bluuebunny/crossref_metadata_2025 huggingface dataset:
Resistance genomics and molecular epidemiology of high-risk clones of ESBL-producing Pseudomonas aeruginosa in young children
Authors: Patil Sandip , Chen Xiaowen , Dong Shaowei , Mai Huirong , Lopes Bruno Silvester , Liu Sixi , Wen Feiqiu
Published: May 2023

Introduction

The emergence of multidrug-resistant Pseudomonas aeruginosa poses a global threat, but the distribution and resistance profiling are unclear, especially in young children. Infections due to P. aeruginosa are common, associated with high mortality, and increasingly β-lactam drug resistant.

Methods

We studied the molecular epidemiology and antibiotic resistance mechanisms in 294 clinicalisolates of P. aeruginosa from a pediatric hospital in China. Non-duplicate isolates were recovered from clinical cases and were identified using an API-20 kit followed by antimicrobial susceptibility testing using the VITEK®2 compact system (BioMerieux, France) and also by broth dilution method. In addition, a double-disc synergy test for the ESBL/E-test for MBL was performed. The presence of beta-lactamases, plasmid types, and sequence types was determined by PCR and sequencing.

Results

Fifty-six percent (n = 164) of the isolates were resistant to piperacillin–tazobactam, followed by cefepime (40%; n = 117), ceftazidime (39%; n = 115), imipenem (36%; n = 106), meropenem (33%; n = 97), and ciprofloxacin (32%; n = 94). Forty-two percent (n = 126) of the isolates were positive for ESBL according to the double-disc synergy test. The blaCTX-M-15 cephalosporinase was observed in 32% (n = 40/126), while 26% (n = 33/126) werepositive for blaNDM-1 carbapenemase. Aminoglycoside resistance gene aac(3)IIIawas observed in 16% (n = 20/126), and glycylcyclines resistance gene tet(A) was observed in 12% (n = 15/126) of the isolates. A total of 23 sequence types were detected, including ST1963 (12%; n = 16), followed by ST381 (11%; n = 14), ST234 (10%; n = 13), ST145 (58%; n = 10), ST304 (57%; n = 9), ST663 (5%; n = 7), and a novel strain. In ESBL-producing P. aeruginosa, 12 different Incompatibility groups (Inc) were observed, the most common being IncFI, IncFIS, and IncA/C. The MOBP was the most common plasmid type, followed by MOBH, MOBF, and MOBQ.

Discussion

Our data suggest that the spread of antibiotic resistance is likely due toclonal spread and dissemination of different clinical strains of P. aeruginosa harbouring different plasmids. This is a growing threat in hospitals particularly in young children which needs robust prevention strategies.
A comparative 18F-FDG and an anti-PD-L1 probe PET/CT imaging of implant-associated Staphylococcus aureus osteomyelitis
Authors: Ren Shu-Qi , Ma Yuan , Fu Li-Lan , Hu Kong-Zhen , Liang Hao-Ran , Yu Bin , Tang Gang-Hua
Published: May 2023

Background

Early and accurate diagnosis of infection-induced osteomyelitis, which often involves increased PD-L1 expression, is crucial for better treatment outcomes. Radiolabeled anti-PD-L1 nuclear imaging allows for sensitive and non-invasive whole-body assessments of PD-L1 expression. This study aimed to compare the efficacy of 18F-FDG and an 18F-labeled PD-L1-binding peptide probe (18F-PD-L1P) in PET imaging of implant-associated Staphylococcus aureus osteomyelitis (IAOM).

Methods

In this study, we synthesized an anti-PD-L1 probe and compared its efficacy with 18F-FDG and 18F-PD-L1P in PET imaging of implant-associated Staphylococcus aureus osteomyelitis (IAOM). The %ID/g ratios (i.e., radioactivity ratios between the infected and non-infected sides) of both probes were evaluated for sensitivity and accuracy in post-infected 7-day tibias and post-infected 21 days, and the intensity of 18F-PD-L1P uptake was compared with pathological changes measured by PD-L1 immunohistochemistry (IHC).

Results

Compared with 18F-FDG, 18F-PDL1P demonstrated higher %ID/g ratios for both post-infected 7-day tibias (P=0.001) and post-infected 21 days (P=0.028). The intensity of 18F-PD-L1P uptake reflected the pathological changes of osteomyelitic bones. In comparison to 18F-FDG, 18F-PDL1P provides earlier and more sensitive detection of osteomyelitis caused by S. aureus.

Conclusion

Our findings suggest that the 18F-PDL1P probe is a promising tool for the early and accurate detection of osteomyelitis caused by S. aureus.
Gut microbiota decreased inflammation induced by chronic unpredictable mild stress through affecting NLRP3 inflammasome
Authors: Huang Li , Ma Zewei , Ze Xiaolei , Zhao Xinrui , Zhang Meilin , Lv Xia , Zheng Yunqin , Liu Huan
Published: May 2023

