bluuebunny/crossref_metadata_2025 huggingface dataset:
Pan-cancer analysis of super enhancer-induced PRR7-AS1 as a potential prognostic and immunological biomarker
Authors: Wang Rui , Liu Na , Li Guiqing , Liu Jing , Ma Xiaolin , Liu Xinling , Li Jiaqiu
Published: April 2023

Introduction: Systematic pan-cancer analysis of the roles and regulatory mechanisms for PRR7-AS1 is currently not available.

Methods: In the present study, a comprehensive bioinformatic approach was used to mine the underlying oncogenic effects of PRR7-AS1, including expression status, prognostic value and immune characteristics.

Results: We discovered that PRR7-AS1 expression was remarkably upregulated in most cancer types and exhibited a negative correlation with the prognosis. Furthermore, PRR7-AS1 expression was inversely connected with the majority of tumor-infiltrating immune cells, immune scores and immune checkpoint gene expression in pancancer. There was also a significant correlation between PRR7-AS1 expression status and tumor mutational burden, microsatellite instability, and neoantigens in certain tumors. PRR7-AS1 had the best predictive power for immune checkpoint blockade efficacy compared to other well-recognized biomarkers. PRR7-AS1 overexpression could affect cytotoxic T cells-mediated antitumor responses. Functional enrichment analysis revealed that PRR7-AS1 might be involved in the metabolic pathways. Super enhancer activity might have participated in the regulation of PRR7-AS1 expression. And we constructed the competitive endogenous RNA networks for PRR7-AS1.

Discussion: In general, PRR7-AS1 had the potential to be a diagnostic, prognostic and immune biomarker for pan cancer. PRR7-AS1 was correlated with an immunosuppressive microenvironment and was a new potential target for immunotherapy. Epigenetic factors were the driving forces for PRR7-AS1 overexpression in tumors.
Thyroid function and associated mood changes after COVID-19 vaccines in patients with Hashimoto thyroiditis
Authors: Ma Yifei , Zeng Jiling , Jiang Yongluo , Xu Yi-Wei , Wang Youlong , Zhong Guanqing , Liu Nianqi , Wang Yanqi , Zhang Zhiying , Li Yiming , Chen Shuqin , Wei Xiao-Long , Zhu Pengfei , Jian Guangmin , Lyu Xiajie , Niu Yu Si , Li Mingwei , Liang Shuang , Fu Guangzhen , He Shaohui , Liu CanTong , Zhang Ao , Wang Xinjia
Published: April 2023

Context

Severe acute respiratory syndrome-coronavirus 2 (COVID-19) vaccines may incur changes in thyroid functions followed by mood changes, and patients with Hashimoto thyroiditis (HT) were suggested to bear a higher risk.

Objectives

We primarily aim to find whether COVID-19 vaccination could induce potential subsequent thyroid function and mood changes. The secondary aim was to find inflammatory biomarkers associated with risk.

Methods

The retrospective, multi-center study recruited patients with HT receiving COVID-19–inactivated vaccines. C-reactive proteins (CRPs), thyroid-stimulating hormones (TSHs), and mood changes were studied before and after vaccination during a follow-up of a 6-month period. Independent association was investigated between incidence of mood state, thyroid functions, and inflammatory markers. Propensity score–matched comparisons between the vaccine and control groups were carried out to investigate the difference.

Results

Final analysis included 2,765 patients with HT in the vaccine group and 1,288 patients in the control group. In the matched analysis, TSH increase and mood change incidence were both significantly higher in the vaccine group (11.9% versus 6.1% for TSH increase and 12.7% versus 8.4% for mood change incidence). An increase in CRP was associated with mood change (p< 0.01 by the Kaplan–Meier method) and severity (r = 0.75) after vaccination. Baseline CRP, TSH, and antibodies of thyroid peroxidase (anti-TPO) were found to predict incidence of mood changes.

Conclusion

COVID-19 vaccination seemed to induce increased levels and incidence of TSH surge followed by mood changes in patients with HT. Higher levels of pre-vaccine serum TSH, CRP, and anti-TPO values were associated with higher incidence in the early post-vaccine phase.
Identification of biomarkers co-associated with M1 macrophages, ferroptosis and cuproptosis in alcoholic hepatitis by bioinformatics and experimental verification
Authors: Hou Shasha , Wang Dan , Yuan Xiaxia , Yuan Xiaohuan , Yuan Qi
Published: April 2023

Backgrounds

Alcoholic hepatitis (AH) is a major health problem worldwide. There is increasing evidence that immune cells, iron metabolism and copper metabolism play important roles in the development of AH. We aimed to explore biomarkers that are co-associated with M1 macrophages, ferroptosis and cuproptosis in AH patients.

Methods

GSE28619 and GSE103580 datasets were integrated, CIBERSORT algorithm was used to analyze the infiltration of 22 types of immune cells and GSVA algorithm was used to calculate ferroptosis and cuproptosis scores. Using the “WGCNA” R package, we established a gene co-expression network and analyzed the correlation between M1 macrophages, ferroptosis and cuproptosis scores and module characteristic genes. Subsequently, candidate genes were screened by WGCNA and differential expression gene analysis. The LASSO-SVM analysis was used to identify biomarkers co-associated with M1 macrophages, ferroptosis and cuproptosis. Finally, we validated these potential biomarkers using GEO datasets (GSE155907, GSE142530 and GSE97234) and a mouse model of AH.

