bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification and Functional Analysis of the G1 Phase Cyclin Dependent Kinase Gene Hc-CDK6 in Pearl Mussels (Hyriopsis cumingii)
Authors: Feng ShangLe , Li XueNan , Wang He , Li WenJuan , Bai ZhiYi
Published: June 2022

Cyclin dependent kinase 6 (CDK6) is a serine/threonine kinase that plays important roles in cell cycle progression and differentiation. In this study, full-length cDNA of Hc-CDK6 was obtained from freshwater pearl mussels (Hyriopsis cumingii, Hc) with 3´,5´ rapid-amplification of cDNA ends (RACE). The Hc-CDK6 expression profiles were analyzed with quantitative real-time PCR and in situ hybridization. The function of the Hc-CDK6 gene was studied with both RNA interference (RNAi) and overexpression in H. cumingii. Hc-CDK6 was found to encode 331 amino acids and to have a CDK4/6-like serine/threonine kinase catalytic structural domain. In terms of the amino acid sequence, the protein Hc-CDK6 was most closely related to its homolog in Crassostrea gigas, with a similarity of 75.23%. Hc-CDK6 was expressed in all examined tissues (adductor, foot, visceral mass, gill, outer mantle, inner mantle and gonads), and the highest expression was observed in the gonads (P<0.05). The relative expression of Hc-CDK6 increased during embryonic development, and was higher in the blastocyst and gastrulation stages, which were characterized by rapid division and differentiation. Hc-CDK6 showed hybridization signals in all parts of the mantle. After knockdown of Hc-CDK6 through RNAi, a significant decrease in CDK6 expression was found, and the percentage of cells in G0/G1 significantly increased. Overexpression of Hc-CDK6 in mantle cells increased the proliferation of cultured cells (P<0.05). Hc-CDK6 appeared to promote the cell cycle in H. cumingii, and overexpression of Hc-CDK6 promoted mantle cell proliferation. The functional study of this gene may provide new ideas for solving the problem of slow proliferation of shellfish cells in in vitro culture.
RETRACTED: Case Report: Treatment of Hypertrophic Cardiomyopathy With Stereotactic Body Radiotherapy
Authors: Xiao Longzihui , Liu Jiayi , Zhang Yingzhe , Liu Yuefei , Tang Yan , Zhang Minping , Ding Zhuyuan , Xiao Enhua , Chen Taili
Published: June 2022

Patients with hypertrophic cardiomyopathy (HCM), which is characterized by left ventricular hypertrophy, is usually treated with medications such as calcium channel blockers or beta-blockers and invasive treatments such as transcatheter alcohol septal ablation, percutaneous radiofrequency ablation, or heart transplantation. However, non-invasive methods have not been employed for the management of patients with HCM. A 71-year-old male who presented with occasional chest pain for approximately 2 months and had been diagnosed with HCM since he was 39 years old due to occasional fainting was treated with a novel method for HCM using stereotactic body radiotherapy (SBRT). The administration of 25 Gy of radiation as one fraction led to an improvement in his quality of life. No toxicity occurred during or immediately after the treatment. Our observations suggest that SBRT may be a reasonable treatment approach for patients with HCM who are not suitable for surgery.
A Prediction Model for Tacrolimus Daily Dose in Kidney Transplant Recipients With Machine Learning and Deep Learning Techniques
Authors: Zhang Qiwen , Tian Xueke , Chen Guang , Yu Ze , Zhang Xiaojian , Lu Jingli , Zhang Jinyuan , Wang Peile , Hao Xin , Huang Yining , Wang Zeyuan , Gao Fei , Yang Jing
Published: June 2022

Tacrolimus is a major immunosuppressor against post-transplant rejection in kidney transplant recipients. However, the narrow therapeutic index of tacrolimus and considerable variability among individuals are challenges for therapeutic outcomes. The aim of this study was to compare different machine learning and deep learning algorithms and establish individualized dose prediction models by using the best performing algorithm. Therefore, among the 10 commonly used algorithms we compared, the TabNet algorithm outperformed other algorithms with the highest R2 (0.824), the lowest prediction error [mean absolute error (MAE) 0.468, mean square error (MSE) 0.558, and root mean square error (RMSE) 0.745], and good performance of overestimated (5.29%) or underestimated dose percentage (8.52%). In the final prediction model, the last tacrolimus daily dose, the last tacrolimus therapeutic drug monitoring value, time after transplantation, hematocrit, serum creatinine, aspartate aminotransferase, weight, CYP3A5, body mass index, and uric acid were the most influential variables on tacrolimus daily dose. Our study provides a reference for the application of deep learning technique in tacrolimus dose estimation, and the TabNet model with desirable predictive performance is expected to be expanded and applied in future clinical practice.
Analysis of Clinical Features and Next-Generation Sequencing of 12 Tuberous Sclerosis Families in China
Authors: Wang Xu , Wang Wenda , Zhao Yang , Wang Zhan , Zhang Yushi
Published: June 2022

Background

Tuberous sclerosis complex (TSC) is a rare autosomal dominant genetic disease with systemic organ involvement. So far, only a few TSC families in China have been reported. Therefore, more data on the clinical and genetic features of TSC families are required.

Materials and Methods

We retrospectively analyzed 12 TSC family probands and their family members. Next-generation sequencing (NGS) has been applied to confirm the type of TSC mutation along with a detailed physical examination.

