bluuebunny/crossref_metadata_2025 huggingface dataset:
Intraocular human cytomegaloviruses of ocular diseases are distinct from those of viremia and are capable of escaping from innate and adaptive immunity by exploiting HLA-E-mediated peripheral and central tolerance
Authors: Shirane Mariko , Yawata Nobuyo , Motooka Daisuke , Shibata Kensuke , Khor Seik-Soon , Omae Yosuke , Kaburaki Toshikatsu , Yanai Ryoji , Mashimo Hisashi , Yamana Satoshi , Ito Takako , Hayashida Akira , Mori Yasuo , Numata Akihiko , Murakami Yusuke , Fujiwara Kohta , Ohguro Nobuyuki , Hosogai Mayumi , Akiyama Masato , Hasegawa Eiichi , Paley Michael , Takeda Atsunobu , Maenaka Katsumi , Akashi Koichi , Yokoyama Wayne M. , Tokunaga Katsushi , Yawata Makoto , Sonoda Koh-Hei
Published: October 2022

Human cytomegalovirus (HCMV) infections develop into CMV diseases that result in various forms of manifestations in local organs. CMV-retinitis is a form of CMV disease that develops in immunocompromised hosts with CMV-viremia after viruses in the peripheral circulation have entered the eye. In the HCMV genome, extensive diversification of the UL40 gene has produced peptide sequences that modulate NK cell effector functions when loaded onto HLA-E and are subsequently recognized by the NKG2A and NKG2C receptors. Notably, some HCMV strains carry UL40 genes that encode peptide sequences identical to the signal peptide sequences of specific HLA-A and HLA-C allotypes, which enables these CMV strains to escape HLA-E-restricted CD8+T cell responses. Variations in UL40 sequences have been studied mainly in the peripheral blood of CMV-viremia cases. In this study, we sought to investigate how ocular CMV disease develops from CMV infections. CMV gene sequences were compared between the intraocular fluids and peripheral blood of 77 clinical cases. UL40 signal peptide sequences were more diverse, and multiple sequences were typically present in CMV-viremia blood compared to intraocular fluid. Significantly stronger NK cell suppression was induced by UL40-derived peptides from intraocular HCMV compared to those identified only in peripheral blood. HCMV present in intraocular fluids were limited to those carrying a UL40 peptide sequence corresponding to the leader peptide sequence of the host’s HLA class I, while UL40-derived peptides from HCMV found only in the peripheral blood were disparate from any HLA class I allotype. Overall, our analyses of CMV-retinitis inferred that specific HCMV strains with UL40 signal sequences matching the host’s HLA signal peptide sequences were those that crossed the blood–ocular barrier to enter the intraocular space. UL40 peptide repertoires were the same in the intraocular fluids of all ocular CMV diseases, regardless of host immune status, implying that virus type is likely to be a common determinant in ocular CMV disease development. We thus propose a mechanism for ocular CMV disease development, in which particular HCMV types in the blood exploit peripheral and central HLA-E-mediated tolerance mechanisms and, thus, escape the antivirus responses of both innate and adaptive immunity.
Hookworm infection associates with a vaginal Type 1/Type 2 immune signature and increased HPV load
Authors: Omondi Millicent A. , Kamassa Eya H. , Katawa Gnatoulma , Tchopba Christèle N. , Vogelbusch Celina , Parcina Marijo , Tchadié Edlom P. , Amessoudji Oukoe M. , Arndts Kathrin , Karou Simplice D. , Ameyapoh Yaovi , Kolou Malewé , Hoerauf Achim , Layland Laura E. , Horsnell William G. C. , Ritter Manuel
Published: October 2022

Helminth infection-driven changes to immunity in the female reproductive tract (FRT) is an immune axis that is currently understudied but can have major implications for the control of FRT infections. Here we address how human hookworm infection associates with vaginal immune profile and risk of Human papillomavirus (HPV) infection. Stool, blood, cervical swabs and vaginal flushes were collected from women from the Central region of Togo to screen for hookworms (Ancylostoma duodenale) and high carcinogenic risk HPV types, via Kato Katz and PCR, respectively. Cytokine, chemokine and immunoglobulin levels were analysed in cervicovaginal lavages and plasma samples. A pronounced mixed Type 1/Type 2 immune response was detected in the vaginal fluids of women with hookworm infection and this immune signature was a notable feature in hookworm-HPV co-infected women. Moreover, hookworm infection is positively associated with increased risk and load of HPV infection. These findings highlight helminth infection as a significant risk factor for acquiring a sexually transmitted viral infection and potentially raising the risk of subsequent pathology.
Targeted delivery of liposomal chemoimmunotherapy for cancer treatment
Authors: Liu Yusheng , Han Joonsu , Bo Yang , Bhatta Rimsha , Wang Hua
Published: October 2022

Chemoimmunotherapy that utilizes the immunomodulatory effect of chemotherapeutics has shown great promise for treating poorly immunogenic solid tumors. However, there remains a significant room for improving the synergy between chemotherapy and immunotherapy, including the efficient, concurrent delivery of chemotherapeutics and immunomodulators into tumors. Here, we report the use of metabolic glycan labeling to facilitate cancer-targeted delivery of liposomal chemoimmunotherapy. 4T1 triple-negative breast cancer cells can be metabolically labeled with azido groups for subsequently targeted conjugation of dibenzocycoloctyne (DBCO)-bearing liposomes loaded with doxorubicin and imiquimod (R837) adjuvant via efficient click chemistry. The encased doxorubicin can induce the immunogenic death of cancer cells and upregulate the expression of CD47 and calreticulin on the surface of cancer cells, while R837 can activate dendritic cells for enhanced processing and presentation of tumor antigens. Targeted delivery of liposomes encapsulating doxorubicin and R837 to 4T1 tumors, enabled by metabolic glycan labeling and click chemistry, showed the promise to reshape the immunosuppressive tumor microenvironment of solid tumors. This cancer-targetable liposomal chemoimmunotherapy could provide a new approach to improving conventional chemotherapy.
Spatial transcriptomics of the lacrimal gland features macrophage activity and epithelium metabolism as key alterations during chronic inflammation
Authors: Mauduit Olivier , Delcroix Vanessa , Umazume Takeshi , de Paiva Cintia S. , Dartt Darlene A. , Makarenkova Helen P.
Published: October 2022

