bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of antithrombin with development of trauma-induced disseminated intravascular coagulation and outcomes
Authors: Wada Takeshi , Shiraishi Atsushi , Gando Satoshi , Kabata Daijiro , Yamakawa Kazuma , Fujishima Seitaro , Saitoh Daizoh , Kushimoto Shigeki , Ogura Hiroshi , Abe Toshikazu , Mayumi Toshihiko , Otomo Yasuhiro
Published: December 2022

Introduction

Trauma activates the innate immune system to modulate hemostasis and minimize the damage caused by physiological bodily responses, including the activation of coagulation. Sufficiently severe trauma overwhelms physiological responses and elicits the systemic inflammatory response syndrome, which leads to the onset of disseminated intravascular coagulation (DIC), characterized by dysregulated inflammatory coagulofibrinolytic responses. Impaired anticoagulant mechanisms, including antithrombin, constitutes the pathology of DIC, while the dynamics of antithrombin and relevance to outcomes in trauma-induced coagulopathy have not been fully elucidated. This study investigated the associations of antithrombin activity with DIC onset and outcomes in severely injured patients.

Methods

This retrospective sub-analysis of a multicenter, prospective study included patients with an injury severity score ≥16. We characterized trauma patients with low antithrombin activity (antithrombin <80% on hospital arrival, n = 75) in comparison with those who had normal antithrombin activity (antithrombin ≥80%, n = 200). Global markers of coagulation and fibrinolysis, molecular biomarkers for thrombin generation (soluble fibrin [SF]), and markers of anticoagulation (antithrombin) were evaluated to confirm the associations of antithrombin with DIC development and outcomes, including in-hospital mortality and the multiple organ dysfunction syndrome (MODS).

Results

Patients with low antithrombin activity had higher prevalence of shock, transfusion requirements, and in-hospital mortality. Higher DIC scores and more severe organ dysfunction were observed in the low AT group compared to that in the normal AT group. Antithrombin activity on arrival at the hospital was an independent predictor of the development of DIC in trauma patients, and levels of SF increased with lower antithrombin values (antithrombin activity > 85%). Antithrombin activity at 3 h showed good predictive performance for in-hospital mortality, and a multivariable Cox proportional-hazard regression model with a cross-product term between the antithrombin and DIC showed that the in-hospital mortality in patients with DIC increased with decreased antithrombin activity. A multivariable logistic regression model showed that the odds for the development of MODS in patients with DIC increased with lower antithrombin values.

Conclusion

Decreased antithrombin activity in trauma-induced coagulopathy is associated with poor outcomes through worsening of DIC.
Humoral immune response following a third SARS-CoV-2 mRNA vaccine dose in solid organ transplant recipients compared with matched controls
Authors: Balsby Daniel , Nilsson Anna Christine , Petersen Inge , Lindvig Susan O. , Davidsen Jesper Rømhild , Abazi Rozeta , Poulsen Mikael K. , Holden Inge K. , Justesen Ulrik S. , Bistrup Claus , Johansen Isik Somuncu
Published: December 2022

Background

Solid organ transplant (SOT) recipients have shown suboptimal antibody response following COVID-19 vaccination. Several risk factors for the diminished response have been identified including immunosuppression and older age, but the influence of different comorbidities is not fully elucidated.

Method

This case-control study consisted of 420 Danish adult SOT recipients and 840 sex- and age-matched controls, all vaccinated with a third homologous dose of either BNT162b2 (Pfizer–BioNTech) or mRNA-1273 (Moderna) vaccine. The primary outcome was differences in humoral immune response. The secondary outcome was breakthrough infections. Additionally, we looked for factors that could predict possible differences between the two groups.

Results

Response rate increased from 186/382 (49%) to 275/358 (77%) in SOT recipients and remained on 781/790 (99%) to 601/609 (99%) in controls following a third vaccine dose. SOT recipients had significantly lower median antibody concentrations after third dose compared to controls (332.6 BAU/ml vs 46,470.0 BAU/ml, p <0.001). Lowest median antibody concentrations were seen in SOT recipients with liver disease (10.3 BAU/ml, IQR 7.1-319) and diabetes (275.3 BAU/ml, IQR 7.3-957.4). Breakthrough infections occurred similarly frequent, 150 (40%) among cases and 301 (39%) among controls (p = 0.80).

Conclusion

A third COVID-19 vaccine dose resulted in a significant increase in humoral immunogenicity in SOT recipients and maintained high response rate in controls. Furthermore, SOT recipients were less likely to produce antibodies with overall lower antibody concentrations and humoral immunity was highly influenced by the presence of liver disease and diabetes. The prevalence of breakthrough infections was similar in the two groups.
Association of complement components with the risk and severity of NAFLD: A systematic review and meta-analysis
Authors: Zhao Jianbo , Wu Yafei , Lu Peng , Wu Xiaoqin , Han Junming , Shi Yingzhou , Liu Yue , Cheng Yiping , Gao Ling , Zhao Jiajun , Wang Zhen , Fan Xiude
Published: December 2022

Background

It is generally believed that complement system is strongly associated with the risk of nonalcoholic fatty liver disease (NAFLD). However, complement system contains a variety of complement components, and the relationship between complement components and the risk and severity of NAFLD is inconsistent. The aim of this meta-analysis was to evaluate the association of complement components with the risk and severity of NAFLD.

