bluuebunny/crossref_metadata_2025 huggingface dataset:
Proteomics profiling of vitreous humor reveals complement and coagulation components, adhesion factors, and neurodegeneration markers as discriminatory biomarkers of vitreoretinal eye diseases
Authors: Santos Fátima M. , Ciordia Sergio , Mesquita Joana , Cruz Carla , Sousa João Paulo Castro e , Passarinha Luís A. , Tomaz Cândida T. , Paradela Alberto
Published: February 2023

Introduction

Diabetic retinopathy (DR) and age-related macular degeneration (AMD) are leading causes of visual impairment and blindness in people aged 50 years or older in middle-income and industrialized countries. Anti-VEGF therapies have improved the management of neovascular AMD (nAMD) and proliferative DR (PDR), no treatment options exist for the highly prevalent dry form of AMD.

Methods

To unravel the biological processes underlying these pathologies and to find new potential biomarkers, a label-free quantitative (LFQ) method was applied to analyze the vitreous proteome in PDR (n=4), AMD (n=4) compared to idiopathic epiretinal membranes (ERM) (n=4).

Results and discussion

Post-hoc tests revealed 96 proteins capable of differentiating among the different groups, whereas 118 proteins were found differentially regulated in PDR compared to ERM and 95 proteins in PDR compared to dry AMD. Pathway analysis indicates that mediators of complement, coagulation cascades and acute phase responses are enriched in PDR vitreous, whilst proteins highly correlated to the extracellular matrix (ECM) organization, platelet degranulation, lysosomal degradation, cell adhesion, and central nervous system development were found underexpressed. According to these results, 35 proteins were selected and monitored by MRM (multiple reaction monitoring) in a larger cohort of patients with ERM (n=21), DR/PDR (n=20), AMD (n=11), and retinal detachment (n=13). Of these, 26 proteins could differentiate between these vitreoretinal diseases. Based on Partial least squares discriminant and multivariate exploratory receiver operating characteristic (ROC) analyses, a panel of 15 discriminatory biomarkers was defined, which includes complement and coagulation components (complement C2 and prothrombin), acute-phase mediators (alpha-1-antichymotrypsin), adhesion molecules (e.g., myocilin, galectin-3-binding protein), ECM components (opticin), and neurodegeneration biomarkers (beta-amyloid, amyloid-like protein 2).
IL-32 is induced by activation of toll-like receptors in multiple myeloma cells
Authors: Aass Kristin Roseth , Tryggestad Synne Stokke , Mjelle Robin , Kastnes Martin H. , Nedal Tonje Marie Vikene , Misund Kristine , Standal Therese
Published: February 2023

Multiple myeloma (MM) is a hematological cancer characterized by accumulation of malignant plasma cells in the bone marrow. The patients are immune suppressed and suffer from recurrent and chronic infections. Interleukin-32 is a non-conventional, pro-inflammatory cytokine expressed in a subgroup of MM patients with a poor prognosis. IL-32 has also been shown to promote proliferation and survival of the cancer cells. Here we show that activation of toll-like receptors (TLRs) promotes expression of IL-32 in MM cells through NFκB activation. In patient-derived primary MM cells, IL-32 expression is positively associated with expression of TLRs. Furthermore, we found that several TLR genes are upregulated from diagnosis to relapse in individual patients, predominantly TLRs sensing bacterial components. Interestingly, upregulation of these TLRs coincides with an increase in IL-32. Taken together, these results support a role for IL-32 in microbial sensing in MM cells and suggest that infections can induce expression of this pro-tumorigenic cytokine in MM patients.
The prognostic effect of sixteen malnutrition/inflammation-based indicators on the overall survival of chemotherapy patients
Authors: Liu Tong , Liu Chenan , Deng Li , Song Mengmeng , Lin Shiqi , Shi Hanping
Published: February 2023

Background

Studies have confirmed the validity of malnutrition/inflammation-based indicators among cancer patients compared to chemotherapy patients. Moreover, it is necessary to identify which indicator is the best prognostic predictor for chemotherapy patients. This study attempted to determine the best nutrition/inflammation-based indicator of overall survival (OS) for chemotherapy patients.

Methods

In this prospective cohort study, we collected 16 nutrition/inflammation-based indicators among 3,833 chemotherapy patients. The maximally selected rank statistics were used to calculate the optimal values of cutoffs for continuous indicators. OS was evaluated using the Kaplan–Meier method. The associations of 16 indicators with survival were evaluated using Cox proportional hazard models. The predictive ability of 16 indicators was assessed via time-dependent receiver operating characteristic curves (time-ROC) and the C-index.

Results

All indicators were significantly associated with worse OS of chemotherapy patients in the multivariate analyses (all P < 0.05). Time-AUC and C-index analyses indicated that the lymphocyte-to-CRP (LCR) ratio (C-index: 0.658) had the best predictive ability for OS in chemotherapy patients. The tumor stage significantly modified the association between inflammatory status and worse survival outcomes (P for interaction < 0.05). Compared to patients with high LCR and I/II tumor stages, patients with low LCR and III/IV tumor stages had a 6-fold higher risk of death.

Conclusions

The LCR has the best predictive value in chemotherapy patients compared with other nutrition/inflammation-based indicators.