The lacrimal gland (LG) is an exocrine gland that produces the watery part of the tear film that lubricates the ocular surface. Chronic inflammation, such as Sjögren’s syndrome (SS), is one of the leading causes of aqueous-deficiency dry eye (ADDE) disease worldwide. In this study we analyzed the chronic inflammation in the LGs of the NOD.B10Sn-H2b/J (NOD.H-2b) mice, a mouse model of SS, utilizing bulk RNAseq and Visium spatial gene expression. With Seurat we performed unsupervised clustering and analyzed the spatial cell distribution and gene expression changes in all cell clusters within the LG sections. Moreover, for the first time, we analyzed and validated specific pathways defined by bulk RNAseq using Visium technology to determine activation of these pathways within the LG sections. This analysis suggests that altered metabolism and the hallmarks of inflammatory responses from both epithelial and immune cells drive inflammation. The most significant pathway enriched in upregulated DEGs was the “TYROBP Causal Network”, that has not been described previously in SS. We also noted a significant decrease in lipid metabolism in the LG of the NOD.H-2b mice. Our data suggests that modulation of these pathways can provide a therapeutic strategy to treat ADDE.
The shared biomarkers and pathways of systemic lupus erythematosus and metabolic syndrome analyzed by bioinformatics combining machine learning algorithm and single-cell sequencing analysis
Authors: Wang Yingyu , Huang Zhongzhou , Xiao Yu , Wan Weiguo , Yang Xue
Published: October 2022

Background

Systemic lupus erythematosus (SLE) is one of the most prevalent systemic autoimmune diseases, and metabolic syndrome (MetS) is the most common metabolic disorder that contains hypertension, dyslipidemia, and obesity. Despite clinical evidence suggested potential associations between SLE and MetS, the underlying pathogenesis is yet unclear.

Methods

The microarray data sets of SLE and MetS were obtained from the Gene Expression Omnibus (GEO) database. To identify the shared genes between SLE and MetS, the Differentially Expressed Genes (DEGs) analysis and the weighted gene co-expression network analysis (WGCNA) were conducted. Then, the GO and KEGG analyses were performed, and the protein-protein interaction (PPI) network was constructed. Next, Random Forest and LASSO algorithms were used to screen shared hub genes, and a diagnostic model was built using the machine learning technique XG-Boost. Subsequently, CIBERSORT and GSVA were used to estimate the correlation between shared hub genes and immune infiltration as well as metabolic pathways. Finally, the significant hub genes were verified using single-cell RNA sequencing (scRNA-seq) data.

Results

Using limma and WGCNA, we identified 153 shared feature genes, which were enriched in immune- and metabolic-related pathways. Further, 20 shared hub genes were screened and successfully used to build a prognostic model. Those shared hub genes were associated with immunological and metabolic processes in peripheral blood. The scRNA-seq results verified that TNFSF13B and OAS1, possessing the highest diagnostic efficacy, were mainly expressed by monocytes. Additionally, they showed positive correlations with the pathways for the metabolism of xenobiotics and cholesterol, both of which were proven to be active in this comorbidity, and shown to be concentrated in monocytes.

Conclusion

This study identified shared hub genes and constructed an effective diagnostic model in SLE and MetS. TNFSF13B and OAS1 had a positive correlation with cholesterol and xenobiotic metabolism. Both of these two biomarkers and metabolic pathways were potentially linked to monocytes, which provides novel insights into the pathogenesis and combined therapy of SLE comorbidity with MetS.
Levels of soluble complement regulators predict severity of COVID-19 symptoms
Authors: Tierney Anna L. , Alali Wajd Mohammed , Scott Thomas , Rees-Unwin Karen S. ,   CITIID-NIHR BioResource COVID-19 Collaboration, Clark Simon J. , Unwin Richard D.
Published: October 2022