Dysbiosis of the gut microbiota is associated with the development of depression, but the underlying mechanism remains unclear. The aim of this study was to determine the relationship between microbiota and NLRP3 inflammasome induced by chronic unpredictable mild stress (CUMS). Fecal transplantation (FMT) experiment was conducted to elucidate the potential mechanism. Levels of NLRP3 inflammasome, microbiota, inflammatory factors and tight junction proteins were measured. CUMS stimulation significantly increased the levels of NLRP3, Caspase-1 and ASC in brain and colon(p<0.05), decreased the levels of tight junction proteins Occludin and ZO-1 (p<0.05). Interestingly, increased NLRP3 inflammasome and inflammatory cytokines and decreased tight junction proteins were found in antibiotic-treated (Abx) rats received CUMS rat fecal microbiota transplantation. Furthermore, fecal microbiota transplantation altered the microbiota in Abx rats, which partially overlapped with that of the donor rats. Importantly, probiotic administration amended the alteration of microbiota induced by CUMS treatment, then reduced the levels of NLRP3 inflammasome and inflammatory factors. In conclusion, these findings suggested that depression-like behaviors induced by CUMS stimulation were related to altered gut microbiota, broke the intestinal barrier, promoted the expression of NLRP3 inflammasome and elevated inflammation. Therefore, improving the composition of microbiota via probiotic can attenuate inflammation by amending the microbiota and suppressing the activation of NLRP3 inflammasome, which is considered as a novel therapeutic strategy for depression.
Ships without crews: IMO and UK responses to cybersecurity, technology, law and regulation of maritime autonomous surface ships (MASS)
Authors: Fenton Adam James , Chapsos Ioannis
Published: May 2023

This article considers the current technological developments in uncrewed Maritime Autonomous Surface Ships (MASS), examines the legal and regulatory challenges that they raise, and describes the ways in which an international body (the International Maritime Organization, IMO) and a national agency (UK Maritime and Coastguard Agency, MCA) are engaging with the massive task of regulating this new development in shipping. To achieve the research aim, the article combines primary data from interviews with industry, government and international regulators, a survey completed by practitioners, experts and academics working in the field, and relevant secondary sources. The article makes an original contribution by noting and analyzing the approaches of the IMO and the UK government–bodies which are highly influential in shaping global attitudes, preparation, adoption and responses to such innovative technologies like MASS–and how they have engaged with the difficult question of regulating the various legal, technical and cybersecurity challenges that they raise. It concludes that for the MASS technology to fulfill its potential and gradually see the integration of such vessels in international shipping in a safe, secure and sustainable way, the international community needs to work together, and update by consensus the key legal instruments and policy documents. In this major task, the UK approach and IMO's leading role can play a protagonist role in developing best practice and implementing respectively.
Hierarchical clustering-based framework for a posteriori exploration of Pareto fronts: application on the bi-objective next release problem
Authors: Casanova Carlos , Schab Esteban , Prado Lucas , Rottoli Giovanni Daián
Published: May 2023

Introduction

When solving multi-objective combinatorial optimization problems using a search algorithm without a priori information, the result is a Pareto front. Selecting a solution from it is a laborious task if the number of solutions to be analyzed is large. This task would benefit from a systematic approach that facilitates the analysis, comparison and selection of a solution or a group of solutions based on the preferences of the decision makers. In the last decade, the research and development of algorithms for solving multi-objective combinatorial optimization problems has been growing steadily. In contrast, efforts in the a posteriori exploration of non-dominated solutions are still scarce.

Methods

This paper proposes an abstract framework based on hierarchical clustering in order to facilitate decision makers to explore such a Pareto front in search of a solution or a group of solutions according to their preferences. An extension of that abstract framework aimed at addressing the bi-objective Next Release Problem is presented, together with a Dashboard that implements that extension. Based on this implementation, two studies are conducted. The first is a usability study performed with a small group of experts. The second is a performance analysis based on computation time consumed by the clustering algorithm.

Results

The results of the initial empirical usability study are promising and indicate directions for future improvements. The experts were able to correctly use the dashboard and properly interpret the visualizations in a very short time. In the same direction, the results of the performance comparison highlight the advantage of the hierarchical clustering-based approach in terms of response time.

Discussion

Based on these excellent results, the extension of the framework to new problems is planned, as well as the implementation of new validity tests with expert decision makers using real-world data.
Microlearning as a new method of teaching soft skills to university students
Authors: Romanenko Yulia N. , Solodovnikova Ekaterina , Maksimenko Nadezhda
Published: May 2023

Soft skills are very important in the modern world, both for communications and planning daily life and, as both employers and students claim, for career and professional activities. The development of soft skills can occur independently, but there are opportunities to teach them, including at university. Different formats can be used for this, and one of them is microlearning, using a cell phone and the student’s interaction with the teacher and the group on social networks and educational platforms. This format has been applied to two courses at ITMO University: study skills and emotional intelligence. An experiment was conducted, which showed that students who took the course in the microlearning format received the same amount of information and were able to apply it just as well as students who took the course in the classical learning format. Based on the successful use of such a format as microlearning and all its advantages described in the article, in the future it is proposed to form other courses using this learning format.
A novel therapeutic approach for endometriosis using adipose-derived stem cell-derived conditioned medium- A new hope for endometriotic patients in improving fertility
Authors: Huang S. Joseph , Huang Chun-Yen , Huang Yu-Hao , Cheng Jai-Hong , Yu Ya-Chun , Lai Jui-Chi , Hung Yi-Pei , Chang Chi-Chang , Shiu Li-Yen
Published: May 2023

Introduction

Endometriosis is defined as the growth of endometrial glands and stromal cells in a heterotopic location with immune dysregulation. It usually leads to chronic pelvic pain and subfertility. Although various treatments are available, the recurrence rate remains high. Adipose tissue is an abundant source of multipotent mesenchymal adipose-derived stem cells (ADSCs). ADSCs display effects on not only tissue regeneration, but also immune regulation. Thus, the current study aims to test the effects of ADSCs on the growth of endometriosis.

