherichia coli BL21. The R1 strain accumulated 182.65 ± 9.04 mg/l riboflavin. Subsequently, the R2 strain was constructed by the overexpression of zwf harboring the constructed plasmid pAC-Z in the R1 strain. Thus, the level of riboflavin in the R2 strain increased to 319.01 ± 20.65 mg/l (74.66% increase). To further enhance ribB transcript levels and riboflavin production, the FMN riboswitch was deleted from E. coli BL21 with CRISPR/Cas9 to generate the R3 strain. The R4 strain was constructed by cotransforming pET-AE and pAC-Z into the R3 strain. Compared to those of E. coli BL21, the ribB transcript levels of R2 and R4 improved 2.78 and 3.05-fold, respectively. The R4 strain accumulated 437.58 ± 14.36 mg/l riboflavin, increasing by 37.17% compared to the R2 strain. These results suggest that the deletion of the FMN riboswitch can improve the transcript level of ribB and facilitate riboflavin production. A riboflavin titer of 611.22 ± 11.25 mg/l was achieved under the optimal fermentation conditions. Ultimately, 1574.60 ± 109.32 mg/l riboflavin was produced through fed-batch fermentation with 40 g/l glucose. This study contributes to the industrial production of riboflavin by the recombinant E. coli BL21.
Bacillus subtilis forms twisted cells with cell wall integrity defects upon removal of the molecular chaperones DnaK and trigger factor
Authors: Matavacas Judith , Hallgren Joel , von Wachenfeldt Claes
Published: January 2023

The protein homeostasis network ensures a proper balance between synthesis, folding, and degradation of all cellular proteins. DnaK and trigger factor (TF) are ubiquitous bacterial molecular chaperones that assist in protein folding, as well as preventing protein misfolding and aggregation. In Escherichia coli, DnaK and TF possess partially overlapping functions. Their combined depletion results in proteostasis collapse and is synthetically lethal at temperatures above 30°C. To increase our understanding on how proteostasis is maintained in Gram-positive bacteria, we have investigated the physiological effects of deleting dnaK and tig (encoding for DnaK and TF) in Bacillus subtilis. We show that combined deletion of dnaK and tig in B. subtilis is non-lethal, but causes a severe pleiotropic phenotype, including an aberrant twisted and filamentous cell morphology, as well as decreased tolerance to heat and to cell wall active antibiotics and hydrolytic enzymes, indicative of defects in cell wall integrity. In addition, cells lacking DnaK and TF have a much smaller colony size due to defects in motility. Despite these physiological changes, we observed no major compromises in important cellular processes such as cell growth, FtsZ localization and division and only moderate defects in spore formation. Finally, through suppressor analyses, we found that the wild-type cell shape can be partially restored by mutations in genes involved in metabolism or in other diverse cellular processes.
A novel cascade machine learning pipeline for Alzheimer’s disease identification and prediction
Authors: Zhou Kun , Piao Sirong , Liu Xiao , Luo Xiao , Chen Hongyi , Xiang Rui , Geng Daoying
Published: January 2023

Introduction

Alzheimer’s disease (AD) is a progressive and irreversible brain degenerative disorder early. Among all diagnostic strategies, hippocampal atrophy is considered a promising diagnostic method. In order to proactively detect patients with early Alzheimer’s disease, we built an Alzheimer’s segmentation and classification (AL-SCF) pipeline based on machine learning.

Methods

In our study, we collected coronal T1 weighted images that include 187 patients with AD and 230 normal controls (NCs). Our pipeline began with the segmentation of the hippocampus by using a modified U2-net. Subsequently, we extracted 851 radiomics features and selected 37 features most relevant to AD by the Hierarchical clustering method and Least Absolute Shrinkage and Selection Operator (LASSO) algorithm. At last, four classifiers were implemented to distinguish AD from NCs, and the performance of the models was evaluated by accuracy, specificity, sensitivity, and area under the curve.

Results

Our proposed pipeline showed excellent discriminative performance of classification with AD vs NC in the training set (AUC=0.97, 95% CI: (0.96-0.98)). The model was also verified in the validation set with Dice=0.93 for segmentation and accuracy=0.95 for classification.

Discussion

The AL-SCF pipeline can automate the process from segmentation to classification, which may assist doctors with AD diagnosis and develop individualized medical plans for AD in clinical practice.
Distinct lesion features and underlying mechanisms in patients with acute multiple infarcts in multiple cerebral territories
Authors: Sha Yuhui , Han Guangsong , Hong Yuehui , Wu Juanjuan , Tang Mingyu , Zhu Yicheng , Zhou Lixin , Ni Jun
Published: January 2023

Objective

To determine the etiology spectrum and lesion distribution patterns of patients with acute multiple infarcts in multiple cerebral territories (AMIMCT) and provide guidance for treatment and prevention strategies in these patients.

Methods

Patients with acute ischemic stroke diagnosed using diffusion-weighted imaging (DWI) were consecutively included in this study between June 2012 and Apr 2022. AMIMCT was defined as non-contiguous focal lesions located in more than one cerebral territory with acute neurological deficits. We retrospectively analyzed the clinical and imaging characteristics, etiology spectra and underlying mechanisms in patients with and without AMIMCT. Infarct lesion patterns on DWI and their relevance to etiology were further discussed.

