bluuebunny/crossref_metadata_2025_split huggingface dataset:
“Seminal testosterone”, rising viewpoint of local spermatogenesis in nonobstructive azoospermia: One center long-term bidirectional cohort study
Authors: Liu Huang , Zheng Houbin , Li Yuehua , Tang Yuqian , Peng Hongbo , Li Qianyi , Zhuang Jiaming , Zhou Yingyi , Zhou Yu , Tu Xiang’an , Zhang Xinzong 
Published: December 2022

ObjectiveReproductive hormones are a traditional good method to evaluate spermatogenesis but might not accurately represent local spermatogenesis. To find a more accurate method, seminal reproductive hormones were studied.MethodsA bidirectional cohort study was performed. A total of 126 infertile men from 2018 to 2019 were retrospectively analyzed. They were divided into nonobstructive azoospermia (NOA), oligozoospermia (OLZ) and normal (NOR) groups. A prospective study was conducted on patients in the NOA and OLZ groups for 2 years. Microscopic testicular sperm extraction was performed for NOA patients, who were divided into a focal spermatogenesis group (FS) and an idiopathic azoospermia group (IA). Drug treatment was for OLZ patients, who were divided into a valid group (VA) and an invalid group (IN). The differences in sperm parameters and reproductive hormones were compared. ANOSIM analysis was used between and within groups. Pearson correlation analysis, CO inertia analysis and Proctor’s analysis were for relationships. ROC curve for the specificity and sensitivity. Time series analysis was for the trends between hormones and time.ResultsThe b-FSH, b-LH, s-T and ΔT in the NOA group were significantly higher than those in the OLZ and NOR groups. However, the s-FSH, s-E2, s-P, ΔFSH, ΔLH, ΔP and ΔE2 were lower. Thirty-one NOA patients underwent MTSE, of whom 12 had sperm (FS) and 19 had no sperm (IA). The s-FSH and s-E2 of the FS group were higher than those of the IA group. Twenty-six OLZ patients completed 30 days of treatment, of which 11 had an improved sperm count (VA) and 15 had no (IN). The ΔT of the VA group was higher than that of the IN group. After follow-up for 2 years, 18 patients’ results showed that b-FSH, b-LH and s-T were different over time, with delays of 19, 3 and -19 days. SC is closely related to pH, s-FSH, s-LH, s-E2, s-P, s-T, b-FSH, b-LH, ΔFSH, ΔLH, ΔP, ΔE2 and ΔT. There were complex common trends and relationships between different kinds of hormones. s-FSH, s-LH, s-E2, s-P, s-T, b-FSH and b-LH were useful to judge spermatogenesis, of which s-T, b-FSH and b-LH were more sensitive. If s-T, b-FSH and b-LH reached 64.4, 9.4 and 4.7, respectively, their prediction performance was the strongest.ConclusionSeminal testosterone is sensitive for judging local spermatogenesis in nonobstructive azoospermia patients, which may be the direction of local spermatogenesis in nonobstructive azoospermia.Clinical trial registrationhttp://www.chictr.org.cn/index.aspx, identifier ChiCTR2200060463.
Sublethal and intergenerational effects of fipronil on Binodoxys communis larvae based on transcriptome sequencing
Authors: Du Lingen , Zhao Likang , Zhu Xiangzhen , Wang Li , Zhang Kaixin , Li Dongyang , Ji Jichao , Niu Lin , Luo Junyu , Cui Jinjie , Gao Xueke 
Published: December 2022