Results

The infiltration level of M1 macrophages was significantly increased in AH patients. Ferroptosis and cuproptosis scores were also increased in AH patients. In addition, M1 macrophages, ferroptosis and cuproptosis were positively correlated with each other. Combining bioinformatics analysis with a mouse model of AH, we found that ALDOA, COL3A1, LUM, THBS2 and TIMP1 may be potential biomarkers co-associated with M1 macrophages, ferroptosis and cuproptosis in AH patients.

Conclusion

We identified 5 potential biomarkers that are promising new targets for the treatment and diagnosis of AH patients.
Role of CD147 in the development and diagnosis of hepatocellular carcinoma
Authors: Huang Defa , Rao Dingyu , Jin Qing , Lai Mi , Zhang Jiali , Lai Zhonghong , Shen Haibin , Zhong Tianyu
Published: April 2023

Hepatocellular carcinoma (HCC) is the most common primary liver cancer, and the third leading cause of cancer-related deaths worldwide. HCC is characterized by insidious onset, and most patients are diagnosed at an advanced stage with a poor prognosis. Identification of biomarkers for HCC onset and progression is imperative to development of effective diagnostic and therapeutic strategies. CD147 is a glycoprotein that is involved in tumor cell invasion, metastasis and angiogenesis through multiple mechanisms. In this review, we describe the molecular structure of CD147 and its role in regulating HCC invasion, metastasis and angiogenesis. We highlight its potential as a diagnostic and therapeutic target for HCC.
H3N2 influenza hemagglutination inhibition method qualification with data driven statistical methods for human clinical trials
Authors: Sawant Sheetal , Gurley Sarah Anne , Overman R. Glenn , Sharak Angelina , Mudrak Sarah V. , Oguin Thomas , Sempowski Gregory D. , Sarzotti-Kelsoe Marcella , Walter Emmanuel B. , Xie Hang , Pasetti Marcela F. , Moody M. Anthony , Tomaras Georgia D.
Published: April 2023

Introduction

Hemagglutination inhibition (HAI) antibody titers to seasonal influenza strains are important surrogates for vaccine-elicited protection. However, HAI assays can be variable across labs, with low sensitivity across diverse viruses due to lack of standardization. Performing qualification of these assays on a strain specific level enables the precise and accurate quantification of HAI titers. Influenza A (H3N2) continues to be a predominant circulating subtype in most countries in Europe and North America since 1968 and is thus a focus of influenza vaccine research.

Methods

As a part of the National Institutes of Health (NIH)-funded Collaborative Influenza Vaccine Innovation Centers (CIVICs) program, we report on the identification of a robust assay design, rigorous statistical analysis, and complete qualification of an HAI assay using A/Texas/71/2017 as a representative H3N2 strain and guinea pig red blood cells and neuraminidase (NA) inhibitor oseltamivir to prevent NA-mediated agglutination.

Results

This qualified HAI assay is precise (calculated by the geometric coefficient of variation (GCV)) for intermediate precision and intra-operator variability, accurate calculated by relative error, perfectly linear (slope of -1, R-Square 1), robust (<25% GCV) and depicts high specificity and sensitivity. This HAI method was successfully qualified for another H3N2 influenza strain A/Singapore/INFIMH-16-0019/2016, meeting all pre-specified acceptance criteria.

Discussion

These results demonstrate that HAI qualification and data generation for new influenza strains can be achieved efficiently with minimal extra testing and development. We report on a qualified and adaptable influenza serology method and analysis strategy to measure quantifiable HAI titers to define correlates of vaccine mediated protection in human clinical trials.
Targeting immune checkpoints in anti-neutrophil cytoplasmic antibodies associated vasculitis: the potential therapeutic targets in the future
Authors: Pan Menglu , Zhao Huanhuan , Jin Ruimin , Leung Patrick S. C. , Shuai Zongwen
Published: April 2023

Anti-neutrophil cytoplasmic autoantibodies (ANCA) associated vasculitis (AAV) is a necrotizing vasculitis mainly involving small blood vessels. It is demonstrated that T cells are important in the pathogenesis of AAV, including regulatory T cells (Treg) and helper T cells (Th), especially Th2, Th17, and follicular Th cells (Tfh). In addition, the exhaustion of T cells predicted the favorable prognosis of AAV. The immune checkpoints (ICs) consist of a group of co-stimulatory and co-inhibitory molecules expressed on the surface of T cells, which maintains a balance between the activation and exhaustion of T cells. CD28, inducible T-cell co-stimulator (ICOS), OX40, CD40L, glucocorticoid induced tumor necrosis factor receptor (GITR), and CD137 are the common co-stimulatory molecules, while the programmed cell death 1 (PD-1), cytotoxic T lymphocyte-associated molecule 4 (CTLA-4), T cell immunoglobulin (Ig) and mucin domain-containing protein 3 (TIM-3), B and T lymphocyte attenuator (BTLA), V-domain Ig suppressor of T cell activation (VISTA), T‐cell Ig and ITIM domain (TIGIT), CD200, and lymphocyte activation gene 3 (LAG-3) belong to co-inhibitory molecules. If this balance was disrupted and the activation of T cells was increased, autoimmune diseases (AIDs) might be induced. Even in the treatment of malignant tumors, activation of T cells by immune checkpoint inhibitors (ICIs) may result in AIDs known as rheumatic immune-related adverse events (Rh-irAEs), suggesting the importance of ICs in AIDs. In this review, we summarized the features of AAV induced by immunotherapy using ICIs in patients with malignant tumors, and then reviewed the biological characteristics of different ICs. Our aim was to explore potential targets in ICs for future treatment of AAV.
Metagenomic insights into the composition and function of the gut microbiota of mice infected with Toxoplasma gondii
Authors: Meng Jin-Xin , Wei Xin-Yu , Guo Huanping , Chen Yu , Wang Wei , Geng Hong-Li , Yang Xing , Jiang Jiang , Zhang Xiao-Xuan
Published: April 2023

Introduction

Despite Toxoplasma gondii infection leading to dysbiosis and enteritis, the function of gut microbiota in toxoplasmosis has not been explored.