Clinical trial registration

http://www.chictr.org.cn, identifier ChiCTR1800020329.
Targeting the recurrent Rac1P29S neoepitope in melanoma with heterologous high-affinity T cell receptors
Authors: Immisch Lena , Papafotiou George , Gallarín Delgado Nerea , Scheuplein Vivian , Paschen Annette , Blankenstein Thomas , Willimsky Gerald
Published: February 2023

Recurrent neoepitopes are cancer-specific antigens common among groups of patients and therefore ideal targets for adoptive T cell therapy. The neoepitope FSGEYIPTV carries the Rac1P29S amino acid change caused by a c.85C>T missense mutation, which is the third most common hotspot mutation in melanoma. Here, we isolated and characterized TCRs to target this HLA-A*02:01-binding neoepitope by adoptive T cell therapy. Peptide immunization elicited immune responses in transgenic mice expressing a diverse human TCR repertoire restricted to HLA-A*02:01, which enabled isolation of high-affinity TCRs. TCR-transduced T cells induced cytotoxicity against Rac1P29S expressing melanoma cells and we observed regression of Rac1P29S expressing tumors in vivo after adoptive T cell therapy (ATT). Here we found that a TCR raised against a heterologous mutation with higher peptide-MHC affinity (Rac2P29L) more efficiently targeted the common melanoma mutation Rac1P29S. Overall, our study provides evidence for the therapeutic potential of Rac1P29S-specific TCR-transduced T cells and reveal a novel strategy by generating more efficient TCRs by heterologous peptides.
Lipidome modulation by dietary omega-3 polyunsaturated fatty acid supplementation or selective soluble epoxide hydrolase inhibition suppresses rough LPS-accelerated glomerulonephritis in lupus-prone mice
Authors: Favor Olivia K. , Chauhan Preeti S. , Pourmand Elham , Edwards Angel M. , Wagner James G. , Lewandowski Ryan P. , Heine Lauren K. , Harkema Jack R. , Lee Kin Sing Stephen , Pestka James J.
Published: February 2023

Introduction

Lipopolysaccharide (LPS)-accelerated autoimmune glomerulonephritis (GN) in NZBWF1 mice is a preclinical model potentially applicable for investigating lipidome-modulating interventions against lupus. LPS can be expressed as one of two chemotypes: smooth LPS (S-LPS) or rough LPS (R-LPS) which is devoid of O-antigen polysaccharide sidechain. Since these chemotypes differentially affect toll-like receptor 4 (TLR4)-mediated immune cell responses, these differences may influence GN induction.

Methods

We initially compared the effects of subchronic intraperitoneal (i.p.) injection for 5 wk with 1) Salmonella S-LPS, 2) Salmonella R-LPS, or 3) saline vehicle (VEH) (Study 1) in female NZBWF1 mice. Based on the efficacy of R-LPS in inducing GN, we next used it to compare the impact of two lipidome-modulating interventions, ω-3 polyunsaturated fatty acid (PUFA) supplementation and soluble epoxide hydrolase (sEH) inhibition, on GN (Study 2). Specifically, effects of consuming ω-3 docosahexaenoic acid (DHA) (10 g/kg diet) and/or the sEH inhibitor 1-(4-trifluoro-methoxy-phenyl)-3-(1-propionylpiperidin-4-yl) urea (TPPU) (22.5 mg/kg diet ≈ 3 mg/kg/day) on R-LPS triggering were compared.

Results

In Study 1, R-LPS induced robust elevations in blood urea nitrogen, proteinuria, and hematuria that were not evident in VEH- or S-LPS-treated mice. R-LPS-treated mice further exhibited kidney histopathology including robust hypertrophy, hyperplasia, thickened membranes, lymphocytic accumulation containing B and T cells, and glomerular IgG deposition consistent with GN that was not evident in VEH- or SLPS-treated groups. R-LPS but not S-LPS induced spleen enlargement with lymphoid hyperplasia and inflammatory cell recruitment in the liver. In Study 2, resultant blood fatty acid profiles and epoxy fatty acid concentrations reflected the anticipated DHA- and TPPU-mediated lipidome changes, respectively. The relative rank order of R-LPS-induced GN severity among groups fed experimental diets based on proteinuria, hematuria, histopathologic scoring, and glomerular IgG deposition was: VEH/CON< R-LPS/DHA ≈ R-LPS/TPPU<<< R-LPS/TPPU+DHA ≈ R-LPS/CON. In contrast, these interventions had modest-to- negligible effects on R-LPS-induced splenomegaly, plasma antibody responses, liver inflammation, and inflammation-associated kidney gene expression.

Discussion

We show for the first time that absence of O-antigenic polysaccharide in R-LPS is critical to accelerated GN in lupus-prone mice. Furthermore, intervention by lipidome modulation through DHA feeding or sEH inhibition suppressed R-LPS-induced GN; however, these ameliorative effects were greatly diminished upon combining the treatments.
Capturing the multifaceted function of adipose tissue macrophages
Authors: Matz Alyssa J. , Qu Lili , Karlinsey Keaton , Vella Anthony T. , Zhou Beiyan
Published: February 2023

Adipose tissue macrophages (ATMs) bolster obesity-induced metabolic dysfunction and represent a targetable population to lessen obesity-associated health risks. However, ATMs also facilitate adipose tissue function through multiple actions, including adipocyte clearance, lipid scavenging and metabolism, extracellular remodeling, and supporting angiogenesis and adipogenesis. Thus, high-resolution methods are needed to capture macrophages’ dynamic and multifaceted functions in adipose tissue. Herein, we review current knowledge on regulatory networks critical to macrophage plasticity and their multifaceted response in the complex adipose tissue microenvironment.
Chemical Prevention and Control of the Green Tide and Fouling Organism Ulva: Key Chemicals, Mechanisms, and Applications
Authors: Tang Tao , Effiong Kokoette , Hu Jing , Li Chao , Xiao Xi
Published: February 2023