Methods

ADSCs isolated from lipoaspiration-generated adipose tissue and their conditioned medium (ADSC-CM) were subjected to quality validation, including karyotyping as well as growth promotion and sterility tests for microbial contamination under Good Tissue Practice and Good Manufacturing Practice regulations. An autologous endometriosis mouse model was established by suturing endometrial tissue to peritoneal wall followed by treating with DMEM/F12 medium, ADSC-CM, ADSCs or ADSC-CM+ADSCs for 28 days. The area of endometriotic cysts and the degree of pelvic adhesion were measured. ICAM-1, VEGF and caspase 3 expression was assessed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry. Moreover, the mice were allowed to mate and deliver. The pregnancy outcomes were recorded. The ADSC-CM was subjected to proteomics analysis with further data mining with Ingenuity Pathway Analysis (IPA).

Results

Both ADSC-CM and ADSCs passed quality validation. ADSC-CM reduced the area of endometriotic cysts. The inhibition by ADSC-CM was obliterated by adding ADSCs. The presence of ADSCs with or without ADSC-CM increased the peritoneal adhesion. ADSC-CM inhibited ICAM-1 and VEGF mRNA and protein expression, whereas the addition of ADSCs not only did not inhibit by itself, but also blocked the inhibition by ADSC-CM. The resorption rate was reduced by ADSC-CM. The number of live birth/dam and the survival rate of pup at 1 week-old were both increased by ADSC-CM in mice with endometriosis. IPA demonstrated that PTX3 was potentially critical for the inhibition of endometriosis by ADSC-CM due to its anti-inflammatory and antiangiogenic properties as well as its importance in implantation.

Conclusion

ADSC-CM inhibited endometriosis development and improved pregnancy outcomes in mice. Potential translation to clinical treatment for human endometriosis is expected.
Cyclocarya paliurus leaves extracts alleviate metabolic phenotypes in Chinese T2DM patients by modulating gut microbiota and metabolites: a clinical randomized controlled trial
Authors: Peng Xiaojuan , Chen Sisi , Zhong Lu , Li Yuting , Wu Chutian , Zhong Lixian , Chen Weiwei , Yang Jinying , Zeng Jiahua , Tang Shaohui
Published: May 2023

Objective

We aimed to investigate the effect of Cyclocarya paliurus leaves extracts (CP) on glucose and blood lipid metabolism and its relationship with intestinal flora in type 2 diabetes mellitus (T2DM) patients.

Methods

In this open-label, 84-day randomized controlled trial, a total of 38 T2DM patients were randomly assigned to the CP group or the Glipizide group (G group) in a 2:1 ratio. T2DM-associated metabolic phenotypes, gut microbiota and metabolites including short-chain fatty acids (SCFAs) and bile acids (BAs) were detected.

Results

At the end of intervention, CP, like Glipizide, significantly improved HbA1c level and other glucose metabolism parameters (fasting plasma glucose (FBG), 2-hour post-meal blood glucose (2hPBG), the area under curve of oral glucose tolerance test glucose (OGTT glucose AUC)). Moreover, CP also resulted in the significant improvement in the levels of blood lipid and blood pressure. Notably, the improvement in blood lipid(triglycerides (TG) and high-density lipoprotein cholesterol (HDL-c)) and blood pressure (diastolic blood pressure (DBP)) was significantly greater in the CP group compared with the G group. Furthermore, the liver and kidney function parameters did not significantly change in both CP group and the G group over the 84-day period. Additionally, the enrichment of potentially beneficial bacteria (Faecalibacterium and Akkermansia), SCFAs and unconjugated BAs and the depletion of potential pathogenic bacteria (Prevotella_9) and conjugated BAs were observed in the CP group, while the abundances of the gut microbial were kept stable in the G group after intervention.

Conclusion

CP displays a more beneficial effect in the alleviation of T2DM-associated metabolic phenotypes than glipizide by regulating gut microbiota and metabolites in T2DM patients, with no significant effects on liver and kidney function.
Identification of cavitation state of centrifugal pump based on current signal
Authors: Liang Chen , Hao Yan , Tengzhou Xie , Zhiguo Li
Published: May 2023

Centrifugal pump, which is widely used in water conservancy, electric power, petrochemical, ship, aerospace, and other technical fields, is the core equipment used to ensure all kinds of energy transfer. Cavitation not only affects the service life of the centrifugal pump but also seriously impacts the reliability of the process flow or device system. Due to the influence of the life, position and number of vibration sensors, the existing cavitation fault feature identification accuracy is not enough. The state analysis and characteristic recognition of the current signal under the cavitation state of the centrifugal pump are conducted in this paper based on soft sensing technology, and the signal component and judgment threshold representing the cavitation state are obtained. The following results are presented. Under different critical cavitation numbers, a small number of bubbles appeared near the suction surface of the inlet edge of the impeller, which verified the reliability of criterion for the critical cavitation number when the head coefficient decreased by 3%. The overall accuracy of binary classification cavitation recognition based on the current signal is 12.9% higher than that of three classification cavitation recognition. The recognition rate of VMD decomposition under different working conditions is higher than that of EMD, in design conditions, for example, overall accuracy improved by 7.3%, which also indicates that the obtained cavitation information of each component by VMD decomposition is richer than that obtained by EMD decomposition. Comparing different working conditions, a large flow rate easily leads to cavitation and high recognition current rate, compared with the flow of 0.75 Q and 1.25 Q, the overall accuracy is improved by 9.6%.
Bacterial and fungal inhibitor interacted impacting growth of invasive Triadica sebifera and soil N2O emissions
Authors: Lai Xiaoqin , Luo Laicong , Fang Haifu , Zhang Ling , Shad Nasir , Bai Jian , Li Aixin , Zhang Xi , Yu Yadi , Wang Hao , Siemann Evan
Published: May 2023