Methods

Here, shotgun metagenomics was employed to characterize the composition and function of mouse microbial community during acute and chronic T. gondii infection, respectively.

Results

The results revealed that the diversity of gut bacteria was decreased immediately after T. gondii infection, and was increased with the duration of infection. In addition, T. gondii infection led to gut microbiota dysbiosis both in acute and chronic infection periods. Therein, several signatures, including depression of Firmicutes to Bacteroidetes ratio and infection-enriched Proteobacteria, were observed in the chronic period, which may contribute to aggravated gut inflammation and disease severity. Functional analysis showed that a large amount of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and carbohydrate-active enzymes (CAZy) family displayed distinct variation in abundance between infected and healthy mice. The lipopolysaccharide biosynthesis related pathways were activated in the chronic infection period, which might lead to immune system imbalance and involve in intestinal inflammation. Moreover, microbial and functional spectrums were more disordered in chronic than acute infection periods, thus implying gut microbiota was more likely to participate in disease process in the chronically infected mice, even exacerbated immunologic derangement and disease progression.

Discussion

Our data indicate that the gut microbiota plays a potentially important role in protecting mice from T. gondii infection, and contributes to better understand the association between gut microbiota and toxoplasmosis.
Fibronectin leucine-rich transmembrane protein 2 drives monocyte differentiation into macrophages via the UNC5B-Akt/mTOR axis
Authors: Fang Yaxiong , Ma Kongyang , Huang Yi-Min , Dang Yuanye , Liu Zhaoyu , Xu Yiming , Zheng Xi-Long , Yang Xiangdong , Huo Yongliang , Dai Xiaoyan
Published: April 2023

Upon migrating into the tissues, hematopoietic stem cell (HSC)-derived monocytes differentiate into macrophages, playing a crucial role in determining innate immune responses towards external pathogens and internal stimuli. However, the regulatory mechanisms underlying monocyte-to-macrophage differentiation remain largely unexplored. Here we divulge a previously uncharacterized but essential role for an axon guidance molecule, fibronectin leucine-rich transmembrane protein 2 (FLRT2), in monocyte-to-macrophage maturation. FLRT2 is almost undetectable in human monocytic cell lines, human peripheral blood mononuclear cells (PBMCs), and mouse primary monocytes but significantly increases in fully differentiated macrophages. Myeloid-specific deletion of FLRT2 (Flrt2ΔMyel) contributes to decreased peritoneal monocyte-to-macrophage generation in mice in vivo, accompanied by impaired macrophage functions. Gain- and loss-of-function studies support the promoting effect of FLRT2 on THP-1 cell and human PBMC differentiation into macrophages. Mechanistically, FLRT2 directly interacts with Unc-5 netrin receptor B (UNC5B) via its extracellular domain (ECD) and activates Akt/mTOR signaling. In vivo administration of mTOR agonist MYH1485 reverses the impaired phenotypes observed in Flrt2ΔMyel mice. Together, these results identify FLRT2 as a novel pivotal endogenous regulator of monocyte differentiation into macrophages. Targeting the FLRT2/UNC5B-Akt/mTOR axis may provide potential therapeutic strategies directly relevant to human diseases associated with aberrant monocyte/macrophage differentiation.
Severe COVID-19 and non-COVID-19 severe sepsis converge transcriptionally after a week in the intensive care unit, indicating common disease mechanisms
Authors: An Andy Y. , Baghela Arjun , Zhang Peter , Falsafi Reza , Lee Amy H. , Trahtemberg Uriel , Baker Andrew J. , dos Santos Claudia C. , Hancock Robert E. W.
Published: April 2023

Introduction

Severe COVID-19 and non-COVID-19 pulmonary sepsis share pathophysiological, immunological, and clinical features. To what extent they share mechanistically-based gene expression trajectories throughout hospitalization was unknown. Our objective was to compare gene expression trajectories between severe COVID-19 patients and contemporaneous non-COVID-19 severe sepsis patients in the intensive care unit (ICU).

Methods

In this prospective single-center observational cohort study, whole blood was drawn from 20 COVID-19 patients and 22 non-COVID-19 adult sepsis patients at two timepoints: ICU admission and approximately a week later. RNA-Seq was performed on whole blood to identify differentially expressed genes and significantly enriched pathways.

Results

At ICU admission, despite COVID-19 patients being almost clinically indistinguishable from non-COVID-19 sepsis patients, COVID-19 patients had 1,215 differentially expressed genes compared to non-COVID-19 sepsis patients. After one week in the ICU, the number of differentially expressed genes dropped to just 9 genes. This drop coincided with decreased expression of antiviral genes and relatively increased expression of heme metabolism genes over time in COVID-19 patients, eventually reaching expression levels seen in non-COVID-19 sepsis patients. Both groups also had similar underlying immune dysfunction, with upregulation of immune processes such as “Interleukin-1 signaling” and “Interleukin-6/JAK/STAT3 signaling” throughout disease compared to healthy controls.