Results

In this study, twenty-seven patients in 12 TSC families were reported, including 12 male and 15 female patients, aged 8–67 years. Skin lesions were detected among all patients with TSC, including 25 cases of facial angiofibromas, 18 cases of hypomelanotic macules, 15 cases of ungual fibromas, and 13 cases of shagreen patch. Other clinical features were also revealed: 14 cases of renal angiomyolipoma, 6 cases of subependymal nodules (SENs), and 3 cases of lymphangioleiomyomatosis. All twenty-seven patients with TSC were tested by NGS. Totally, TSC2 mutations were reported in 19 cases (7 frameshift mutations, 10 nonsense mutations, and 2 missense mutations), TSC1 mutations were reported in 4 cases (4 nonsense mutations), and 4 cases were genetically negative. The novel causal mutations (TSC2: c.208dup, c.1874C > G, c.1852del) identified in three families were first reported in TSC.

Conclusion

Our findings expand the mutation spectrum of patients with TSC in China. The clinical characteristics can vary among patients with TSC with the same pathogenic mutation. The genetic results and summary of clinical features of 12 TSC families contribute to a more accurate diagnosis and further genetic counseling.
Potential Serum Biomarkers in Prenatal Diagnosis of Placenta Accreta Spectrum
Authors: Zhang Tianyue , Wang Shaowei
Published: June 2022

Placenta accreta spectrum (PAS) refers to the abnormal invasion of trophoblastic tissues. Because of its increasing morbidity and possibility of catastrophic outcomes, PAS requires an antenatal diagnosis and making full preparations in advance to realize safe delivery. Current clinical screening modalities for PAS are not always conclusive. Recently, it has been reported that bio-markers detected in maternal serum have the potential for predicting PAS during pregnancy. Some of these biomarkers, such as β-hcg, AFP, PAPP-A, and cffDNA, can be clinically detected. It is convenient for us to test and compare with standard threshold. However, how can we distinguishing PAS from other pregnancy complications through these biomarkers remains complicated. Some biomarkers are specific, such as microRNA and placenta-specific mRNA. They are stability and reliability. These biomarkers are currently research hotspots. This study aims to summarize the characteristics of the newly reported biomarkers and to point out their potential application and current limitations to provide a basis for future research. Finally, the combination of imageological examination and biomarkers will be an attractive future theme to study in diagnosing this challenging condition.
Effects of Inappropriate Administration of Empirical Antibiotics on Mortality in Adults With Bacteraemia: Systematic Review and Meta-Analysis
Authors: Hung Yuan-Pin , Lee Ching-Chi , Ko Wen-Chien
Published: June 2022

Introduction

Bloodstream infections are associated with high mortality rates and contribute substantially to healthcare costs, but a consensus on the prognostic benefits of appropriate empirical antimicrobial therapy (EAT) for bacteraemia is lacking.

Methods

We performed a systematic search of the PubMed, Cochrane Library, and Embase databases through July 2021. Studies comparing the mortality rates of patients receiving appropriate and inappropriate EAT were considered eligible. The quality of the included studies was assessed using Joanna Briggs Institute checklists.

Results

We ultimately assessed 198 studies of 89,962 total patients. The pooled odds ratio (OR) for the prognostic impacts of inappropriate EAT was 2.06 (P < 0.001), and the funnel plot was symmetrically distributed. Among subgroups without between-study heterogeneity (I2 = 0%), those of patients with severe sepsis and septic shock (OR, 2.14), Pitt bacteraemia scores of ≥4 (OR, 1.88), cirrhosis (OR, 2.56), older age (OR, 1.78), and community-onset/acquired Enterobacteriaceae bacteraemia infection (OR, 2.53) indicated a significant effect of inappropriate EAT on mortality. The pooled adjusted OR of 125 studies using multivariable analyses for the effects of inappropriate EAT on mortality was 2.02 (P < 0.001), and the subgroups with low heterogeneity (I2 < 25%) exhibiting significant effects of inappropriate EAT were those of patients with vascular catheter infections (adjusted OR, 2.40), pneumonia (adjusted OR, 2.72), or Enterobacteriaceae bacteraemia (adjusted OR, 4.35). Notably, the pooled univariable and multivariable analyses were consistent in revealing the negligible impacts of inappropriate EAT on the subgroups of patients with urinary tract infections and Enterobacter bacteraemia.

Conclusion

Although the current evidence is insufficient to demonstrate the benefits of prompt EAT in specific bacteraemic populations, we indicated that inappropriate EAT is associated with unfavorable mortality outcomes overall and in numerous subgroups. Prospective studies designed to test these specific populations are needed to ensure reliable conclusions.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/, identifier: CRD42021270274.
Long-Term Kidney Prognosis and Pathological Characteristics of Late-Onset Lupus Nephritis
Authors: Tian Na , Zhou Qian , Yin PeiRan , Chen WenFang , Hong LingYao , Luo QiMei , Chen MengHua , Yu XueQing , Chen Wei
Published: June 2022

Background

Arguments still exist on prognosis of late-onset SLE, especially their kidney function. The purpose of this study was to investigate long-term kidney outcomes in patients with late-onset lupus nephritis (LN).

Methods

A retrospective long-term cohort study was conducted in adult Chinese patients with LN. The patients were divided into late- (>50 years) and early-onset (<50 years) LN groups. The baseline characteristics, especially the kidney pathological characteristics, were compared. The cohort was followed-up for kidney outcome defined as doubling of serum creatinine or ESRD. Cox regression analysis was used to examine the association between late onset LN and its outcomes.