Results

A total of 1,213 patients were enrolled, of whom 145 (12%) were diagnosed with AMIMCT. Patients with AMIMCT tended to be younger (P = 0.016), more often female (P = 0.001), and exhibited less common conventional vascular risk factors (P < 0.05) compared to those without AMIMCT. The constitution of the Trial of Org 10,172 in Acute Stroke Treatment classification was significantly different between patients with and without AMIMCT (P = 0.000), with a higher proportion of stroke of other determined causes (67.6% vs. 12.4%). For detailed etiologies, autoimmune or hematologic diseases were the most common (26.2%) etiologies of AMIMCT, followed by periprocedural infarcts (15.2%), cardioembolism (12.4%), tumor (12.4%), large artery atherosclerosis (10.3%), and sudden drop in blood pressure (8.3%). Hypercoagulability and systemic hypoperfusion are common underlying mechanisms of AMIMCT. Distinctive lesion distribution patterns were found associated with stroke etiologies and mechanisms in AMIMCT. Most of patients with large artery atherosclerosis (73.3%), autoimmune/hematologic diseases (57.9%) manifested the disease as multiple infarct lesions located in bilateral supratentorial regions. However, 66.7% of cardioembolism and 83.8% of cardiovascular surgery related stroke presented with both supratentorial and infratentorial infarct lesions.

Conclusion

The etiologies and mechanisms of patients with AMIMCT were more complex than those without AMIMCT. The distribution characteristics of infarct lesions might have important implications for the identification of etiology and mechanism in the future, which could further guide and optimize clinical diagnostic strategies.
Phenotypic variability within the desminopathies: A case series of three patients
Authors: Yeow Dennis , Katz Matthew , Henderson Robert , Prasad Sandhir , Denman Russell , Blum Stefan , Davis Mark , Robertson Thomas , McCombe Pamela
Published: January 2023

The DES gene encodes desmin, a key intermediate filament of skeletal, cardiac and smooth muscle. Pathogenic DES variants produce a range of skeletal and cardiac muscle disorders collectively known as the desminopathies. We report three desminopathy cases which highlight the phenotypic heterogeneity of this disorder and discuss various factors that may contribute to the clinical differences seen between patients with different desmin variants and also between family members with the same variant.
Protection effect of gut microbiota composition and acetate absorption against hypertension-induced damages on the longevity population in Guangxi, China
Authors: Zhang Qinren , Meng Ning , Liu Yu , Zhao Haiyan , Zhao Zhengtao , Hao Dan , Li Ruiding , Han Kunchen , Li He , Ma Jinke , Yu Xiaohan , Qi Zhongquan , Li Quanyang
Published: January 2023

Introduction

Recent evidence supports a role for the gut microbe-metabolites in longevity. However, the phenomenon of hypertension is more common in the longevity area and whether hypertension is associated with longevity remains unclear. Here, we hypothesize that the levels of gut microbiota, SCFAs, and urine metabolites were different between hypertension elderly and hypertension longevity.

Methods

We recruited 46 elderly volunteers from Donglan County, Guangxi, and 32 were selected and included in the experiment. The subjects with hypertension were divided into two groups according to age, Hypertension Elderly (HTE, aged 70.5 ± 8.59, n = 19) and Hypertension Longevity (HTL, aged 100 ± 5.72, n = 13). The gut microbiota, SCFAs, and urine metabolites were determined by three-generation 16S rRNA full-length sequencing, GC-MS, and 1H-NMR, respectively.

Results

Compared with the HTL group, the HTE group had higher levels of hypertension-related genera Klebsiella and Streptococcus, while having lower levels of the SCFA-producing genera Bacteroides, Faecalibacterium, and Alistipes. Based on LEFse analysis, Klebsiella pneumoniae, Lactobacillus gasseri, Streptococcus salivarius, Ruminococcus, Actinomyces, Rikenellaceae, f_Saccharimonadaceae, Clostridium perfringens, and Bacteroids, Faecalibacterium prausnitzii, Parabacteroides, Alistipes were biomarkers that showed significant differences between the groups. In addition, the microbial pathways associated with K. pneumoniae and E. coli may promote hypertension, while A. muciniphila may play a role in reversing the development of hypertension in long-lived elderly. Metabolomics revealed that HTL contained a lower concentration of fecal acetate and propionate than HTE, while it contained a higher concentration of serum acetate and urine acetate. Furthermore, their immune cells exhibited no significant changes in SCFAs receptors.

Conclusion

Although long-lived elderly have extremely high systolic blood pressure, their unique gut microbiota composition and efficient acetate absorption in the colon may offset the damages caused by hypertension and maintain healthy homeostasis.
Algal oil alleviates antibiotic-induced intestinal inflammation by regulating gut microbiota and repairing intestinal barrier
Authors: Zhang Huimin , Xu Zhenxia , Chen Wenchao , Huang Fenghong , Chen Shouwen , Wang Xu , Yang Chen
Published: January 2023

Introduction

Taking antibiotics would interfere with gut microbiota and increase the risk of opportunistic pathogen infection and inflammation.

Methods

In this study, 36 male C57BL/6 mice were divided into 4 groups (n = 9) to investigate whether two kinds of algal oil could alleviate the intestinal damage induced by CS (Ceftriaxone sodium). These algal oils were obtained from Schizochytrium sp. cultures using Yeast extract (YE) and Rapeseed meal (RSM) as substrate, respectively. All tested mice were administrated with CS for 8 days and then the colon pathological morphology, the expression levels of inflammatory factors and the gut microbial profile were analyzed in mice supplemented with or without algal oil.