Discussion

Early on, COVID-19 patients had elevated antiviral responses and suppressed heme metabolism processes compared to non-COVID-19 severe sepsis patients, although both had similar underlying immune dysfunction. However, after one week in the ICU, these diseases became indistinguishable on a gene expression level. These findings highlight the importance of early antiviral treatment for COVID-19, the potential for heme-related therapeutics, and consideration of immunomodulatory therapies for both diseases to treat shared immune dysfunction.
Community-managed coral reef restoration in southern Kenya initiates reef recovery using various artificial reef designs
Authors: Knoester EG. , Rienstra JJ. , Schürmann QJF. , Wolma AE. , Murk AJ. , Osinga R.
Published: April 2023

Monitoring of reef restoration efforts and artificial reefs (ARs) has typically been limited to coral fragment survival, hampering evaluation of broader objectives such as ecosystem recovery. This study aimed to determine to what extent AR design influences the ecological recovery of restored reefs by monitoring outplanted coral fragments, benthic cover, coral recruitment and fish and invertebrate communities for two years. Four AR designs (16 m2), unrestored controls and natural reef patches as reference (n = 10) were established in Mkwiro, Kenya. ARs consisted either of concrete disks with bottles, layered concrete disks, metal cages or a combination thereof. A mixture of 18 branching coral species (mainly Acropora spp.) was outplanted on ARs at a density of 7 corals m-2. After two years, 60% of all outplanted fragments had survived, already resulting in coral cover on most ARs comparable (though Acropora-dominated) to reference patches. Coral survival differed between ARs, with highest survival on cages due to the absence of crown-of-thorns sea star predation on this design. In total, 32 coral genera recruited on ARs and recruit densities were highest on reference patches, moderate on concrete ARs and low on cages. ARs and reference patches featured nearly twice the fish species richness and around an order of magnitude higher fish abundance and biomass compared to control patches. Fish abundance and biomass strongly correlated with coral cover on ARs. AR, reference and control patches all had distinct fish species compositions, but AR and reference patches were similar in terms of trophic structure of their fish communities. Motile invertebrates including gastropods, sea urchins, sea cucumbers and sea stars were present at ARs, but generally more abundant and diverse at natural reference patches. Taken together, all studied ecological parameters progressed towards reef ecosystem recovery, with varying influences of AR design and material. We recommend a combination of metal cages and layered concrete ARs to promote high fragment survival as well as natural coral recruitment. Ultimately, a longer period of monitoring is needed to fully determine the effectiveness reef restoration as conservation tool to support coral reef ecosystem recovery.
Challenges, limitations, and measurement strategies to ensure data quality in deep-sea sensors
Authors: Skålvik Astrid Marie , Saetre Camilla , Frøysa Kjell-Eivind , Bjørk Ranveig N. , Tengberg Anders
Published: April 2023

In this paper we give an overview of factors and limitations impairing deep-sea sensor data, and we show how automatic tests can give sensors self-validation and self-diagnostic capabilities. This work is intended to lay a basis for sophisticated use of smart sensors in long-term autonomous operation in remote deep-sea locations. Deep-sea observation relies on data from sensors operating in remote, harsh environments which may affect sensor output if uncorrected. In addition to the environmental impact, sensors are subject to limitations regarding power, communication, and limitations on recalibration. To obtain long-term measurements of larger deep-sea areas, fixed platform sensors on the ocean floor may be deployed for several years. As for any observation systems, data collected by deep-sea observation equipment are of limited use if the quality or accuracy (closeness of agreement between the measurement and the true value) is not known. If data from a faulty sensor are used directly, this may result in an erroneous understanding of deep water conditions, or important changes or conditions may not be detected. Faulty sensor data may significantly weaken the overall quality of the combined data from several sensors or any derived model. This is particularly an issue for wireless sensor networks covering large areas, where the overall measurement performance of the network is highly dependent on the data quality from individual sensors. Existing quality control manuals and initiatives for best practice typically recommend a selection of (near) real-time automated checks. These are mostly limited to basic and straight forward verification of metadata and data format, and data value or transition checks against pre-defined thresholds. Delayed-mode inspection is often recommended before a final data quality stamp is assigned.
Dose-response relationship of resistance training for muscle morphology and strength in elderly cancer patients: A meta-analysis
Authors: Zhai Haiting , Wei Hongwen , Xia Jixiang , Wang Wei
Published: April 2023

Objective

To systematically evaluate the effects of resistance training (RT) on muscle strength and muscle hypertrophy in elderly cancer patients, and to provide dose–response relationships of RT variables that could improve muscle strength and morphology in elderly cancer patients.

Method

The Review Manager 5.3 was applied to analyze the 12 literatures (616 participants) through random or fixed effects model and global effect size to examine upper limb strength, lower extremity strength, and muscle hypertrophy. Sub-group analysis was made on five variables: the total number of repeated training times/week, load intensity, exercise frequency/week, exercise duration and gender. This study also examines the heterogeneity and publication bias.

Results

Twelve literatures (616 participants, 60–80 years) were included in meta-analysis. RT significantly increased the upper limb muscular strength (SMD = 0.51, 95% CI: 0.10–0.93; Z = 2.41; p = 0.02) and lower extremity strength (SMD = 0.48, 95% CI: 0.28–0.67; Z = 4.82; p < 0.00001), but had no significant effect on muscle morphology(SMD = 0.21, 95% CI: 0.01–0.42; Z = 1.88; p = 0.06). In subgroup analysis for lower extremity muscle strength in elderly male cancer patients, it was found that male intensity of 70–90%1RM, volume of 400–500 times per week, frequencies of 3 times per week, and session of 12–24 weeks, revealed the greatest effect. Funnel plot of the three studies shows that the results were reliable, and no publication bias was found.