Results

A total of 1,264 patients were recruited, who were assigned to late-onset LN with 102 patients and early-onset LN with 1,162 patients. The late-onset LN group showed a worse baseline kidney function and more chronic pathological lesions than the early-onset LN group. During a follow-up time of 55 (3, 207) months, 114 (13.1%) deaths occurred, 107 (12.2%) had doubling of creatinine, and 80 (9.1%) developed end-stage kidney disease. The 5- and 10-year survival rates of the late-onset LN group were 67.6 and 50.5%, respectively, which were much worse than those of the early-onset LN group (89.8 and 84.6%, respectively). However, no significant difference was found on kidney survival (log-rank chi-square = 3.55, p = 0.06). Cox regression analysis showed that late-onset LN was an independent risk factor for patient survival (hazard ratio = 3.03, 95% CI (1.39, 6.58), p = 0.005). Increased baseline serum creatinine was an independent risk factor for kidney survival of patients with late-onset LN.

Conclusions

Patients with late-onset LN had milder active lesions but severer chronic lesions in kidney pathology. They have poorer overall outcome but relatively favorable kidney outcome.

Trial Registration

ClinicalTrials.gov Identifier: NCT03001973, 22 December 2016 retrospectively registered.
Phase-Sensitive Measurements of Depth-Dependent Signal Transduction in the Inner Plexiform Layer
Authors: Pfäffle Clara , Spahr Hendrik , Gercke Katharina , Puyo Léo , Höhl Svea , Melenberg David , Miura Yoko , Hüttmann Gereon , Hillmann Dierck
Published: June 2022

Non-invasive spatially resolved functional imaging in the human retina has recently attracted considerable attention. Particularly functional imaging of bipolar and ganglion cells could aid in studying neuronal activity in humans, including an investigation of processes of the central nervous system. Recently, we imaged the activity of the inner neuronal layers by measuring nanometer-size changes of the cells within the inner plexiform layer (IPL) using phase-sensitive optical coherence tomography (OCT). In the IPL, there are connections between the neuronal cells that are dedicated to the processing of different aspects of the visual information, such as edges in the image or temporal changes. Still, so far, it was not possible to assign functional changes to single cells or cell classes in living humans, which is essential for studying the vision process. One characteristic of signal processing in the IPL is that different aspects of the visual impression are only processed in specific sub-layers (strata). Here, we present an investigation of these functional signals for three different sub-layers in the IPL with the aim to separate different properties of the visual signal processing. Whereas the inner depth-layer, closest to the ganglion cells, exhibits an increase in the optical path length, the outer depth-layer, closest to the bipolar cell layer, exhibits a decrease in the optical path length. Additionally, we found that the central depth is sensitive to temporal changes, showing a maximum response at a stimulation frequency of around 12.5 Hz. The results demonstrate that the signals from different cell types can be distinguished by phase-sensitive OCT.
Improving Suicide Prevention in Primary Care for Differing Levels of Behavioral Health Integration: A Review
Authors: Spottswood Margaret , Lim Christopher T. , Davydow Dimitry , Huang Hsiang
Published: June 2022

Importance

Suicide prevention implementation in primary care is needed due to the increasing rate of suicide in the past few decades, particularly for young and marginalized people. Primary care is the most likely point of contact for suicidal patients in the healthcare system. Attention to the level of medical integration with behavioral health is vital to suicide prevention and is applied throughout this review.

Methods

A narrative review was performed.

Observations

Many interventions help improve suicide prevention care. PCP education, screening, safety planning/lethal means reduction, care transitions, psychotherapy, and medication management are all evidence-based strategies. Additionally, the pragmatic topics of financing suicide prevention, supporting providers, enacting suicide postvention, and preparing for future directions in the field at each level of primary care/behavioral health integration are discussed.

Conclusions and Relevance

The findings are clinically relevant for practices interested in implementing evidence-based suicide prevention strategies by attending to the behavioral health/medical interface. Leveraging the patient/provider relationship to allow for optimal suicide prevention care requires clinics to structure provider time to allow for emotionally present care. Defining clear roles for staff and giving attention to provider well being are also critical factors to supporting primary care-based suicide prevention efforts.
Delayed Impact of 2-Oxoadipate Dehydrogenase Inhibition on the Rat Brain Metabolism Is Linked to Protein Glutarylation
Authors: Boyko Alexandra I. , Karlina Irina S. , Zavileyskiy Lev G. , Aleshin Vasily A. , Artiukhov Artem V. , Kaehne Thilo , Ksenofontov Alexander L. , Ryabov Sergey I. , Graf Anastasia V. , Tramonti Angela , Bunik Victoria I.
Published: June 2022

Background

The DHTKD1-encoded 2-oxoadipate dehydrogenase (OADH) oxidizes 2-oxoadipate—a common intermediate of the lysine and tryptophan catabolism. The mostly low and cell-specific flux through these pathways, and similar activities of OADH and ubiquitously expressed 2-oxoglutarate dehydrogenase (OGDH), agree with often asymptomatic phenotypes of heterozygous mutations in the DHTKD1 gene. Nevertheless, OADH/DHTKD1 are linked to impaired insulin sensitivity, cardiovascular disease risks, and Charcot-Marie-Tooth neuropathy. We hypothesize that systemic significance of OADH relies on its generation of glutaryl residues for protein glutarylation. Using pharmacological inhibition of OADH and the animal model of spinal cord injury (SCI), we explore this hypothesis.