The SARS-CoV-2 virus continues to cause significant morbidity and mortality worldwide from COVID-19. One of the major challenges of patient management is the broad range of symptoms observed. While the majority of individuals experience relatively mild disease, a significant minority of patients require hospitalisation, with COVID-19 still proving fatal for some. As such, there remains a desperate need to better understand what drives this severe disease, both in terms of the underlying biology, but also to potentially predict at diagnosis which patients are likely to require further interventions, thus enabling better outcomes for both patients and healthcare systems. Several lines of evidence have pointed to dysregulation of the complement cascade as a major factor in severe COVID-19 outcomes. How this is underpinned mechanistically is not known. Here, we have focussed on the role of the soluble complement regulators Complement Factor H (FH), its splice variant Factor H-like 1 (FHL-1) and five Factor H-Related proteins (FHR1-5). Using a targeted mass spectrometry approach, we quantified these proteins in a cohort of 188 plasma samples from controls and SARS-CoV-2 patients taken at diagnosis. This analysis revealed significant elevations in all FHR proteins, but not FH, in patients with more severe disease, particularly FHR2 and FHR5 (FHR2: 1.97-fold, p<0.0001; FHR5: 2.4-fold, p<0.0001). Furthermore, for a subset of 77 SARS-CoV-2 +ve patients we also analysed time course samples taken approximately 28 days post-diagnosis. Here, we see complement regulator levels drop in all individuals with asymptomatic or mild disease, but regulators remain high in those with more severe outcomes, with elevations in FHR2 over baseline levels in this group. These data support the hypothesis that elevation of circulating levels of the FHR family of proteins could predict disease severity in COVID-19 patients, and that the duration of elevation (or lack of immune activation resolution) may be partly responsible for driving poor outcomes in COVID-19.
A novel twelve-gene signature to predict neoadjuvant chemotherapy response and prognosis in breast cancer
Authors: Wu Jin , Tian Yuan , Liu Wei , Zheng Hong , Xi Yuanyin , Yan Yuzhao , Hu Ying , Liao Bin , Wang Minghao , Tang Peng
Published: October 2022

Background

Accurate evaluation of the response to neoadjuvant chemotherapy (NAC) provides important information about systemic therapies for breast cancer, which implies pharmacological response, prognosis, and guide further therapy. Gene profiles overcome the shortcomings of the relatively limited detection indicators of the classical pathological evaluation criteria and the subjectivity of observation, but are complicated and expensive. Therefore, it is essential to develop a more accurate, repeatable, and economical evaluation approach for neoadjuvant chemotherapy responses.

Methods

We analyzed the transcriptional profiles of chemo-resistant breast cancer cell lines and tumors of chemo-resistant breast cancer patients in the GSE25066 dataset. We preliminarily screened out common significantly differentially expressed genes and constructed a NAC response risk model using LASSO regression and univariate and multivariate analyses. The differences in bioinformatic features of tumor cells, immune characteristics, and prognosis were compared between high and low-risk group. The potential drugs that could reverse chemotherapy resistance in breast cancer were screened by the CMap database.

Results

Thirty-six genes were commonly up/down-regulated in both NAC chemo-resistant tumors and cells compared to the sensitive tumors and wild-type cells. Through LASSO regression, we obtained a risk model composed of 12 genes. The risk model divided patients into high and low-risk groups. Univariate and multivariate Cox regression analyses suggested that the risk score is an independent prognostic factor for evaluating NAC response in breast cancer. Tumors in risk groups exhibited significant differences in molecular biological characteristics, tumor-infiltrating lymphocytes, and immunosuppressive molecule expression. Our results suggested that the risk score was also a good prognostic factor for breast cancer. Finally, we screened potential drugs that could reverse chemotherapy resistance in breast cancer.

Conclusion

A novel 12 gene-signature could be used to predict NAC response and predict prognosis in breast cancer.
Evaluation of porcine GM-CSF during PRRSV infection in vitro and in vivo indicating a protective role of GM-CSF related with M1 biased activation in alveolar macrophage during PRRSV infection
Authors: Ji Qi , Qu Guanggang , Liu Bing , Bai Yang , Wang Guihua , Chen Rui , Zheng Xu , Zhang Zhigang , Yang Yonglin , Wu Chunyan
Published: October 2022

Granulocyte-macrophage colony stimulating factor (GM-CSF), participates in diverse biological processes associated with innate and adaptive immunity, has unknown effects during PRRSV infection. Here, a double-antibody sandwich ELISA for pGM-CSF was developed in-house for evaluation of pGM-CSF level during PRRSV infection both in vitro and in vivo. In in vitro assay, it was notable that PRRSV-infected porcine alveolar macrophages (PAMs) yielded inconsistent pGM-CSF protein- and mRNA-level, suggesting a post-transcriptional inhibition of pGM-CSF mRNA was employed by PRRSV. Meanwhile, concurrent analysis of pGM-CSF levels in serum samples from PRRSV-infected piglets suggested that effect of PRRSV infection demonstrated minimum effect on pGM-CSF levels regardless of PRRSV virulence phenotypes. Moreover, in vitro treatment of PAMs with pGM-CSF prior PRRSV inoculation did not inhibit PRRSV replication in PAMs although genes downstream of pGM-CSF in PAMs could be upregulated by pGM-CSF treatment. Meanwhile, knockdown of pGM-CSF using siRNA did not enhance PRRSV replication as well. Intriguingly, therapeutic antibody treatment of HP-PRRSV-infected piglets led to significantly increased serum pGM-CSF levels, thus aligning with low pneumonia incidence and low intracellular PRRSV-RNA levels in PAMs of therapeutic antibody treated piglets. Furthermore, transcriptome analysis of PAMs from infected piglets revealed increased serum pGM-CSF levels correlated with activation of downstream signal of pGM-CSF in PAMs as evidenced by a M1-like phenotypes of gene expression pattern, implying a potential host-protective role played by pGM-CSF for PRRSV infection in vivo. In conclusion, our results demonstrated developments of a highly sensitive and specific ELISA for pGM-CSF and revealed a potential protective role conferred by pGM-CSF during PRRSV infection.
Comparative effects of human-equivalent low, moderate, and high dose oral prednisone intake on autoimmunity and glucocorticoid-related toxicity in a murine model of environmental-triggered lupus
Authors: Heine Lauren K. , Benninghoff Abby D. , Ross Elizabeth A. , Rajasinghe Lichchavi D. , Wagner James G. , Lewandowski Ryan P. , Richardson Alexa L. , Li Quan-Zhen , Buchweitz John P. , Zyskowski Justin , Tindle Ashleigh N. , Skedel Anna E. , Chargo Nicholas J. , McCabe Laura R. , Harkema Jack R. , Pestka James J.
Published: October 2022