Results

The results showed that both YE and RSM algal oils markedly reduced mucosal damage and intestinal inflammatory response in CS-treated mice by inhibiting the pro-inflammatory cytokine tumor necrosis factor (TNF)-α, interleukin (IL)-6 and myeloperoxidase (MPO) activity. In addition, fluorescence immunohistochemistry showed that the tight junction protein ZO-1 was increased in mice supplemented with YE and RSM algal oil. Furthermore, YE algal oil promoted the beneficial intestinal bacteria such as Lachnospiraceae and S24_7 compared with the CS group, while supplementation with RSM algal oil enriched the Robinsoniella. Spearman’s correlation analysis exhibited that Melissococcus and Parabacteroides were positively correlated with IL-6 but negatively correlated with IL-10.

Discussion

This study suggested that supplementation with algal oil could alleviate intestinal inflammation by regulating gut microbiota and had a protective effect on maintaining intestinal barrier against antibiotic-induced damage in mice.
Identification of autophagy-associated genes and prognostic implications in adults with acute myeloid leukemia by integrated bioinformatics analysis
Authors: Zhang Jing , Wang Ying-Jun , Han Yan-Qiu
Published: January 2023

Acute myeloid leukemia (AML) is one of the most common malignant blood neoplasma in adults. The prominent disease heterogeneity makes it challenging to foresee patient survival. Autophagy, a highly conserved degradative process, played indispensable and context-dependent roles in AML. However, it remains elusive whether autophagy-associated stratification could accurately predict prognosis of AML patients. Here, we developed a prognostic model based on autophagy-associated genes, and constructed scoring systems that help to predicte the survival of AML patients in both TCGA data and independent AML cohorts. The Nomogram model also confirmed the autophagy-associated model by showing the high concordance between observed and predicted survivals. Additionally, pathway enrichment analysis and protein-protein interaction network unveiled functional signaling pathways that were associated with autophagy. Altogether, we constructed the autophagy-associated prognostic model that might be likely to predict outcome for AML patients, providing insights into the biological risk stratification strategies and potential therapeutic targets.
Advanced development of biomarkers for immunotherapy in hepatocellular carcinoma
Authors: Peng Xuenan , Gong Caifeng , Zhang Wen , Zhou Aiping
Published: January 2023

Hepatocellular carcinoma (HCC) is the most common liver cancer and one of the leading causes of cancer-related deaths in the world. Mono-immunotherapy and combination therapy with immune checkpoint inhibitors (ICIs) and multitargeted tyrosine kinase inhibitors (TKIs) or anti-vascular endothelial growth factor (anti-VEGF) inhibitors have become new standard therapies in advanced HCC (aHCC). However, the clinical benefit of these treatments is still limited. Thus, proper biomarkers which can predict treatment response to immunotherapy to maximize clinical benefit while sparing unnecessary toxicity are urgently needed. Contrary to other malignancies, up until now, no acknowledged biomarkers are available to predict resistance or response to immunotherapy for HCC patients. Furthermore, biomarkers, which are established in other cancer types, such as programmed death ligand 1 (PD-L1) expression and tumor mutational burden (TMB), have no stable predictive effect in HCC. Thus, plenty of research focusing on biomarkers for HCC is under exploration. In this review, we summarize the predictive and prognostic biomarkers as well as the potential predictive mechanism in order to guide future research direction for biomarker exploration and clinical treatment options in HCC.
Local control and patient reported outcomes after online MR guided stereotactic body radiotherapy of liver metastases
Authors: Uder Laura , Nachbar Marcel , Butzer Sarah , Boldt Jessica , Baumeister Sabrina , Bitzer Michael , Königsrainer Alfred , Seufferlein Thomas , Hoffmann Rüdiger , Gatidis Sergios , Nikolaou Konstantin , Zips Daniel , Thorwarth Daniela , Gani Cihan , Boeke Simon
Published: January 2023

Introduction

Stereotactic body radiotherapy (SBRT) is used to treat liver metastases with the intention of ablation. High local control rates were shown. Magnetic resonance imaging guided radiotherapy (MRgRT) provides the opportunity of a marker-less liver SBRT treatment due to the high soft tissue contrast. We report herein on one of the largest cohorts of patients treated with online MRgRT of liver metastases focusing on oncological outcome, toxicity, patient reported outcome measures (PROMs), quality of life.

Material and methods

Patients treated for liver metastases with online MR-guided SBRT at a 1,5 T MR-Linac (Unity, Elekta, Crawley, UK) between March 2019 and December 2021 were included in this prospective study. UK SABR guidelines were used for organs at risk constraints. Oncological endpoints such as survival parameters (overall survival, progression-free survival) and local control as well as patient reported acceptance and quality of life data (EORTC QLQ-C30 questionnaire) were assessed. For toxicity scoring the Common Toxicity Criteria Version 5 were used.

Results

A total of 51 patients with 74 metastases were treated with a median of five fractions. The median applied BED GTV D98 was 84,1 Gy. Median follow-up was 15 months. Local control of the irradiated liver metastasis after 12 months was 89,6%, local control of the liver was 40,3%. Overall survival (OS) after 12 months was 85.1%. Progression free survival (PFS) after 12 months was 22,4%. Local control of the irradiated liver lesion was 100% after three years when a BED ≥100 Gy was reached. The number of treated lesions did not impact local control neither of the treated or of the hepatic control. Patient acceptance of online MRgSBRT was high. There were no acute grade ≥ 3 toxicities. Quality of life data showed no significant difference comparing baseline and follow-up data.