Conclusion

RT had medium effects on improving muscle strength in elderly cancer patients, but it is not effective in improving muscle hypertrophy. In addition, when RT is performed, different training protocols can have an effect on the growth of muscle strength. Therefore, a lower extremity training protocol with a training intensity of 70–90% 1RM, a total of 400–500 repetitions per week, 3 times per week, and an exercise session of 12–24 weeks is most effective in improving lower extremity strength in elderly male cancer patients.
Different endoscopic treatments for small colorectal polyps: A systematic review, pair-wise, and network meta-analysis
Authors: Li Xuanhan , Zhu He , Li Fudong , Li Ri , Xu Hong
Published: April 2023

Background and study aims

In recent years, cold snare polypectomy (CSP) has been increasingly used for small polyps (<10 mm) instead of hot snare polypectomy (HSP). However, evidence-based research regarding the effectiveness and safety of CSP and HSP are still lacking. Additionally, for 4–10 -mm non-pedunculated polyps, the polyp removal method is still controversial. Therefore, it is clinically significant to conduct pair-wise and network meta-analyses to assess such resection methods.

Methods

We searched PubMed, Embase, and the Cochrane library for randomized controlled trials (RCTs). Only studies that involved the resection of polyps <10 mm were included. Outcomes included the complete resection rate, polyp retrieval rate, procedure-related complications, and procedure times.

Results

Overall, 23 RCTs (5,352 patients) were identified. In meta-analysis compared CSP versus HSP for polyps <10 mm, CSP showed lower complete resection rate than HSP although with no statistically significant difference [odds ratio (OR): 0.77, 95% confidence interval (CI): 0.56–1.06]. CSP showed a lower risk of major post-polypectomy complications compared to HSP (OR: 0.28, 95% CI: 0.11–0.73). In the network meta-analysis for 4–10 mm non-pedunculated polyps, HSP, and endoscopic mucosal resection (EMR) showed a higher complete resection rate than CSP (OR: 2.7, 95% CI: 1.3–9.2 vs. OR: 2.6, 95% CI: 1.0–10) but a significantly longer time than CSP (WMD: 16.55 s, 95% CI [7.48 s, 25.25 s], p < 0.001), (WMD: 48.00 s, 95% CI [16.54 s, 79.46 s], p = 0.003). Underwater CSP ranked third for complete resection with no complications.

Conclusion

For <10 mm polyps, CSP is safer than HSP, especially for patients taking antithrombotic drugs. For 4–10 mm non-pedunculated polyps, HSP, and EMR have higher complete resection rates than CSP.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022315575.
Corrective surgery for nipple depression in patients with plasmacytic mastitis – A single-center experience
Authors: Xu Yajun , Da Bu , Zhao Fengxia , Gao Mingjuan , Xue Lihua , Zheng Hao , Shi Hongzhi , Hou Lihua , Miao Shan , Liu Xinwei , Wang Yajing , Xu Hong
Published: April 2023

Background

Plasma cell mastitis (PCM) is a complex breast disease in the clinic. Currently, there are no unified diagnostic criteria for the disease and no standard treatment methods. The effects of hormone, Conventional Chinese medicine and other treatments are uncertain, with long treatment duration and notable side effects. Surgery is the preferred treatment, but the recurrence rate after conventional surgery is very high, which may be related to depression of the nipple. This study aimed to evaluate the efficacy of a novel corrective procedure in patients with cellular mastitis and depressed nipples.

Methods

Patients with PCM who received surgical treatment in the Third Medical Center of PLA General Hospital from January 1996 to January 2018 were retrospectively analyzed. According to the presence or absence of nipple depression before surgery, the patients were divided into the nipple depression group and the non-nipple depression group. In the nipple depression group, patients were subdivided into a novel corrective surgery group (“one” suture or half pocket suture) and a conventional corrective surgery group (oil yarn traction valgus correction of nipple depression). Demographic, clinical, therapeutic, and postoperative relapse data were collected and analyzed.

Results

Compared with the patients in the non-nipple depression group, patients in the nipple depression group had a significantly higher recurrence risk after surgery (HR = 2.129 95% CI: 1.110–4.083, p = 0.023). Patients who underwent novel corrective surgery had a significantly lower recurrence risk than those who underwent conventional corrective surgery (HR = 0.363 95% CI: 0.150–0.880, p = 0.025). In addition, the novel corrective surgery significantly reduced the postoperative recurrence risk (HR = 0.088 95% CI: 0.009–0.886, p = 0.037).

Conclusion

How to correct nipple depression is a critical factor for postoperative recurrence of PCM, and this novel corrective surgery for nipple depression can effectively reduce the postoperative recurrence rate in patients with nipple depression.
Freshwater transfer affected intestinal microbiota with correlation to cytokine gene expression in Asian sea bass
Authors: Morshed Syed Monzur , Chen Yu-Yi , Lin Chia-Hao , Chen Yen-Po , Lee Tsung-Han
Published: April 2023