Methods

The weight-drop model of SCI, a single intranasal administration of an OADH-directed inhibitor trimethyl adipoyl phosphonate (TMAP), and quantification of the associated metabolic changes in the rat brain employ established methods.

Results

The TMAP-induced metabolic changes in the brain of the control, laminectomized (LE) and SCI rats are long-term and (patho)physiology-dependent. Increased glutarylation of the brain proteins, proportional to OADH expression in the control and LE rats, represents a long-term consequence of the OADH inhibition. The proportionality suggests autoglutarylation of OADH, supported by our mass-spectrometric identification of glutarylated K155 and K818 in recombinant human OADH. In SCI rats, TMAP increases glutarylation of the brain proteins more than OADH expression, inducing a strong perturbation in the brain glutathione metabolism. The redox metabolism is not perturbed by TMAP in LE animals, where the inhibition of OADH increases expression of deglutarylase sirtuin 5. The results reveal the glutarylation-imposed control of the brain glutathione metabolism. Glutarylation of the ODP2 subunit of pyruvate dehydrogenase complex at K451 is detected in the rat brain, linking the OADH function to the brain glucose oxidation essential for the redox state. Short-term inhibition of OADH by TMAP administration manifests in increased levels of tryptophan and decreased levels of sirtuins 5 and 3 in the brain.

Conclusion

Pharmacological inhibition of OADH affects acylation system of the brain, causing long-term, (patho)physiology-dependent changes in the expression of OADH and sirtuin 5, protein glutarylation and glutathione metabolism. The identified glutarylation of ODP2 subunit of pyruvate dehydrogenase complex provides a molecular mechanism of the OADH association with diabetes.
Identification of Senescence-Related Subtypes, the Development of a Prognosis Model, and Characterization of Immune Infiltration and Gut Microbiota in Colorectal Cancer
Authors: Dai Ju-Ji , Fu Yang-Yang , Zhong Xi-Qiang , Cen Wei , Ye Mao-Fei , Chen Xi-Han , Pan Yi-Fei , Ye Le-Chi
Published: June 2022

Cellular senescence is associated with tumorigenesis, and the subtype and prognostic signatures of senescence-related genes (SRGs) in the tumor microenvironment (TME) and gut microbiota have not been fully determined. Analysis of 91 SRGs obtained from the GSEA and MSigDB, and mRNA sequencing of genes in the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases enabled the identification of two distinct molecular types of colorectal cancer (CRC). Patient samples were clustered into two subtypes, with Kaplan-Meier survival analyses showing significant differences in patient survival between the two subtypes. Cluster C2 was associated with patient clinicopathological features, high immune score, high abundance of immune infiltrating cells and somewhat high abundance of bacteria. A risk model based on eight SRGs showed that a low risk score was characterized by inhibition of immune activity and was indicative of better prognosis in patients with CRC. In combination with clinical characteristics, risk score was found to be an independent prognostic predictor of survival in patients with CRC. In conclusion, the present study showed that senescence-related subtypes and a signature consisting of eight SRGs were associated with CRC patient prognosis, as well as with immune cell infiltration and gut microbiota. These findings may enable better prediction of CRC patient prognosis and facilitate individualized treatments.
Neurologic Complication Due to Crystallization After Drug Interaction Between Alkalized Lidocaine and Ropivacaine: A Case Report and in vitro Study
Authors: Zhu Afang , Pei Lijian , Liu Wei , Cheng Wencong , Zhang Yu , Huang Yuguang
Published: June 2022

Background

For pregnant women transferred to emergency cesarean section after receiving epidural labor analgesia, there is still a debate over the effective and safe means of rapidly delivering surgical anesthesia. Alkalized lidocaine is often adopted for fast onset time; however, crystallization of the anesthetic may cause severe neurologic symptoms.

Case Presentation

We report a case of a pregnant woman who underwent emergency cesarean section with satisfied analgesia but experienced severe weakness and paranaesthesia in the lower limb. After excluding lumbar disc herniation, obstetric nerve injury, and anesthesia technique causes by symptoms signs and magnetic resonance imaging, drug-related injury became the most likely cause. Our in vitro testing confirmed the obvious precipitation of additional anesthetic-concentrated ropivacaine (0.5–1%) with pretreated alkalized lidocaine. With trophic neurotherapy, the parturient attained prompt relief of weakness by day four, but delayed recovery of numbness, which lasted for 4 weeks.

Conclusion

To date, this is the first case reporting neurologic complication possibly due to drug crystallization in cesarean section. Our study confirmed the rapid onset of alkalized lidocaine and its safety to pretreated routine labor dose of ropivacaine (0.09%). However, additional anesthetic-concentrated ropivacaine (0.5–1%) to maintain the anesthesia and analgesia level is not suggested.
Optimization of Monascus purpureus for Natural Food Pigments Production on Potato Wastes and Their Application in Ice Lolly
Authors: Abdel-Raheam Hossam E. F. , Alrumman Sulaiman A. , Gadow Samir I. , El-Sayed Mohamed H. , Hikal Dalia M. , Hesham Abd El-Latif , Ali Maysa M. A.
Published: June 2022