Conclusion

Online MR guided radiotherapy is a noninvasive, well-tolerated and effective treatment for liver metastases. Further prospective trials with the goal to define patients who actually benefit most from an online adaptive workflow are currently ongoing.
Diagnostic significance of noncoding RNAs in kawasaki disease: A systematic review and meta-analysis
Authors: Zhong Xiaoling , Jia Xufeng , Wang Hui , Chen Guihua , Li Hongxia , Li Pingping , Yang Taoyi , Xie Jiang
Published: January 2023

Objective

Kawasaki disease (KD) is a systemic vasculitis disease, and early effective intervention would reduce the occurrence of coronary artery lesions (CALs). Recently, many scholars have been committed to studying the relationship between noncoding RNAs and KD. This systematic review aimed to analyze the diagnostic value of noncoding RNAs(ncRNAs) in distinguishing different KD status.

Methods

We searched for the literature about diagnostic values of ncRNAs in KD in CNKI, VIP, Wanfang, China Biomedical Literature Database as well as PubMed, Web of Science, Embase, and Cochrane Library up to April 15, 2022. All included studies were further analyzed using STATA 12.0, Meta-disc 1.4 and RevMan 5.4 software.

Results

A total of six studies investigating the diagnostic performance of ncRNAs in differentiating KD-CAL (n = 101) from KD-NCAL patients (n = 123) were included in this this meta-analysis. The calculated area under the curve(AUC) was 0.83 (0.80–0.86). Four studies on the diagnostic performance of ncRNAs in differentiating acute KD patients (n = 139) from convalescent KD patients (n = 109) were included. The calculated AUC was 0.87 (0.84–0.90). Four studies focused on the diagnostic performance of ncRNAs combined with other laboratory indexes in KD by assessing 137 KD patients and 152 febrile controls. The calculated AUC was 0.90 (0.87–0.92). Four studies assessed the diagnostic performance of ncRNAs in differentiating intravenous immunoglobulin (IVIG)-resistant KD patients from IVIG-responsive KD patients. The calculated AUC was 0.9135 ± 0.0307. These results indicated that ncRNAs have a good diagnostic efficacy in KD.

Conclusions

This meta-analysis showed that ncRNAs have potential as a biomarker for distinguishing different KD status. However, since limited studies were included in this meta-analysis, larger and well-designed diagnostic studies should be conducted to validate these results.

Systematic Review Registration

INPLASY.COM, identifier: doi: 10.37766/inplasy2022.10.0035.
Case report: Bordetella holmesii: A rare pathogen causing infective endocarditis associated glomerulonephritis
Authors: Gavcovich Tara , Al Barbandi Malek , Millan Pamela , Isner Elizabeth , Defreitas Marissa J. , Glaberson Wendy , Katsoufis Chryso P. , Chandar Jayanthi , Sigurjonsdottir Vaka , Gonzalez Ivan A. , Swaminathan Sethuraman , Zuo Yiqin , Abitbol Carolyn L. , Seeherunvong Wacharee
Published: January 2023

Infective endocarditis (IE) can cause multiorgan dysfunction and chronic kidney disease, in addition to cardiac sequelae. The presentation may be vague and can manifest as acute glomerulonephritis. While the most common pathogens of infective endocarditis are Staphylococcus and Streptococcus species, we report a rare pathogen Bordetella holmesii causing infective endocarditis associated glomerulonephritis. A 20-year-old male patient with tetralogy of Fallot with pulmonary atresia and aortopulmonary collaterals underwent several cardiac surgeries including prosthetic pulmonary valve replacement in the past. He was admitted for 3 days at an outside hospital for fever, cough, and hemoptysis, and diagnosed with streptococcal pharyngitis, for which he received antibiotics. Five weeks later, he presented to our institution with lower extremity edema and gross hematuria. On examination, he was afebrile, normotensive, had a 7-kg weight gain with anasarca, and a systolic murmur, without rash. Investigations revealed elevated serum creatinine, nephrotic range proteinuria, hematuria, and hypocomplementemia, consistent with acute glomerulonephritis. Given his cardiac history, blood cultures were collected from three sites. Broad-spectrum antibiotics were initiated when he subsequently developed fever. Renal pathology on biopsy showed diffuse proliferative immune complex-mediated glomerulonephritis. Transesophageal echocardiogram visualized a vegetation on the pulmonary valve. Bordetella holmesii was ultimately cultured from the prior and current hospitalization. A serum sample detecting microbial cell-free DNA sequencing confirmed Bordetella holmesii at very high levels. After completing 6 weeks of intravenous antibiotics with concurrent angiotensin receptor blockade, his kidney function recovered with improvement in hypocomplementemia and proteinuria. This case report highlights the early recognition and comprehensive evaluation of a rare organism causing IE-associated GN, which allowed for renal recovery and preserved cardiac function.
Use of blinatumomab and CAR T-cell therapy in children with relapsed/refractory leukemia: A case series study
Authors: Wang Songmi , Liu Aiguo , Wang Na , Wang Yaqin , Zhang Ai , Wang Li , Yu Wen , Li Chunrui , Zhang Yicheng , Hu Qun
Published: January 2023

Background

The 5-year event-free survival rate for childhood acute lymphoblastic leukemia (ALL) has increased to more than 85%. However, the 5-year overall survival rate in children with relapsed/refractory ALL did not exceed 50%. In the past decade, immunotherapies (such as blinatumomab and chimeric antigen receptor T-cell therapy) were approved for relapsed/refractory B-ALL, transforming the treatment environment for children with relapsed/refractory ALL.

Objective

This study aimed to explore how immunotherapy can be incorporated into salvage regimens for pediatric patients with relapsed/refractory ALL by retrospectively analyzing the diagnosis and treatment process of seven children with relapsed/refractory leukemia and observing the side effects of the two strategies and long-term survival.