As a catadromous fish, Asian sea bass (Lates calcarifer) juveniles migrate from seawater (SW) to freshwater (FW) for growth and development. During migration, they undergo physiological changes to acclimate to environmental salinity. Thus, it is crucial to understand how SW-to-FW migration affects the gut microbiota of catadromous fish. To the best of our knowledge, no study has revealed the effects of transfer to hypotonic environments on a catadromous fish microbiota. In this study, we aimed to determine the effects of FW transfer on the microbiota and cytokine gene expression in the intestines of juvenile catadromous Asian sea bass. The relationship between the water and the gut microbiota of this euryhaline species was also examined. We found that FW transfer affected both mucosa- and digesta-associated microbiota of Asian sea bass. Plesiomonas and Cetobacterium were dominant in both the mucosa- and digesta-associated microbiota of FW-acclimated sea bass. The pathogenic genera Vibrio, Staphylococcus, and Acinetobacter were dominant in the SW group. Although dominant fish microbes were present in the water, fish had their own unique microbes. Vitamin B6 metabolism was highly expressed in the FW fish microbiota, whereas arginine, proline, and lipid metabolism were highly expressed in the SW fish microbiota. Additionally, the correlation between cytokine gene expression and microbiota was found to be affected by FW transfer. Taken together, our results demonstrated that FW transfer altered the composition and functions of mucosa- and digesta-associated microbiota of catadromous Asian sea bass intestines, which correlated with cytokine gene expression.
Integrated enzymes activity and transcriptome reveal the effect of exogenous melatonin on the strain degeneration of Cordyceps militaris
Authors: Zu Zhichao , Wang Siqi , Zhao Yingming , Fan Wenli , Li Tianlai
Published: April 2023

As a valuable medicinal and edible fungus, Cordyceps militaris has been industrialized with broad development prospects. It contains a lot of bioactive compounds that are beneficial to our health. However, during artificial cultivation, strain degeneration is a challenge that inhibits the industrialization utility of C. militaris. Exogenous melatonin (MT) can scavenge for reactive oxygen species (ROS) in fungus and can alleviate strain degeneration. To establish the significance and molecular mechanisms of MT on strain degeneration, we investigated the third-generation strain (W5-3) of C. militaris via morphological, biochemical, and transcriptomic approaches under MT treatment. Morphological analyses revealed that colony angulation of C. militaris was significantly weakened, and the aerial hypha was reduced by 60 μmol L–1 MT treatment. Biochemical analyses showed low levels of ROS and malondialdehyde (MDA), as well as increasing endogenous MT levels as exogenous MT increased. RNA-Seq revealed that compared with the control, several antioxidant enzyme-related genes were up-regulated under 60 μmol L–1 MT treatment. Among them, glutathione s-transferase genes were up-regulated by a factor of 11.04. In addition, genes that are potentially involved in cordycepin, adenosine and active compound biosynthesis for the growth and development of mycelium were up-regulated. Collectively, these findings provide the basis for further elucidation of the molecular mechanisms involved in C. militaris strain degeneration.
The associations of gut microbiota, endocrine system and bone metabolism
Authors: Tu Ye , Kuang Xinyi , Zhang Ling , Xu Xin
Published: April 2023

Gut microbiota is of great importance in human health, and its roles in the maintenance of skeletal homeostasis have long been recognized as the “gut-bone axis.” Recent evidence has indicated intercorrelations between gut microbiota, endocrine system and bone metabolism. This review article discussed the complex interactions between gut microbiota and bone metabolism-related hormones, including sex steroids, insulin-like growth factors, 5-hydroxytryptamine, parathyroid hormone, glucagon-like peptides, peptide YY, etc. Although the underlying mechanisms still need further investigation, the regulatory effect of gut microbiota on bone health via interplaying with endocrine system may provide a new paradigm for the better management of musculoskeletal disorders.
Tell me if you prefer bovine or poultry sectors and I’ll tell you who you are: Characterization of Salmonella enterica subsp. enterica serovar Mbandaka in France
Authors: De Sousa Violante Madeleine , Michel Valérie , Romero Karol , Bonifait Laetitia , Baugé Louise , Perrin-Guyomard Agnès , Feurer Carole , Radomski Nicolas , Mallet Ludovic , Mistou Michel-Yves , Cadel-Six Sabrina
Published: April 2023

Introduction

In north-western France, Salmonella enterica susp. enterica serovar Mbandaka (S. Mbandaka) is most frequently isolated from bovine and dairy samples. While this serovar most often results in asymptomatic carriage, for a number of years it has caused episodes of abortions, which have serious economic consequences for the sector. Interestingly, this serovar is also isolated from Gallus gallus in the same geographic zone. Despite its prevalence in bovines in north-western France, S. Mbandaka has not been broadly studied at the genomic level, and its prevalence and host adaptation are still not fully understood.

Methods

In this study, we analyzed the genomic diversity of 304 strains of S. Mbandaka isolated from the bovine and poultry sectors in this area over a period of 5 years. A phylogenetic analysis was carried out and two approaches were followed to identify conserved genes and mutations related to host associations. The first approach targeted the genes compiled in the MEGARESv2, Resfinder, VFDB and SPI databases. Plasmid and phage contents were also investigated. The second approach refers to an in-house algorithm developed for this study that computes sensitivity, specificity, and accuracy of accessory genes and core variants according to predefined genomes groups.

Results and discussion

All the analyzed strains belong to the multi-locus sequence type profile ST413, and the phylogenomic analysis revealed main clustering by host (bovine and poultry), emphasizing the circulation of 12 different major clones, of which seven circulate in poultry and five in the bovine sector in France and a likely food production chain adaptation of these clones. All strains present resistance determinants including heavy metals and biocides that could explain the ability of this serovar to survive and persist in the environment, within herds, and in food processing plants. To explore the wild animal contribution to the spread of this serovar in north-western France, we retrieved S. Mbandaka genomes isolated from wild birds from EnteroBase and included them in the phylogenomic analysis together with our collection. Lastly, screening of accessory genes and major variants allowed us to identify conserved specific mutations characteristic of each major cluster. These mutations could be used to design useful probes for food safety surveillance.
PuCRZ1, an C2H2 transcription factor from Polyporus umbellatus, positively regulates mycelium response to osmotic stress
Authors: Han Pengjie , Hua Zhongyi , Zhao Yuyang , Huang Luqi , Yuan Yuan
Published: April 2023