Plant invasions affect biodiversity and seriously endanger the stability of ecosystems. Invasive plants show strong adaptability and growth advantages but are influenced by various factors. Soil bacteria and fungi are critical to plant growth and are important factors affecting plant invasions. Plant invasions also affect soil N2O emissions, but the effects of invasive plants from different population origins on N2O emissions and their microbial mechanisms are not clear. In this experiment, we grew Triadica sebifera from native (China) and invasive (USA) populations with or without bacterial (streptomycin) and/or fungal (iprodione) inhibitors in a factorial experiment in which we measured plant growth and soil N2O emissions of T. sebifera. Plants from invasive populations had higher leaf masses than those from native populations when soil bacteria were not inhibited (with or without fungal inhibition) which might reflect that they are more dependent on soil bacteria. Cumulative N2O emissions were higher for soils with invasive T. sebifera than those with a plant from a native population. Bacterial inhibitor application reduced cumulative N2O emissions but reductions were larger with application of the fungal inhibitor either alone or in combination with the bacterial inhibitor. This suggests that fungi play a strong role in plant performance and soil N2O emissions. Therefore, it is important to further understand the effects of soil microorganisms on the growth of T. sebifera and soil N2O emissions to provide a more comprehensive scientific basis for understanding the causes and consequences of plant invasions.
IL11 activates the placental inflammasome to drive preeclampsia
Authors: Menkhorst Ellen , Santos Leilani L. , Zhou Wei , Yang Guannan , Winship Amy L. , Rainczuk Katarzyna E. , Nguyen Philana , Zhang Jian-Guo , Moore Paddy , Williams Michelle , Lê Cao Kim-Anh , Mansell Ashley , Dimitriadis Evdokia
Published: May 2023

Introduction

Preeclampsia is a life-threatening disorder of pregnancy unique to humans. Interleukin (IL)11 is elevated in serum from pregnancies that subsequently develop early-onset preeclampsia and pharmacological elevation of IL11 in pregnant mice causes the development of early-onset preeclampsia-like features (hypertension, proteinuria, and fetal growth restriction). However, the mechanism by which IL11 drives preeclampsia is unknown.

Method

Pregnant mice were administered PEGylated (PEG)IL11 or control (PEG) from embryonic day (E)10-16 and the effect on inflammasome activation, systolic blood pressure (during gestation and at 50/90 days post-natal), placental development, and fetal/post-natal pup growth measured. RNAseq analysis was performed on E13 placenta. Human 1st trimester placental villi were treated with IL11 and the effect on inflammasome activation and pyroptosis identified by immunohistochemistry and ELISA.

Result

PEGIL11 activated the placental inflammasome causing inflammation, fibrosis, and acute and chronic hypertension in wild-type mice. Global and placental-specific loss of the inflammasome adaptor protein Asc and global loss of the Nlrp3 sensor protein prevented PEGIL11-induced fibrosis and hypertension in mice but did not prevent PEGIL11-induced fetal growth restriction or stillbirths. RNA-sequencing and histology identified that PEGIL11 inhibited trophoblast differentiation towards spongiotrophoblast and syncytiotrophoblast lineages in mice and extravillous trophoblast lineages in human placental villi.

Discussion

Inhibition of ASC/NLRP3 inflammasome activity could prevent IL11-induced inflammation and fibrosis in various disease states including preeclampsia.
Effect and mechanism of chlorogenic acid on cognitive dysfunction in mice by lipopolysaccharide-induced neuroinflammation
Authors: Xiong Siyuan , Su Xuyang , Kang Yingjie , Si Junqiang , Wang Lu , Li Xinzhi , Ma Ketao
Published: May 2023

Background

Neuroinflammation is an important factor causing numerous neurodegenerative pathologies. Inflammation can lead to abnormal neuronal structure and function and even death, followed by cognitive dysfunction. There is growing evidence that chlorogenic acid has anti-inflammatory effects and immunomodulatory activity.

Purpose

The aim of this study was to elucidate the potential targets and molecular mechanisms of chlorogenic acid in the treatment of neuroinflammation.

Methods

We used the lipopolysaccharide-induced neuroinflammation mouse model and the lipopolysaccharide-stimulated BV-2 cells in vitro model. Behavioral scores and experiments were used to assess cognitive dysfunction in mice. HE staining and immunohistochemistry were used to assess neuronal damage in the mouse brain. Immunofluorescence detected microglia polarization in mouse brain. Western blot and flow cytometry detected the polarization of BV-2 cells. The migration of BV-2 cells was detected by wound healing assay and transwell assay. Potential targets for chlorogenic acid to exert protective effects were predicted by network pharmacology. These targets were then validated using molecular docking and experiments.

