bluuebunny/crossref_metadata_2025 huggingface dataset:
COVID-19 vaccination and Atypical hemolytic uremic syndrome
Authors: Bouwmeester Romy N. , Bormans Esther M.G. , Duineveld Caroline , van Zuilen Arjan D. , van de Logt Anne-Els , Wetzels Jack F.M. , van de Kar Nicole C.A.J.
Published: December 2022

Introduction

COVID-19 vaccination has been associated with rare but severe complications characterized by thrombosis and thrombocytopenia.

Methods and Results

Here we present three patients who developed de novo or relapse atypical hemolytic uremic syndrome (aHUS) in native kidneys, a median of 3 days (range 2-15) after mRNA-based (Pfizer/BioNTech’s, BNT162b2) or adenoviral (AstraZeneca, ChAdOx1 nCoV-19) COVID-19 vaccination. All three patients presented with evident hematological signs of TMA and AKI, and other aHUS triggering or explanatory events were absent. After eculizumab treatment, kidney function fully recovered in 2/3 patients. In addition, we describe two patients with dubious aHUS relapse after COVID-19 vaccination. To assess the risks of vaccination, we retrospectively evaluated 29 aHUS patients (n=8 with native kidneys) without complement-inhibitory treatment, who received a total of 73 COVID-19 vaccinations. None developed aHUS relapse after vaccination.

Conclusion

In conclusion, aHUS should be included in the differential diagnosis of patients with vaccine-induced thrombocytopenia, especially if co-occuring with mechanical hemolytic anemia (MAHA) and acute kidney injury (AKI). Still, the overall risk is limited and we clearly advise continuation of COVID-19 vaccination in patients with a previous episode of aHUS, yet conditional upon clear patient instruction on how to recognize symptoms of recurrence. At last, we suggest monitoring serum creatinine (sCr), proteinuria, MAHA parameters, and blood pressure days after vaccination.
Autologous bone marrow-derived MSCs engineered to express oFVIII-FLAG engraft in adult sheep and produce an effective increase in plasma FVIII levels
Authors: Trevisan Brady , Rodriguez Martin , Medder Hailey , Lankford Shannon , Combs Rebecca , Owen John , Atala Anthony , Porada Christopher D. , Almeida-Porada Graça
Published: December 2022

Introduction

Hemophilia A (HA) is the most common X-linked bleeding disorder, occurring in 1 in 5,000 live male births and affecting >1 million individuals worldwide. Although advances in protein-based HA therapeutics have improved health outcomes, current standard-of-care requires infusion 2-3 times per week for life, and 30% of patients develop inhibitors, significantly increasing morbidity and mortality. There are thus unmet medical needs requiring novel approaches to treat HA.

Methods

We tested, in a highly translational large animal (sheep) model, whether the unique immunological and biological properties of autologous bone marrow (BM)-derived mesenchymal stromal cells (MSCs) could enable them to serve as cellular delivery vehicles to provide long-term expression of FVIII, avoiding the need for frequent infusions.

Results

We show that autologous BM-MSCs can be isolated, transduced with a lentivector to produce high levels of ovine (o)FVIII, extensively expanded, and transplanted into adult animals safely. The transplanted cells engraft in multiple organs, and they stably produce and secrete sufficient quantities of FVIII to yield elevated plasma FVIII levels for at least 15 weeks.

Discussion

These studies thus highlight the promise of cellular-based gene delivery approaches for treating HA.
A case report of hepatitis B virus reactivation 19 months after cessation of chemotherapy with rituximab
Authors: Guo Xiangjuan , Ji Tongtong , Xin Shengliang , Xu Jinghang , Yu Yanyan
Published: December 2022

A 72-year-old woman presented to our hospital with elevation of serum transaminases. Her blood tests showed the hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) negative. Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) were given for the diffuse large B-cell lymphoma. She didn’t receive anti- hepatitis B virus (HBV) drug for the isolated HBcAb positive. HBV reactivation confirmed based on the serum HBV DNA detectable until 19 months after stopping R-CHOP regimen. HBV DNA became undetectable after 4 weeks therapy with Tenofovir alafenamide fumarate (TAF). Serum transaminases went down to normal 3 months later after receiving TAF. HBV reactivation is a substantial risk for patients with isolated HBcAb positive receiving rituximab-containing chemotherapy without anti- HBV drug. Regular monitoring with a frequency of 1-3 months is the basis for timely diagnosis and treatment of HBV reactivation. Serum transaminases abnormalities may be the initial manifestation of HBV reactivation.
Lifecycle, culture, and maintenance of the emerging cephalopod models Euprymna berryi and Euprymna morsei
Authors: Jolly Jeffrey , Hasegawa Yuko , Sugimoto Chikatoshi , Zhang Lin , Kawaura Risa , Sanchez Gustavo , Gavriouchkina Daria , Marlétaz Ferdinand , Rokhsar Daniel
Published: December 2022

Cephalopod research remains limited by the inability to culture species under laboratory conditions for multiple generations to provide continuous access to animals at all stages of the life cycle. Here, we describe a multi-generational laboratory culture system for two emerging cephalopod models: the hummingbird or Berry’s bobtail squid,Euprymna berryiSasaki, 1929, and Morse’s bobtail squid,Euprymna morseiVerrill, 1881, which are primarily found off mainland Japan.E. berryiwild adults were spawned and raised to the third filial generation, andE. morseiwild adults were spawned and raised to the second filial generation in a closed system at 20°C. We report growth and survivorship data for a cohort of 30 individuals across the first generation raised in captivity.E. berryiandE. morseigrew exponentially during the first 90 and 60 days post-hatching, respectively. Survivorship at the first spawning event forE. berryiandE. morseiwas 90% and 77%.E. berryiandE. morseifemales spawned after days 112 and 71 days post-hatching, respectively. We describe the life history of each species and how to distinguish sexes. We discuss the challenges of cephalopod culture and how culturing these species address those problems.
Differential responding patterns of the nirK-type and nirS-type denitrifying bacterial communities to an Ulva prolifera green tide in coastal Qingdao areas
Authors: Zhao Guihua , He Hui , Yue Ming , Wang Hualong , Shao Hongbing , Wang Min
Published: December 2022