Autoimmune diseases can be triggered by environmental toxicants such as crystalline silica dust (cSiO2). Here, we characterized the dose-dependent immunomodulation and toxicity of the glucocorticoid (GC) prednisone in a preclinical model that emulates onset and progression of cSiO2-triggered lupus. Two cohorts of 6-wk-old female NZBWF1 mice were fed either control AIN-93G diet or one of three AIN-93G diets containing prednisone at 5, 15, or 50 mg/kg diet which span human equivalent oral doses (HED) currently considered to be low (PL; 5 mg/d HED), moderate (PM; 14 mg/d HED), or high (PH; 46 mg/d HED), respectively. At 8 wk of age, mice were intranasally instilled with either saline vehicle or 1 mg cSiO2 once weekly for 4 wk. The experimental plan was to 1) terminate one cohort of mice (n=8/group) 14 wk after the last cSiO2 instillation for pathology and autoimmunity assessment and 2) to maintain a second cohort (n=9/group) to monitor glomerulonephritis development and survival. Mean blood concentrations of prednisone’s principal active metabolite, prednisolone, in mice fed PL, PM, and PH diets were 27, 105, 151 ng/ml, respectively, which are consistent with levels observed in human blood ≤ 12 h after single bolus treatments with equivalent prednisone doses. Results from the first cohort revealed that consumption of PM, but not PL diet, significantly reduced cSiO2-induced pulmonary ectopic lymphoid structure formation, nuclear-specific AAb production, inflammation/autoimmune gene expression in the lung and kidney, splenomegaly, and glomerulonephritis in the kidney. Relative to GC-associated toxicity, PM diet, but not PL diet, elicited muscle wasting, but these diets did not affect bone density or cause glucosuria. Importantly, neither PM nor PL diet improved latency of cSiO2-accelerated death. PH-fed mice in both cohorts displayed robust GC-associated toxicity including body weight loss, reduced muscle mass, and extensive glucosuria 7 wk after the final cSiO2 instillation requiring their early removal from the study. Taken together, our results demonstrate that while moderate doses of prednisone can reduce important pathological endpoints of cSiO2-induced autoimmunity in lupus-prone mice, such as upstream ectopic lymphoid structure formation, these ameliorative effects come with unwanted GC toxicity, and, crucially, none of these three doses extended survival time.
DOCK2 and phosphoinositide-3 kinase δ mediate two complementary signaling pathways for CXCR5-dependent B cell migration
Authors: Wissmann Stefanie , Stolp Bettina , Jímenez Ana Marcos , Stein Jens V.
Published: October 2022

Naive B cells use the chemokine receptor CXCR5 to enter B cell follicles, where they scan CXCL13-expressing ICAM-1+ VCAM-1+ follicular dendritic cells (FDCs) for the presence of antigen. CXCL13-CXCR5-mediated motility is mainly driven by the Rac guanine exchange factor DOCK2, which contains a binding domain for phosphoinositide-3,4,5-triphosphate (PIP3) and other phospholipids. While p110δ, the catalytic subunit of the class IA phosphoinositide-3-kinase (PI3K) δ, contributes to CXCR5-mediated B cell migration, the precise interdependency of DOCK2, p110δ, or other PI3K family members during this process remains incompletely understood. Here, we combined in vitro chemotaxis assays and in vivo imaging to examine the contribution of these two factors during murine naïve B cell migration to CXCL13. Our data confirm that p110δ is the main catalytic subunit mediating PI3K-dependent migration downstream CXCR5, whereas it does not contribute to chemotaxis triggered by CXCR4 or CCR7, two other chemokine receptors expressed on naïve B cells. The contribution of p110δ activity to CXCR5-driven migration was complementary to that of DOCK2, and pharmacological or genetic interference with both pathways completely abrogated B cell chemotaxis to CXCL13. Intravital microscopy of control and gene-deficient B cells migrating on FDCs confirmed that lack of DOCK2 caused a profound migration defect, whereas p110δ contributed to cell speed and directionality. B cells lacking active p110δ also displayed defective adhesion to ICAM-1; yet, their migration impairment was maintained on ICAM-1-deficient FDCs. In sum, our data uncover two complementary signaling pathways mediated by DOCK2 and p110δ, which enable CXCR5-driven naïve B cell examination of FDCs.
A synonymous mutation in PI4KA impacts the transcription and translation process of gene expression
Authors: Zhang Kaihui , Kang Lili , Zhang Haozheng , Bai Lu , Pang Huanping , Liu Qinghua , Zhang Xinyi , Chen Dong , Yu Haihua , Lv Yuqiang , Gao Min , Liu Yi , Gai Zhongtao , Wang Dong , Li Xiaoying
Published: October 2022