Methods

We searched PubMed, Embase, Cochrane Library, Google Scholar, Scopus, and ZhiWang Chinese databases from inception to May 2022 for observational studies reporting the risk of NAFLD with complement components. Random-effects meta-analysis was used to obtain pooled estimates of the effect due to heterogeneity.

Results

We identified 18 studies with a total of 18560 included subjects. According to recent studies, levels of complement component 3 (C3) (mean difference (MD): 0.43, 95% confidence interval (CI) 0.26-0.60), complement component 4 (C4) (MD: 0.04, 95% CI 0.02-0.07), complement component 5(C5) (MD: 34.03, 95% CI 30.80-37.27), complement factor B (CFB) (MD: 0.22, 95% CI 0.13-0.31) and acylation stimulating protein (ASP) (standard mean difference (SMD): 5.17, 95% CI 2.57-7.77) in patients with NAFLD were significantly higher than those in the control group. However, no statistical significance was obtained in complement factor D (CFD) levels between NAFLD and non-NAFLD (MD=156.51, 95% CI -59.38-372.40). Moreover, the levels of C3, C5, CFB, and ASP in patients with moderate and severe NAFLD were significantly higher than those in patients with mild NAFLD. Except for C4 and CFD, the included studies did not explore the changes in the severity of NAFLD according to the concentration of C4 and CFD.

Conclusions

This meta-analysis demonstrates that an increase in complement components including C3, C5, CFB, and ASP is associated with an increased risk and severity of NAFLD, indicating that they may be good biomarkers and targets for the diagnosis and treatment of NAFLD.

Systematic review registration

PROSPERO [https://www.crd.york.ac.uk/PROSPERO/], identifier CRD42022348650.
Molecular and anatomical roadmap of stroke pathology in immunodeficient mice
Authors: Weber Rebecca Z. , Mulders Geertje , Perron Patrick , Tackenberg Christian , Rust Ruslan
Published: December 2022

Background

Stroke remains a leading cause of disability and death worldwide. It has become apparent that inflammation and immune mediators have a pre-dominant role in initial tissue damage and long-term recovery. Still, different immunosuppressed mouse models are necessary in stroke research e.g., to evaluate therapies using human cell grafts. Despite mounting evidence delineating the importance of inflammation in the stroke pathology, it is poorly described to what extent immune deficiency influences overall stroke outcome.

Methods

Here, we assessed the stroke pathology of popular genetic immunodeficient mouse models, i.e., NOD scid gamma (NSG) and recombination activating gene 2 (Rag2–/–) mice as well as pharmacologically immunosuppressed mice and compared them to immune competent, wildtype (WT) C57BL/6J mice three weeks after injury. We performed histology, gene expression, blood serum and behavioural analysis to identify the impact of immunosuppression on stroke progression.

Results

We detected changes in microglia activation/macrophage infiltration, scar-forming and vascular repair in immune-suppressed mice three weeks after injury. Transcriptomic analysis of stroked tissue revealed the strongest deviation from WT was observed in NSG mice affecting immunological and angiogenic pathways. Pharmacological immunosuppression resulted in the least variation in gene expression compared with the WT. These anatomical and genetic changes did not affect functional recovery in a time course of three weeks. To determine whether timing of immunosuppression is critical, we compared mice with acute and delayed pharmacological immunosuppression after stroke. Mice with delayed immunosuppression (7d) showed increased inflammatory and scarring responses compared to animals acutely treated with tacrolimus, thus more closely resembling WT pathology. Transplantation of human cells in the brains of immunosuppressed mice led to prolonged cell survival in all immunosuppressed mouse models, which was most consistent in NSG and Rag2–/– mice.

Conclusions

We detected distinct anatomical and molecular changes in the stroke pathology between individual immunosuppressed mouse models that should be considered when selecting an appropriate mouse model for stroke research.
Integrated single-cell transcriptome analysis of the tumor ecosystems underlying cervical cancer metastasis
Authors: Li Chunbo , Liu Danyang , Yang Shimin , Hua Keqin
Published: December 2022

Cervical cancer (CC) is one of the most frequent female malignancies worldwide. However, the molecular mechanism of lymph node metastasis in CC remains unclear. In this study, we investigated the transcriptome profile of 51,507 single cells from primary tumors, positive lymph nodes (P-LN), and negative lymph nodes (N-LN) using single-cell sequencing. Validation experiments were performed using bulk transcriptomic datasets and immunohistochemical assays. Our results indicated that epithelial cells in metastatic LN were associated with cell- cycle-related signaling pathways, such as E2F targets, and mitotic spindle, and immune response-related signaling pathways, such as allograft rejection, IL2_STAT5_signaling, and inflammatory response. However, epithelial cells in primary tumors exhibited high enrichment of epithelial-mesenchymal translation (EMT), oxidative phosphorylation, and interferon alpha response. Our analysis then indicated that metastasis LN exhibited an early activated tumor microenvironment (TME) characterized by the decrease of naive T cells and an increase of cytotoxicity CD8 T cells, NK cells, FOXP3+ Treg cells compared with normal LN. By comparing the differently expressed gene of macrophages between tumor and metastatic LN, we discovered that C1QA+ MRC1low macrophages were enriched in a tumor, whereas C1QA+ MRC1high macrophages were enriched in metastatic LN. Finally, we demonstrated that cancer-associated fibroblasts (CAFs) in P-LN were associated with immune regulation, while CAFs in tumor underwent EMT. Our findings offered novel insights into the mechanisms of research, diagnosis, and therapy of CC metastasis.
Pam2CSK4-adjuvanted SARS-CoV-2 RBD nanoparticle vaccine induces robust humoral and cellular immune responses
Authors: Qiao Yidan , Zhan Yikang , Zhang Yongli , Deng Jieyi , Chen Achun , Liu Bingfeng , Zhang Yiwen , Pan Ting , Zhang Wangjian , Zhang Hui , He Xin
Published: December 2022