The green algae, Ulva spp., have been causing environmental problems worldwide, e.g., green tides and biofoulings. Green tides resulted from bloom floating Ulva have caused substantial economic losses. Ulva foulings increase the maintenance cost of marine facilities and contribute to the biomass of floating algae. Chemical methods are generally very inexpensive and convenient for suppression of Ulva spp. during their early life stages, thus solving the green tide and fouling problem at the source. In this paper, classical chemical methods that have been or are in use and emerging chemical methods under research are systematically reviewed. The advantages, disadvantages, mechanisms, and applications of these methods are also summarized. Highly toxic reagents are used in classical chemical methods, including oxidants, acids, heavy metal compounds, and synthetic biocides directly used or applied in antifouling coatings to kill or inhibit Ulva effectively. However, these toxic reagents have a high risk of resulting in secondary environmental problems. In order to minimize other environmental impacts while solving the current problem, emerging, and environmentally friendly chemical methods have been developed, such as the utilization of degradable natural products (mainly allelochemicals) and semi-natural products for Ulva inhibition and fouling control, and the use of flocculating agents to prevent microscopic propagules from germinating. All these chemical methods provide a promising direction for the prevention and control of Ulva.
Designing transdisciplinarity for transformative ocean governance
Authors: Hills Jeremy Maxwell , Maharaj Payal Nandini
Published: February 2023

The 2030 Agenda for Sustainable Development sets out a transformative vision which has yet to be realised for SDG14 and oceans. Recognition of the “indivisibility” of the Goals and enhanced integration of ocean governance support this transformation, but require at least multidisciplinary, or probably transdisciplinary, approaches. For regions which are highly dependent on development finance, a powerful leverage point for a transdisciplinary transformation is in the design of development investments. The work presented here identifies design features of ocean development-financed projects involving substantial amounts of research in two Pacific Small Island Developing States (SIDS): Fiji and the Solomon Islands. Transdisciplinary approaches were closely aligned to what is established as Mode 2 research modalities which focus on participation and multi-knowledge systems, as opposed to Mode 1 which have a predominantly scientific basis. From the literature an analytical indicator framework was developed which scored projects on their Modes of research within four categories: Product, Process, Policy and People. This framework was applied to five development-financed projects, and permitted the balance of Mode 1 and Mode 2 to be assessed and significant differences between projects identified. The work surfaces project features which can be embedded in the design of ocean investments which promote transdisciplinarity. This tractable and practical recognition of transdisciplinarity has connotations to the UN Ocean Decade in its ability to deliver on its transformation rhetoric. With capacity weaknesses and constrained financial resources in developing countries, and urgent ocean-related challenges especially in SIDS, moving to designed-in transdisciplinary and transformational outcomes remains a priority.
Impact of an exceptional winter flood on benthic oxygen and nutrient fluxes in a temperate macrotidal estuary: Potential consequences on summer deoxygenation
Authors: Hulot Vivien , Metzger Edouard , Thibault de Chanvalon Aubin , Mouret Aurelia , Schmidt Sabine , Deflandre Bruno , Rigaud Sylvain , Beneteau Eric , Savoye Nicolas , Souchu Philippe , Le Merrer Yoann , Maillet Grégoire M.
Published: February 2023

Despite 20 years of control on eutrophication, episodes of summer hypoxia still occur in the Loire estuary, impacting water quality and posing a key scientific and management challenge. This work aimed to quantify the contribution of the benthic compartment to hypoxia in the Loire estuary by direct measurement of water–sediment fluxes and an in-depth understanding of the seasonal variations of oxides and phosphorus stocks. During the summer’s low-discharge period, results show that the iron oxide-rich deposit is stable under hypoxic conditions, limiting the release of dissolved phosphorus into the overlying water column. The high nitrate content of the water column appears to be an important oxidizer of iron during hypoxic periods, limiting dissolved phosphorus leakage and aggravation of hypoxia. During the exceptional winter flood, significant sediment erosion associated with bubbling phenomena (attributed to methane efflux) created severe fractures in the sediment and stimulated water–sediment exchange. During the following months, these fractures were progressively filled, which decreased the intensity of benthic fluxes. However, due to the high residence time in the water during the summer period, a simple model demonstrated that benthic contributions were sufficient to directly (by direct oxygen consumption) or indirectly (by promoting ammonia oxidation) affect the oxygen stock in the water column during the low-discharge period. Our study demonstrates the importance of the benthic compartment in the occurrence of hypoxia and the obvious lack of knowledge to illustrate and model the biogeochemical functioning of the estuary.
Pentacyclic triterpenoids saponins pannosides A-E from Tripolium pannonicum
Authors: Um Soohyun , Lee Jaeyoun , Lee Yechan , Namkung Wan , Kim Seung Hyun
Published: February 2023

Five previously undescribed pentacyclic triterpenoid saponins, pannoside A–E (1–5), were discovered from the whole plant of seashore aster, Tripolium pannonicum, collected from the Songdo tidal flat, Incheon, Korea. The planar structures of pannosides were elucidated as pentacyclic triterpenoids bearing sugar moieties and 3-hydroxybutyrate (3-HB) based on the interpretation of the NMR, IR spectroscopic and MS data. The relative configurations of the aglycone and sugar moieties of 1–5 were determined based on careful analysis of ROESY correlations. To determine the absolute configuration of 3-hydroxybutyrate, we utilized the phenylglycine methyl ester (PGME) derivatization with LC-MS chromatographic analysis. Pannoside E (5) exhibited inhibitory activities against diverse cancer cell lines including prostate carcinoma and non-small cell lung carcinoma, with IC50 values of 0.34 and 0.89 μM, respectively. Pannosides are the first triterpenoid saponin isolated from T. pannonicum, implying that undiscovered secondary metabolites from a halophyte could be a good source of bioactive compounds.
Effect of different targeted calyxes on the treatment of multi-site calculi in the postural drainage lithotripsy system
Authors: Yang Tao , Wu Chong , Dai Liangliang , Hu Zhixiong , Song Rijin , Meng Xianghu , Shi Honglei
Published: February 2023

Objectives

We developed a postural drainage lithotripsy system (PDLS) that can provide an individualized inversion and overturning angle and uses gravity to remove residual fragments (RFs). This study aimed to evaluate the effect of different targeted calyces on treating multi-site stones in PDLS.