Results

The results of in vivo experiments showed that chlorogenic acid had an obvious ameliorating effect on neuroinflammation-induced cognitive dysfunction. We found that chlorogenic acid was able to inhibit BV-2 cells M1 polarization and promote BV-2 cells M2 polarization in vitro while also inhibiting the abnormal migration of BV-2 cells. Based on the network pharmacology results, we identified the TNF signaling pathway as a key signaling pathway in which chlorogenic acid exerts anti-neuroinflammatory effects. Among them, Akt1, TNF, MMP9, PTGS2, MAPK1, MAPK14, and RELA are the core targets for chlorogenic acid to function.

Conclusion

Chlorogenic acid can inhibit microglial polarization toward the M1 phenotype and improve neuroinflammation-induced cognitive dysfunction in mice by modulating these key targets in the TNF signaling pathway.
Regulatory role of the programmed cell death 1 signaling pathway in sepsis induced immunosuppression
Authors: Zhong Shubai , Yin Yuanqin
Published: May 2023

Sepsis is a multiple organ dysfunction syndrome caused by the host’s immune response to infection, with extremely high incidence and mortality. Immunosuppression is an essential pathophysiological alteration that influences the clinical treatment and prognosis of sepsis. Recent studies have suggested that the programmed cell death 1 signaling pathway is involved in the formation of immunosuppression in sepsis. In this review, we systematically present the mechanisms of immune dysregulation in sepsis and elucidate the expression and regulatory effects of the programmed cell death 1 signaling pathway on immune cells associated with sepsis. We then specify current research developments and prospects for the application of the programmed cell death 1 signaling pathway in immunomodulatory therapy for sepsis. Several open questions and future research are discussed at the end.
Efficacy and safety of chimeric antigen receptor T cell therapy in relapsed/refractory diffuse large B-cell lymphoma with different HBV status: a retrospective study from a single center
Authors: Kong Danqing , Ping Nana , Gao Xin , Zou Rui , Wang Peng , Wu Depei , Jin Zhengming , Qu Changju
Published: May 2023

Background

Chimeric antigen receptor T cell (CAR-T) therapy is an effective salvage treatment in relapsed or refractory(r/r) diffuse large B-cell lymphoma (DLBCL), but the impact of hepatitis B virus (HBV) infection has not been studied.

Methods and results

Here, 51 patients with r/r DLBCL receiving CAR-T therapy were enrolled and analyzed at the First Affiliated Hospital of Soochow University. The overall response rate and the complete remission rate (CR) of CAR-T therapy were 74.5% and 39.2%, respectively. With a median follow-up of 21.1 months after CAR-T, the probabilities of overall survival (OS) and progression-free survival (PFS) at 36 months were 43.4% and 28.7%, respectively. These patients were divided into three cohorts including chronic HBV infection group (n=6), resolved HBV infection group (n=25) and non-HBV infection group (n=20). Bone marrow involvement was significantly higher in the HBV infection group(P<0.001), other basic characteristics before CAR-T therapy were comparable. Subgroup analysis showed that HBV infection status did not affect the efficacy of CAR-T therapy in CR rate, OS or PFS, and there was no significant difference in CAR-T related toxicities between three cohorts. Only one cirrhosis patient with chronic HBV infection experienced HBV reactivation.

Conclusions

CAR-T therapy was effective and can be used safely in r/r DLBCL with HBV infection under proper monitoring and antiviral prophylaxis.
Gut epithelial barrier dysfunction in lupus triggers a differential humoral response against gut commensals
Authors: Botía-Sánchez María , Galicia Georgina , Albaladejo-Marico Lorena , Toro-Domínguez Daniel , Morell Maria , Marcos-Fernández Raquel , Margolles Abelardo , Alarcón-Riquelme Marta E.
Published: May 2023

Introduction

Systemic lupus erythematosus is an autoimmune disease with multisystemic involvement including intestinal inflammation. Lupus-associated intestinal inflammation may alter the mucosal barrier where millions of commensals have a dynamic and selective interaction with the host immune system. Here, we investigated the consequences of the intestinal inflammation in a TLR7-mediated lupus model.

Methods

IgA humoral and cellular response in the gut was measured. The barrier function of the gut epithelial layer was characterised. Also, microbiota composition in the fecal matter was analysed as well as the systemic humoral response to differential commensals.

Results

The lupus-associated intestinal inflammation modifies the IgA+ B cell response in the gut-associated lymphoid tissue in association with dysbiosis. Intestinal inflammation alters the tight junction protein distribution in the epithelial barrier, which correlated with increased permeability of the intestinal barrier and changes in the microbiota composition. This permeability resulted in a differential humoral response against intestinal commensals.

Discussion

Lupus development can cause alterations in microbiota composition, allowing specific species to colonize only the lupus gut. Eventually, these alterations and the changes in gut permeability induced by intestinal inflammation could lead to bacterial translocation.
The distribution and emission of CO2, CH4 and light hydrocarbons in an anticyclonic eddy of the Kuroshio extension
Authors: Li Xiao-Jun , Wang Jian , Qiao Hao , Zhu Rui-Chen , Zhang Hong-Hai , Chen Zhao-Hui , Montgomery Andrew , Zheng Shan , Zhuang Guang-Chao
Published: May 2023