As the global COVID-19 pandemic continues and new SARS-CoV-2 variants of concern emerge, vaccines remain an important tool for preventing the pandemic. The inactivated or subunit vaccines themselves generally exhibit low immunogenicity, which needs adjuvants to improve the immune response. We previously developed a receptor binding domain (RBD)-targeted and self-assembled nanoparticle to elicit a potent immune response in both mice and rhesus macaques. Herein, we further improved the RBD production in the eukaryote system by in situ Crispr/Cas9-engineered CHO cells. By comparing the immune effects of various Toll-like receptor-targeted adjuvants to enhance nanoparticle vaccine immunization, we found that Pam2CSK4, a TLR2/6 agonist, could mostly increase the titers of antigen-specific neutralizing antibodies and durability in humoral immunity. Remarkably, together with Pam2CSK4, the RBD-based nanoparticle vaccine induced a significant Th1-biased immune response and enhanced the differentiation of both memory T cells and follicular helper T cells. We further found that Pam2CSK4 upregulated migration genes and many genes involved in the activation and proliferation of leukocytes. Our data indicate that Pam2CSK4 targeting TLR2, which has been shown to be effective in tuberculosis vaccines, is the optimal adjuvant for the SARS-CoV-2 nanoparticle vaccine, paving the way for an immediate clinical trial.
Diagnostic accuracy of loop-mediated isothermal amplification for pulmonary tuberculosis in China
Authors: Lin Jing-Jing , Xi Xiu-Hong , Xia Lu , Tan Yao-Ju , Chen Yu , Di Hong-Qin , Chen Zhen-Hua , Yu Ting , Wei Jian-Hao , Fang Peng , Lin Xiao-Ma , Su Bi-Yi , Yan Ming-Zhe , Yu Yong-Min , Okada Kosuke , Noguchi Norihisa , Annaka Toshimitsu , Liu Xu-Hui , Lu Shui-Hua
Published: December 2022

Objectives

To evaluate the diagnostic accuracy of Loop-Mediated Isothermal Amplification Platform (LAMP) in detecting pulmonary tuberculosis (PTB).

Methods

This multicenter prospective study was conducted at six sites in China from June, 2018 to December, 2019. Patients with suspected PTB were consecutively recruited and respiratory samples were collected from all patients. LAMP, Xpert MTB/RIF assay (Xpert), fluorescence smear microscopy, and BACTEC MGIT 960 liquid culture (Mtb culture) were performed for each sample. Diagnostic accuracy indices were calculated against Mtb culture results.

Results

A total of 845 participants were enrolled, but only 799 were included in the analysis. The sensitivities of LAMP, Xpert, and smear microscopy were 78.6% (239/304), 82.2% (250/304), and 63.8% (194/304), respectively, and their specificities were 88.7% (439/495), 86.1% (426/495), and 94.9% (470/495), respectively. The LAMP assay showed substantial agreement with other tests (kappa 0.64–0.79).

Conclusion

The LAMP assay performs as well as Xpert MTB/RIF assay and Mtb culture in tertiary-care hospitals. It can be used as an alternative test for detecting PTB with the advantages of being fast, inexpensive, and easy to operate.
Circadian clock genes Bmal1 and Period may regulate nocturnal spawning by controlling sex hormone secretion in razor clam Sinonovacula constricta
Authors: Liu Yanzi , He Qinyuan , Yao Hanhan , Lin Zhihua , Dong Yinghui
Published: December 2022

The circadian clock is an endogenous regulation mechanism that coordinates biological processes with daily changes, which are regulated by circadian clock genes. Bmal1 and Period are key circadian clock genes and their roles in reproductive development have been widely studied. The spawning time of Sinonovacula constricta is limited to the night even under external artificial stimulation, and it might be regulated by the internal circadian clock. In this study, the heart rate of S. constricta was higher between 20:00-04:00 at night and lower between 12:00-16:00 during the day, and the sex hormone contents were the highest at 00:00 and the lowest at 18:00 (P < 0.01). Therefore, these obvious changes in the circadian rhythm indicate that S. constricta is a nocturnal animal. The open reading frame (ORF) of Bmal1 comprises 1944 bp encoding 647 aa, while the ORF of Period comprises 3111 bp encoding 1036 aa. Bmal1 and Period were both expressed in four tissues, but they had opposite rhythmic expression patterns. Bmal1 expression was higher at 00:00-06:00 and lower at 12:00-18:00, and Period expression was opposite, thereby suggesting that Bmal1 and Period are involved in positive and negative pathways regulated by the circadian clock, respectively. Strong protein fluorescence signals of Bmal1 and Period proteins were observed in mature oocytes, spermatids, hepatocytes, and epithelial cells of siphons. After siRNA interference, the expression of both Bmal1 and Period significantly decreased (P < 0.01), and the sex hormone contents decreased significantly from 3 to 7 days in the siRNA treatment groups (P < 0.01). Therefore Bmal1 and Period may regulate nocturnal spawning by controlling sex hormone secretion. These findings provide a theoretical basis for understanding the molecular mechanism related to spawning, and may facilitate the artificial propagation of mollusks.
Recent advances in marine ornamental breeding and seed production at Vizhinjam Regional Centre of CMFRI India
Authors: Anil M. K. , Rohini Krishna M. V. , Gomathi P. , Surya S. , Gop Ambarish P. , Santhosh B. , Siju R. , Anand V. , Krishnapriya P. M. , Shalini O. , Raju B. , Madhu K. , Gopalakrishnan A.
Published: December 2022