During potato chips manufacturing, large amounts of wastewater and potato powder wastes are produced. The wastewater obtained at washing after cutting the peeled potatoes into slices was analyzed, and a large quantity of organic compounds and minerals such as starch (1.69%), protein (1.5%), total carbohydrate (4.94%), reducing sugar (0.01%), ash (0.14%), crude fat (0.11%), Ca (28 mg/L), Mg (245 mg/L), Fe (45.5 mg/L), and Zn (6.5 mg/L) were recorded; these wastes could be considered as valuable by-products if used as a fermentation medium to increase the value of the subsequent products and to exceed the cost of reprocessing. In this study, we used wastewater and potato powder wastes as a growth medium for pigment and biomass production by Monascus purpureus (Went NRRL 1992). The response surface methodology was used to optimize total pigment and fungal biomass production. The influence of potato powder waste concentration, fermentation period, and peptone concentration on total pigment and biomass production was investigated using the Box-Behnken design method with 3-factors and 3-levels. The optimal production parameters were potato powder waste concentration of 7.81%, fermentation period of 12.82 days, and peptone concentration of 2.87%, which produced a maximum total pigment of 29.86 AU/ml that include, respectively, a maximum biomass weight of 0.126 g/ml and the yield of pigment of 236.98 AU/g biomass. The pigments produced were used as coloring agents for ice lolly. This study has revealed that the ice lolly preparations supplemented with these pigments received high acceptability. Finally, we recommend using wastewater and potato powder wastes for pigment and biomass production, which could reduce the cost of the pigment production process on an industrial scale in the future.
Pharmacokinetics and Pharmacodynamics of Fungal Defensin NZX Against Staphylococcus aureus-Induced Mouse Peritonitis Model
Authors: Zheng Xueling , Yang Na , Mao Ruoyu , Hao Ya , Teng Da , Wang Jianhua
Published: June 2022

Staphylococcus aureus (S. aureus) is one of the most common pathogenic bacteria responsible for causing a life-threatening peritonitis disease. NZX, as a variant of fungal defensin plectasin, displayed potent antibacterial activity against S. aureus. In this study, the antibacterial and resistance characteristics, pharmacokinetics, and pharmacodynamics of NZX against the S. aureus E48 and S. aureus E48-induced mouse peritonitis model were studied, respectively. NZX exhibited a more rapid killing activity to S. aureus (minimal inhibitory concentration, 1 μg/ml) compared with linezolid, ampicillin and daptomycin, and serial passaging of S. aureus E48 for 30 days at 1/2 × MIC, NZX had a lower risk of resistance compared with ampicillin and daptomycin. Also, it displayed a high biocompatibility and tolerance to physiological salt, serum environment, and phagolysosome proteinase environment, except for acid environment in phagolysosome. The murine serum protein-binding rate of NZX was 89.25% measured by ultrafiltration method. Based on the free NZX concentration in serum after tail vein administration, the main pharmacokinetic parameters for T1/2, Cmax, Vd, MRT, and AUC ranged from 0.32 to 0.45 h, 2.85 to 20.55 μg/ml, 1469.10 to 2073.90 ml/kg, 0.32 to 0.56 h, and 1.11 to 8.89 μg.h/ml, respectively. Additionally, the in vivo pharmacodynamics against S. aureus demonstrated that NZX administrated two times by tail vein at 20 mg/kg could rescue all infected mice in the lethal mouse peritonitis model. And NZX treatment (20 mg/kg) significantly reduced CFU counts in the liver, lung, and spleen, especially for intracellular bacteria in the peritoneal fluid, which were similar or superior to those of daptomycin. In vivo efficacies of NZX against total bacteria and intracellular bacteria were significantly correlated with three PK/PD indices of ƒAUC/MIC, ƒCmax/MIC, and ƒT% > MIC analyzed by a sigmoid maximum-effect model. These results showed that NZX may be a potential candidate for treating peritonitis disease caused by intracellular S. aureus.
Future Prospect of Oral Microbiota Influencing Allergy/Asthma Development
Authors: Cai Yue , Zhao Yanqin , Kang Yongbo , Yang Ying
Published: June 2022

Allergic diseases have become a primary public health issue in a moderately prosperous society. Colonization of microorganisms early in life appears to be significant in guiding the regulation of childhood immune system maturation and allergy development. Since the oral cavity is the first position where most foreign antigens meet the immune system, the oral microbiota may play a key role in the development of allergies. However, the study on the effects of oral microorganisms on allergy/asthma is very restricted and should be actively investigated. It requires considerable effort to enrich our knowledge in this area of the relationship between the oral cavity and allergy/asthma. To promote the rapid progress of relevant research. In this review, we aimed to provide several insights into the role of the oral microbiota in allergy/asthma while prospecting future directions.
Swimming Using a Unidirectionally Rotating, Single Stopping Flagellum in the Alpha Proteobacterium Rhodobacter sphaeroides
Authors: Armitage Judith P.
Published: June 2022

Rhodobacter sphaeroides has 2 flagellar operons, one, Fla2, encoding a polar tuft that is not expressed under laboratory conditions and a second, Fla1, encoding a single randomly positioned flagellum. This single flagellum, unlike the flagella of other species studied, only rotates in a counterclockwise direction. Long periods of smooth swimming are punctuated by short stops, caused by the binding of one of 3 competing CheY homologs to the motor. During a stop, the motor is locked, not freely rotating, and the flagellar filament changes conformation to a short wavelength, large amplitude structure, reforming into a driving helix when the motor restarts. The cell has been reoriented during the brief stop and the next period of smooth swimming is a new direction.
Enhancing Biomethane Production From Lignite by an Anaerobic Polycyclic Aromatic Hydrocarbon Degrading Fungal Flora Enriched From Produced Water
Authors: Gong Kaiyi , Zhang Yixuan , Guo Hongguang , Huang Zaixing , Urynowicz Michael , Ali Muhammad Ishtiaq
Published: June 2022