Methods

The clinical features and treatment responses of patients aged <14 years with relapsed/refractory leukemia who received immunotherapy (including Chimeric Antigen Receptor T cell treatment and blinatumomab) at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology between February 2014 and April 2022 were retrospectively analyzed.

Results

Seven children underwent immunotherapy. Five patients received immunotherapy and sequential allogeneic hematopoietic stem cell transplantation (HSCT), whereas the other two received only immunotherapy. Five patients achieved complete remission (71.4%). None of the patients had severe cytokine release syndrome. However, one developed grade 3 immune effector cell-associated neurotoxicity syndrome with prior leukoencephalopathy. The median follow-up period was 541 days (range, 186–3,180 days). No deaths were related to treatment. Three patients relapsed, two had CD19-negative recurrences, and the third showed CD19 antigen reduction. One patient died after disease progression, whereas the other died of HSCT-related complications. One patient abandoned the treatment after relapse and was lost to follow-up.

Conclusion

Blinatumomab and CAR T-cell therapy showed excellent remission rates and manageable toxicity in pediatric patients with relapsed/refractory leukemia. However, the duration of the remission was limited. Therefore, further prospective randomized clinical studies should be conducted to improve the long-term efficacy of immunotherapy.
Birth asphyxia, determinants, and its management among neonates admitted to NICU in Harari and Dire Dawa Public Hospitals, eastern Ethiopia
Authors: Amsalu Sewmehon , Dheresa Merga , Dessie Yadeta , Eshetu Bajrond , Balis Bikila
Published: January 2023

Background

Despite a declining neonatal mortality rate globally, Ethiopia has scored 29–30 deaths per 1,000 live births. Birth asphyxia is a major contributor to neonatal mortality, where 4–9 million newborns develop birth asphyxia each year. This study aimed to assess the prevalence of birth asphyxia, its determinants, and its management among neonates admitted to the NICU in Harari and Dire Dawa public hospitals.

Methods

A facility-based cross-sectional study was conducted among 409 randomly selected neonates and their index mothers admitted to neonatal intensive care units of public hospitals in Harari and Dire Dawa from June 20 to August 20, 2021. Data were collected through card review and interviewer-administered questionnaires. The collected data were entered into Epi data version 3.1 and exported to SPSS version 20 for analysis. Logistic regression models were fitted to identify factors associated with birth asphyxia. Adjusted odds ratios along with 95% CIs were estimated to measure the strength of the association, and statistical significance was declared at p-value <0.05.

Results

One-fifth of neonates [20.8% (95% CI: 16.4, 24.6%)] had birth asphyxia. Neonates born by instrumental delivery (AOR = 2.29, 95% CI: 1.10, 4.76) and neonates born to mother with PIH (AOR = 3.49, 95% CI: 1.47, 8.27), PROM (AOR = 2.23, 95% CI: 1.17, 4.26), and chorioamnionitis (AOR = 3.26, 95% CI: 1.10, 9.61) were more likely to have birth asphyxia compared to their counterpart. Ventilation with a bag and mask 50(58.8), putting on free oxygen 19(22.4), and endotracheal intubation 15(17.6) were taken as management methods.

Conclusion

One out of five neonates had birth asphyxia. This urges care providers to adhere to national guidelines of obstetrics and neonatal continuum care. They also need to decrease instrumental delivery and treat PIH, PROM, and chorioamnionitis.
Targeting type I interferons in systemic lupus erythematous
Authors: Bruera Sebastian , Chavula Thandiwe , Madan Riya , Agarwal Sandeep K.
Published: January 2023

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with systemic clinical manifestations including, but not limited to, rash, inflammatory arthritis, serositis, glomerulonephritis, and cerebritis. Treatment options for SLE are expanding and the increase in our understanding of the immune pathogenesis is leading to the development of new therapeutics. Autoantibody formation and immune complex formation are important mediators in lupus pathogenesis, but an important role of the type I interferon (IFN) pathway has been identified in SLE patients and mouse models of lupus. These studies have led to the development of therapeutics targeting type I IFN and related pathways for the treatment of certain manifestations of SLE. In the current narrative review, we will discuss the role of type I IFN in SLE pathogenesis and the potential translation of these data into strategies using type I IFN as a biomarker and therapeutic target for patients with SLE.
Specific gene module pair-based target identification and drug discovery
Authors: Li Peng , Bai Chujie , Zhan Lingmin , Zhang Haoran , Zhang Yuanyuan , Zhang Wuxia , Wang Yingdong , Zhao Jinzhong
Published: January 2023

Identification of the biological targets of a compound is of paramount importance for the exploration of the mechanism of action of drugs and for the development of novel drugs. A concept of the Connectivity Map (CMap) was previously proposed to connect genes, drugs, and disease states based on the common gene-expression signatures. For a new query compound, the CMap-based method can infer its potential targets by searching similar drugs with known targets (reference drugs) and measuring the similarities into their specific transcriptional responses between the query compound and those reference drugs. However, the available methods are often inefficient due to the requirement of the reference drugs as a medium to link the query agent and targets. Here, we developed a general procedure to extract target-induced consensus gene modules from the transcriptional profiles induced by the treatment of perturbagens of a target. A specific transcriptional gene module pair (GMP) was automatically identified for each target and could be used as a direct target signature. Based on the GMPs, we built the target network and identified some target gene clusters with similar biological mechanisms. Moreover, a gene module pair-based target identification (GMPTI) approach was proposed to predict novel compound–target interactions. Using this method, we have discovered novel inhibitors for three PI3K pathway proteins PI3Kα/β/δ, including PU-H71, alvespimycin, reversine, astemizole, raloxifene HCl, and tamoxifen.
Comparative metabolism and tolerability of racemic primaquine and its enantiomers in human volunteers during 7-day administration
Authors: Khan Washim , Wang Yan-Hong , Chaurasiya Narayan D. , Nanayakkara N. P. Dhammika , Bandara Herath H. M. , Harrison Kerri A. , Dale Gray , Stanford Donald A. , Dahl Eric P. , McChesney James D. , Gul Waseem , ElSohly Mahmoud A. , Jollow David , Tekwani Babu L. , Walker Larry A.
Published: January 2023