The marine ornamental fish trading industry is an ever-expanding one, as indicated by its bolstering statistics, which amount to about US$ 300 million. Although the trade is booming, the natural habitats that foster these fishes, such as coral reefs, are steadily declining. One of the reasons for this is the overdependency of the industry on wild-caught fishes. To surpass this, the Central Marine Fisheries Research Institute (CMFRI) has developed hatchery technology for breeding marine ornamental fishes such as seahorses, clownfishes, damsels, and serranids. It began with the breeding of Hippocampus kuda. This progressed to breeding clownfishes such as Amphiprion chrysogaster, A. ocellaris, A. nigripes, A. peridarion, and A. ephippium and Premnas biaculeatus. Damsel fishes that were bred successfully include Chrysiptera cyanea, C. hemicyanea Neopomacentrus cyanomos, N. nemurus, and Dascyllus carneus. The recirculating aquaculture system (RAS) designed in the Vizhinjam Regional Centre of CMFRI is being used for broodstock development of serranids, tangs, squirrel fishes, and soldier fishes. A standard method was developed for captive breeding and hatchery rearing of anthias Pseudanthias marcia and P. squamipinnis in an advanced indigenous RAS system. The present article provides a bird’s eye view of the important research work done in India concerning marine ornamental fish breeding and reviews important breeding work carried out at Vizhinjam Regional Centre of CMFRI.
Competing with each other: Fish isotopic niche in two resource availability contexts
Authors: Pelage Latifa , Lucena-Frédou Flávia , Eduardo Leandro Nole , Le Loc’h François , Bertrand Arnaud , Lira Alex Souza , Frédou Thierry
Published: December 2022

Introduction

Competition embodies species struggle for space and food and is, therefore, a critical evolutionary mechanism influencing species spatiotemporal patterns and persistence. One of the main drivers of competition is resource availability. In marine ecosystems, resource availability is determined, among other things, by habitat structural complexity, as it increases biodiversity and species abundance. In this context, our study aims at understanding how the differences in substrate complexity affect potential trophic competition between demersal fishes in Northeast Brazil.

Methods

We selected two zones contrasted in terms of substrates, one dominated by sand (zone A) and the other by complex substrates such as reefs and calcareous algae (zone B). We used Stable Isotope Analysis (SIA) to quantify intraspecific and interspecific interactions of demersal fishes in both zones. We compared the competitive interactions between zones using social network analysis (SNA), a suitable method to quantitatively study a set of interactions.

Results

In the sand-dominated zone, demersal fish showed greater interspecific competition and occupied a larger isotopic niche suggesting that a resource-limited context led to diet diversification in the community. Some species expanded their niche through diet plasticity, while others showed higher intraspecific competition than in Zone B to cope with the greater interspecific competition.

Discussion

Combining SNA and SIA provided a new method to investigate competition. This study potentially gives a perspective on the future ecological response of the demersal fishes at the community and species level. With habitat degradation and climate change, the complex substrates in zone B will probably disappear gradually, transforming this zone into an ecosystem akin to zone A. This would be detrimental to species more vulnerable to interspecific competition, particularly those targeted by fisheries.
Cutaneous vasculitis: Lessons from COVID-19 and COVID-19 vaccination
Authors: Corrà Alberto , Verdelli Alice , Mariotti Elena Biancamaria , Ruffo di Calabria Valentina , Quintarelli Lavinia , Aimo Cristina , Sunderkötter Cord H. , Caproni Marzia
Published: December 2022

Cutaneous vasculitis (CV) is an inflammatory skin-limited vascular disease affecting the dermal and/or hypodermal vessel wall. From the pathogenetic point of view, idiopathic forms are described as well as the induction from various triggers, such as drugs, infections, and vaccines. Following SARS-CoV-2 pandemic outbreak, cases of CV induced by both COVID-19 and COVID-19 vaccinations have been reported in literature. The aim of our work was to collect multiple cases available in the literature and analyze the frequency of the different forms of induced vasculitis, as well as their histological and immunopathological features. Although rare, CV induced by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and vaccines may provide interesting insights into the pathogenesis of these inflammatory processes that may in the future be useful to understand the mechanisms underlying cutaneous and systemic vasculitis.
An assessment of burden of hospital-acquired pneumonia among abdominal surgical patients in tertiary university hospital in Serbia: A matched nested case-control study
Authors: Taušan Ðorde , Rančić Nemanja , Kostić Zoran , Ljubenović Nenad , Rakonjac Bojan , Šuljagić Vesna
Published: December 2022

Background

In the population of abdominal surgical patients hospital-acquired pneumonia (HAP) significantly increases morbidity and mortality.