The coal-degrading ability of microorganisms is essential for the formation of biogenic coalbed methane. The ability to degrade the aromatic compound of coal is more important because it is perceived as the main refractory component for bioconversion. In this paper, a polycyclic aromatic hydrocarbon (PAH) degrading fungal community (PF) was enriched from produced water using phenanthrene as sole carbon source. The goal was to improve both the microbial structure of the methanogenic microflora and its coal-degrading ability. Two strategies were pursued. The first used coal pretreatment with PF (PP), followed by methane production by methanogenic microflora; the second used methane production directly from coal by mixed culture of PF and methanogenic microflora (PM). The results showed that methane productions of PP and PM increased by 29.40 and 39.52%, respectively. After 7 days of cultivation, the fungal community has been altered in PP and PM, especially for Penicillium the proportions of which were 67.37 and 89.81% higher than that in methanogenic microflora, respectively. Furthermore, volatile fatty acid accumulations increased by 64.21 and 58.15%, respectively. The 13C-NMR results showed that PF addition promoted the transformation of aromatic carbons in coal to carboxyl and carbonyl carbons, which contributed greatly to the production of methane together with oxygen-containing functional groups. These results suggest that methane production can be increased by indigenous PAH-degrading fungi by improving the fermentation of aromatics in coal and the generation of volatile fatty acids. This provided a feasible method for enhancing biomethane generation in the coal seam.
A Novel Breakthrough in Leptospira spp. Mutagenesis: Knockout by Combination of CRISPR/Cas9 and Non-homologous End-Joining Systems
Authors: Fernandes Luis G. V. , Nascimento Ana L. T. O.
Published: June 2022

Leptospirosis is of general concern as it is a widespread zoonotic disease caused by pathogenic species of the genus Leptospira, although this genus also includes free-living saprophytic strains. Understanding the pathophysiology of leptospirosis is still in its infancy even after several years of its discovery, because of the lack of effective genetic tools. The use of the Streptococcus pyogenes CRISPR/Cas9 system and its variations have pushed the leptospirosis research forward, relying on the simplicity of the technique. However, the lethality of double-strand breaks (DSB) induced by the RNA-guided Cas9 enzyme has limited the generation of knockout mutants. In this work, we demonstrated sustained cell viability after concurrent expression of CRISPR/Cas9 and Mycobacterium tuberculosis non-homologous end-joining components in a single-plasmid strategy in L. biflexa. Scarless mutations resulting in null phenotypes could be observed in most of the colonies recovered, with deletions in the junctional site ranging from 3 to almost 400 bp. After plasmid curing by in vitro passages in a medium without antibiotic, selected marker-free and targeted mutants could be recovered. Knockout mutants for LipL32 protein in the pathogen L. interrogans could be obtained using M. smegmatis NHEJ machinery, with deletions ranging from 10 to 345 bp. In conclusion, we now have a powerful genetic tool for generating scarless and markerless knockout mutants for both saprophytic and pathogenic strains of Leptospira.
Machine Learning Advances in Microbiology: A Review of Methods and Applications
Authors: Jiang Yiru , Luo Jing , Huang Danqing , Liu Ya , Li Dan-dan
Published: June 2022

Microorganisms play an important role in natural material and elemental cycles. Many common and general biology research techniques rely on microorganisms. Machine learning has been gradually integrated with multiple fields of study. Machine learning, including deep learning, aims to use mathematical insights to optimize variational functions to aid microbiology using various types of available data to help humans organize and apply collective knowledge of various research objects in a systematic and scaled manner. Classification and prediction have become the main achievements in the development of microbial community research in the direction of computational biology. This review summarizes the application and development of machine learning and deep learning in the field of microbiology and shows and compares the advantages and disadvantages of different algorithm tools in four fields: microbiome and taxonomy, microbial ecology, pathogen and epidemiology, and drug discovery.
Chemical Communication in Artificial Cells: Basic Concepts, Design and Challenges
Authors: Karoui Hedi , Patwal Pankaj Singh , Pavan Kumar B. V. V. S. , Martin Nicolas
Published: June 2022

In the past decade, the focus of bottom-up synthetic biology has shifted from the design of complex artificial cell architectures to the design of interactions between artificial cells mediated by physical and chemical cues. Engineering communication between artificial cells is crucial for the realization of coordinated dynamic behaviours in artificial cell populations, which would have implications for biotechnology, advanced colloidal materials and regenerative medicine. In this review, we focus our discussion on molecular communication between artificial cells. We cover basic concepts such as the importance of compartmentalization, the metabolic machinery driving signaling across cell boundaries and the different modes of communication used. The various studies in artificial cell signaling have been classified based on the distance between sender and receiver cells, just like in biology into autocrine, juxtacrine, paracrine and endocrine signaling. Emerging tools available for the design of dynamic and adaptive signaling are highlighted and some recent advances of signaling-enabled collective behaviours, such as quorum sensing, travelling pulses and predator-prey behaviour, are also discussed.
Pathophysiological Significance of GM3 Ganglioside Molecular Species With a Particular Attention to the Metabolic Syndrome Focusing on Toll-Like Receptor 4 Binding
Authors: Inokuchi Jin-ichi , Kanoh Hirotaka
Published: June 2022