Primaquine (PQ) is an 8-aminoquinoline antimalarial, active against dormant Plasmodium vivax hypnozoites and P. falciparum mature gametocytes. PQ is currently used for P. vivax radical cure and prevention of malaria transmission. PQ is a racemic drug and since the metabolism and pharmacology of PQ’s enantiomers have been shown to be divergent, the objectives of this study were to evaluate the comparative tolerability and metabolism of PQ with respect to its two enantiomers in human volunteers in a 7 days’ treatment schedule. Fifteen subjects with normal glucose-6-phosphate dehydrogenase (G6PDn) completed four arms, receiving each of the treatments, once daily for 7 days, in a crossover fashion, with a 7–14 days washout period in between: R-(−) enantiomer (RPQ) 22.5 mg; S-(+) enantiomer (SPQ) 22.5 mg; racemic PQ (RSPQ) 45 mg, and placebo. Volunteers were monitored for any adverse events (AEs) during the study period. PQ and metabolites were quantified in plasma and red blood cells (RBCs) by UHPLC-UV-MS/MS. Plasma PQ was significantly higher in SPQ treatment group than for RPQ. Carboxy-primaquine, a major plasma metabolite, was much higher in the RPQ treated group than SPQ; primaquine carbamoyl glucuronide, another major plasma metabolite, was derived only from SPQ. The ortho-quinone metabolites were also detected and showed differences for the two enantiomers in a similar pattern to the parent drugs. Both enantiomers and racemic PQ were well tolerated in G6PDn subjects with the 7 days regimen; three subjects showed mild AEs which did not require any intervention or discontinuation of the drug. The most consistent changes in G6PDn subjects were a gradual increase in methemoglobin and bilirubin, but these were not clinically important. However, the bilirubin increase suggests mild progressive damage to a small fraction of red cells. PQ enantiomers were also individually administered to two G6PD deficient (G6PDd) subjects, one heterozygous female and one hemizygous male. These G6PDd subjects showed similar results with the two enantiomers, but the responses in the hemizygous male were more pronounced. These studies suggest that although the metabolism profiles of individual PQ enantiomers are markedly different, they did not show significant differences in the safety and tolerability in G6PDn subjects.
Effect of Bi-B-Si-Zn-Al glass additive on the properties of low-temperature sintered silicon carbide ceramics
Authors: Zhang Lan , Yang Shuquan , Xiao Meihui , Chen Lin , Sun Jun , Ding Jianjun , Li Xiaoxiao , Gong Yi , Zheng Kang , Zhang Xian , Tian Xingyou
Published: January 2023

In this study, the performance of low-temperature sintered Bi-B-Si-Zn-Al glass/SiC composites by vacuum hot-press sintering between 700°C and 1000°C was investigated. The specimen had a relatively preferable density of 95.5% and thermal conductivity of 8.660 Wm−1K−1 after sintering at 900°C for 2 h. The dielectric constant and dielectric loss tangle of the composite were 32.9 and 0.57 at 20 GHz, respectively. The XRD analysis indicated the formation of Bi, Zn and ZnAl2O4 crystals, and the microstructure showed the low contact angle of the glass and SiC grain. Such low-temperature sintered SiC ceramic may have a promising application in the electronic field.
Lamb waves manipulation by piezoelectric metasurface with tunable diffraction orders
Authors: Shao Shixuan , Chen Jiyue , Xia Rongyu , Li Zheng
Published: January 2023

In this paper, a piezoelectric metasurface is proposed to manipulate the anti-symmetric mode Lamb wave by altering the diffraction order. The metasurface attached to a host plate is symmetrically arranged by out-of-plane polarized piezoelectric patches connected with synthetic inductance circuits. Without changing the physical configuration, the transmitted phase of the anti-symmetric mode Lamb wave can be shifted arbitrarily in 0 ∼ 2π range by the metasurface. Furthermore, the relationship between the phase gradient and diffraction order is investigated, and different orders of diffraction waves can be obtained by adjusting the shunting inductance circuits. The symmetric transmission and asymmetric transmission from a couple of axis symmetric incident waves can be realized by utilizing +1st-order and −1st-order diffraction. Moreover, omnidirectional wave reflection and wave trapping in channelized waveguides can also be realized by utilizing the 0th-order diffraction. The results indicate that the proposed piezoelectric metasurface has great potentials in manipulating guided waves with a large incident angle and isolating wave propagation.
Frequency and spectrum of M2 mutants and genetic variability in cyto-agronomic characteristics of fenugreek induced by caffeine and sodium azide
Authors: Naaz Neha , Choudhary Sana , Sharma Nidhi , Hasan Nazarul , Al Shaye Najla A. , Abd El-Moneim Diaa
Published: January 2023