Methods

A total of 20 stones with different sizes and diameters of 0–4 mm were placed in the kidney model through ureteroscopy, and 20 stones were evenly scattered in the middle calyx and the lower calyx of the model. The ventral-middle calyx, the dorsal-middle calyx, the ventral-lower calyx, and the dorsal-lower calyx were used as the targeted calyx of PDLS to treat multi-site stones. During treatment, if the stone moved from the starting position of the renal calyx to the ureteropelvic junction, it was recorded as “passing through.” The clearance rate was recorded, and the efficacy of different targeted calyxes in the treatment of multiple-site calyx was compared. Each model was treated with four different targeted calyxes, and 20 models were tested 80 times.

Results

When the lower calyx was the targeted calyx, the total stone clearance rate was higher than when the middle calyx was the locating calyx (94.5 vs. 64%, P = 0.000), and the result was statistically significant.

Conclusions

Choosing the lower calyx as the targeted calyx, we can obtain a better stone clearance rate. However, there is no significant difference between the ventral lower calyx and the dorsal lower calyx.
Leadership during airway management in the intensive care unit: A video-reflexive ethnography study
Authors: Brewster David J. , Butt Warwick W. , Gordon Lisi J. , Sarkar Mahbub A. , Begley Jonathan L. , Rees Charlotte E.
Published: February 2023

Effective leadership is crucial to team performance within the intensive care unit. This novel study aimed to explore how staff members from an intensive care unit conceptualize leadership and what facilitators and barriers to leadership exist within a simulated workplace. It also aimed to identify factors that intersect with their perceptions of leadership. This study was underpinned by interpretivism, and video-reflexive ethnography was chosen as the methodology for the study. The use of both video recording (to capture the complex interactions occurring in the ICU) and team reflexivity allowed repeated analysis of those interactions by the research team. Purposive sampling was used to recruit participants from an ICU in a large tertiary and private hospital in Australia. Simulation groups were designed to replicate the typical clinical teams involved in airway management within the intensive care unit. Twenty staff participated in the four simulation activities (five staff per simulation group). Each group simulated the intubations of three patients with hypoxia and respiratory distress due to severe COVID-19. All 20 participants who completed the study simulations were invited to attend video-reflexivity sessions with their respective group. Twelve of the 20 participants (60%) from the simulations took part in the reflexive sessions. Video-reflexivity sessions (142 min) were transcribed verbatim. Transcripts were then imported into NVivo software for analysis. The five stages of framework analysis were used to conduct thematic analysis of the video-reflexivity focus group sessions, including the development of a coding framework. All transcripts were coded in NVivo. NVivo queries were conducted to explore patterns in the coding. The following key themes regarding participants’ conceptualizations of leadership within the intensive care were identified: (1) leadership is both a group/shared process and individualistic/hierarchical; (2) leadership is communication; and (3) gender is a key leadership dimension. Key facilitators identified were: (1) role allocation; (2) trust, respect and staff familiarity; and (3) the use of checklists. Key barriers identified were: (1) noise and (2) personal protective equipment. The impact of socio-materiality on leadership within the intensive care unit is also identified.
Bloodletting cupping combined with conventional measures therapy for psoriasis: A systematic review and meta-analysis of randomized controlled trials
Authors: Ma Xiaoyu , Li Dilong , Zhao Minghui , He Jiaming , Yang Fan , Kong Jingyan
Published: February 2023

Background

Psoriasis is an immune-mediated inflammatory disease prone to recurrence. Some studies indicated that bloodletting cupping combined with conventional measures therapy had been proposed as a treatment strategy for psoriasis. Therefore, we performed a systematic review and meta-analysis to assess the effectiveness of this combination therapy in reducing the severity of disease in patients with psoriasis.

Methods

The following electronic databases were searched for articles from January 1, 2000 to March 1, 2022: PubMed, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), Chinese Biomedical Literature Database (CBM), Chinese Scientific Journal Database (VIP database), Wan-Fang Database, and China National Knowledge Infrastructure (CNKI). The language was not restricted while performing the search. The quality of articles was evaluated using Rev. Man 5.4 software (provided by the Cochrane Collaboration), comparing bloodletting cupping combined with conventional measures therapy to conventional measures treatments. The studies obtained randomized controlled trials (RCTs) of bloodletting cupping combined with conventional standard treatment for treating psoriasis. Two trained researchers (Xiaoyu Ma and Jiaming He) independently reviewed the literature, extracted data based on exclusion and inclusion criteria, and assessed the quality of the included studies. We estimated the aggregate data using a random effects model.