GM3 ganglioside, the first molecule in ganglioside family biosynthesis, is formed by transfer of sialic acid to lactosylceramide. Several dozen GM3 molecular species exist, based on diversity of ceramide structures. Among ceramide structures composed of sphingosine and fatty acids, there is a great diversity resulting from different combinations of chain length, hydroxylation, and unsaturation of fatty acid chains. Expression patterns of GM3 species in serum vary during pathogenesis of metabolic syndrome. Physiological activity of each species, and significance of the variability, are poorly understood. Our studies revealed that GM3 species with differing fatty acid structures act as pro- or anti-inflammatory endogenous Toll-like receptor 4 (TLR4) ligands. Very long-chain fatty acid (VLCFA) and α-hydroxyl VLCFA GM3 variants strongly enhanced TLR4 activation. In contrast, long-chain fatty acid (LCFA) and ω-9 unsaturated VLCFA GM3 variants suppressed TLR4 activation. GM3 interacted with extracellular TLR4/myeloid differentiation factor 2 (MD-2) complex, thereby promoting dimerization/oligomerization. In obesity and metabolic syndrome, VLCFA-variant GM3 species were elevated in serum and adipose tissue, whereas LCFA-variant species were reduced, and such imbalances were correlated with disease progression. Our findings summarized in this review demonstrate that GM3 molecular species are disease-related endogenous TLR4 ligands and modulate homeostatic and pathogenic innate immune responses.
Study on Low-Frequency Repetitive Transcranial Magnetic Stimulation Improves Speech Function and Mechanism in Patients With Non-fluent Aphasia After Stroke
Authors: Bai Guangtao , Jiang Liang , Huan Sai , Meng Pingping , Wang Yuyang , Pan Xiaona , Yin Shuai , Zhao Yuyang , Wang Qiang
Published: June 2022

Objective

To explore the therapeutic effect and mechanism of low-frequency repetitive transcranial magnetic stimulation on the speech function of patients with non-fluent aphasia after stroke.

Methods

According to the inclusion and exclusion criteria, 60 patients with post-stroke non-fluent aphasia were included and randomly divided into treatment group (rTMS group) and sham stimulation group (S-rTMS group). Patients in rTMS group were given low-frequency rTMS + ST training. Patients in the S-rTMS group were given sham low-frequency rTMS + ST training. Once a day, 5 days a week, for a total of 4 weeks. The Western Aphasia Battery and the short-form Token test were used to evaluate the language function of the patients in the two groups before and after treatment. Part of the enrolled patients were subjected to functional magnetic resonance imaging examination, and the morning fasting venous blood of the enrolled patients was drawn before and after treatment to determine the content of BDNF and TNF-α.

Results

In the comparison before and after treatment within the group, all dimensions of the WAB scale of the patients in the rTMS group increased significantly. Only two dimensions of the WAB scale of the patients in the S-rTMS group improved significantly after treatment. The results of the short-form Token test showed that patients in the rTMS group improved significantly before and after treatment. The resting state functional magnetic resonance imaging of the two groups of patients before and after treatment showed: the activation of multiple brain regions in the left hemisphere of the rTMS group increased compared with the control group. The serum BDNF content of the patients in the rTMS group was significantly higher than that of the patients in the S-rTMS group after treatment.

Conclusion

Low-frequency rTMS combined with conventional speech training can significantly improve the speech function of patients with non-fluent aphasia after stroke.
General Transcription Factor IIF Polypeptide 2: A Novel Therapeutic Target for Depression Identified Using an Integrated Bioinformatic Analysis
Authors: Zhang Chi , Cheng Min , Dong Naifu , Sun Dongjie , Ma Haichun
Published: June 2022

Depression currently affects 4% of the world’s population; it is associated with disability in 11% of the global population. Moreover, there are limited resources to treat depression effectively. Therefore, we aimed to identify a promising novel therapeutic target for depression using bioinformatic analysis. The GSE54568, GSE54570, GSE87610, and GSE92538 gene expression data profiles were retrieved from the Gene Expression Omnibus (GEO) database. We prepared the four GEO profiles for differential analysis, protein–protein interaction (PPI) network construction, and weighted gene co-expression network analysis (WGCNA). Gene Ontology functional enrichment and Kyoto Encyclopedia of Genes and Genomes metabolic pathway analyses were conducted to determine the key functions of the corresponding genes. Additionally, we performed correlation analyses of the hub genes with transcription factors, immune genes, and N6-methyladenosine (m6A) genes to reveal the functional landscape of the core genes associated with depression. Compared with the control samples, the depression samples contained 110 differentially expressed genes (DEGs), which comprised 56 downregulated and 54 upregulated DEGs. Moreover, using the WGCNA and PPI clustering analysis, the blue module and cluster 1 were found to be significantly correlated with depression. GTF2F2 was the only common gene identified using the differential analysis and WGCNA; thus, it was used as the hub gene. According to the enrichment analyses, GTF2F2 was predominantly involved in the cell cycle and JAK-STAT, PI3K-Akt, and p53 signaling pathways. Furthermore, differential and correlation analyses revealed that 9 transcription factors, 12 immune genes, and 2 m6A genes were associated with GTF2F2 in depression samples. GTF2F2 may serve as a promising diagnostic biomarker and treatment target of depression, and this study provides a novel perspective and valuable information to explore the molecular mechanism of depression.
Mutual Shaping of Circadian Body-Wide Synchronization by the Suprachiasmatic Nucleus and Circulating Steroids
Authors: Yao Yifan , Silver Rae
Published: June 2022

Background

Steroids are lipid hormones that reach bodily tissues through the systemic circulation, and play a major role in reproduction, metabolism, and homeostasis. All of these functions and steroids themselves are under the regulation of the circadian timing system (CTS) and its cellular/molecular underpinnings. In health, cells throughout the body coordinate their daily activities to optimize responses to signals from the CTS and steroids. Misalignment of responses to these signals produces dysfunction and underlies many pathologies.