Coastal eutrophication may be a vital inducement of green tide. Denitrification is an important nitrogen removal pathway that involves a series of enzymatic reactions. The rate-limiting step in the conversion of nitrite to nitric oxide is encoded by two functionally equivalent but structurally distinct genes, copper-containing nitrite reductase gene (nirK) and cytochrome cd1-containing nitrite reductase gene (nirS). Here, we used Illumina Miseq sequencing approach to examine the variations in denitrifying bacterial community characteristics and interactions during an Ulva prolifera green tide in coastal Qingdao areas. Our findings suggested that the variations in the denitrifying bacterial community structure during the green tide were closely related to the changes of chlorophyll a content, salinity and dissolved oxygen content. The nirK-type denitrifying bacteria were more sensitive to green tide than the nirS-type denitrifying bacteria. Additionally, the nirK-type denitrifying bacterial interactions were more stable and complex during the outbreak phase, while the nirS-type denitrifying bacterial interactions were more stable and complex during the decline phase. All of these characters demonstrated that the nirK-type and nirS-type denitrifying bacteria respond differently to the green tide, implying that they may occupy different niches during the green tide in coastal Qingdao areas.
Effects of Bacillus sp. and Lactobacillus sp. combination as a water additive on the culture pond water and growth performance of hybrid grouper (Epinephelus fuscoguttatus × Epinephelus polyphekadion)
Authors: Huang Jianpeng , Amenyogbe Eric , Ou Guanghai , Li Yu , Wen Zhenwei , Jiang Xingtao , Chen Gang
Published: December 2022

The individual Probiotic application has become increasingly widespread in aquaculture and has been extensively studied. However, investigating probiotics as water additives in the grouper culture is still lacking. This study evaluated the functional efficacy of the Bacillus subtilis CICC 10071 (3 × 1011 CFU / g) and Lactobacillus sp. (8 × 1011 CFU / g) combination in a 1:1 ratio on the rearing water quality, water microbial community structure, and growth performance of hybrid grouper. Depending on the additive concentrations of probiotics, we designed four groups, each in triplicate: control (WT, 0g/m3), low concentration (WL, 0.038g/m3), middle concentration (WM, 0.075g/m3), and high concentration (WH, 0.113g/m3). The result shows that throughout the 22-day feeding period, the water supplementation of probiotics significantly decreased Ammonia (NH3) and nitrite (NO2-) in culture water. Final weight (FW), Specific growth rate (SGR), and Weight gain rate (WGR) in treated groups were higher than that in the control group (P<0.05). Analysis of water microbiota revealed that the dominant phylum Bacteroidetes, Proteobacteria, Cyanobacteria, and Actinobacteria enriched in the culture water. Furthermore, we found that the Probiotics combination could significantly reduce the abundance of Cetobacterium (phyla Fusobacteria) related to ammonia and nitrite. The Phylogenetic Investigation of Communities by Reconstruction of Unobserved States 2 (PICRUSt2) also shows that the 'metabolism of other amino acids and ‘Fatty acid biosynthesis’ functions of water microbiota were reinforced by the addition of the probiotic combination. Thus, the probiotic combination exhibited a range of advantages in the grouper culture environment, and further in-depth studies are needed.
Seasonal variability of eddy kinetic energy in the East Australian current region
Authors: Liu Jia , Zheng Shaojun , Feng Ming , Xie Lingling , Feng Baoxin , Liang Peng , Wang Lei , Yang Lina , Yan Li
Published: December 2022

The East Australian Current (EAC) is an important western boundary current of the South Pacific subtropical Circulation with high mesoscale eddy kinetic energy (EKE). Based on satellite altimeter observations and outputs from the eddy-resolving ocean general circulation model (OGCM) for the Earth Simulator (OFES), the seasonal variability of EKE and its associated dynamic mechanism in the EAC region are studied. High EKE is mainly concentrated in the shear-region between the poleward EAC southern extension and the equatorward EAC recirculation along Australia's east coast, which is confined within the upper ocean (0-300 m). EKE in this area exhibits obvious seasonal variation, strong in austral summer with maximum (465±89 cm² s-²) in February and weak in winter with minimum (334±48 cm² s-²) in August. Energetics analysis from OFES suggests that the seasonal variability of EKE is modulated by the mixed instabilities composed of barotropic and baroclinic instabilities confined within the upper ocean, and barotropic instability (baroclinic instability) is the main energy source of EKE in austral summer (winter). The barotropic process is mainly controlled by the zonal shear of meridional velocities of the EAC southern extension and the EAC recirculation. The poleward EAC southern extension and the equatorward EAC recirculation are synchronously strengthened (weakened) due to the local positive (negative) sea level anomalies (SLA) under geostrophic equilibrium, and the barotropic instability dominated by zonal shear is enhanced (slackened), which results in a high (low) level of EKE in the EAC region.
Extending the Monod model of microbal growth with memory
Authors: Amirian Mohammad M. , Irwin Andrew J. , Finkel Zoe V.
Published: December 2022