Patients and methods

Through regular hospital surveillance of patients who received abdominal operations, we identified postoperative HAP from 2007 to 2019. In an initial nested case-control study, every surgical patient with HAP was compared with three control patients without HAP. Control patients were matched to the cases by age, gender, the American Society of Anesthesiologists score, and type of surgical operation. Also, the patients with HAP, who died were compared with those who survived.

Results

Multivariate logistic regression analysis (MLRA) revealed that other postoperative infections, length of intensive care unit stay, use of H2RA, use of PPI/ H2RA, multiple transfusion, and use of vancomycin in surgical prophylaxis were independent RFs for occurrence of HAP. Also, MLRA identified that age, lenght of hospital stay, use of mechanical ventilation and ceftriaxone in HAP therapy were indepedenttly associated with poor outcome of HAP. All Acinetobacter baumannii isolates were resistant to aminoglycoside antimicrobial agents and showed carbapenem resistance. The most frequently used antibiotics in patients with HAP and without HAP were vancomycin and metronidazole, respectively.

Conclusion

Our study provided an insight into the burden of HAP in abdominal surgical patients, and highlighted several priority areas and targets for quality improvement.
A pilot study on the efficacy of topical lotion containing anti-acne postbiotic in subjects with mild -to -moderate acne
Authors: Cui Hongchang , Guo Chaoqun , Wang Qian , Feng Congrui , Duan Zhi
Published: December 2022

Introduction

Acne can compromise facial esthetics and become a mental burden, especially when it occurs in puberty. Skincare cosmetics with anti-acne efficiency is more convenient than other treatment modalities, such as dietary supplements, in certain circumstances. The purpose of this study was to investigate the efficacy of an anti-acne lotion in alleviating acne.

Methods

In our study, an anti-acne lotion containing ferment lysate produced by Lactiplantibacillus plantarum VHProbi® E15 were applied to subjects with mild -to -moderate acne over 4 weeks. The efficacy was evaluated based on instrumental measurements using Visia®-CR and CK-MPA® system.

Results and discussion

The anti-acne lotion exhibited favorable safety, meeting the stringent criteria for the detection of microbes, heavy metals, toxicity, and irritation. After 2 weeks of treatment, a statistically significant improvement in acne lesions was observed compared to baseline (P < 0.01), and this continued to the end of the study. After 4 weeks of treatment, the transepidermal water loss (P < 0.05) and sebum production (P < 0.05) were significantly decreased in subjects compared to baseline. In addition, the pore/area of interest (AOI) and stratum corneum hydration displayed slightly positive changes throughout treatment. Thus, we conclude that applying topical anti-acne lotion may be safe and confer effective benefits in people with mild -to -moderate acne and represents a promising therapeutic option for acne.
Modulation of adipose tissue metabolism by microbial-derived metabolites
Authors: Liu Wenyun , Yang Ge , Liu Pinyi , Jiang Xin , Xin Ying
Published: December 2022

Obesity and its complications, including type 2 diabetes, cardiovascular disease, and certain cancers, have posed a significant burden on health and healthcare systems over the years due to their high prevalence and incidence. Gut microbial derivatives are necessary for the regulation of energy metabolism and host immunity, as well as for maintaining homeostasis of the intestinal environment. Gut flora metabolites may be a link between gut microbes and diseases, such as obesity, and help understand why alterations in the microbiota can influence the pathophysiology of human disease. This is supported by emerging evidence that microbial-derived metabolites, such as short-chain fatty acids, bile acids, tryptophan, trimethylamine-N-oxide, and lipopolysaccharides, can be beneficial or detrimental to the host by affecting organs outside the gut, including adipose tissue. Adipose tissue is the largest lipid storage organ in the body and an essential endocrine organ that plays an indispensable role in the regulation of lipid storage, metabolism, and energy balance. Adipose tissue metabolism includes adipocyte metabolism (lipogenesis and lipolysis), thermogenesis, and adipose tissue metabolic maladaptation. Adipose tissue dysfunction causes the development of metabolic diseases, such as obesity. Here, we review the current understanding of how these microbial metabolites are produced and discuss both established mechanisms and the most recent effects of microbial products on host adipose tissue metabolism. We aimed to identify novel therapeutic targets or strategies for the prevention and treatment of obesity and its complications.
Effect of antiplatelet agents on Escherichia coli sepsis mechanisms: A review
Authors: Mariotti Antoine , Ezzraimi Amina Ezzeroug , Camoin-Jau Laurence
Published: December 2022

Despite ever-increasing improvements in the prognosis of sepsis, this condition remains a frequent cause of hospitalization and mortality in Western countries. Sepsis exposes the patient to multiple complications, including thrombotic complications, due to the ability of circulating bacteria to activate platelets. One of the bacteria most frequently implicated in sepsis, Escherichia coli, a Gram-negative bacillus, has been described as being capable of inducing platelet activation during sepsis. However, to date, the mechanisms involved in this activation have not been clearly established, due to their multiple characteristics. Many signaling pathways are thought to be involved. At the same time, reports on the use of antiplatelet agents in sepsis to reduce platelet activation have been published, with variable results. To date, their use in sepsis remains controversial. The aim of this review is to summarize the currently available knowledge on the mechanisms of platelet activation secondary to Escherichia coli sepsis, as well as to provide an update on the effects of antiplatelet agents in these pathological circumstances.
Pectin supplement alleviates gut injury potentially through improving gut microbiota community in piglets
Authors: Dang Guoqi , Wang Wenxing , Zhong Ruqing , Wu Weida , Chen Liang , Zhang Hongfu
Published: December 2022