Questions Addressed

To explore relationships between the CTS and circulating steroids, we examine the brain clock located in the suprachiasmatic nucleus (SCN), the daily fluctuations in plasma steroids, the mechanisms producing regularly recurring fluctuations, and the actions of steroids on their receptors within the SCN. The goal is to understand the relationship between temporal control of steroid secretion and how rhythmic changes in steroids impact the SCN, which in turn modulate behavior and physiology.

Evidence Surveyed

The CTS is a multi-level organization producing recurrent feedback loops that operate on several time scales. We review the evidence showing that the CTS modulates the timing of secretions from the level of the hypothalamus to the steroidogenic gonadal and adrenal glands, and at specific sites within steroidogenic pathways. The SCN determines the timing of steroid hormones that then act on their cognate receptors within the brain clock. In addition, some compartments of the body-wide CTS are impacted by signals derived from food, stress, exercise etc. These in turn act on steroidogenesis to either align or misalign CTS oscillators. Finally this review provides a comprehensive exploration of the broad contribution of steroid receptors in the SCN and how these receptors in turn impact peripheral responses.

Conclusion

The hypothesis emerging from the recognition of steroid receptors in the SCN is that mutual shaping of responses occurs between the brain clock and fluctuating plasma steroid levels.
Semiactive Knee Orthotic Using a MR Damper and a Smart Insole to Control the Damping Force Sensing the Plantar Pressure
Authors: Alvarado-Rivera David , Niño-Suárez Paola A. , Corona-Ramírez Leonel G.
Published: June 2022

This work presents the development of semiactive knee orthosis prototype that focus to absorb the forces and impacts in this joint during the human gait. This prototype consists of three subsystems: the first is a wireless and portable system capable of measuring the ground reaction forces in the stance phase of the gait cycle, by means of an instrumented insole with force sensing resistors strategically placed on the sole of the foot, an electronic device allows processing and transmit this information via Bluetooth to the control system. The second is a semiactive actuator, which has inside a magnetorheological fluid, highlighting its ability to modify its damping force depending on the intensity of the magnetic field that circulates through the MR fluid. It is regulated by a Proportional Derivative (PD) controller system according to the values of plantar pressure measured by the insole. The third component is a mechanical structure manufactured by 3D printing, which adapts to the morphology of the human leg. This exoskeleton is designed to support the forces on the knee controlling the action of the magnetorheological actuator by ground reaction forces. The purpose of this assistance system is to reduce the forces applied to the knee during the gait cycle, providing support and stability to this joint. The obtained experimental results indicate that the device fulfills the function by reducing 12 % of the impact forces on the user's knee.
Reach Space Analysis of Baseline Differential Extrinsic Plasticity Control
Authors: Birrell Simon , Abdulali Arsen , Iida Fumiya
Published: June 2022

The neuroplasticity rule Differential Extrinsic Plasticity (DEP) has been studied in the context of goal-free simulated agents, producing realistic-looking, environmentally-aware behaviors, but no successful control mechanism has yet been implemented for intentional behavior. The goal of this paper is to determine if “short-circuited DEP,” a simpler, open-loop variant can generate desired trajectories in a robot arm. DEP dynamics, both transient and limit cycles are poorly understood. Experiments were performed to elucidate these dynamics and test the ability of a robot to leverage these dynamics for target reaching and circular motions.
Green Supply Chain Optimization Based on BP Neural Network
Authors: Wang Huan
Published: June 2022

With the emergence and development of the Back Propagation neural network (BPNN), its unique learning, generalization, and non-linear characteristics have been gradually excavated and fully applied in the field of prediction. To improve the economic and green benefits of enterprises, the BPNN algorithm is applied to the green supply chain assisted by intelligent logistics robots. The BPNN algorithm can be used to output the characteristics of different information and optimize the green supply chain according to the input parameters and the influencing factors in the network. Firstly, an evaluation index system is established for selecting suppliers, which includes 4 first-level indicators: operational indicators, economic indicators, green indicators, social indicators, and 14 corresponding secondary indicators. Secondly, the evaluation indicator system is modeled through the BPNN. Finally, using the BPNN model, a supply chain enterprise's selection of cooperative enterprises in Xi'an is taken as the research object and simulation. Finally, the output results of the five alternative enterprises are 0.77, 0.75, 0.68, 0.72, and 0.65, respectively. The enterprise with the highest output results is selected as the cooperative enterprise and the enterprise with the second highest output results as an alternate. The green supply chain model based on the proposed BPNN is scientific and effective through specific simulation experiments. It has certain reference significance for the relevant issues related to subsequent optimization of the green supply chain.