Monod’s model describes the growth of microorganisms using a hyperbolic function of extracellular resource concentration. Under fluctuating or limited resource concentrations this model performs poorly against experimental data, motivating the more complex Droop model with a time-varying internal storage pool. We extend the Monod model to incorporate memory of past conditions, adding a single parameter motivated by a fractional calculus analysis. We show how to interpret the memory element in a biological context and describe its connection to a resource storage pool. Under nitrogen starvation at non-equilibrium conditions, we validate the model with simulations and empirical data obtained from lab cultures of diatoms (T. pseudonana and T. weissflogii) and prasinophytes (Micromonas sp. and O. tauri), globally influential phytoplankton taxa. Using statistical analysis, we show that our Monod-memory model estimates the growth rate, cell density and resource concentration as well as the Droop model, while requiring one less state variable. Our simple model may improve descriptions of phytoplankton dynamics in complex earth system models at a lower computational cost than is presently achievable.
Analytical modeling of cross-ply cylindrical composite submersible shell with elastic buckling using first order shear deformation theory
Authors: Waqas Hafiz Muhammad , Shi Dongyan , Khan Sohaib Z. , Helal Mahmoud , Fathallah Elsayed
Published: December 2022

The main objective of this study is to design composite shells i.e. long, short, thin and thick for the different underwater applications. These shells can be a part of pressure hulls, underwater vehicles, pressurized tanks, underwater cables and underwater pipelines etc. This paper presents comprehensive procedures for the mathematical modeling of elastic buckling for submersible composite shells under hydrostatic pressure. First order shear deformation theory (FOSDT) was used for modeling. FOSDT theory was mathematically derived under hydrostatic pressure for composite shells, and it can be used for all types of submersible shells. After the derivation of the theory, mathematical code was formed on MATLAB for this modeling. From the given formulation one can design the shell structure according to his needs on different environment conditions. Different types of composite shells, including moderately thick, thick, long, and short, are investigated for the FOSDT formulation to check the accuracy range. The results were compared with previous studies and finite element analysis FEA. Three types of materials, Carbon/Epoxy, Glass/Epoxy, and Boron/Epoxy, were used with different cross-ply symmetric and unsymmetrical angle configurations. The layups used for the analysis were [0/90/0]s [90/0/90/0]s [02/902]s [90/02/90]s [0/902/0]s [0/0/0/90]s [90/90/90/0]s and [0/90].
Case report: Recurrent angioedema: Diagnosing the rare and the frequent
Authors: Buttgereit Thomas , Fijen Lauré M. , Vera Carolina , Bergmann Karl-Christian , Maurer Marcus , Magerl Markus
Published: December 2022

Hereditary angiodema with normal C1 inhibitor and unknown mutation (HAE-nC1INH-UNK), an exceedingly rare subtype of HAE, appears to be often diagnosed in patients who do not have this condition, but have mast cell-mediated angioedema. Here, we report two patients diagnosed with HAE-nC1INH-UNK by their physicians, who referred them to our center for treatment continuation with costly kallikrein-kinin-system targeted therapies. We describe how we established the correct diagnosis of recurrent mast cell-mediated angioedema after thorough investigation of both patients and initiated effective treatment with omalizumab. Also, we present and discuss the consensus criteria for diagnosing the very rare condition HAE-nC1INH in light of recent research and based on our own clinical experience. In conclusion, HAE-nC1INH-UNK should only be considered after more common differential diagnoses, i.e., mast cell-mediated angioedema, have thoroughly been investigated and ruled out. This approach reduces both the patients’ disease burden and healthcare costs and contributes to meaningful research.
Effect of prone positioning on end-expiratory lung volume, strain and oxygenation change over time in COVID-19 acute respiratory distress syndrome: A prospective physiological study
Authors: Dilken Olcay , Rezoagli Emanuele , Yartaş Dumanlı Güleren , Ürkmez Seval , Demirkıran Oktay , Dikmen Yalım
Published: December 2022

Background

Prone position (PP) is a recommended intervention in severe classical acute respiratory distress syndrome (ARDS). Changes in lung resting volume, respiratory mechanics and gas exchange during a 16-h cycle of PP in COVID-19 ARDS has not been yet elucidated.

Methods

Patients with severe COVID-19 ARDS were enrolled between May and September 2021 in a prospective cohort study in a University Teaching Hospital. Lung resting volume was quantitatively assessed by multiple breath nitrogen wash-in/wash-out technique to measure the end-expiratory lung volume (EELV). Timepoints included the following: Baseline, Supine Position (S1); start of PP (P0), and every 4-h (P4; P8; P12) until the end of PP (P16); and Supine Position (S2). Respiratory mechanics and gas exchange were assessed at each timepoint.

Measurements and main results

40 mechanically ventilated patients were included. EELV/predicted body weight (PBW) increased significantly over time. The highest increase was observed at P4. The highest absolute EELV/PBW values were observed at the end of the PP (P16 vs S1; median 33.5 ml/kg [InterQuartileRange, 28.2–38.7] vs 23.4 ml/kg [18.5–26.4], p < 0.001). Strain decreased immediately after PP and remained stable between P4 and P16. PaO2/FiO2 increased during PP reaching the highest level at P12 (P12 vs S1; 163 [138–217] vs 81 [65–97], p < 0.001). EELV/PBW, strain and PaO2/FiO2 decreased at S2 although EELV/PBW and PaO2/FiO2 were still significantly higher as compared to S1. Both absolute values over time and changes of strain and PaO2/FiO2 at P16 and S2 versus S1 were strongly associated with EELV/PBW levels.