As pectin is widely used as a food and feed additive due to its tremendous prebiotic potentials for gut health. Yet, the underlying mechanisms associated with its protective effect remain unclear. Twenty-four piglets (Yorkshire × Landrace, 6.77 ± 0.92 kg) were randomly divided into three groups with eight replicates per treatment: (1) Control group (CON), (2) Lipopolysaccharide-challenged group (LPS), (3) Pectin-LPS group (PECL). Piglets were administrated with LPS or saline on d14 and 21 of the experiment. Piglets in each group were fed with corn-soybean meal diets containing 5% citrus pectin or 5% microcrystalline cellulose. Our result showed that pectin alleviated the morphological damage features by restoring the goblet numbers which the pig induced by LPS in the cecum. Besides, compared with the LPS group, pectin supplementation elevated the mRNA expression of tight junction protein [Claudin-1, Claudin-4, and zonula occludens-1 (ZO-1)], mucin (Muc-2), and anti-inflammatory cytokines [interleukin 10 (IL-10), and IL-22]. Whereas pectin downregulated the expression of proinflammatory cytokines (IL-1β, IL-6, IL-18), tumor necrosis factor-&alpha (TNF-α), and NF-κB. What is more, pectin supplementation also significantly increased the abundance of beneficial bacteria (Lactobacillus, Clostridium_sensu_stricto_1, Blautia, and Subdoligranulum), and significantly reduced the abundance of harmful bacteria, such as Streptococcus. Additionally, pectin restored the amount of short-chain fatty acids (SCFAs) after being decreased by LPS (mainly Acetic acid, Propionic acid, and Butyric acid) to alleviate gut injury and improve gut immunity via activating relative receptors (GPR43, GPR109, AhR). Mantel test and correlation analysis also revealed associations between intestinal microbiota and intestinal morphology, and intestinal inflammation in piglets. Taken together, dietary pectin supplementation enhances the gut barrier and improves immunity to ameliorate LPS-induced injury by optimizing gut microbiota and their metabolites.
Nucleic acid testing of SARS-CoV-2: A review of current methods, challenges, and prospects
Authors: Zhu Yuanshou , Zhang Meng , Jie Zhijun , Tao Shengce
Published: December 2022

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has brought a huge threat to public health and the global economy. Rapid identification and isolation of SARS-CoV-2-infected individuals are regarded as one of the most effective measures to control the pandemic. Because of its high sensitivity and specificity, nucleic acid testing has become the major method of SARS-CoV-2 detection. A deep understanding of different diagnosis methods for COVID-19 could help researchers make an optimal choice in detecting COVID-19 at different symptom stages. In this review, we summarize and evaluate the latest developments in current nucleic acid detection methods for SARS-CoV-2. In particular, we discuss biosensors and CRISPR-based diagnostic systems and their characteristics and challenges. Furthermore, the emerging COVID-19 variants and their impact on SARS-CoV-2 diagnosis are systematically introduced and discussed. Considering the disease dynamics, we also recommend optional diagnostic tests for different symptom stages. From sample preparation to results readout, we conclude by pointing out the pain points and future directions of COVID-19 detection.
fNIRS-based brain functional response to robot-assisted training for upper-limb in stroke patients with hemiplegia
Authors: Huo Congcong , Sun Zhifang , Xu Gongcheng , Li Xinglou , Xie Hui , Song Ying , Li Zengyong , Wang Yonghui
Published: December 2022

Background

Robot-assisted therapy (RAT) has received considerable attention in stroke motor rehabilitation. Characteristics of brain functional response associated with RAT would provide a theoretical basis for choosing the appropriate protocol for a patient. However, the cortical response induced by RAT remains to be fully elucidated due to the lack of dynamic brain functional assessment tools.

Objective

To guide the implementation of clinical therapy, this study focused on the brain functional responses induced by RAT in patients with different degrees of motor impairment.

Methods

A total of 32 stroke patients were classified into a low score group (severe impairment, n = 16) and a high score group (moderate impairment, n = 16) according to the motor function of the upper limb and then underwent RAT training in assistive mode with simultaneous cerebral haemodynamic measurement by functional near-infrared spectroscopy (fNIRS). Functional connectivity (FC) and the hemisphere autonomy index (HAI) were calculated based on the wavelet phase coherence among fNIRS signals covering bilateral prefrontal, motor and occipital areas.

Results

Specific cortical network response related to RAT was observed in patients with unilateral moderate-to-severe motor deficits in the subacute stage. Compared with patients with moderate dysfunction, patients with severe impairment showed a wide range of significant FC responses in the bilateral hemispheres induced by RAT with the assistive mode, especially task-related involvement of ipsilesional supplementary motor areas.