Trigonella foenum graecum L. (Fenugreek) is a valuable medicinal plant cultivated for decades for its therapeutic characteristics. Still no pronounced improvement concerning wild form was accomplished as it is a self-pollinating crop. Induced mutagenesis is encouraged as a remarkable tool on this plant to circumvent the genetic bottleneck of cultivated germplasms. As a result, novel allelomorphic combinations for short-term agronomic attributes were developed. Fenugreek cultivar Pusa Early Bunching, selected for the present experiment, was mutagenized with five doses (0.2%, 0.4%, 0.6%, 0.8%, and 1.0%) of caffeine and sodium azide (SA) to evaluate its impact on the qualitative and quantitative traits of M1 and M2 generation conducted in a Complete Randomized Block Design (CRBD), replicated five times during 2019–2020 and 2020–2021, respectively. The frequency of induced phenotypic variations was assessed in M2 progenies, resulting in the identification and isolation of a broad spectrum of mutants with altered phenotypes. Mutagenic effectiveness and efficiency were found to be maximum at lower concentrations of the mutagen treatments and highest in SA, followed by caffeine. Various morphological mutants with modified characters were observed at different concentrations in M2 generation. The spectrum of mutations was wider in SA than in caffeine, as caffeine produced 51 while SA produced 54 individual mutants under seven major categories. The maximum frequency of morphological mutants was associated with leaf, followed by plant size, plant growth habit, pod, seed size, seed shape, and seed color. Morphological and structural variations in the guard cells of stomata and seeds were observed through scanning electron microscopy. The variations created in the economically important traits may enrich the genetic diversity of this plant species. Moreover, these morphological mutants may serve as a source of elite genes in further breeding programs of fenugreek.
Quantitative trait locus mapping and candidate gene analysis for salt tolerance at bud stage in rice
Authors: Yin Wenjing , Lu Tianqi , Chen Zhengai , Lu Tao , Ye Hanfei , Mao Yijian , Luo Yiting , Lu Mei , Zhu Xudong , Yuan Xi , Rao Yuchun , Wang Yuexing
Published: January 2023

Soil salinization has a serious influence on rice yield and quality. How to enhance salt tolerance in rice is a topical issue. In this study, 120 recombinant inbred line populations were generated through nonstop multi-generation selfing using a male indica rice variety Huazhan (Oryza sativa L. subsp. indica cv. ‘HZ’) and a female variety of Nekken2 (Oryza sativa L. subsp. japonica cv. ‘Nekken2’) as the parents. Germination under 80 mM NaCl conditions was measured and analyzed, and quantitative trait locus (QTL) mapping was completed using a genetic map. A total of 16 salt-tolerance QTL ranges were detected at bud stage in rice, which were situated on chromosomes 3, 4, 6, 8, 9, 10, 11, and 12. The maximum limit of detection was 4.69. Moreover, the qST12.3 was narrowed to a 192 kb region on chromosome 12 using map-based cloning strategy. Statistical analysis of the expression levels of these candidate genes under different NaCl concentrations by qRT-PCR revealed that qST12.3 (LOC_Os12g25200) was significantly down-regulated with increasing NaCl concentration, and the expression level of the chlorine-transporter-encoding gene LOC_Os12g25200 in HZ was significantly higher than that of Nekken2 under 0 mM NaCl. Sequencing analysis of LOC_Os12g25200 promoter region indicated that the gene expression difference between parents may be due to eight base differences in the promoter region. Through QTL mining and analysis, a plurality of candidate genes related to salt tolerance in rice was obtained, and the results showed that LOC_Os12g25200 might negatively regulate salt tolerance in rice. The results provide the basis for further screening and cultivation of salt-tolerant rice varieties and have laid the foundation for elucidating further molecular regulation mechanisms of salt tolerance in rice.
Transcriptome profiling disclosed the effect of single and combined drought and heat stress on reprogramming of genes expression in barley flag leaf
Authors: Mikołajczak Krzysztof , Kuczyńska Anetta , Krajewski Paweł , Kempa Michał , Nuc Maria
Published: January 2023

Despite numerous studies aimed at unraveling the genetic background of barley’s response to abiotic stress, the modulation of the transcriptome induced by combinatorial drought and increased temperature remains largely unrecognized. Very limited studies were done, especially on the flag leaf, which plays an important role in grain filling in cereals. In the present study, transcriptome profiles, along with chlorophyll fluorescence parameters and yield components, were compared between barley genotypes with different flag leaf sizes under single and combined drought and heat stress. High-throughput mRNA sequencing revealed 2,457 differentially expressed genes, which were functionally interpreted using Gene Ontology term enrichment analysis. The transcriptomic signature under double stress was more similar to effects caused by drought than by elevated temperature; it was also manifested at phenotypic and chlorophyll fluorescence levels. Both common and stress-specific changes in transcript abundance were identified. Genes regulated commonly across stress treatments, determining universal stress responses, were associated, among others, with responses to drought, heat, and oxidative stress. In addition, changes specific to the size of the flag leaf blade were found. Our study allowed us to identify sets of genes assigned to various processes underlying the response to drought and heat, including photosynthesis, the abscisic acid pathway, and lipid transport. Genes encoding LEA proteins, including dehydrins and heat shock proteins, were especially induced by stress treatments. Some association between genetic composition and flag leaf size was confirmed. However, there was no general coincidence between SNP polymorphism of genotypes and differential expression of genes induced by stress factors. This research provided novel insight into the molecular mechanisms of barley flag leaf that determine drought and heat response, as well as their co-occurrence.
Effect of boron deficiency on the photosynthetic performance of sugar beet cultivars with contrasting boron efficiencies
Authors: Song Xin , Song Baiquan , Huo Jialu , Liu Huajun , Adil Muhammad Faheem , Jia Qiue , Wu Wenyu , Kuerban Abudukadier , Wang Yan , Huang Wengong
Published: January 2023