Fipronil is widely used in the agricultural world as an efficient phenylpyrazole insecticide to control pests. Binodoxys communis is a key parasitic natural enemy of major homopteran pests and can successfully control the population of pests such as cotton aphids. It has not yet been studied what effects would sublethal doses of fipronil have on Binodoxys communis larvae. Here, this study evaluated the effect of fipronil on Binodoxys communis larvae and analyze the transcriptome results. The results showed that LC10 (1.19 mg/L) and LC25 (1.73 mg/L) had significant negative effects on the survival rate and parasitism rate of F0 generation. Moreover, exposure to high concentrations (LC25) of fipronil still had obvious passive effect on the F1 generation of Binodoxys communis. These results indicated that sublethal doses of fipronil have malignant effects on the biological functions of parasitoids and their offspring. The results of transcriptome analysis showed that differentially expressed genes (DEGs) of Binodoxys communis after LC10 treatment are mainly related to immunity and detoxification. LC25 treatment instead resulted in changes in the expression of genes related to nutrition, energy and metabolism reactions. Seven of the identified DEGs were selected for real-time fluorescence quantitative PCR analysis. To the best of our knowledge, this is the first report to evaluate the sublethal, intergenerational, and transcriptomic side effects of fipronil on larvae of parasitic natural pest enemies. Our findings provide data to accurately assess the risk of fipronil usage on Binodoxys communis larvae, and provide important theoretical support for the comprehensive prevention and control of natural enemies and pesticides.
Estimating genetic gains for tolerance to stress combinations in tropical maize hybrids
Authors: Menkir Abebe , Dieng Ibnou , Meseka Silvestro , Bossey Bunmi , Mengesha Wende , Muhyideen Oyekunle , Riberio Priscillia F. , Coulibaly Mmadou , Yacoubou Abdoul-Madjidou , Bankole Folusho A. , Adu Gloria Boakyewaa , Ojo Tayo 
Published: December 2022

Maize is a strategic food crop in sub-Saharan Africa. However, most maize growing tropical savannas particularly in West and Central African experience the occurrence of frequent droughts and Striga infestation, resulting in 30–100% yield losses. This production zones need maize cultivars that combine tolerance to the two stresses. IITA in collaboration with national partners has thus employed a sequential selection scheme to incorporate both drought tolerance and Striga resistance in topical maize hybrids using reliable screening protocols. The main objective of the present study was therefore to use grain yield and other agronomic traits recorded in regional collaborative hybrid trials conducted for 8 years under manged stressful and non-stressful conditions and across rainfed field environments to estimate genetic gains in grain yields using mixed model analyses. The results showed significant (p &lt; 0.05) annual yield gains of 11.89 kg ha−1 under manged drought stress (MDS) and 86.60 kg ha−1 under Striga infestation (STRIN) with concomitant yield increases of 62.65 kg ha−1 under full irrigation (WW), 102.44 kg ha−1 under Striga non-infested (STRNO) conditions and 53.11 kg ha−1 across rainfed field environments. Grain yield displayed significant but not strong genetic correlation of 0.41 ± 0.07 between MDS and STRIN, indicating that gene expression was not consistent across the two stress conditions. Furthermore, grain yield recorded in MET had significant moderate genetic correlations of 0.58 ± 0.06 and 0.44 ± 0.07It with MDS and STRIN, respectively. These results emphasize the need to screen inbred linens under both stress conditions to further enhance the rate of genetic gain in grain yield in hybrids for areas where the two stresses co-occur. Nonetheless, this study demonstrated that the sequential selection scheme has been successful in generating hybrids with dependable yields that can reduce chronic food deficits in rural communities experiencing simultaneous presence of drought and S. hermonthica infestation in their production fields.
Integrated single-cell and bulk RNA sequencing analyses reveal a prognostic signature of cancer-associated fibroblasts in head and neck squamous cell carcinoma
Authors: Yang Yichen , Ma Ben , Han Litao , Xu Weibo , Du Xiaoxue , Wei Wenjun , Liao Tian , Ji Qinghai , Qu Ning , Wang Yu 
Published: December 2022

Objectives: To identify a prognosis-related subtype of cancer-associated fibroblasts (CAFs) in head and neck squamous cell carcinoma (HNSCC) and comprehend its contributions to molecular characteristics, immune characteristics, and their potential benefits in immunotherapy and chemotherapy for HNSCC.Materials and Methods: We performed single-cell RNA sequencing (scRNA-seq) analysis of CAFs from the samples of HNSCC patients derived from Gene Expression Omnibus (GEO), to identify the prognosis-related subtype of CAFs. CAFs were clustered into five subtypes, and a prognosis-related subtype was identified. Univariate and multivariate cox regression analyses were performed on the cohort selected from The Cancer Genome Atlas (TCGA) to determine signature construction, which was validated in GSE65858 and GSE42743. A prognostic signature based on 4 genes was constructed, which were derived from prognosis-related CAFs. The molecular characteristics, immune characteristics as well as the predicted chemosensitivity and immunotherapeutic response in the signature-defined subgroups were analyzed subsequently.Results: The patients with higher CAF scores correlated with poor survival outcomes. Additionally, a high CAF score correlated with lower infiltration levels of many immune cells including M1 macrophages, CD8+ T cells, follicular T helper cells, monocytes, and naïve B cells. High CAF score also demonstrated different enrichment pathways, mutation genes and copy number variated genes. Furthermore, patients with high CAF scores showed lower sensitivity for chemotherapy and immunotherapy than those with low CAF scores.Conclusion: The results of our study indicate the potential of the CAF signature as a biomarker for the prognosis of HNSCC patients. Furthermore, the signature could be a prospective therapeutic target in HNSCC.
Pan-cancer analysis reveals NAA50 as a cancer prognosis and immune infiltration-related biomarker
Authors: Fang Tao , Wang Dingxin , Li Rongyang , Yu Wenhao , Tian Hui 
Published: December 2022