Conclusion

Under assisted mode, RAT-related extensive cortical response in patients with severe dysfunction might contribute to brain functional organization during motor performance, which is considered the basic neural substrate of motor-related processes. In contrast, the limited cortical response related to RAT in patients with moderate dysfunction may indicate that the training intensity needs to be adjusted in time according to the brain functional state. fNIRS-based assessment of brain functional response assumes great importance for the customization of an appropriate protocol training in the clinical practice.
Application of nanomaterials against SARS-CoV-2: An emphasis on their usefulness against emerging variants of concern
Authors: Iqbal Reema , Khan Sadia , Ali Haroon Muhammad , Khan Maham , Wahab Shahid , Khan Tariq
Published: December 2022

Researchers are now looking to nanomaterials to fight serious infectious diseases that cause outbreaks and even pandemics. SARS-CoV-2 brought chaos to almost every walk of life in the past 2 years and has challenged every available treatment method. Although vaccines were developed in no time against it, the most pressing issue was the emergence of variants of concern arising because of the rapidly evolving viral strains. The higher pathogenicity and, in turn, the higher mortality rate of infections caused by these variants renders the existing vaccines less effective and the effort to produce further vaccines a costly endeavor. While several techniques, such as immunotherapy and repurposed pharmaceutical research, are being studied to minimize viral infection, the fundamentals of nanotechnology must also be considered to enhance the anti-SARS-CoV-2 efforts. For instance, silver nanoparticles (AgNPs) have been applied against SARS-CoV-2 effectively. Similarly, nanomaterials have been tested in masks, gloves, and disinfectants to aid in controlling SARS-CoV-2. Nanotechnology has also contributed to diagnoses such as rapid and accurate detection and treatment such as the delivery of mRNA vaccines and other antiviral agents into the body. The development of polymeric nanoparticles has been dubbed a strategy of choice over traditional drugs because of their tunable release kinetics, specificity, and multimodal drug composition. Our article explores the potential of nanomaterials in managing the variants of concern. This will be achieved by highlighting the inherent ability of nanomaterials to act against the virus on fronts such as inhibition of SARS-CoV-2 entry, inhibition of RNA replication in SARS-CoV-2, and finally, inhibition of their release. In this review, a detailed discussion on the potential of nanomaterials in these areas will be tallied with their potential against the current and emerging future variants of concern.
Role of locomotor efference copy in vertebrate gaze stabilization
Authors: Straka Hans , Lambert François M. , Simmers John
Published: December 2022

Vertebrate locomotion presents a major challenge for maintaining visual acuity due to head movements resulting from the intimate biomechanical coupling with the propulsive musculoskeletal system. Retinal image stabilization has been traditionally ascribed to the transformation of motion-related sensory feedback into counteracting ocular motor commands. However, extensive exploration of spontaneously active semi-intact and isolated brain/spinal cord preparations of the amphibian Xenopus laevis, have revealed that efference copies (ECs) of the spinal motor program that generates axial- or limb-based propulsion directly drive compensatory eye movements. During fictive locomotion in larvae, ascending ECs from rostral spinal central pattern generating (CPG) circuitry are relayed through a defined ascending pathway to the mid- and hindbrain ocular motor nuclei to produce conjugate eye rotations during tail-based undulatory swimming in the intact animal. In post-metamorphic adult frogs, this spinal rhythmic command switches to a bilaterally-synchronous burst pattern that is appropriate for generating convergent eye movements required for maintaining image stability during limb kick-based rectilinear forward propulsion. The transition between these two fundamentally different coupling patterns is underpinned by the emergence of altered trajectories in spino-ocular motor coupling pathways that occur gradually during metamorphosis, providing a goal-specific, morpho-functional plasticity that ensures retinal image stability irrespective of locomotor mode. Although the functional impact of predictive ECs produced by the locomotory CPG matches the spatio-temporal specificity of reactive sensory-motor responses, rather than contributing additively to image stabilization, horizontal vestibulo-ocular reflexes (VORs) are selectively suppressed during intense locomotor CPG activity. This is achieved at least in part by an EC-mediated attenuation of mechano-electrical encoding at the vestibular sensory periphery. Thus, locomotor ECs and their potential suppressive impact on vestibular sensory-motor processing, both of which have now been reported in other vertebrates including humans, appear to play an important role in the maintenance of stable vision during active body displacements.
Case Report: A case of PLA2G6 gene-related early-onset Parkinson's disease and review of literature
Authors: Gao Lili , Shi Chunlan , Lin Qing , Wu Yujing , Hu Liqi , Wang Mingwang , Guan Jianhua , Lin Sheng , Liao Yuansheng , Wu Chenghan
Published: December 2022

Background

Early onset Parkinson's disease (EOPD) is a neurodegenerative disease associated with the action ofto genetic factors. A mutated phospholipase A2 type VI gene (PLA2G6) is considered to be one of pathogenic genes involved in EOPD development. Although EOPD caused by a mutated PLA2G6 has been recorded in major databases, not all mutant genotypes have been reported. Here, we report a case of PLA2G6-related EOPD caused by a novel compound heterozygous mutation.

Case presentation

The case was an of 26-year-old young male with a 2-year course of disease. The onset of the disease was insidious and developed gradually. The patient presented with unsteady walking, bradykinesia, unresponsiveness, and decreased facial expression. Auxiliary examination showed a compound heterozygous mutation of the PLA2G6gene with c.991G > T and c.1427 + 1G > A. Mild atrophy of the cerebrum and cerebellum was detected on brain MRI. The patient was diagnosed with EOPD. We administered treatment with Madopar, which was effective. After a two-year disease course, we observed progression to stage 5 according to the Hoehn-Yahr Scale (without medicine in the off-stage). An MDS-UPDRS III score of 62 was obtained, with characteristics of severe disease and rapid progress. The diagnosis was an EOPD phenotype caused by a combination of mutations at the c.991G > T and c.1427 + 1G > A sites of the PLA2G6gene.