Phosphatidylinositol-4-kinase alpha (PI4KIIIα), encoded by the PI4KA gene, can synthesize phosphatidylinositol-4-phosphate (PI-4-P), which serves as a specific membrane marker and is instrumental in signal transduction. PI4KA mutations can cause autosomal recessive diseases involving neurological, intestinal, and immunological conditions (OMIM:619621, 616531, 619708). We detected sepsis, severe diarrhea, and decreased immunoglobulin levels in one neonate. Two novel compound heterozygous mutations, c.5846T>C (p.Leu1949Pro) and c.3453C>T (p.Gly1151=), were identified in the neonate from the father and the mother, respectively. Sanger sequencing and reverse transcription polymerase chain reaction (RT-PCR) for peripheral blood and minigene splicing assays showed a deletion of five bases (GTGAG) with the c.3453C>T variant at the mRNA level, which could result in a truncated protein (p.Gly1151GlyfsTer17). The missense mutation c.5846T>C (p.Leu1949Pro) kinase activity was measured, and little or no catalytic activity was detected. According to the clinical characteristics and gene mutations with functional verification, our pediatricians diagnosed the child with a combined immunodeficiency and intestinal disorder close to gastrointestinal defects and immunodeficiency syndrome 2 (GIDID2; OMIM: 619708). Medicines such as immunomodulators are prescribed to balance immune dysregulation. This study is the first report of a synonymous mutation in the PI4KA gene that influences alternative splicing. Our findings expand the mutation spectrum leading to PI4KIIIa deficiency-related diseases and provide exact information for genetic counseling.
Divergent outcomes of anti-PD-L1 treatment coupled with host-intrinsic differences in TCR repertoire and distinct T cell activation states in responding versus non-responding tumors
Authors: John Jessy , Woolaver Rachel A. , Popolizio Vince , Chen Samantha M. Y. , Ge Huaibin , Krinsky Alexandra L. , Vashisht Monika , Kramer Yonatan , Chen Zhangguo , Wang Jing H.
Published: October 2022

Differential responses to immune checkpoint inhibitors (ICI) may be attributed to tumor-intrinsic factors or environmental cues; however, these mechanisms cannot fully explain the variable ICI responses in different individuals. Here, we investigate the potential contribution of immunological heterogeneity with a focus on differences in T-cell receptor (TCR) repertoire to ICI responses, which has not been defined previously. To reveal additional factors underlying heterogeneous responses to ICI, we employed a squamous cell carcinoma (SCC) mouse model in which tumor-bearing recipients unambiguously diverged into responders (R) or non-responders (NR) upon anti-PD-L1 treatment. Treatment efficacy absolutely required CD8 T-cells and correlated positively with effector functions of CD8 tumor-infiltrating lymphocytes (TILs). We showed that TCR repertoires exhibited a similar magnitude of clonal expansion in R vs. NR CD8 TILs. However, the top expanded TCR clonotypes appeared to be mutually exclusive between R and NR CD8 TILs, which also occurred in a recipient-specific manner, demonstrating preferential expansion of distinct TCR clonotypes against the same SCC tumor. Unexpectedly, R vs. NR CD8 TILs reached all activation clusters and did not exhibit substantial global differences in transcriptomes. By linking single-cell transcriptomic data with unique TCR clonotypes, CD8 TILs harboring top TCR clonotypes were found to occupy distinct activation clusters and upregulate genes favoring anti-tumor immunity to different extents in R vs. NR. We conclude that stochastic differences in CD8 TIL TCR repertoire and distinct activation states of top TCR clonotypes may contribute to differential anti-PD-L1 responses. Our study suggests that host-intrinsic immunological heterogeneity may offer a new explanation for differential ICI responses in different individuals, which could impact on strategies for personalized cancer immunotherapy.
COVID-19: A unique opportunity to improve laboratory capacity for neglected tropical diseases in sub-Saharan Africa
Authors: Adeniran Adebiyi A. , Hamill Louise Claire , Selby Richard , Downs Philip
Published: October 2022

While many public health and university laboratories have become involved in COVID-19 testing during the pandemic, these laboratories now run the risk of being underutilized as COVID-19 testing wanes. This is particularly true of established COVID-19 laboratories in many low- and middle-income countries (LMICs). In this article, we make a case for repurposing many of these laboratories to support control programs for neglected tropical diseases (NTDs) in endemic countries as they contemplate how to strengthen laboratory capacity for all endemic and emerging epidemiological diseases.
Genome-wide association and transcriptome studies reveal the segregation mechanism of mantle markings in three-way cross hybrid abalone
Authors: Xiao Qizhen , Gong Shihai , Shen Yawei , Lu Yisha , Lai Xinlian , Peng Wenzhu , Huang Zekun , Han Zhaofang , Ji Hongjing , Gan Yang , Luo Xuan , You Weiwei , Ke Caihuan
Published: October 2022

Trait separation which often appears in shellfish progeny, has been commercially used in shellfish breeding projects. A three-way cross hybrid abalone was produced with heterosis in growth performance and thermal tolerance, and with segregation in mantle marking. However, the inheritance mechanism of mantle marking is unclear. In this study, mantle marking was demonstrated to be a qualitative trait, following simple Mendelian inheritance, through inheritance pattern analysis of the presence of black markings on the mantle in five families of three-way cross of hybrid abalone. Thermal tolerance of abalone was assessed by the Arrhenius breakpoint temperature (ABT) of cardiac performance and a correlation between mantle marking and thermal tolerance of abalone was verified. A genome-wide association study (GWAS) for mantle marking was conducted using 603,067 high-quality single nucleotide polymorphisms (SNPs) derived from 57 individuals with mantle markings (Y group) and 58 individuals without mantle markings (N group). A total of 493 SNPs that were significantly (p < 2.32E–07) associated with mantle markings were mainly distributed on chromosome 15. In the potential significantly associated region, 80 genes, including pigmentation-related genes PTPRT, PTPRC, PNCA, and CALM4 were annotated. Transcriptome analysis of the two groups showed that the expression levels of these genes (PTPRT, DDT-b, ATOX1, SLC6A3, and GSTO1) were significantly different, and they may play important roles in the formation of mantle markings in the three-way cross hybrid abalone. Overall, our data provide valuable information for deciphering the phenotype differences of mantle marking in three-way cross hybrid abalone and help in the molecular marker-assisted breeding in abalone.
Effects of jet nebulization on ventilator performance with different invasive ventilation modes: A bench study
Authors: Li Xinyu , Tan Wei , Zhao Hongwen , Wang Wei , Dai Bing , Hou Haijia
Published: October 2022

Background

The effects of jet nebulization on ventilator performance in the volume control mode (VC) and pressure control mode (PC) of ventilation have not been determined.