Findings

We identified 164 studies. Ten studies met the inclusion criteria for the meta-analysis. The primary outcome indicator was the total number of effective individuals. Secondary outcomes included the Psoriasis Area and Severity Index (PASI), adverse effects, and the Dermatology Life Quality Index (DLQI). Compared with conventional treatments, bloodletting cupping combined with conventional medicine yielded an improved total effective number of persons (RR = 1.15, 95%CI: 1.07 to 1.22, p < 0.00001), PASI (MD = −1.11, 95%CI: −1.40 to −0.82, p < 0.00001) and DLQI scores (MD = −0.99, 95%CI: −1.40 to −0.59, p < 0.0001). We found no significant difference in adverse reactions (RR = 0.93, 95%CI: 0.46 to 1.90, p = 0.85). The heterogeneity test showed the total effective numbers (p < 0.00001, I2 = 43%) and PASI (p < 0.00001, I2 = 44%) and DLQI scores (p < 0.00001, I2 = 0%).

Interpretation

Bloodletting cupping combined with conventional treatment can achieve the ideal treatment for psoriasis. However, the combined treatment in psoriasis needs to be further evaluated in high-quality RCTs with large sample sizes to enable future studies in clinical use.
SARS-CoV-2-encoded small RNAs are able to repress the host expression of SERINC5 to facilitate viral replication
Authors: Meseguer Salvador , Rubio Mari-Paz , Lainez Begoña , Pérez-Benavente Beatriz , Pérez-Moraga Raúl , Romera-Giner Sergio , García-García Francisco , Martinez-Macias Olalla , Cremades Antonio , Iborra Francisco J. , Candelas-Rivera Oscar , Almazan Fernando , Esplugues Enric
Published: February 2023

Serine incorporator protein 5 (SERINC5) is a key innate immunity factor that operates in the cell to restrict the infectivity of certain viruses. Different viruses have developed strategies to antagonize SERINC5 function but, how SERINC5 is controlled during viral infection is poorly understood. Here, we report that SERINC5 levels are reduced in COVID-19 patients during the infection by SARS-CoV-2 and, since no viral protein capable of repressing the expression of SERINC5 has been identified, we hypothesized that SARS-CoV-2 non-coding small viral RNAs (svRNAs) could be responsible for this repression. Two newly identified svRNAs with predicted binding sites in the 3′-untranslated region (3’-UTR) of the SERINC5 gene were characterized and we found that the expression of both svRNAs during the infection was not dependent on the miRNA pathway proteins Dicer and Argonaute-2. By using svRNAs mimic oligonucleotides, we demonstrated that both viral svRNAs can bind the 3’UTR of SERINC5 mRNA, reducing SERINC5 expression in vitro. Moreover, we found that an anti-svRNA treatment to Vero E6 cells before SARS-CoV-2 infection recovered the levels of SERINC5 and reduced the levels of N and S viral proteins. Finally, we showed that SERINC5 positively controls the levels of Mitochondrial Antiviral Signalling (MAVS) protein in Vero E6. These results highlight the therapeutic potential of targeting svRNAs based on their action on key proteins of the innate immune response during SARS-CoV-2 viral infection.
Eugenol eliminates carbapenem-resistant Klebsiella pneumoniae via reactive oxygen species mechanism
Authors: Liu Wei , Chen Guang , Dou Keke , Yi Bingcheng , Wang Danyang , Zhou Qihui , Sun Yunbo
Published: February 2023

Multidrug-resistant (MDR) bacterial infections have gained increasing attention due to the high incidence rates and high mortality, especially for the carbapenem-resistant Klebsiella pneumoniae (CRKP) infection that can cause severe complications (e.g., pneumonia and sepsis) in multiple organs. Therefore, the development of new antibacterial agents against CRKP is imperative. Inspired by natural plant antibacterial agents with broad-spectrum antibacterial properties, the antibacterial/biofilm activity of eugenol (EG) on CRKP and their underlying mechanisms are investigated in our work. It is found that EG exhibits remarkable inhibitory effects on planktonic CRKP in a dose-dependent fashion. Meanwhile, the destruction of membrane integrity induced by the formation of reactive oxygen species (ROS) and glutathione reduction results in the leakage of bacterial cytoplasmic components, including DNA, β-galactosidase, and protein. Moreover, when EG contacts with bacterial biofilm, the whole thickness of the dense biofilm matrix decreases, and the integrity is destroyed. Overall, this work verified that EG could eliminate CRKP via ROS-induced membrane rupture, which offers vital evidence to explain the antibacterial ability of EG against CRKP.
Characterization of a lytic Escherichia coli phage CE1 and its potential use in therapy against avian pathogenic Escherichia coli infections
Authors: Tang Zhaohui , Tang Ning , Wang Xinwei , Ren Huiying , Zhang Can , Zou Ling , Han Lei , Guo Longzong , Liu Wenhua
Published: February 2023

The high incidence of Avian pathogenic Escherichia coli (APEC) in poultry has resulted in significant economic losses. It has become necessary to find alternatives to antibiotics due to the alarming rise in antibiotic resistance. Phage therapy has shown promising results in numerous studies. In the current study, a lytic phage vB_EcoM_CE1 (short for CE1) against Escherichia coli (E. coli) was isolated from broiler feces, showing a relatively wide host range and lysing 56.9% (33/58) of high pathogenic strains of APEC. According to morphological observations and phylogenetic analysis, phage CE1 belongs to the Tequatrovirus genus, Straboviridae family, containing an icosahedral capsid (80 ~ 100 nm in diameter) and a retractable tail (120 nm in length). This phage was stable below 60°C for 1 h over the pH range of 4 to 10. Whole-genome sequencing revealed that phage CE1 contained a linear double-stranded DNA genome spanning 167,955 bp with a GC content of 35.4%. A total of 271 ORFs and 8 tRNAs were identified. There was no evidence of virulence genes, drug-resistance genes, or lysogeny genes in the genome. The in vitro test showed high bactericidal activity of phage CE1 against E. coli at a wide range of MOIs, and good air and water disinfectant properties. Phage CE1 showed perfect protection against broilers challenged with APEC strain in vivo. This study provides some basic information for further research into treating colibacillosis, or killing E. coli in breeding environments.
Integrative ATAC-seq and RNA-seq analyses of IPEC-J2 cells reveals porcine transcription and chromatin accessibility changes associated with Escherichia coli F18ac inhibited by Lactobacillus reuteri
Authors: Qin Weiyun , Xie Yunxiao , Ren Zhanshi , Xu Chao , Sun Ming-an , Yin Zongjun , Bao Wenbin
Published: February 2023