Background: N-Alpha-Acetyltransferase 50 (NAA50) has acetyltransferase activity and is important for chromosome segregation. However, the function and mechanism of NAA50 expression in cancer development was still unclear. Here, we systematically researched the function and mechanism of NAA50 in pan-cancer, and further verified the results of NAA50 in lung adenocarcinoma (LUAD).Methods: In this study, using the online databases TIMER2.0, SangerBox3.0, HPA, UCSC, GEPIA, cBioPortal, UALCAN, TISIDB, CancerSEA and LinkedOmics, we focused on the relevance between NAA50 and oncogenesis, progression, methylation, immune infiltration, function and prognosis. In addition, the proliferation of cells was detected by CCK-8 and Edu assay. Finally, we analyzed the relationship between the expression of NAA50 and cell cycle related proteins.Results: Pan-cancer analysis indicated that NAA50 was overexpressed in most cancers. And there was a significant correlation between NAA50 expression and the prognosis of cancer patients. In the meantime, NAA50 gene changes occur in a variety of tumors. Compared with normal tissues, the methylation level of NAA50 promoter increased in most cancer tissues. In addition, the results exhibited that in most cancers, NAA50 was significantly positively correlated with bone myeloid-derived suppressor cell (MDSC) infiltration and negatively correlated with T cell NK infiltration. Moreover, functional enrichment indicated that NAA50 regulates cell cycle and proliferation in LUAD. In vitro experiments testified that knockout of NAA50 could significantly inhibit the proliferation of LUAD.Conclusion: NAA50 may be a potential biomarker and oncogene of pan-cancer, especially LUAD, which may promote the occurrence and development of tumors through different mechanisms. Furthermore, NAA50 was bound up with to immune cell infiltration in pan-cancer, meaning NAA50 may be an important therapeutic target for human cancers.
Clinical, biochemical, and molecular genetic characteristics of patients with primary carnitine deficiency identified by newborn screening in Shanghai, China
Authors: Chang Siyu , Yang Yi , Xu Feng , Ji Wenjun , Zhan Xia , Gao Xiaolan , Chen Ting , Qiu Wenjuan , Zhang Huiwen , Liang Lili , Lu Deyun , Zhang Kaichuang , Gu Xuefan , Han Lianshu 
Published: December 2022

Background: Primary carnitine deficiency (PCD) is an autosomal recessive disease caused by mutations in the SLC22A5 gene, which encodes the organic cation transporter 2 (OCTN2). Patients with PCD may be at risk of skeletal or cardiac myopathy, metabolic decompensation, and even sudden death. This study aimed to analyze the biochemical, clinical, and genetic characteristics of PCD patients identified by newborn screening (NBS) in Shanghai.Methods: Dried blood spot (DBS) samples of newborns were analyzed through tandem mass spectrometry (MS/MS) from January 2003 to December 2021. Newborns with low free carnitine (C0) levels were recalled. Mutation in the SLC22A5 gene was analyzed on suspected positive newborns with low C0 levels after recall.Results: 1,247,274 newborns were screened by MS/MS and 40 newborns were diagnosed with PCD, therefore the incidence of PCD in Shanghai was approximately 1:31,200. The mean C0 level in newborns with PCD was 5.37 ± 1.79 μmol/L before treatment and increased to 24.45 ± 10.87 μmol/L after treatment with L-carnitine. Twenty-three different variants were identified in the SLC22A5 gene, including 8 novel variants, of which c.51C&gt;G (p.F17L) was the most frequent (27.27%, 18/66), followed by c.1400C&gt;G (p.S467C) (25.76%, 17/66). Almost all the screened PCD patients were asymptomatic.Conclusion: NBS via MS/MS was a quick and efficient method for the early diagnosis of PCD. The incidence of PCD in Shanghai was 1:31,200. Eight novel variants were identified, which greatly expanded the variant spectrum of SLC22A5. MS/MS combined with genetic testing could effectively improve the diagnostic accuracy of PCD.
Trickle infection with Heligmosomoides polygyrus results in decreased worm burdens but increased intestinal inflammation and scarring
Authors: Ariyaratne Anupama , Kim Sang Yong , Pollo Stephen M. J. , Perera Shashini , Liu Hongrui , Nguyen William N. T. , Coria Aralia Leon , Luzzi Mayara de Cassia , Bowron Joel , Szabo Edina K. , Patel Kamala D. , Wasmuth James D. , Nair Meera G. , Finney Constance A. M. 
Published: December 2022