Objectives

The present study investigated the impact of jet nebulization on ventilator performance in different modes in vitro.

Methods

Two types of jet nebulizer (ventilator-integrated jet nebulizers, external jet nebulizer) and six types of ventilator were connected with a simulated lung to simulate aerosol therapy during mechanical ventilation. The ventilation modes were set to VC and PC, and the driving flows of external jet nebulizer were set at 4 L/min and 8 L/min, respectively. Jet nebulizers were placed between patient airway and Y-piece or at 15 cm from the Y-piece in the inspiratory limb. The effects of jet nebulization were compared with the baseline of triggering performance, control performance, and tidal volume under different experimental conditions.

Results

Ventilator-integrated jet nebulizers had no effect on ventilator performance in different modes (all P > 0.05). However, the effects of external jet nebulizers on ventilator performance varied widely: for triggering performance, all parameters were increased in different modes and nebulization positions (all P < 0.05), including the time from the beginning of the inspiratory effort to the lowest value of airway pressure needed to trigger the ventilator (TPmin), the time to trigger (Ttrig), and the magnitude of airway pressure drop needed to trigger (Ptrig); for control performance, peak inspiratory pressure (Ppeak) and peak inspiratory flow(Pflow) were increased in the VC mode (P < 0.05), but not significantly changed in the PC mode (P > 0.05);the actual tidal volume (VT) and expiratory tidal volume monitored (VTe) were significantly increased (P < 0.05), however, the inspiratory tidal volume monitored (VTi) was not affected by jet nebulization in the VC mode. In the PC mode, there were no significant changes in VT, whereas VTi decreased and VTe increased (P < 0.05). The higher the driving flow of external jet nebulizers, the stronger the impact on ventilator performance (all P < 0.05).

Conclusion

Triggering performance was decreased in both the VC and PC modes when using an external jet nebulizer, while the effects of nebulization on control performance and tidal volume varied significantly.
Resistant ovary syndrome: Pathogenesis and management strategies
Authors: Mu Zhenni , Shen Sinan , Lei Lei
Published: October 2022

Resistant ovary syndrome (ROS) is a rare and difficult gynecological endocrine disorder that poses a serious risk to women’s reproductive health. The clinical features are normal sex characteristics, regular female karyotype, and usual ovarian reserve, but elevated endogenous gonadotropin levels and low estrogen levels with primary or secondary amenorrhea. Although there have been many case reports of the disease over the past 50 years, the pathogenesis of the disease is still poorly understood, and there are still no effective clinical management strategies. In this review, we have collected all the current reports on ROS and summarized the pathogenesis and treatment strategies for this disease, intending to provide some clinical references for the management and treatment of this group of patients and provide the foothold for future studies.
Oncology and cardiology positron emission tomography/computed tomography faced with COVID-19: A review of available literature data
Authors: Minamimoto Ryogo
Published: October 2022

The COVID-19 pandemic has forced people to significantly change their lifestyles and attitudes, and has greatly burdened healthcare delivery systems worldwide. The redistribution of the medical delivery system to maintain normal medical care while responding generously to COVID-19 is a continuing challenge that weighs heavily on medical institutions. Among imaging modalities, chest X-rays and computed tomography (CT) examinations have clearly made a large contribution to treatment of COVID-19. In contrast, it is difficult to express the standpoint of nuclear medicine examinations in a straightforward manner, as the greatest emphasis in this modality has been on how necessary medical care can continue to be provided. Many clinical reports of nuclear medicine examinations related to COVID-19 have been published, and knowledge continues to accumulate. This review provides a summary of the current state of oncology and cardiology positron emission tomography (PET) examinations related to COVID-19, and includes preparation of the nuclear medicine department, trends in PET examinations, specific imaging findings on 18F-fluorodeoxyglucose (FDG) PET/CT, imaging of complications of COVID-19, PET tracers other than FDG, and the effects of vaccines on PET imaging findings.
An innovation on clinical placement for occupational therapy mental health during the COVID-19: A mixed-methods feasibility study
Authors: Wan Yunus Farahiyah , Romli Muhammad Hibatullah , Mohd Rasdi Hanif Farhan , Harun Dzalani , Kadar Masne
Published: October 2022

The COVID-19 pandemic altered the health profession's education. Educational activities were shifted to online, and clinical placements were compromised in certain countries. A mixed-methods study included 17 undergraduates undergoing a mental health placement. The first 3 weeks of clinical placement applied online case-based learning in written and in video format. The last 2 weeks involved hybrid remote and physical onsite clinical placement. SPICES model utilizing various active learning activities, case studies and client attendance, facilitator engagement, discussion and feedback were implemented. A self-administered System Usability Scale (SUS), e-learning preference level, focus group discussion, and reflective writing was conducted at the end of each week and the students' final marks were compared with the past cohort who attended conventional physical clinical placement. Two-way mixed ANOVA indicates no significant interaction was found on the SUS (p= 0.062,ηp2= 0.062) and preference scores (p= 0.285,ηp2= 0.079) according to week and practical site. There was no significant difference in the final mark among the online and onsite placement of the current cohort (p= 0.350, d = 0.47). The current cohort reported better marks than the previous cohort who attended conventional placement (p= 0.006, d = 0.99). Qualitative findings show positive responses where online activities have minimal restriction on the learning process. This innovative approach is acceptable for substituting conventional clinical learning during this restricted situation.
Multi-omics analyses reveal the specific changes in gut metagenome and serum metabolome of patients with polycystic ovary syndrome
Authors: Yang Zhandong , Fu Huijiao , Su Huihui , Cai Xuzi , Wang Yan , Hong Yanjun , Hu Jing , Xie Zhiyong , Wang Xuefeng
Published: October 2022

Objective

The purpose of this study was to investigate the specific alterations in gut microbiome and serum metabolome and their interactions in patients with polycystic ovary syndrome (PCOS).