Escherichia coli is the main cause of postweaning diarrhea in pigs, leading to economic loss. As a probiotic, Lactobacillus reuteri has been used to inhibit E. coli in clinical applications; however, its integrative interactions with hosts remain unclear, especially in pigs. Here, we found that L. reuteri effectively inhibited E. coli F18ac adhering to porcine IPEC-J2 cells, and explored the genome-wide transcription and chromatin accessibility landscapes of IPEC-J2 cells by RNA-seq and ATAC-seq. The results showed that some key signal transduction pathways, such as PI3K-AKT and MAPK signaling pathways, were enriched in the differentially expressed genes (DEGs) between E. coli F18ac treatment with and without L. reuteri groups. However, we found less overlap between RNA-seq and ATAC-seq datasets; we speculated that this might be caused by histones modification through ChIP-qPCR detection. Furthermore, we identified the regulation of the actin cytoskeleton pathway and a number of candidate genes (ARHGEF12, EGFR, and DIAPH3) that might be associated with the inhibition of E. coli F18ac adherence to IPEC-J2 cells by L. reuteri. In conclusion, we provide a valuable dataset that can be used to seek potential porcine molecular markers of E. coli F18ac pathogenesis and L. reuteri antibacterial activity, and to guide the antibacterial application of L. reuteri.
That H9N2 avian influenza viruses circulating in different regions gather in the same live-poultry market poses a potential threat to public health
Authors: Liu Tengfei , Xie Shumin , Yang Zhiyi , Zha Aimin , Shi Yuting , Xu Lingyu , Chen Junhong , Qi Wenbao , Liao Ming , Jia Weixin
Published: February 2023

H9N2 avian influenza viruses are endemic and persistent in China, but those that are prevalent in different provinces are also causes of wide epidemics, related to the spread of wild birds and the cross-regional trade in live poultry. For the past 4 years, beginning in 2018, we have sampled a live-poultry market in Foshan, Guangdong, in this ongoing study. In addition to the prevalence of H9N2 avian influenza viruses in China during this period, we identified isolates from the same market belonging to clade A and clade B, which diverged in 2012–2013, and clade C, which diverged in 2014–2016, respectively. An analysis of population dynamics revealed that, after a critical divergence period from 2014 to 2016, the genetic diversity of H9N2 viruses peaked in 2017. Our spatiotemporal dynamics analysis found that clade A, B, and C, which maintain high rates of evolution, have different prevalence ranges and transmission paths. Clades A and B were mainly prevalent in East China in the early stage, and then spread to Southern China, becoming epidemic with clade C. Strains from different regions converge at the same live-poultry market to communicate, which may be one reasons the H9N2 viruses are difficult to eradicate and increasingly dominant throughout China. Selection pressure and molecular analysis have demonstrated that single amino acid polymorphisms at key receptor binding sites 156, 160, and 190 under positive selection pressure, suggesting that H9N2 viruses are undergoing mutations to adapt to new hosts. Live-poultry markets are important because people who visit them have frequent contact with poultry, H9N2 viruses from different regions converge at these markets and spread through contact between live birds and humans, generating increased risks of human exposure to these viruses and threatening public health safety. Thus, it is important to reducing the cross-regional trade of live poultry and strengthening the monitoring of avian influenza viruses in live-poultry markets to reduce the spread of avian influenza viruses.
Role of two RpoN in Bradyrhizobium sp. strain DOA9 in symbiosis and free-living growth
Authors: Wongdee Jenjira , Piromyou Pongdet , Songwattana Pongpan , Greetatorn Teerana , Teaumroong Neung , Boonkerd Nantakorn , Giraud Eric , Nouwen Nico , Tittabutr Panlada
Published: February 2023

RpoN is an alternative sigma factor (sigma 54) that recruits the core RNA polymerase to promoters of genes. In bacteria, RpoN has diverse physiological functions. In rhizobia, RpoN plays a key role in the transcription of nitrogen fixation (nif) genes. The Bradyrhizobium sp. DOA9 strain contains a chromosomal (c) and plasmid (p) encoded RpoN protein. We used single and double rpoN mutants and reporter strains to investigate the role of the two RpoN proteins under free-living and symbiotic conditions. We observed that the inactivation of rpoNc or rpoNp severely impacts the physiology of the bacteria under free-living conditions, such as the bacterial motility, carbon and nitrogen utilization profiles, exopolysaccharide (EPS) production, and biofilm formation. However, free-living nitrogen fixation appears to be under the primary control of RpoNc. Interestingly, drastic effects of rpoNc and rpoNp mutations were also observed during symbiosis with Aeschynomene americana. Indeed, inoculation with rpoNp, rpoNc, and double rpoN mutant strains resulted in decreases of 39, 64, and 82% in the number of nodules, respectively, as well as a reduction in nitrogen fixation efficiency and a loss of the bacterium’s ability to survive intracellularly. Taken together, the results show that the chromosomal and plasmid encoded RpoN proteins in the DOA9 strain both play a pleiotropic role during free-living and symbiotic states.
Biasing AlphaFold2 to predict GPCRs and kinases with user-defined functional or structural properties
Authors: Sala Davide , Hildebrand Peter W. , Meiler Jens
Published: February 2023