Conclusion

In severe COVID-19 ARDS, EELV steadily increased over a 16-h cycle of PP peaking at P16. Strain gradually decreased, and oxygenation improved over time. Changes in strain and oxygenation at the end of PP and back to SP were strongly associated with changes in EELV/PBW. Whether the change in EELV and oxygenation during PP may play a role on outcomes in COVID-ARDS deserves further investigation.

Clinical trial registration

[www.ClinicalTrials.gov], identifier [NCT 04818164].
Genetic and compositional analysis of biofilm formed by Staphylococcus aureus isolated from food contact surfaces
Authors: Avila-Novoa María Guadalupe , Solis-Velazquez Oscar Alberto , Guerrero-Medina Pedro Javier , González-Gómez Jean-Pierre , González-Torres Berenice , Velázquez-Suárez Noemí Yolanda , Martínez-Chávez Liliana , Martínez-Gonzáles Nanci Edid , De la Cruz-Color Lucia , Ibarra-Velázquez Luz María , Cardona-López Marco Antonio , Robles-García Miguel Ángel , Gutiérrez-Lomelí Melesio
Published: December 2022

Introduction

Staphylococcus aureus is an important pathogen that can form biofilms on food contact surfaces (FCS) in the dairy industry, posing a serious food safety, and quality concern. Biofilm is a complex system, influenced by nutritional-related factors that regulate the synthesis of the components of the biofilm matrix. This study determines the prevalence of biofilm-associated genes and evaluates the development under different growth conditions and compositions of biofilms produced by S. aureus.

Methods

Biofilms were developed in TSB, TSBG, TSBNaCl, and TSBGNaCl on stainless-steel (SS), with enumeration at 24 and 192 h visualized by epifluorescence and scanning electron microscopy (SEM). The composition of biofilms was determined using enzymatic and chemical treatments and confocal laser scanning microscopy (CLSM).

Results and discussion

A total of 84 S. aureus (SA1–SA84) strains were collected from 293 dairy industry FCS (FCS-stainless steel [n = 183] and FCS-polypropylene [n = 110]) for this study. The isolates harbored the genes sigB (66%), sar (53%), agrD (52%), clfB/clfA (38%), fnbA/fnbB (20%), and bap (9.5%). 99. In particular, the biofilm formed by bap-positive S. aureus onto SS showed a high cell density in all culture media at 192 h in comparison with the biofilms formed at 24 h (p < 0.05). Epifluorescence microscopy and SEM revealed the metabolically active cells and the different stages of biofilm formation. CLSM analysis detected extracellular polymeric of S. aureus biofilms on SS, such as eDNA, proteins, and polysaccharides. Finally, the level of detachment on being treated with DNase I (44.7%) and NaIO 4(42.4%) was greater in the biofilms developed in TSB compared to culture medium supplemented with NaCl at 24 h; however, there was no significant difference when the culture medium was supplemented with glucose. In addition, after treatment with proteinase K, there was a lower level of biomass detachment (17.7%) of the biofilm developed in TSBNaCl (p < 0.05 at 24 h) compared to that in TSB, TSBG, and TSBGNaCl (33.6, 36.9, and 37.8%, respectively). These results represent a deep insight into the composition of S. aureus biofilms present in the dairy industry, which promotes the development of more efficient composition-specific disinfection strategies.
Gut-microbiome-based predictive model for ST-elevation myocardial infarction in young male patients
Authors: Liu Mingchuan , Wang Min , Peng Tingwei , Ma Wenshuai , Wang Qiuhe , Niu Xiaona , Hu Lang , Qi Bingchao , Guo Dong , Ren Gaotong , Geng Jing , Wang Di , Song Liqiang , Hu Jianqiang , Li Yan
Published: December 2022

Background

ST-segment elevation myocardial infarction (STEMI) in young male patients accounts for a significant proportion of total heart attack events. Therefore, clinical awareness and screening for acute myocardial infarction (AMI) in asymptomatic patients at a young age is required. The gut microbiome is potentially involved in the pathogenesis of STEMI. The aim of the current study is to develop an early risk prediction model based on the gut microbiome and clinical parameters for this population.

Methods

A total of 81 young males (age < 44 years) were enrolled in this study. Forty-one young males with STEMI were included in the case group, and the control group included 40 young non-coronary artery disease (CAD) males. To identify the differences in gut microbiome markers between these two groups, 16S rRNA-based gut microbiome sequencing was performed using the Illumina MiSeq platform. Further, a nomogram and corresponding web page were constructed. The diagnostic efficacy and practicability of the model were analyzed using K-fold cross-validation, calibration curves, and decision curve analysis (DCA).

Results

Compared to the control group, a significant decrease in tendency regarding α and β diversity was observed in patients in the case group and identified as a significantly altered gut microbiome represented by Streptococcus and Prevotella. Regarding clinical parameters, compared to the control group, the patients in the case group had a higher body mass index (BMI), systolic blood pressure (SBP), triglyceride (TG), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) and low blood urea nitrogen (BUN). Additionally, BMI and SBP were significantly (p<0.05) positively correlated with Streptococcus and [Ruminococcus]. Further, BMI and SBP were significantly (p<0.05) negatively correlated with Prevotella and Megasphaera. A significant negative correlation was only observed between Prevotella and AST (p < 0.05). Finally, an early predictive nomogram and corresponding web page were constructed based on the gut microbiome and clinical parameters with an area under the receiver-operating characteristic (ROC) curve (AUC) of 0.877 and a C-index of 0.911. For the internal validation, the stratified K-fold cross-validation (K = 3) was as follows: AUC value of 0.934. The calibration curves of the model showed good consistency between the actual and predicted probabilities. The DCA results showed that the model had a high net clinical benefit for use in the clinical setting.