Methods

The stool samples from 32 PCOS patients and 18 healthy controls underwent the intestinal microbiome analysis using shotgun metagenomics sequencing approach. Serum metabolome was analyzed by ultrahigh performance liquid chromatography quadrupole time-of-flight mass spectrometry. An integrative network by combining metagenomics and metabolomics datasets was constructed to explore the possible interactions between gut microbiota and circulating metabolites in PCOS, which was further assessed by fecal microbiota transplantation (FMT) in a rat trial.

Results

Fecal metagenomics identified 64 microbial strains significantly differing between PCOS and healthy subjects, half of which were enriched in patients. These changed species showed an ability to perturb host metabolic homeostasis (including insulin resistance and fatty acid metabolism) and inflammatory levels (such as PI3K/Akt/mTOR signaling pathways) by expressing sterol regulatory element-binding transcription factor-1, serine/threonine-protein kinase mTOR, and 3-oxoacyl-[acyl-cattier-protein] synthase III, possibly suggesting the potential mechanisms of gut microbiota underlying PCOS. By integrating multi-omics datasets, the panel comprising seven strains (Achromobacter xylosoxidans, Pseudomonas sp. M1, Aquitalea pelogenes, Porphyrobacter sp. HL-46, Vibrio fortis, Leisingera sp. ANG-Vp, and Sinorhizobium meliloti) and three metabolites [ganglioside GM3 (d18:0/16:0), ceramide (d16:2/22:0), and 3Z,6Z,9Z-pentacosatriene] showed the highest predictivity of PCOS (AUC: 1.0) with sensitivity of 0.97 and specificity of 1.0. Moreover, the intestinal microbiome modifications by FMT were demonstrated to regulate PCOS phenotypes including metabolic variables and reproductive hormones.

Conclusion

Our findings revealed key microbial and metabolite features and their interactions underlying PCOS by integrating multi-omics approaches, which may provide novel insights into discovering clinical diagnostic biomarkers and developing efficient therapeutic strategies for PCOS.
Cordyceps mushroom with increased cordycepin content by the cultivation on edible insects
Authors: Turk Ayman , Abdelhamid Mohamed A. A. , Yeon Sang Won , Ryu Se Hwan , Lee Solip , Ko Sung Min , Kim Beom Seok , Pack Seung Pil , Hwang Bang Yeon , Lee Mi Kyeong
Published: October 2022

Cordycepin is the major constituent of Cordyceps mushroom (or Cordyceps militaris) with therapeutic potential. Insects are the direct sources of nutrients for Cordyceps in nature. Therefore, optimized condition of Cordyceps cultivation for efficient cordycepin production was explored using six edible insects as substrates. The highest yield of cordycepin was produced by the cultivation on Allomyrina dichotoma and was 34 times that on Bombyx mori pupae. Among insect components, fat content was found to be important for cordycepin production. Especially, a positive correlation was deduced between oleic acid content and cordycepin production. The transcriptional levels of cns1 and cns2, genes involved in cordycepin biosynthesis, were higher in Cordyceps grown on A. dichotoma than on other insects tested. The addition of oleic acid to the substrates increased cordycepin production together with the transcriptional levels of cns1 and cns2. Therefore, Cordyceps with high content of cordycepin can be secured by the cultivation on insects.
The secreted FoAPY1 peptidase promotes Fusarium oxysporum invasion
Authors: Qian Hengwei , Song Limin , Wang Lulu , Wang Baoshan , Liang Wenxing
Published: October 2022

The secretion of peptidases from several pathogens has been reported, but the biological function of these proteins in plant-pathogen interactions is poorly understood. Fusarium oxysporum, a soil-borne plant pathogenic fungus that causes Fusarium wilt in its host, can secrete proteins into host plant cells during the infection process to interfere with the host plant defense response and promote disease occurrence. In this study, we identified a peptidase, FoAPY1, that could be secreted from F. oxysporum depending on the N-terminal signal peptide of the protein. FoAPY1 belongs to the peptidase M28 family and exerts peptidase activity in vitro. Furthermore, the FoAYP1 gene knockout strain (∆FoAYP1) presented reduced virulence to tomato plants, but its mycelial growth and conidiation were unchanged. Moreover, FoAYP1 overexpression tomato seedlings exhibited enhanced susceptibility to F. oxysporum and Botrytis cinerea strains. These data demonstrated that FoAYP1 contributes to the virulence of F. oxysporum may through peptidase activity against host plant proteins.
Advances in endogenous RNA pull-down: A straightforward dextran sulfate-based method enhancing RNA recovery
Authors: Desideri Fabio , D’Ambra Eleonora , Laneve Pietro , Ballarino Monica
Published: October 2022