Mesoscale eddies are energetic and swirling circulations that frequently occur in the open ocean. The effects of mesoscale eddies on the biogeochemical cycling of climate-relevant gases remain poorly constrained. We investigated the distribution and air-sea fluxes of CO2, methane, and five non–methane hydrocarbons (NMHCs) in an anticyclone eddy of Kuroshio Extension during September 2019. Within eddy core, intense stratification hindered the replenishment of nutrients and favored the growth of small-size phytoplankton, such as Prochlorococcus. Seawater pCO2 decreased from 406.1 μatm at the eddy outside to 377.5 μatm at the eddy core, accompanied by a decrease in surface seawater temperature from 26.7 °C to 25.2 °C. The vertical distribution of methane (0.3-9.9 nmol L-1) was influenced by the eddy process, with a maximum at 80 m in the eddy core, which might be attributed to the degradation of phosphonates sustained by Prochlorococcus. The concentrations of five NMHCs (ethane, ethylene, propane, propylene, and isoprene) ranged from 17.2-126.2, 36.7-168.1, 7.5-29.2, 22.6-64.1, 54.5-172.1, 3.5-27.9 pmol L-1, respectively. Isoprene correlated well with Chl-a concentrations at the eddy core, while no significant correlation was observed at the eddy outside. Air-sea fluxes of CO2 and isoprene associated with the eddy core were higher than those of the eddy outside, while the maximum ventilation of methane and other NMHCs (ethane, ethylene, propane, and propylene) was found at the eddy outside. Collectively, physical processes such as eddies impact the production and distribution of light hydrocarbons in seawater and further influence their regional emissions to the atmosphere.
Microscopic polyangiitis initially presenting with idiopathic pulmonary fibrosis: a case report
Authors: Shao Chi , Chen Ruxuan , Huang Hui , Zhao Yang , Chen Keqi , Xu Kai
Published: May 2023

Usual interstitial pneumonia is the most common type of microscopic polyangiitis (MPA)-associated interstitial lung disease, and patients may initially present with isolated pulmonary fibrosis, which often leads to a misdiagnosis of idiopathic pulmonary fibrosis (IPF). Here, we describe a patient who developed fever of unknown origin, microscopic hematuria and renal insufficiency, who then tested positive for antineutrophil cytoplasmic antibody (ANCA) and was diagnosed with MPA after receiving antifibrotic medication for IPF (original diagnosis) for almost 10 years. The patient's symptoms were ameliorated after administration of additional glucocorticoids and immunosuppressants.
Serum proteomics hint at an early T-cell response and modulation of SARS-CoV-2-related pathogenic pathways in COVID-19-ARDS treated with Ruxolitinib
Authors: Völkel Sara , Tarawneh Thomas S. , Sacher Laura , Bhagwat Aditya M. , Karim Ihab , Mack Hildegard I. D. , Wiesmann Thomas , Beutel Björn , Hoyer Joachim , Keller Christian , Renz Harald , Burchert Andreas , Neubauer Andreas , Graumann Johannes , Skevaki Chrysanthi , Mack Elisabeth K. M.
Published: May 2023

Background

Acute respiratory distress syndrome (ARDS) in corona virus disease 19 (COVID-19) is triggered by hyperinflammation, thus providing a rationale for immunosuppressive treatments. The Janus kinase inhibitor Ruxolitinib (Ruxo) has shown efficacy in severe and critical COVID-19. In this study, we hypothesized that Ruxo’s mode of action in this condition is reflected by changes in the peripheral blood proteome.

Methods

This study included 11 COVID-19 patients, who were treated at our center’s Intensive Care Unit (ICU). All patients received standard-of-care treatment and n = 8 patients with ARDS received Ruxo in addition. Blood samples were collected before (day 0) and on days 1, 6, and 10 of Ruxo treatment or, respectively, ICU admission. Serum proteomes were analyzed by mass spectrometry (MS) and cytometric bead array.

Results

Linear modeling of MS data yielded 27 significantly differentially regulated proteins on day 1, 69 on day 6 and 72 on day 10. Only five factors (IGLV10-54, PSMB1, PGLYRP1, APOA5, WARS1) were regulated both concordantly and significantly over time. Overrepresentation analysis revealed biological processes involving T-cells only on day 1, while a humoral immune response and complement activation were detected at day 6 and day 10. Pathway enrichment analysis identified the NRF2-pathway early under Ruxo treatment and Network map of SARS-CoV-2 signaling and Statin inhibition of cholesterol production at later time points.

Conclusion

Our results indicate that the mechanism of action of Ruxo in COVID-19-ARDS can be related to both known effects of this drug as a modulator of T-cells and the SARS-CoV-2-infection.
Mobile nutrition and health management platform for perioperative recovery: an interdisciplinary research achievement using WeChat Applet
Authors: Wu YuJia , Wang Xin , Gao Feng , Liao JinRong , Zeng Jie , Fan Lin
Published: May 2023

Background

In recent years, the number of people using mobile applications to promote health and welfare has exponentially increased. However, there are fewer applications in the field of ERAS. How to promote the rapid rehabilitation of patients with malignant tumor surgery during perioperative period and the mastery of its long-term nutritional state is a problem to be solved.

Objective

The purpose of this study is to design and develop a mobile application, and use Internet technology to better manage nutritional health to achieve rapid recovery of patients with malignant tumor surgery.

Methods

This study is divided into three stages: (1) Design: use participating design to make the MHEALTH APP adapt to the clinical practice of nutritional health management; (2) Development: the WeChat Applet of Nutrition and Health Assessment (WANHA) developed using the Internet technology development, and web management programs. (3) Procedure test: patients and medical staff evaluate WANHA’s quality (UMARS), availability (SUS), and satisfaction, and conduct semi-structured interviews.