IntroductionIntestinal roundworms cause chronic debilitating disease in animals, including humans. Traditional experimental models of these types of infection use a large single-dose infection. However, in natural settings, hosts are exposed to parasites on a regular basis and when mice are exposed to frequent, smaller doses of Heligmosomoides polygyrus, the parasites are cleared more quickly. Whether this more effective host response has any negative consequences for the host is not known.ResultsUsing a trickle model of infection, we found that worm clearance was associated with known resistance-related host responses: increased granuloma and tuft cell numbers, increased levels of granuloma IgG and decreased intestinal transit time, as well as higher serum IgE levels. However, we found that the improved worm clearance was also associated with an inflammatory phenotype in and around the granuloma, increased smooth muscle hypertrophy/hyperplasia, and elevated levels of Adamts gene expression.DiscussionTo our knowledge, we are the first to identify the involvement of this protein family of matrix metalloproteinases (MMPs) in host responses to helminth infections. Our results highlight the delicate balance between parasite clearance and host tissue damage, which both contribute to host pathology. When continually exposed to parasitic worms, improved clearance comes at a cost.
Upregulated antimicrobial immune response mediated by neutrophils in the development from allergic rhinitis to asthma
Authors: Li Lisha , Zhang Hao , Wang Xiujie , Wang Zixi , Cui Le , Xu Yingyang , Guan Kai 
Published: December 2022

BackgroundAllergic rhinitis (AR) and asthma are closely related, and AR is regarded as an important risk factor for the onset of asthma. However, the pathogenesis of the development of asthma from AR is still undefined.ObjectiveThe aim of this study was to investigate the mechanisms underlying the development of asthma from AR by comparing the transcriptome features of patients with AR with and without asthma.MethodsPatients with AR with or without asthma caused by weed pollen who presented to the Allergy Clinic of Peking Union Medical College Hospital were recruited for this study. Peripheral blood samples of all the patients were collected during the weed pollen season (September) when the patients had allergic symptoms and outside the pollen season (November) when the patients had no symptoms. Transcriptomic analysis was conducted, and the differentially expressed genes (DEGs) and enriched immune pathways between the patients with AR with asthma (AR-asthma group) and those without asthma (AR group) were identified. In addition, the expression levels of some pivotal differentially expressed RNAs were quantified using quantitative polymerase chain reaction (PCR).ResultsDuring the weed pollen season, the immune-related Gene Ontology (GO) terms with P value &lt; 0.05, enriched by the upregulated genes in the AR-asthma group compared to the AR group included antifungal humoral response, neutrophil-mediated killing of bacterium, antibacterial humoral response, antimicrobial humoral immune response mediated by antimicrobial peptides, and regulation of the T cell receptor signaling pathway. The immune-related GO terms with P values &lt;0.05 enriched by downregulated genes were positive regulation of natural killer cell-mediated cytotoxicity, microglial cell activation, natural killer cell activation, and leukocyte-mediated cytotoxicity. The GO term of antimicrobial humoral immune response mediated by antimicrobial peptides was upregulated both during and outside the pollen season, and the upregulated expression of three DEGs (LTF, PF4, and ELANE) included in this term was verified through quantitative PCR.ConclusionsThe activation of the antimicrobial immune response mediated by neutrophils and the depression of cytotoxicity mediated by natural killer cells may play roles in the progression from AR to asthma.
Combination TIGIT/PD-1 blockade enhances the efficacy of neoantigen vaccines in a model of pancreatic cancer
Authors: Peng Hui , Li Lijin , Zuo Chong , Chen Michael Y. , Zhang Xiuli , Myers Nancy B. , Hogg Graham D. , DeNardo David G. , Goedegebuure S. Peter , Hawkins William G. , Gillanders William E. 
Published: December 2022