Polyporus umbellatus is an edible and medicinal mushroom with the capacity to produce sclerotia. However, the mechanism of P. umbellatus sclerotia formation is unclear. CRZ1 is a C2H2 family transcription factor involved in the Ca2+-calcineurin signaling pathway, which has the function of regulating sclerotia formation, maintaining ion homeostasis, and responding to stress. In this study, we identified 28 C2H2 transcription factors in P. umbellatus genome, 13 of which are differentially expressed between mycelium and sclerotia, including PuCRZ1. Combining DNA affinity purification and sequencing (DAP-seq) and quantitative real-time PCR (qRT-PCR), three genes (PuG10, PuG11, PuG12) were identified as putative PuCRZ1 target genes containing a putative binding motif (GTGGCG) within their promoter. Yeast single hybridization (Y1H) and EMSA further confirmed that PuCRZ1 can bind to the promoter region of PuG10, PuG11, and PuG12. PuCRZ1 gene could reduce the sensitivity of NaCl in yeast cells. Furthermore, overexpression of the PuCRZ1 target gene, especially the FVLY domain containing gene PuG11, could improve the mycelia growth rate and mannitol tolerance in P. umbellatus. These results demonstrate that PuCRZ1 in the Ca2+-calcineurin signaling pathway plays an important role in mycelia growth, as well as osmotic stress tolerance.
Non-targeted metabolomics of moldy wheat by ultra-performance liquid chromatography – quadrupole time-of-flight mass spectrometry
Authors: Gao Boyan , Lu Weiying , Jin Mengchu , Chen Yumei
Published: April 2023

Introduction

As one of the staple foods for the world’s major populations, the safety of wheat is critical in ensuring people’s wellbeing. However, mildew is one of the prevalent safety issues that threatens the quality of wheat during growth, production, and storage. Due to the complex nature of the microbial metabolites, the rapid identification of moldy wheat is challenging.

Methods

In this research, identification of moldy wheat samples was studied using ultra-performance liquid chromatography - quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) coupled with chemometrics. The non-targeted PCA model for identifying moldy wheat from normal wheat was established by using previously established compounds database of authentic wheat samples. The partial least squares-discriminant analysis (PLS-DA) was performed.

Results and discussion

By optimizing the model parameters, correct discrimination of the moldy wheat as low as 5% (w/w) adulteration level could be achieved. Differential biomarkers unique to moldy wheat were also extracted to identify between the moldy and authentic wheat samples. The results demonstrated that the chemical information of wheat combined with the existing PCA model could efficiently discriminate between the constructed moldy wheat samples. The study offered an effective method toward screening wheat safety.
Gut microbiota from sigma-1 receptor knockout mice induces depression-like behaviors and modulates the cAMP/CREB/BDNF signaling pathway
Authors: Li Jia-Hao , Liu Jia-Li , Li Xiu-Wen , Liu Yi , Yang Jian-Zheng , Chen Li-Jian , Zhang Kai-Kai , Xie Xiao-Li , Wang Qi
Published: April 2023

Introduction

Depression is a common mental disorder that affects approximately 350 million people worldwide. Much remains unknown about the molecular mechanisms underlying this complex disorder. Sigma-1 receptor (Sig-1R) is expressed at high levels in the central nervous system. Increasing evidence has demonstrated a close association between the Sig-1R and depression. Recently, research has suggested that the gut microbiota may play a crucial role in the development of depression.

Methods

Male Sig-1R knockout (Sig-1R KO) and wild-type (WT) mice were used for this study. All transgenic mice were of a pure C57BL/6J background. Mice received a daily gavage of vancomycin (100 mg/kg), neomycin sulfate (200 mg/kg), metronidazole (200 mg/kg), and ampicillin (200 mg/kg) for one week to deplete gut microbiota. Fecal microbiota transplantation (FMT) was conducted to assess the effects of gut microbiota. Depression-like behaviors was evaluated by tail suspension test (TST), forced swimming test (FST) and sucrose preference test (SPT). Gut microbiota was analyzed by 16s rRNA and hippocampal transcriptome changes were assessed by RNA-seq.

Results

We found that Sig-1R knockout induced depression-like behaviors in mice, including a significant reduction in immobility time and an increase in latency to immobility in the FST and TST, which was reversed upon clearance of gut microbiota with antibiotic treatment. Sig-1R knockout significantly altered the composition of the gut microbiota. At the genus level, the abundance of Alistipes, Alloprevotella, and Lleibacterium decreased significantly. Gut microbiota dysfunction and depression-like phenotypes in Sig-1R knockout mice could be reproduced through FMT experiments. Additionally, hippocampal RNA sequencing identified multiple KEGG pathways that are associated with depression. We also discovered that the cAMP/CREB/BDNF signaling pathway is inhibited in the Sig-1R KO group along with lower expression of neurotrophic factors including CTNF, TGF-α and NGF. Fecal bacteria transplantation from Sig-1R KO mice also inhibited cAMP/CREB/BDNF signaling pathway.