Results

In this study, 192 patients with malignant tumor surgery, 20 medical staff used WANHA. Patients with nutritional risks are supported by supporting treatment. The results show that patients who have not been treated during the perioperative period, the incidence of postoperative complications (22.4%) and the average hospitalization time after surgery decreased significantly. The incidence of nutritional risks is nearly more than the preoperative level. 45 patients and 20 medical staff participated in the survey of WANHA’s SUS, UMARS, and satisfaction. In the interview, most patients and medical personnel believe that the procedure can improve the current medical services and nutritional health knowledge levels, promote the communication of medical staff and patients, and strengthen the nutritional health management of patients with malignant tumors under the concept of ERAS.

Conclusion

WeChat Applet of Nutrition and Health Assessment is a MHEALTH APP that enhances the nutrition and health management of patients with perioperative period. It can play a huge role in improving medical services, increasing patient satisfaction, and ERAS.
Wastewater treatment plants, an “escape gate” for ESCAPE pathogens
Authors: Marutescu Luminita Gabriela , Popa Marcela , Gheorghe-Barbu Irina , Barbu Ilda Czobor , Rodríguez-Molina Daloha , Berglund Fanny , Blaak Hetty , Flach Carl-Fredrik , Kemper Merel Aurora , Spießberger Beate , Wengenroth Laura , Larsson D. G. Joakim , Nowak Dennis , Radon Katja , de Roda Husman Ana Maria , Wieser Andreas , Schmitt Heike , Pircalabioru Gradisteanu Gratiela , Vrancianu Corneliu Ovidiu , Chifiriuc Mariana Carmen
Published: May 2023

Antibiotics are an essential tool of modern medicine, contributing to significantly decreasing mortality and morbidity rates from infectious diseases. However, persistent misuse of these drugs has accelerated the evolution of antibiotic resistance, negatively impacting clinical practice. The environment contributes to both the evolution and transmission of resistance. From all anthropically polluted aquatic environments, wastewater treatment plants (WWTPs) are probably the main reservoirs of resistant pathogens. They should be regarded as critical control points for preventing or reducing the release of antibiotics, antibiotic-resistant bacteria (ARB), and antibiotic-resistance genes (ARGs) into the natural environment. This review focuses on the fate of the pathogens Enterococcus faecium, Staphylococcus aureus, Clostridium difficile, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacteriaceae spp. (ESCAPE) in WWTPs. All ESCAPE pathogen species, including high-risk clones and resistance determinants to last-resort antibiotics such as carbapenems, colistin, and multi-drug resistance platforms, were detected in wastewater. The whole genome sequencing studies demonstrate the clonal relationships and dissemination of Gram-negative ESCAPE species into the wastewater via hospital effluents and the enrichment of virulence and resistance determinants of S. aureus and enterococci in WWTPs. Therefore, the efficiency of different wastewater treatment processes regarding the removal of clinically relevant ARB species and ARGs, as well as the influence of water quality factors on their performance, should be explored and monitored, along with the development of more effective treatments and appropriate indicators (ESCAPE bacteria and/or ARGs). This knowledge will allow the development of quality standards for point sources and effluents to consolidate the WWTP barrier role against the environmental and public health AR threats.
Thermostable DNA ligases from hyperthermophiles in biotechnology
Authors: Shi Jingru , Oger Philippe M. , Cao Peng , Zhang Likui
Published: May 2023

DNA ligase is an important enzyme ubiquitous in all three kingdoms of life that can ligate DNA strands, thus playing essential roles in DNA replication, repair and recombination in vivo. In vitro, DNA ligase is also used in biotechnological applications requiring in DNA manipulation, including molecular cloning, mutation detection, DNA assembly, DNA sequencing, and other aspects. Thermophilic and thermostable enzymes from hyperthermophiles that thrive in the high-temperature (above 80°C) environments have provided an important pool of useful enzymes as biotechnological reagents. Similar to other organisms, each hyperthermophile harbors at least one DNA ligase. In this review, we summarize recent progress on structural and biochemical properties of thermostable DNA ligases from hyperthermophiles, focusing on similarities and differences between DNA ligases from hyperthermophilic bacteria and archaea, and between these thermostable DNA ligases and non-thermostable homologs. Additionally, altered thermostable DNA ligases are discussed. Possessing improved fidelity or thermostability compared to the wild-type enzymes, they could be potential DNA ligases for biotechnology in the future. Importantly, we also describe current applications of thermostable DNA ligases from hyperthermophiles in biotechnology.
Untargeted metabolomics approach and molecular networking analysis reveal changes in chemical composition under the influence of altitudinal variation in bamboo species
Authors: Chitiva Luis Carlos , Lozano-Puentes Hair Santiago , Londoño Ximena , Leão Tiago F. , Cala Mónica P. , Ruiz-Sanchez Eduardo , Díaz-Ariza Lucía Ana , Prieto-Rodríguez Juliet A. , Castro-Gamboa Ian , Costa Geison M.
Published: May 2023