Conclusion

In this study, we combined the gut microbiome and common clinical parameters to construct a prediction model. Our analysis shows that the constructed model is a non-invasive tool with potential clinical application in predicting STEMI in the young males.
Rumen-protected glucose supplementation alters fecal microbiota and its metabolic profiles in early lactation dairy cows
Authors: Wang Yapin , Zhao Yiguang , Nan Xuemei , Wang Yue , Cai Meng , Jiang Linshu , Luo Qingyao , Xiong Benhai
Published: December 2022

Introduction

Negative energy balance (NEB) is the pathological basis of metabolic disorders in early lactation dairy cows. Rumen-protected glucose (RPG) is a feed additive to relieve NEB of cows in early lactation. The aims of the current study were to evaluate the impact of different doses of RPG supply on fecal microbiota and metabolome in early lactation dairy cows, and their correlation with each other.

Methods

A total of 24 multiparous Holstein dairy cows in early lactation were randomly assigned to one of four treatments for the first 35 days of the early lactation period, as follows: control group, a basal diet without RPG (CON); low RPG, a basal diet plus 200 g/d RPG (LRPG); medium RPG, a basal diet plus 350 g/d RPG (MRPG); or HRPG, high RPG, a basal diet plus 500 g/d RPG (HRPG). After 35 days, fecal samples were obtained from cows in all groups individually and using 16S rRNA gene sequencing to evaluate their microbiotas, while their metabolites were evaluated through metabolomics.

Results

As expected, Firmicutes and Bacteroidetes were the core bacteria phyla. After RPG supplementation, there were an increase in Firmicutes and a decrease in Bacteroidetes. MRPG increased the relative abundance of cellulolytic bacteria, including Ruminococcaceae_UCG-005, Lachnospiraceae_UCG-008, Lachnospiraceae_FCS020_group, and Ruminiclostridium_9, while it decreased the relative abundance of Alistipes, Prevotellaceae_UCG-003, and Dorea. RPG supplementation could regulate the carbohydrate metabolism and amino acid metabolism pathway significantly and relieve lipolysis in dairy cows. Correlation analysis of fecal microbiome and metabolome showed that some major differential bacteria were the crucial contributors to differential metabolites.

Conclusion

In conclusion, RPG supplementation can affect the fecal microbial components and microbial metabolism, and 350 g RPG might be the ideal dose as a daily supplement.
Influence of Lactobacillus plantarum inoculation on the silage quality of intercropped Lablab purpureus and sweet sorghum grown in saline-alkaline region
Authors: Li Huangkeyi , Wang Tianwei , Tahir Muhammad , Zhang Jiaqi , Sun Jiahao , Xia Tianqi , Huang Fuqing , Liu Yayong , Liu Zhiquan , Zhong Jin
Published: December 2022

Ensiling legume with cereal is an effective method to ensure the energy rich-feed, but no information is available on the microbial fermentation mechanism of intercropped Lablab purpureus (Lablab) and sweet sorghum in the saline-alkaline region. Therefore, the present study investigated the silage quality and microbial community of intercropped Lablab and sweet sorghum silages grown in the saline-alkaline region with or without inoculation of Lactobacillus plantarum (LP). The experimental treatments were prepared according to the Lablab and sweet sorghum planting patterns: Lablab and sweet sorghum sowing seed ratios were 1:1 (L), 5:1 (M), and 9:1 (H). After harvesting, each mixture was treated with LP or sterilized water (CK), followed by 60 days of fermentation. Results showed that both LP inoculation and intercropping significantly raised the lactic acid (LA) content and decreased the pH value, acetic acid (AA), and ammonia-N in intercropped silages. The LP addition and intercropping also improved the relative feed value by reducing structural carbohydrates. Moreover, LP silages had a greater relative abundance of Lactobacillus than CK silages, and its relative abundance increased with an increased seed-sowing ratio of Lablab in intercropping. LP was the prevalent species in LP silages compared to CK silages, and its relative abundance also increased with an increased seed-sowing ratio of Lablab in intercropping. The genus Lactobacillus was negatively correlated with ammonia-N (R = −0.6, p = 0.02) and AA (R = −0.7, p < 0.01) and positively correlated with LA (R = 0.7, p < 0.01) and crude protein (R = 0.6, p = 0.04). Overall, the intercropped seeding ratios of Lablab and sweet sorghum of ≥ 5:1 with LP inoculation resulted in better fermentation quality and preservation of nutritional components providing theoretical support and guidance for future intercropped protein-rich silage production in the saline-alkaline region.
The metal chaperone protein MtmA plays important roles in antifungal drug susceptibility in Aspergillus fumigatus
Authors: Zhai Pengfei , Ma Yinyan , Du Wenlong , Lu Ling
Published: December 2022