Detecting RNA/RNA interactions in the context of a given cellular system is crucial to gain insights into the molecular mechanisms that stand beneath each specific RNA molecule. When it comes to non-protein coding RNA (ncRNAs), and especially to long noncoding RNAs (lncRNAs), the reliability of the RNA purification is dramatically dependent on their abundance. Exogenous methods, in which lncRNAs are in vitro transcribed and incubated with protein extracts or overexpressed by cell transfection, have been extensively used to overcome the problem of abundance. However, although useful to study the contribution of single RNA sub-modules to RNA/protein interactions, these exogenous practices might fail in revealing biologically meaningful contacts occurring in vivo and risk to generate non-physiological artifacts. Therefore, endogenous methods must be preferred, especially for the initial identification of partners specifically interacting with elected RNAs. Here, we apply an endogenous RNA pull-down to lncMN2-203, a neuron-specific lncRNA contributing to the robustness of motor neurons specification, through the interaction with miRNA-466i-5p. We show that both the yield of lncMN2-203 recovery and the specificity of its interaction with the miRNA dramatically increase in the presence of Dextran Sulfate Sodium (DSS) salt. This new set-up may represent a powerful means for improving the study of RNA-RNA interactions of biological significance, especially for those lncRNAs whose role as microRNA (miRNA) sponges or regulators of mRNA stability was demonstrated.
The NLR family pyrin domain containing 3 inflammasome in the mechanism of electroacupuncture: Current status and future perspectives
Authors: Yuan Min , Wang Dong , Yang Jiaen , Lan Hai
Published: October 2022

Electroacupuncture, which is the most widely used alternative medicine treatment, has been gradually recognized for its effectiveness; however, its mechanism of action is not fully understood. The NLR family pyrin domain containing 3 (NLRP3) inflammasome is a thoroughly studied inflammasome that is closely associated with Alzheimer’s disease, spinal cord injury, and other diseases and plays an important role in the diagnosis and treatment of human immune system diseases. In recent years, some scholars have found that the NLRP3 inflammasome is a part of the mechanism of action of electroacupuncture, which has attracted further attention. In the current review, using “electroacupuncture” and “NLRP3 inflammasome” as keywords and based on the existing randomized controlled trials or clinical trials, we summarize the mechanisms of electroacupuncture targeting NLRP3 inflammasome in the treatment of different diseases and discuss how to optimize the electroacupuncture protocol to obtain thorough mechanisms of NLRP3 inflammasome in electroacupuncture and improve the level of evidence.
Case report: Wallerian degeneration: The innate-immune response to adult-onset Still's disease peripheral nerve injury
Authors: Cheng Hao , Lv He , Wang Yan , Wang Gui-Qiang
Published: October 2022

Peripheral nerve injury is one of the rare complications of adult-onset Still's disease (AOSD). We report a 20-year-old woman diagnosed with AOSD combined with severe sensory neuropathy. She presented with a sore throat, joint pain, rash, and lymphadenopathy. After receiving glucocorticoid therapy, her fever, rash, and inflammatory markers improved. Unexpectedly, 3 weeks after the onset, she experienced sudden paresthesia in her extremities, decreased muscle strength, and diminished tendon reflexes. The electrophysiological examination and peripheral nerve biopsy confirmed immune-mediated severe sensory neuropathy. For the first time, we report typical Wallerian degeneration in AOSD patients with sensory neuropathy by nerve biopsy. Compared with other common symptoms, the delayed aggravation of neurological symptoms may be an important characteristic of sensory neuropathy secondary to AOSD. We emphasize that intensive attention to neurological symptoms after general symptoms control, administration of adequate and appropriate prolonged immunosuppressive therapy, and long-term follow-up are essential for these patients.
Association of Obstructive Sleep Apnea-Hypopnea Syndrome with hearing loss: A systematic review and meta-analysis
Authors: Wang Chaoyu , Xu Fu , Chen Mingdi , Chen Xiaojuan , Li Chunhe , Sun Xishi , Zhang Yu , Liao Huizhao , Wu Qinglan , Chen Huimin , Li Shunhong , Zhu Jinru , Lin Junyan , Ou Xudong , Zou Zhihong , Li Yuming , Chen Riken , Zheng Zhenzhen , Wang Yang
Published: October 2022

Objective

This study seeks to investigate the relationship between Obstructive Sleep Apnea-Hypopnea Syndrome (OSAHS) and hearing impairment by meta-analysis.

Methods

Cochrane Library, PubMed, Embase, Web of Science and other databases are searched from their establishment to July 1st, 2022. Literature on the relationship between OSAHS and hearing loss is collected, and two researchers independently perform screening, data extraction and quality evaluation on the included literature. Meta-analysis is performed using RevMan 5.4.1 software. According to the heterogeneity between studies, a random-effects model or fixed-effects model is used for meta-analysis.

Results

A total of 10 articles are included, with 7,867 subjects, 1,832 in the OSAHS group and 6,035 in the control group. The meta-analysis shows that the incidence of hearing impairment in the OSAHS group is higher than in the control group (OR = 1.38; 95% CI 1.18–1.62, Z = 4.09, P < 0.001), and the average hearing threshold of OSAHS patients is higher than that of the control group (MD = 5.89; 95% CI 1.87–9.91, Z = 2.87, P = 0.004). After stratifying the included studies according to hearing frequency, the meta-analysis shows that the OSAHS group has a higher threshold of 0.25, and the response amplitudes at frequencies 2, 4, 6, and 8 kHz are all higher than those of the control group.

Conclusion

Compared with the control group, the OSAHS group has a higher incidence of hearing loss, mainly high-frequency hearing loss. Thus, OSAHS is closely associated with and a risk factor for hearing loss.