Determining the three-dimensional structure of proteins in their native functional states has been a longstanding challenge in structural biology. While integrative structural biology has been the most effective way to get a high-accuracy structure of different conformations and mechanistic insights for larger proteins, advances in deep machine-learning algorithms have paved the way to fully computational predictions. In this field, AlphaFold2 (AF2) pioneered ab initio high-accuracy single-chain modeling. Since then, different customizations have expanded the number of conformational states accessible through AF2. Here, we further expanded AF2 with the aim of enriching an ensemble of models with user-defined functional or structural features. We tackled two common protein families for drug discovery, G-protein-coupled receptors (GPCRs) and kinases. Our approach automatically identifies the best templates satisfying the specified features and combines those with genetic information. We also introduced the possibility of shuffling the selected templates to expand the space of solutions. In our benchmark, models showed the intended bias and great accuracy. Our protocol can thus be exploited for modeling user-defined conformational states in an automatic fashion.
High ratio of C-reactive protein to albumin is associated with hemorrhagic transformation and poor functional outcomes in acute ischemic stroke patients after thrombolysis
Authors: Xu Tong , Xia Lingfan , Wu Yucong , Xu Ye , Xu Xuan , Zhang Wangyu , Zhou Congcong , Fu Fangwang , Cao Yungang , Han Zhao
Published: February 2023

Background

In patients with acute ischemic stroke, hemorrhagic transformation (HT) is a common complication after intravenous thrombolysis (IVT). In this study, we evaluated the relationship between the ratio of C-reactive protein to albumin (CAR) before thrombolysis, HT, and functional outcomes in patients with acute ischemic stroke.

Methods

We retrospectively analyzed data from 354 patients who received thrombolytic therapy at the Second Affiliated Hospital of the Wenzhou Medical University in China between July 2014 and May 2022. CAR was measured on admission, and HT was identified by cranial computed tomography (CT) within 24–36 h after treatment. Poor outcome was defined as a score on the modified Rankin Scale (mRS) > 2 at discharge. The multivariate logistic regression model was used to investigate the association between CAR, HT, and poor outcome after thrombolysis, respectively.

Results

A total of 354 patients were analyzed, and their median CAR was 0.61 (interquartile range, 0.24–1.28). CAR was significantly higher in the 56 patients (15.8%) who experienced HT than in those who did not (0.94 vs. 0.56, p < 0.001), and the 131 patients (37.0%) who experienced poor outcome than in those who did not (0.87 vs. 0.43, p < 0.001). Multivariate logistic regression indicated that CAR was an independent risk factor for both HT and poor outcome. The risk of HT was significantly higher among patients whose CAR fell in the fourth quartile than among those with CAR in the first quartile (OR 6.64, 95% CI 1.83 to 24.17, p = 0.004). Patients with CAR in the third quartile were more likely to experience poor outcome (OR 3.35, 95% CI 1.32 to 8.51, p = 0.01), as were those in the fourth quartile (OR 7.33, 95% CI 2.62 to 20.50, p < 0.001), compared to patients with CAR in the first quartile.

Conclusion

High ratio of C-reactive protein to albumin in individuals with ischemic stroke is associated with an increased risk of HT and poor functional outcomes after thrombolysis.
Exosomes may be the carrier of acupuncture treatment for major depressive disorder
Authors: Lyu Qin , Zhou Xin , Shi Liu-Qing , Chen Hai-Yang , Lu Mei , Ma Xian-De , Ren Lu
Published: February 2023

The incidence of major depressive disorder (MDD) is increasing all over the world. There is a great need for complementary or alternative therapies with high safety, few side effects, and precise efficacy to care for MDD. In China, acupuncture has significant laboratory data and clinical trials to demonstrate its antidepressant efficacy. However, there is no clear answer as to how it works. Exosomes are membranous vesicles that rely on cellular multivesicular bodies (MVBs) fused to the cell membrane for release into the extracellular matrix. Almost all cell types are capable of producing and releasing exosomes. As a result, exosomes contain complex RNAs and proteins from their relatives (Cells that secretes exosomes). They can cross biological barriers and participate in biological activities, such as cell migration, angiogenesis, and immune regulation. These properties have made them a popular research topic. Some experts have suggested that exosomes may serve as delivery vehicles for acupuncture to work. This presents both an opportunity and a new challenge for improving the protocols of acupuncture as a treatment for MDD. To better define the relationship between MDD, exosomes, and acupuncture, we reviewed the literature from the last few years. Inclusion criteria included randomized controlled trials and basic trials evaluating acupuncture in the treatment or prevention of MDD, the role of exosomes in the development and progression of MDD, and the role of exosomes in acupuncture. We believe that acupuncture may affect the distribution of exosomes in vivo, and exosomes may be a new carrier for acupuncture treatment of MDD in the future.
An N400 identification method based on the combination of Soft-DTW and transformer
Authors: Ma Yan , Tang Yiou , Zeng Yang , Ding Tao , Liu Yifu
Published: February 2023