Discussion

In our study, we found that the gut-brain axis may be a potential mechanism through which Sig-1R regulates depression-like behaviors. Our study provides new insights into the mechanisms by which Sig-1R regulates depression and further supports the concept of the gut-brain axis.
New insights into the epidemiology of Listeria monocytogenes – A cross-sectoral retrospective genomic analysis in the Netherlands (2010–2020)
Authors: Coipan Claudia E. , Friesema Ingrid H. M. , van Hoek Angela H. A. M. , van den Bosch Tijs , van den Beld Maaike , Kuiling Sjoerd , Gras Lapo Mughini , Bergval Indra , Bosch Thijs , Wullings Bart , van der Voort Menno , Franz Eelco
Published: April 2023

Introduction

Listeriosis, caused by infection withListeria monocytogenes(Lm), is a relatively rare but severe disease with one of the highest mortality rates among bacterial foodborne illnesses. A better understanding on the degree ofLmclustering, the temporal distribution of the clusters, and their association with the various food sources is expected to lead to improved source tracing and risk-based sampling.

Methods

We investigated the genomic epidemiology ofLmin the Netherlands between 2010 and 2020 by analyzing whole-genome-sequencing (WGS) data of isolates from listerioss patients and food sources from nationwide integrated surveillance and monitoring. WGS data of 756 patient and 770 food/environmental isolates was assessed using core-genome multi-locus sequence typing (cgMLST) with Hamming distance as measure for pairwise distances. Associations of genotype with the epidemiological variables such as patient’s age and gender, and systematic use of specific drugs were tested by multinomial logistic regressions. Genetic differentiation of theLmwithin and between food categories was calculated based on allele frequencies at the 1701 cgMLST loci in each food category.

Results

We confirmed previous results that some clonal complexes (CCs) are overrepresented among clinical isolates but could not identify any epidemiological risk factors. The main findings of this study include the observation of a very weak attribution ofLmtypes to food categories and a much better attribution to the producer level. In addition, we identified a high degree of temporal persistence of food, patient and mixed clusters, with more than half of the clusters spanning over more than 1 year and up to 10  years.

Discussion

Taken together this would indicate that identifying persistent contamination in food production settings, and producers that process a wide variety of raw food produce, could significantly contribute to lowering theLmdisease burden.
Biocontrol potential and action mechanism of Bacillus amyloliquefaciens DB2 on Bipolaris sorokiniana
Authors: Luan Pengyu , Yi Yanjie , Huang Yifan , Cui Liuqing , Hou Zhipeng , Zhu Lijuan , Ren Xiujuan , Jia Shao , Liu Yang
Published: April 2023

Introduction

Bipolaris sorokiniana is the popular pathogenic fungi fungus which lead to common root rot and leaf spot on wheat. Generally, chemical fungicides are used to control diseases. However, the environmental pollution resulting from fungicides should not be ignored. It is important to study the mode of antagonistic action between biocontrol microbes and plant pathogens to design efficient biocontrol strategies.

Results

An antagonistic bacterium DB2 was isolated and identified as Bacillus amyloliquefaciens. The inhibition rate of cell-free culture filtrate (CF, 20%, v/v) of DB2 against B. sorokiniana reached 92.67%. Light microscopy and scanning electron microscopy (SEM) showed that the CF significantly altered the mycelial morphology of B. sorokiniana and disrupted cellular integrity. Fluorescence microscopy showed that culture filtrate destroyed mycelial cell membrane integrity, decreased the mitochondrial transmembrane potential, induced reactive oxygen species (ROS) accumulation, and nuclear damage which caused cell death in B. sorokiniana. Moreover, the strain exhibited considerable production of protease and amylase, and showed a significant siderophore and indole-3-acetic acid (IAA) production. In the detached leaves and potted plants control assay, B. amyloliquefacien DB2 had remarkable inhibition activity against B. sorokiniana and the pot control efficacy was 75.22%. Furthermore, DB2 suspension had a significant promotion for wheat seedlings growth.

Conclusion

B. amyloliquefaciens DB2 can be taken as a potential biocontrol agent to inhibit B. sorokiniana on wheat and promote wheat growth.
African swine fever virus pA104R protein acts as a suppressor of type I interferon signaling
Authors: Chen Qichao , Li Liang , Guo Shibang , Liu Zhankui , Liu Lixinjie , Tan Chen , Chen Huanchun , Wang Xiangru
Published: April 2023

This study evaluates the role of the late viral protein, pA104R, in African swine fever virus immunosuppression. ASFV-encoded pA104R is a putative histone-like protein that is highly conserved throughout different virulent and non-virulent isolates. Previous studies have demonstrated that pA104R plays a vital role in the ASFV replication cycle and is a potential target for antiviral therapy. Here, we demonstrated that pA104R is a potent antagonist of type I interferon signaling. IFN-stimulated response element activity and subsequent transcription of co-transfected and endogenous interferon-stimulated genes were attenuated by pA104R treatment in HEK-293 T cells. Immunoprecipitation assay and reciprocal pull-down showed that pA104R does not interact directly with STAT1, STAT2, or IRF9. However, pA104R could inhibit IFN signaling by attenuating STAT1 phosphorylation, and we identified the critical amino acid residues (R/H69,72 and K/R92,94,97) involved through the targeted mutation functional assays. Although pA104R is a histone-like protein localized to the nucleus, it did not inhibit IFN signaling through its DNA-binding capacity. In addition, activation of the ISRE promoter by IRF9-Stat2(TA), a STAT1-independent pathway, was inhibited by pA104R. Further results revealed that both the transcriptional activation and recruitment of transcriptional stimulators by interferon-stimulated gene factor 3 were not impaired. Although we failed to determine a mechanism for pA104R-mediated IFN signaling inhibition other than attenuating the phosphorylation of STAT1, these results might imply a possible involvement of epigenetic modification by ASFV pA104R. Taken together, these findings support that pA104R is an antagonist of type I interferon signaling, which may interfere with multiple signaling pathways.