Conclusion

After active treatment, the disease was set under control, with no significant progression during the three-month follow-up period. Dyskinesia did not recur after reducing the Madopar dose. The freezing sign was slightly decreased and the wearing-off was delayed to 2 h.
Anosmia in COVID-19 could be associated with long-term deficits in the consolidation of procedural and verbal declarative memories
Authors: Llana Tania , Mendez Marta , Zorzo Candela , Fidalgo Camino , Juan M.-Carmen , Mendez-Lopez Magdalena
Published: December 2022

Background and purpose

Long-COVID describes the long-term effects of the coronavirus disease 2019 (COVID-19). In long-COVID patients, neuropsychological alterations are frequently reported symptoms. Research points to medial temporal lobe dysfunction and its association with anosmia in long-COVID patients. This study aims to investigate the acquisition and consolidation of declarative and procedural memory in long-COVID patients and to explore whether anosmia is related to these dissociated memory functions.

Methods

Forty-two long-COVID participants and 30 controls (C) were recruited. The sample of long-COVID patients was divided into two groups based on the presence or absence of anosmia, group A and group NA, respectively. Objective performance in verbal declarative memory (Paired-Associate Learning, PAL), procedural memory (Mirror Tracing Test, MTT), general cognitive function (Montreal Cognitive Assessment scale), psychomotor speed, and incidental learning (Digit Symbol Substitution Test) were assessed and compared among the A, NA, and C groups. Long-term retention of PAL and MTT were assessed 24 h after acquisition.

Results

Lower scores in general cognition, psychomotor speed, and sustained attention were found in A and NA compared with C. However, incidental learning, both cue-guided and free-recalled, was diminished in group A compared with C, with no differences with group NA. General cognition and incidental learning were related to declarative memory function exclusively in long-COVID groups. Long-COVID groups presented lower long-term retention of verbal declarative memory than controls in recall tests but no differences in recognition tests. No group differences were found in the acquisition of procedural memory. However, long-term retention of this memory was worse in group A as compared to the NA and C groups, respectively, when errors and time of execution were considered.

Conclusion

Findings support that consolidation of both procedural and declarative memories is more affected than the acquisition of these memories in long-COVID patients, who are also more vulnerable to deficits in delayed recall than in recognition of declarative memories. Deficits in the consolidation of procedural memory and immediate recall of declarative information are especially relevant in long-COVID participants with anosmia. This indicates that anosmia in COVID-19 could be associated with a long-term dysfunction of the limbic system.
Isolation of living dopaminergic neurons labeled with a fluorescent ligand of the dopamine transporter from mouse substantia nigra as a new tool for basic and applied research
Authors: Troshev Dmitry , Blokhin Victor , Ukrainskaya Valeria , Kolacheva Anna , Ugrumov Michael
Published: December 2022

Dopaminergic neurons (DNs) of the nigrostriatal system control the motor function, and their degeneration leads to the development of Parkinson’s disease (PD). A stumbling block in the study of DNs in the whole substantia nigra (SN) is the lack of tools to analyze the expression of most of the genes involved in neurotransmission, neurodegeneration, and neuroplasticity, since they are also expressed in other cells of the SN. Therefore, this study aimed to develop a fluorescence-activated cell sorting method for isolating living DNs from the SN of wild-type mice using two fluorescent dyes, DRAQ5 (nuclear stain) and a dopamine uptake inhibitor GBR 12909 coupled to a fluorophore (DN stain). We have developed a method for selecting a population of DNs from the SN of mice, as evidenced by: (i) immunopositivity of 95% of the sorted cells for tyrosine hydroxylase, the first enzyme of dopamine synthesis; (ii) the sorted cells expressing the genes for specific proteins of the dopaminergic phenotype, tyrosine hydroxylase, the dopamine transporter, and vesicular monoamine transporter 2 and non-specific proteins, such as aromatic L-amino acid decarboxylase, non-specific enzyme of dopamine synthesis. We then compared the changes in gene expression found in the sorted DNs and in the SN homogenate in a PD model we developed, reproduced in mice by treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Using quantitative PCR, we obtained evidence of the same changes in the expression of specific genes in the sorted DNs of SN and in the SN homogenate of a MPTP mouse model of PD, compared with the control. The undoubted advantage of our approach is the possibility of obtaining a large amount of readily available and relatively cheap primary material (SN) from wild-type mice, which can be used to solve both research and applied problems. In addition, this method can be easily adapted to the isolation of DNs from the SN in other animal species, including non-human primates.
Cation interdiffusion in uranium–plutonium mixed oxide fuels: Where are we now?
Authors: Vauchy Romain , Hirooka Shun , Matsumoto Taku , Kato Masato
Published: December 2022

The diffusion phenomena in uranium–plutonium mixed oxides U1−yPuyO2dictate the physicochemical properties of mixed oxides (MOX) nuclear fuel throughout manufacturing, irradiation, and storage. More precisely, it is paramount to estimate the cation interdiffusion insofar as it dovetails with the actinide redistribution during sintering and under irradiation. This paper draws a critical review of the existing experimental data of U and Pu interdiffusion coefficients in MOX fuel.