As a time-domain EEG feature reflecting the semantic processing of the human brain, the N400 event-related potentials still lack a mature classification and recognition scheme. To address the problems of low signal-to-noise ratio and difficult feature extraction of N400 data, we propose a Soft-DTW-based single-subject short-distance event-related potential averaging method by using the advantages of differentiable and efficient Soft-DTW loss function, and perform partial Soft-DTW averaging based on DTW distance within a single-subject range, and propose a Transformer-based ERP recognition classification model, which captures contextual information by introducing location coding and a self-attentive mechanism, combined with a Softmax classifier to classify N400 data. The experimental results show that the highest recognition accuracy of 0.8992 is achieved on the ERP-CORE N400 public dataset, verifying the effectiveness of the model and the averaging method.
CNS demyelinating events in primary Sjögren's syndrome: A single-center case series on the clinical phenotype
Authors: Afzali Ali M. , Moog Philipp , Kalluri Sudhakar Reddy , Hofauer Benedikt , Knopf Andreas , Kirschke Jan Stefan , Hemmer Bernhard , Berthele Achim
Published: February 2023

Objective

The study aimed to assess the prevalence, clinical characteristics, and therapeutic outcomes of the central nervous system (CNS) demyelinating disease in a large cohort of primary Sjögren's syndrome (pSS).

Methods

This is an explorative cross-sectional study of patients with pSS seen in the departments of rheumatology, otorhinolaryngology, or neurology of a tertiary university center between January 2015 and September 2021.

Results

In a cohort of 194 pSS patients, 22 patients had a CNS manifestation. In this CNS group, 19 patients had a lesion pattern suggestive of demyelination. While there were no obvious differences in the patients' epidemiological disposition or rate of other extraglandular manifestations, the CNS group differed from the remaining patients with pSS by having less glandular manifestations but a higher seroprevalence for anti-SSA/Ro antibodies. Notably, patients with CNS manifestations were often diagnosed with multiple sclerosis (MS) and treated as such, although age and disease course were atypical of MS. Many first-line MS agents were ineffective in these “MS look-alikes”; however, the disease course was benign with B-cell-depleting agents.

Conclusion

Neurological symptoms of pSS are common and clinically manifest mainly as myelitis or optic neuritis. Notably, in the CNS, the pSS phenotype can overlap with MS. The prevailing disease is crucial since it has a major impact on the long-term clinical outcome and the choice of disease-modifying agents. Although our observations neither confirm pSS as a more appropriate diagnosis nor rule out simple comorbidity, physicians should consider pSS in the extended diagnostic workup of CNS autoimmune diseases.
An online hybrid BCI combining SSVEP and EOG-based eye movements
Authors: Zhang Jun , Gao Shouwei , Zhou Kang , Cheng Yi , Mao Shujun
Published: February 2023

Hybrid brain-computer interface (hBCI) refers to a system composed of a single-modality BCI and another system. In this paper, we propose an online hybrid BCI combining steady-state visual evoked potential (SSVEP) and eye movements to improve the performance of BCI systems. Twenty buttons corresponding to 20 characters are evenly distributed in the five regions of the GUI and flash at the same time to arouse SSVEP. At the end of the flash, the buttons in the four regions move in different directions, and the subject continues to stare at the target with eyes to generate the corresponding eye movements. The CCA method and FBCCA method were used to detect SSVEP, and the electrooculography (EOG) waveform was used to detect eye movements. Based on the EOG features, this paper proposes a decision-making method based on SSVEP and EOG, which can further improve the performance of the hybrid BCI system. Ten healthy students took part in our experiment, and the average accuracy and information transfer rate of the system were 94.75% and 108.63 bits/min, respectively.
Algorithm-based mapping of products in a branded Canadian food and beverage database to their equivalents in Health Canada’s Canadian Nutrient File
Authors: Gilbert Sappho Z. , Morrison Conor L. , Chen Qiuyu J. , Punian Jesman , Bernstein Jodi T. , Jessri Mahsa
Published: February 2023

Introduction

There is increasing recognition of the value of linking food sales databases to national food composition tables for population nutrition research.

Objectives

Expanding upon automated and manual database mapping approaches in the literature, our aim was to match 1,179 food products in the Canadian data subset of Euromonitor International’s Passport Nutrition to their closest respective equivalents in Health Canada’s Canadian Nutrient File (CNF).

Methods

Matching took place in two major steps. First, an algorithm based on thresholds of maximal nutrient difference (between Euromonitor and CNF foods) and fuzzy matching was executed to offer match options. If a nutritionally appropriate match was available among the algorithm suggestions, it was selected. When the suggested set contained no nutritionally sound matches, the Euromonitor product was instead manually matched to a CNF food or deemed unmatchable, with the unique addition of expert validation to maximize meticulousness in matching. Both steps were independently performed by at least two team members with dietetics expertise.

Results

Of 1,111 Euromonitor products run through the algorithm, an accurate CNF match was offered for 65% of them; missing or zero-calorie data precluded 68 products from being run in the algorithm. Products with 2 or more algorithm-suggested CNF matches had higher match accuracy than those with one (71 vs. 50%, respectively). Overall, inter-rater agreement (reliability) rates were robust for matches chosen among algorithm options (51%) and even higher regarding whether manual selection would be required (71%); among manually selected CNF matches, reliability was 33%. Ultimately, 1,152 (98%) Euromonitor products were matched to a CNF equivalent.

Conclusion

Our reported matching process successfully bridged a food sales database’s products to their respective CNF matches for use in future nutritional epidemiological studies of branded foods sold in Canada. Our team’s novel utilization of dietetics expertise aided in match validation at both steps, ensuring rigor and quality of resulting match selections.