Drug-resistant fungal infections are emerging as an important clinical problem. In general, antifungal resistance results from increased target expression or mutations within the target protein sequence. However, the molecular mechanisms of non-drug target mutations of antifungal resistance in fungal pathogens remain to be explored. Previous studies indicated that the metal chaperone protein Mtm1 is required for mitochondrial Sod2 activation and responses to oxidative stress in yeast and in the fungal pathogen Aspergillus fumigatus, but there is no report of MtmA-related antifungal resistance. In this study, we found that repressed expression of MtmA (only 10% expression) using a conditional promoter resulted in significantly enhanced itraconazole resistance, which was not the result of highly expressed drug targets Erg11A and Erg11B. Furthermore, we demonstrated that repressed expression of MtmA results in upregulation of a series of multidrug resistance-associated transport genes, which may cause multidrug resistance. Further mechanistic studies revealed that inhibition of MtmA expression led to abnormal activation of the calcium signaling system and prompted persistent nucleation of the calcium signaling transcription factor CrzA. Our findings suggest that the metal chaperone protein MtmA is able to negatively regulate fungal resistance via affecting calcium signaling pathway.
Glutamine potentiates gentamicin to kill lab-evolved gentamicin-resistant and clinically isolated multidrug-resistant Escherichia coli
Authors: Chen Yue-tao , Ma Yan-mei , Peng Xuan-xian , Li Hui
Published: December 2022

Introduction

Gentamicin is a conventional antibiotic in clinic. However, with the wide use of antibiotics, gentamicin-resistant Escherichia coli (E. coli) is an ever-increasing problem that causes infection in both humans and animals. Thus, it is especially important to restore gentamicin-mediated killing efficacy.

Method

E. coli K12 BW25113 cells were passaged in medium with and without gentamicin and obtain gentamicin-resistant (K12-RGEN) and control (K12-S) strains, respectively. Then, the metabonomics of the two strains were analyzed by GC-MS approach.

Results

K12-RGEN metabolome was characterized as more decreased metabolites than increased metabolites. Meantime, in the most enriched metabolic pathways, almost all of the metabolites were depressed. Alanine, aspartate and glutamate metabolism and glutamine within the metabolic pathway were identified as the most key metabolic pathways and the most crucial biomarkers, respectively. Exogenous glutamine potentiated gentamicin-mediated killing efficacy in glutamine and gentamicin dose-and time-dependent manners in K12-RGEN. Further experiments showed that glutamine-enabled killing by gentamicin was effective to clinically isolated multidrug-resistant E. coli.

Discussion

These results suggest that glutamine provides an ideal metabolic environment to restore gentamicin-mediated killing, which not only indicates that glutamine is a broad-spectrum antibiotic synergist, but also expands the range of metabolites that contribute to the bactericidal efficiency of aminoglycosides.
Gastrodia elata Blume extract improves high-fat diet-induced type 2 diabetes by regulating gut microbiota and bile acid profile
Authors: Wang Danqi , Wang Jun-Xia , Yan Chunri , Liu Yize , Liu Hongye , Li Dongxu , Zhu Jun , Luo Zhao-Bo , Han Sheng-Zhong , Jin Zheng-Yun , Chang Shuang-Yan , Yang Liu-Hui , Kang Jin-Dan , Quan Lin-Hu
Published: December 2022

In this study, we aimed to characterize the anti-type 2 diabetes (T2D) effects of Gastrodia elata Blume extract (GEBE) and determine whether these are mediated through modification of the gut microbiota and bile acids. Mice were fed a high-fat diet (HFD), with or without GEBE, and we found that GEBE significantly ameliorated the HFD-induced hyperglycemia, insulin resistance, and inflammation by upregulating glucose transporter 4 (GLUT4) and inhibiting the toll-like receptor 4-nuclear factor kappa-B signaling pathway in white adipose tissue (WAT). In addition, we found that GEBE increased the abundance of Faecalibaculum and Lactobacillus, and altered the serum bile acid concentrations, with a significant increase in deoxycholic acid. The administration of combined antibiotics to mice to eliminate their intestinal microbiota caused a loss of the protective effects of GEBE. Taken together, these findings suggest that GEBE ameliorates T2D by increasing GLUT4 expression in WAT, remodeling the gut microbiota, and modifying serum bile acid concentrations.
Hatchery tanks induce intense reduction in microbiota diversity associated with gills and guts of two endemic species of the São Francisco River
Authors: Damasceno Maria Rosilene Alves , Lemes Camila Gracyelle de Carvalho , Braga Lucélia Sandra Silva Barbosa , Tizioto Polyana Cristine , Montenegro Horácio , Paduan Marcela , Pereira Josielda Gomes , Cordeiro Isabella Ferreira , Rocha Lorrana Cachuite Mendes , da Silva Sibele Aryadne , Sanchez Angélica Bianchini , Lima Wanderson Geraldo , Yazbeck Gabriel Menezes , Moreira Leandro Marcio , Garcia Camila Carrião Machado
Published: December 2022

The São Francisco River (SFR), one of the main Brazilian rivers, has suffered cumulative anthropogenic impacts, leading to ever-decreasing fish stocks and environmental, economic, and social consequences. Rhinelepis aspera and Prochilodus argenteus are medium-sized, bottom-feeding, and rheophilic fishes from the SFR that suffer from these actions. Both species are targeted for spawning and restocking operations due to their relevance in artisanal fisheries, commercial activities, and conservation concerns. Using high-throughput sequencing of the 16S rRNA gene, we characterized the microbiome present in the gills and guts of these species recruited from an impacted SFR region and hatchery tanks (HT). Our results showed that bacterial diversity from the gill and gut at the genera level in both fish species from HT is 87% smaller than in species from the SFR. Furthermore, only 15 and 29% of bacterial genera are shared between gills and guts in R. aspera and P. argenteus from SFR, respectively, showing an intimate relationship between functional differences in organs. In both species from SFR, pathogenic, xenobiont-degrading, and cyanotoxin-producer bacterial genera were found, indicating the critical pollution scenario in which the river finds itself. This study allowed us to conclude that the conditions imposed on fish in the HT act as important modulators of microbial diversity in the analyzed tissues. It also raises questions regarding the effects of these conditions on hatchery spawn fish and their suitability for restocking activities, aggravated by the narrow genetic diversity associated with such freshwater systems.
Postmortem submersion interval estimation of cadavers recovered from freshwater based on gut microbial community succession
Authors: Zhang Fuyuan , Wang Pengfei , Zeng Kuo , Yuan Huiya , Wang Ziwei , Li Xinjie , Yuan Haomiao , Du Shukui , Guan Dawei , Wang Linlin , Zhao Rui
Published: December 2022