Boron (B) deficiency severely affects the quality of sugar beet production, and the employment of nutrient-efficient varieties for cultivation is a crucial way to solve environmental and resource-based problems. However, the aspect of leaf photosynthetic performance among B-efficient sugar beet cultivars remains uncertain. The B deficient and B-sufficient treatments were conducted in the experiment using KWS1197 (B-efficient) and KWS0143 (B-inefficient) sugar beet cultivars as study materials. The objective of the present study was to determine the impacts of B deficiency on leaf phenotype, photosynthetic capacity, chloroplast structure, and photochemical efficiency of the contrasting B-efficiency sugar beet cultivars. The results indicated that the growth of sugar beet leaves were dramatically restricted, the net photosynthetic rate was significantly decreased, and the energy flux, quantum yield, and flux ratio of PSII reaction centers were adversely affected under B deficiency. Compared to the KWS0143 cultivar, the average leaf area ratio of the KWS1197 cultivar experienced less impact, and its leaf mass ratio (LMR) increased by 26.82% under B deficiency, whereas for the KWS0143 cultivar, the increase was only 2.50%. Meanwhile, the light energy capture and utilization capacity of PSII reaction centers and the proportion of absorbed light energy used for electron transfer were higher by 3.42% under B deficiency; KWS1197 cultivar managed to alleviate the photo-oxidative damage, which results from excessive absorbed energy (ABS/RC), by increasing the dissipated energy (DIo/RC). Therefore, in response to B deprivation, the KWS1197 cultivar demonstrated greater adaptability in terms of morphological indices and photosynthetic functions, which not only explains the improved performance but also renders the measured parameters as the key features for varietal selection, providing a theoretical basis for the utilization of efficient sugar beet cultivars in future.
Fusarium head blight monitoring in wheat ears using machine learning and multimodal data from asymptomatic to symptomatic periods
Authors: Mustafa Ghulam , Zheng Hengbiao , Li Wei , Yin Yuming , Wang Yongqing , Zhou Meng , Liu Peng , Bilal Muhammad , Jia Haiyan , Li Guoqiang , Cheng Tao , Tian Yongchao , Cao Weixing , Zhu Yan , Yao Xia
Published: January 2023

The growth of the fusarium head blight (FHB) pathogen at the grain formation stage is a deadly threat to wheat production through disruption of the photosynthetic processes of wheat spikes. Real-time nondestructive and frequent proxy detection approaches are necessary to control pathogen propagation and targeted fungicide application. Therefore, this study examined the ch\lorophyll-related phenotypes or features from spectral and chlorophyll fluorescence for FHB monitoring. A methodology is developed using features extracted from hyperspectral reflectance (HR), chlorophyll fluorescence imaging (CFI), and high-throughput phenotyping (HTP) for asymptomatic to symptomatic disease detection from two consecutive years of experiments. The disease-sensitive features were selected using the Boruta feature-selection algorithm, and subjected to machine learning-sequential floating forward selection (ML-SFFS) for optimum feature combination. The results demonstrated that the biochemical parameters, HR, CFI, and HTP showed consistent alterations during the spike–pathogen interaction. Among the selected disease sensitive features, reciprocal reflectance (RR=1/700) demonstrated the highest coefficient of determination (R2) of 0.81, with root mean square error (RMSE) of 11.1. The multivariate k-nearest neighbor model outperformed the competing multivariate and univariate models with an overall accuracy of R2 = 0.92 and RMSE = 10.21. A combination of two to three kinds of features was found optimum for asymptomatic disease detection using ML-SFFS with an average classification accuracy of 87.04% that gradually improved to 95% for a disease severity level of 20%. The study demonstrated the fusion of chlorophyll-related phenotypes with the ML-SFFS might be a good choice for crop disease detection.
Genome-wide identification and characterization of LcCCR13 reveals its potential role in lignin biosynthesis in Liriodendron chinense
Authors: Li Wei , Hao Ziyuan , Yang Lichun , Xia Hui , Tu Zhonghua , Cui Zhengkun , Wu Junpeng , Li Huogen
Published: January 2023

Introduction

Wood formation is closely related to lignin biosynthesis. Cinnamoyl-CoA reductase (CCR) catalyzes the conversion of cinnamoyl-CoA to cinnamaldehydes, which is the initiation of the lignin biosynthesis pathway and a crucial point in the manipulation of associated traits. Liriodendron chinense is an economically significant timber tree. Nevertheless, the underlying mechanism of wood formation in it remains unknown; even the number of LcCCR family members in this species is unclear.

Materials and Results

This study aimed to perform a genome-wide identification of genes(s) involved in lignin biosynthesis in L. chinense via RT-qPCR assays and functional verification. Altogether, 13 LcCCR genes were identified that were divided into four major groups based on structural and phylogenetic features. The gene structures and motif compositions were strongly conserved between members of the same groups. Subsequently, the expression patterns analysis based on RNA-seq data indicated that LcCCR5/7/10/12/13 had high expression in the developing xylem at the stem (DXS). Furthermore, the RT-qPCR assays showed that LcCCR13 had the highest expression in the stem as compared to other tissues. Moreover, the overexpression of the LcCCR13 in transgenic tobacco plants caused an improvement in the CCR activity and lignin content, indicating that it plays a key role in lignin biosynthesis in the stems.

Discussion

Our research lays a foundation for deeper investigation of the lignin synthesis and uncovers the genetic basis of wood formation in L. chinense.