BackgroundCancer neoantigens are important targets of cancer immunotherapy and neoantigen vaccines are currently in development in pancreatic ductal adenocarcinoma (PDAC) and other cancer types. Immune regulatory mechanisms in pancreatic cancer may limit the efficacy of neoantigen vaccines. Targeting immune checkpoint signaling pathways in PDAC may improve the efficacy of neoantigen vaccines.MethodsWe used KPC4580P, an established model of PDAC, to test whether neoantigen vaccines can generate therapeutic efficacy against PDAC. We focused on two immunogenic neoantigens associated with genetic alterations in the CAR12 and CDK12 genes. We tested a neoantigen vaccine comprised of two 20-mer synthetic long peptides and poly IC, a Toll-like receptor (TLR) agonist. We investigated the ability of neoantigen vaccine alone, or in combination with PD-1 and TIGIT signaling blockade to impact tumor growth. We also assessed the impact of TIGIT signaling on T cell responses in human PDAC.ResultsNeoantigen vaccines induce neoantigen-specific T cell responses in tumor-bearing mice and slow KPC4580P tumor growth. However, KPC4580P tumors express high levels of PD-L1 and the TIGIT ligand, CD155. A subset of neoantigen-specific T cells in KPC4580P tumors are dysfunctional, and express high levels of TIGIT. PD-1 and TIGIT signaling blockade in vivo reverses T cell dysfunction and enhances neoantigen vaccine-induced T cell responses and tumor regression. In human translational studies, TIGIT signaling blockade in vitro enhances neoantigen-specific T cell function following vaccination.ConclusionsTaken together, preclinical and human translational studies support testing neoantigen vaccines in combination with therapies targeting the PD-1 and TIGIT signaling pathways in patients with PDAC.
Pathogen spectrum and immunotherapy in patients with anti-IFN-γ autoantibodies: A multicenter retrospective study and systematic review
Authors: Qiu Ye , Fang Gaoneng , Ye Feng , Zeng Wen , Tang Mengxin , Wei Xuan , Yang Jinglu , Li Zhengtu , Zhang Jianquan 
Published: December 2022

BackgroundAnti-interferon-γ autoantibody (AIGA) positivity is an emerging immunodeficiency syndrome closely associated with intracellular infection in individuals without human immunodeficiency virus (HIV). However, the information on epidemiology, pathogen spectrum, and immunotherapy among these patients lack a systematic description of large data.MethodsThis systematic literature review and multicenter retrospective study aimed to describe the pathogen spectrum and review treatment strategies among patients with AIGA positivity.ResultsWe included 810 HIV-negative patients with AIGA positivity infected with one or more intracellular pathogens. Excluding four teenagers, all the patients were adults. The most common pathogen was nontuberculous mycobacteria (NTM) (676/810, 83.5%). A total of 765 NTM isolates were identified in 676 patients with NTM, including 342 (44.7%) rapid-grower mycobacteria, 273 (35.7%) slow-grower mycobacteria, and 150 (19.6%) unidentified NTM subtype. Even with long-term and intensive antimicrobial treatments, 42.6% of patients with AIGA positivity had recurrence and/or persistent infection. Sixty-seven patients underwent immunoregulatory or immunosuppressive therapy, and most (60) achieved remission. The most common treatment strategy was rituximab (27/67, 40.3%) and cyclophosphamide (22/67, 32.8%), followed by cyclophosphamide combined with glucocorticoids (8/67, 11.9%).ConclusionsIntracellular pathogen was the most common infection in patients with AIGA positivity. The predominant infection phenotypes were NTM, varicella-zoster virus, Talaromyces marneffei, and Salmonella spp., with or without other opportunistic infections. AIGA immunotherapy, including rituximab or cyclophosphamide, has yielded good preliminary results in some cases.