Microbial community succession during decomposition has been proven to be a useful tool for postmortem interval (PMI) estimation. Numerous studies have shown that the intestinal microbial community presented chronological changes after death and was stable in terrestrial corpses with different causes of death. However, the postmortem pattern of intestinal microbial community succession in cadavers retrieved from water remains unclear. For immersed corpses, the postmortem submersion interval (PMSI) is a useful indicator of PMI. To provide reliable estimates of PMSI in forensic investigations, we investigated the gut microbial community succession of corpses submersed in freshwater and explored its potential application in forensic investigation. In this study, the intestinal microbial community of mouse submersed in freshwater that died of drowning or CO2 asphyxia (i.e., postmortem submersion) were characterized by 16S rDNA amplification and high-throughput sequencing, followed by bioinformatic analyses. The results demonstrated that the chronological changes in intestinal bacterial communities were not different between the drowning and postmortem submersion groups. α-diversity decreased significantly within 14 days of decomposition in both groups, and the β-diversity bacterial community structure ordinated chronologically, inferring the functional pathway and phenotype. To estimate PMSI, a regression model was established by random forest (RF) algorithm based on the succession of postmortem microbiota. Furthermore, 15 genera, including Proteus, Enterococcus, and others, were selected as candidate biomarkers to set up a concise predicted model, which provided a prediction of PMSI [MAE (± SE) = 0.818 (± 0.165) d]. Overall, our present study provides evidence that intestinal microbial community succession would be a valuable marker to estimate the PMSI of corpses submerged in an aquatic habitat.
Role of angiotensin II in aging
Authors: Yi Wenmin , Chen Fei , Zhang Huiji , Tang Peng , Yuan Minghao , Wen Jie , Wang Shengyuan , Cai Zhiyou
Published: December 2022

Aging is an inevitable progressive decline in physiological organ function that increases the chance of disease and death. The renin–angiotensin system (RAS) is involved in the regulation of vasoconstriction, fluid homeostasis, cell growth, fibrosis, inflammation, and oxidative stress. In recent years, unprecedented advancement has been made in the RAS study, particularly with the observation that angiotensin II (Ang II), the central product of the RAS, plays a significant role in aging and chronic disease burden with aging. Binding to its receptors (Ang II type 1 receptor – AT1R in particular), Ang II acts as a mediator in the aging process by increasing free radical production and, consequently, mitochondrial dysfunction and telomere attrition. In this review, we examine the physiological function of the RAS and reactive oxygen species (ROS) sources in detail, highlighting how Ang II amplifies or drives mitochondrial dysfunction and telomere attrition underlying each hallmark of aging and contributes to the development of aging and age-linked diseases. Accordingly, the Ang II/AT1R pathway opens a new preventive and therapeutic direction for delaying aging and reducing the incidence of age-related diseases in the future.
The association of γδT lymphocytes with cystic leukomalacia in premature infants
Authors: Yuan Mengjie , Jin Xinyun , Qin Fanyue , Zhang Xiaoli , Wang Xiaoyang , Yuan Enwu , Shi Ying , Xu Falin
Published: December 2022

Background

Periventricular leukomalacia (PVL) is an essential cause of cerebral palsy in preterm infants, and cystic PVL (cPVL) is the most severe form of the disease. The pathogenesis of cPVL is complex, and immune imbalances and inflammatory responses may play an essential role in it.

Objective

This study aimed to investigate the correlation between peripheral blood lymphocyte subsets, especially γδT cells with the pathogenesis of cPVL in preterm infants.

Methods

Peripheral blood from preterm infants with GA < 32 weeks and BW < 1,500 g was used in this study and was collected at 34 weeks corrected gestational age and within 24 h after the diagnosis with cranial MRI or cranial ultrasound. The infants were divided into cPVL groups and control groups. Flow cytometry was used to detect peripheral blood γδT, CD3+, CD4+, CD8+, and the proportion of total lymphocytes. Multiplex cell assays were used to detect the concentration of extracellular serum cytokines IL-6, IL-2, IL-8, IL-17A, IL-10, IL-1RA, eotaxin (CCL11), MCP-1 (CCL2), CXCL1, G-CSF, and IFNγ. A follow-up visit was carried out when the patient was 3 years old.

Results

After correcting for confounding factors, the proportion of peripheral blood γδT in the cPVL group was significantly lower than that in the control group (β: 0.216; 95% CI: 0.058–0.800, P < 0.022). Peripheral blood γδT (AUC: 0.722, P=0.006) and multivariate binary regression model (AUC: 0.865, P < 0.000) have good diagnostic values for cPVL. Peripheral blood γδT has some predictive power for neurodevelopmental outcomes in preterm infants (AUC: 0.743, P = 0.002).

Conclusion

It seems that peripheral blood γδT cells are inversely correlated with cPVL, which is not only a risk factor for cPVL disease but also neurodevelopmental outcomes in preterm infants. However, the causality of cPVL and various lymphocytes is unclear and needs further study.
Suppressing interferences of EIT on synchronous recording EEG based on comb filter for seizure detection
Authors: Wang Lei , Zhu Wenjing , Wang Rong , Li Weichen , Liang Guohua , Ji Zhenyu , Dong Xiuzhen , Shi Xuetao
Published: December 2022

Background and objective

The purpose of this study was to eliminate the interferences of electrical impedance tomography (EIT) on synchronous recording electroencephalography (EEG) for seizure detection.