Bamboo species have traditionally been used as building material and potential source of bioactive substances, as they produce a wide variety of phenolic compounds, including flavonoids and cinnamic acid derivatives that are considered biologically active. However, the effects of growth conditions such as location, altitude, climate, and soil on the metabolome of these species still need to be fully understood. This study aimed to evaluate variations in chemical composition induced by altitudinal gradient (0–3000 m) by utilizing an untargeted metabolomics approach and mapping chemical space using molecular networking analysis. We analyzed 111 samples from 12 bamboo species collected from different altitudinal ranges using liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (LC-QTOF-MS). We used multivariate and univariate statistical analyses to identify the metabolites that showed significant differences in the altitude environments. Additionally, we used the Global Natural Products Social Molecular Networking (GNPS) web platform to perform chemical mapping by comparing the metabolome among the studied species and the reference spectra from its database. The results showed 89 differential metabolites between the altitudinal ranges investigated, wherein high altitude environments significantly increased the profile of flavonoids. While, low altitude environments significantly boosted the profile of cinnamic acid derivatives, particularly caffeoylquinic acids (CQAs). MolNetEnhancer networks confirmed the same differential molecular families already found, revealing metabolic diversity. Overall, this study provides the first report of variations induced by altitude in the chemical profile of bamboo species. The findings may possess fascinating active biological properties, thus offering an alternative use for bamboo.
Cell-specific transcriptome changes in the hypothalamic arcuate nucleus in a mouse deoxycorticosterone acetate-salt model of hypertension
Authors: Wagner Valerie A. , Deng Guorui , Claflin Kristin E. , Ritter McKenzie L. , Cui Huxing , Nakagawa Pablo , Sigmund Curt D. , Morselli Lisa L. , Grobe Justin L. , Kwitek Anne E.
Published: May 2023

A common preclinical model of hypertension characterized by low circulating renin is the “deoxycorticosterone acetate (DOCA)-salt” model, which influences blood pressure and metabolism through mechanisms involving the angiotensin II type 1 receptor (AT1R) in the brain. More specifically, AT1R within Agouti-related peptide (AgRP) neurons of the arcuate nucleus of the hypothalamus (ARC) has been implicated in selected effects of DOCA-salt. In addition, microglia have been implicated in the cerebrovascular effects of DOCA-salt and angiotensin II. To characterize DOCA-salt effects upon the transcriptomes of individual cell types within the ARC, we used single-nucleus RNA sequencing (snRNAseq) to examine this region from male C57BL/6J mice that underwent sham or DOCA-salt treatment. Thirty-two unique primary cell type clusters were identified. Sub-clustering of neuropeptide-related clusters resulted in identification of three distinct AgRP subclusters. DOCA-salt treatment caused subtype-specific changes in gene expression patterns associated with AT1R and G protein signaling, neurotransmitter uptake, synapse functions, and hormone secretion. In addition, two primary cell type clusters were identified as resting versus activated microglia, and multiple distinct subtypes of activated microglia were suggested by sub-cluster analysis. While DOCA-salt had no overall effect on total microglial density within the ARC, DOCA-salt appeared to cause a redistribution of the relative abundance of activated microglia subtypes. These data provide novel insights into cell-specific molecular changes occurring within the ARC during DOCA-salt treatment, and prompt increased investigation of the physiological and pathophysiological significance of distinct subtypes of neuronal and glial cell types.
Relationship between serum bicarbonate levels and the risk of death within 30 days in ICU patients with acute ischemic stroke
Authors: Huang Xia , Zhang Yuanyuan
Published: May 2023

Aim

To explore the relationship between baseline bicarbonate levels and their changes with 30-day mortality in patients with acute ischemic stroke who were admitted to the intensive care unit (ICU).

Methods

This cohort study collected the data of 4,048 participants from the Medical Information Mart for Intensive Care (MIMIC)-III and MIMIC-IV databases. Univariate and multivariable Cox proportional risk models were utilized to explore the relationship between bicarbonate T0 and Δbicarbonate with 30-day mortality in patients with acute ischemic stroke. The Kaplan–Meier curves were plotted to measure the 30-day survival probability of patients with acute ischemic stroke.

Results

The median follow-up time was 30 days. At the end of the follow-up, 3,172 patients survived. Bicarbonate T0 ≤ 21 mEq/L [hazard ratio (HR) = 1.24, a 95% confidence interval (CI): 1.02–1.50] or 21 mEq/L < bicarbonate T0 ≤ 23 mEq/L (HR = 1.29, 95%CI: 1.05–1.58) were associated with an increased risk of 30-day mortality in patients with acute ischemic stroke compared with bicarbonate T0 > 26 mEq/L. −2 mEq/L < Δbicarbonate ≤ 0 mEq/L (HR = 1.40, 95%CI: 1.14–1.71), 0 mEq/L < Δbicarbonate ≤ 2 mEq/L (HR = 1.44, 95%CI: 1.17–1.76), and Δbicarbonate >2 mEq/L (HR = 1.40, 95%CI: 1.15–1.71) were correlated with an elevated risk of 30-day mortality in acute ischemic stroke patients. The 30-day survival probability of acute ischemic stroke patients with 21 mEq/L < bicarbonate T0 ≤ 23 mEq/L, 23 mEq/L < bicarbonate T0 ≤ 26 mEq/L, or bicarbonate T0 >26 mEq/L was higher than that of patients with bicarbonate T0 ≤ 21 mEq/L. The 30-day survival probability was greater for patients in the Δbicarbonate ≤ -2 mEq/L group than for those in the Δbicarbonate >2 mEq/L group.

Conclusion

Low baseline bicarbonate levels and decreased bicarbonate levels during the ICU stay were associated with a high risk of 30-day mortality in acute ischemic stroke patients. Special interventions should be offered to those with low baseline and decreased bicarbonate levels during their ICU stay.