Methods

The simulated EIT signal generated by COMSOL Multiphysics was superimposed on the clinical EEG signal obtained from the CHB-MIT Scalp EEG Database, and then the spectrum features of superimposed mixed signals were analyzed. According to the spectrum analysis, in addition to high-frequency interference at 51.2 kHz related to the drive current, there was also low-frequency interference caused by switching of electrode pairs, which were used to inject drive current. A low pass filter and a comb filter were used to suppress the high-frequency interference and low-frequency interference, respectively. Simulation results suggested the low-pass filter and comb filter working together effectively filtered out the interference of EIT on EEG in the process of synchronous monitoring.

Results

As a result, the normal EEG and epileptic EEG could be recognized effectively. Pearson correlation analysis further confirmed the interference of EIT on EEG was effectively suppressed.

Conclusions

This study provides a simple and effective interference suppression method for the synchronous monitoring of EIT and EEG, which could be served as a reference for the synchronous monitoring of EEG and other medical electromagnetic devices.
Case report: Bilateral posterior ischemic optic neuropathy in a patient with atrial fibrillation and multifocal embolic stroke
Authors: Kang Jin-Ju , Lee Eun-Su , Lee Haeng-Jin , Hwang Seungbae , Chung Myung-Ja , Oh Sun-Young
Published: December 2022

An 80-year-old female with a history of diabetes mellitus (DM) and hypertension presented with sudden onset of sequential bilateral visual loss. The best visual acuity was light perception in the right eye and finger counting in the left eye, however, bilateral fundus did not reveal optic disc edema. Diffusion-weighted magnetic resonance imaging (MRI) of the brain revealed acute embolic stroke and diffusion restriction in the posterior portion of both optic nerves. The 24-h Holter monitor showed persistent atrial fibrillation (AF) with rapid ventricular response. The presence of painless and severe visual loss at onset unaccompanied by optic disc edema in the patient with newly detected uncontrolled AF and multiple embolic infarctions favored a diagnosis of non-arteritic posterior ischemic optic neuropathy (PION). The current case contributes to better understanding of PION pathophysiology and associated risk factors, indicating a possible relationship between non-arteritic PION and uncontrolled AF and embolic cerebral infarction.
The effect and mechanism of exercise for post-stroke pain
Authors: Ma Yue , Luo Jing , Wang Xue-Qiang
Published: December 2022

One of the common negative effects of a stroke that seriously lowers patients’ quality of life is post-stroke pain (PSP). Thus, exercise in PSP management has become a hot research topic. The main advantages of exercise therapy are affordability and ease of acceptance by patients compared to other treatment methods. Therefore, this article reviews the effectiveness and possible mechanisms of exercise interventions for PSP. Exercise training for patients with PSP not only improves physical function but also effectively reduces pain intensity and attenuates the behavioral response to pain. In addition, exercise therapy can improve brain function and modulate levels of pro-inflammatory and neurotrophic factors to exert specific analgesic effects. Potential mechanisms for exercise intervention include modulation of synaptic plasticity in the anterior cingulate gyrus, modulation of endogenous opioids in vivo, reversal of brain-derived neurotrophic factor overexpression, inhibition of purinergic receptor (P2X4R, P2X7R) expression, and inhibition of microglia activation. However, current research on exercise for PSP remains limited, and the sustainable benefits of exercise interventions for PSP need to be further investigated.
Miro1 R272Q disrupts mitochondrial calcium handling and neurotransmitter uptake in dopaminergic neurons
Authors: Schwarz Lisa , Sharma Karan , Dodi Lorenzo D. , Rieder Lara-Sophie , Fallier-Becker Petra , Casadei Nicolas , Fitzgerald Julia C.
Published: December 2022

The Rho GTPase Miro1, located at the mitochondrial outer membrane is known to properly distribute mitochondria to synapses, aid calcium buffering and initiate PINK1-Parkin mediated mitophagy. Several heterozygous RHOT1/Miro1 variants were identified in sporadic Parkinson’s disease patients. Miro1 R272Q is located within a calcium binding domain, but the functional outcome of this point mutation and its contribution to the development of disease are unclear. To address this, we introduced a heterozygous RHOT1/Miro1 R272Q point mutation in healthy induced pluripotent stem cells. In dopaminergic neurons, Miro1 R272Q does not affect Miro1 protein levels, CCCP-induced mitophagy, nor mitochondrial movement yet causes the fragmentation of mitochondria with reduction of cristae and ATP5A. Inhibition of the mitochondrial calcium uniporter phenocopied Miro1 R272Q cytosolic calcium response to Thapsigargin in active neurons, a similar effect was observed during the calcium buffering phase in Miro1 knockdown neuroblastoma cells. Altered mitochondrial calcium regulation is associated with reduced mitochondrial respiration and reduced catecholamine neurotransmitter uptake. Synaptic changes are not coupled to dopamine distribution or dopamine transporters but are linked to Miro1 R272Q-related calcium handling via the mitochondria concomitant with defective dopamine regulation at the mitochondrial surface by monoamine oxidase. We conclude that the Miro1 R272Q heterozygous point mutation dampens mitochondrial-calcium regulation and mitochondrial capacity via events at the outer membrane that are sufficient to disrupt dopaminergic function.