bluuebunny/crossref_metadata_2025 huggingface dataset:
Convalescent human IgG, but not IgM, from COVID-19 survivors confers dose-dependent protection against SARS-CoV-2 replication and disease in hamsters
Authors: King Hannah A. D. , Dussupt Vincent , Mendez-Rivera Letzibeth , Slike Bonnie M. , Tran Ursula , Jackson Nathan D. , Barkei Erica , Zemil Michelle , Tourtellott-Fogt Emily , Kuklis Caitlin H. , Soman Sandrine , Ahmed Aslaa , Porto Maciel , Kitajewski Christopher , Spence Brittany , Benetiene Dalia , Wieczorek Lindsay , Kar Swagata , Gromowski Gregory , Polonis Victoria R. , Krebs Shelly J. , Modjarrad Kayvon , Bolton Diane L.
Published: March 2023

Introduction

Antibody therapeutic strategies have served an important role during the COVID-19 pandemic, even as their effectiveness has waned with the emergence of escape variants. Here we sought to determine the concentration of convalescent immunoglobulin required to protect against disease from SARS-CoV-2 in a Syrian golden hamster model.

Methods

Total IgG and IgM were isolated from plasma of SARS-CoV-2 convalescent donors. Dose titrations of IgG and IgM were infused into hamsters 1 day prior to challenge with SARS-CoV-2 Wuhan-1.

Results

The IgM preparation was found to have ~25-fold greater neutralization potency than IgG. IgG infusion protected hamsters from disease in a dose-dependent manner, with detectable serum neutralizing titers correlating with protection. Despite a higher in vitro neutralizing potency, IgM failed to protect against disease when transferred into hamsters.

Discussion

This study adds to the growing body of literature that demonstrates neutralizing IgG antibodies are important for protection from SARS-CoV-2 disease, and confirms that polyclonal IgG in sera can be an effective preventative strategy if the neutralizing titers are sufficiently high. In the context of new variants, against which existing vaccines or monoclonal antibodies have reduced efficacy, sera from individuals who have recovered from infection with the emerging variant may potentially remain an efficacious tool.
Single-cell RNA analysis to identify five cytokines signaling in immune-related genes for melanoma survival prognosis
Authors: Pu Zuhui , Zhao Qing , Chen Jiaqun , Xie Yubin , Mou Lisha , Zha Xushan
Published: March 2023

Melanoma is one of the deadliest skin cancers. Recently, developed single-cell sequencing has revealed fresh insights into melanoma. Cytokine signaling in the immune system is crucial for tumor development in melanoma. To evaluate melanoma patient diagnosis and treatment, the prediction value of cytokine signaling in immune-related genes (CSIRGs) is needed. In this study, the machine learning method of least absolute selection and shrinkage operator (LASSO) regression was used to establish a CSIRG prognostic signature of melanoma at the single-cell level. We discovered a 5-CSIRG signature that was substantially related to the overall survival of melanoma patients. We also constructed a nomogram that combined CSIRGs and clinical features. Overall survival of melanoma patients can be consistently predicted with good performance as well as accuracy by both the 5-CSIRG signature and nomograms. We compared the melanoma patients in the CSIRG high- and low-risk groups in terms of tumor mutation burden, infiltration of the immune system, and gene enrichment. High CSIRG-risk patients had a lower tumor mutational burden than low CSIRG-risk patients. The CSIRG high-risk patients had a higher infiltration of monocytes. Signaling pathways including oxidative phosphorylation, DNA replication, and aminoacyl tRNA biosynthesis were enriched in the high-risk group. For the first time, we constructed and validated a machine-learning model by single-cell RNA-sequencing datasets that have the potential to be a novel treatment target and might serve as a prognostic biomarker panel for melanoma. The 5-CSIRG signature may assist in predicting melanoma patient prognosis, biological characteristics, and appropriate therapy.
The impacts of extreme marine weather and marine scientific and technological innovation on marine economic development: Evidence form China’s coastal regions
Authors: Li Chenggang , Jia Hongye , Wan Yikang , Hu Yongxiang , Zeng Bingying , Zhang Wanyue , Fan Xiangbo , Lin Tao , Shang Guofei , Wang Weiyan
Published: March 2023

The extreme marine weather is a very vital factor and has important implications for of marine economic development. However, there is a lack of systematic and quantitative analyses of its impact on the marine economic development. Here, we study the impacts of extreme marine weather on marine economic development of 11 coastal regions in China, using the dynamic panel model. We found that extreme marine weather exerts a significant negative impact on the marine economic development. The marine scientific and technological innovation promotes marine economic development in a prominent manner. The marine scientific and technological innovation slows down the unfavorable impact of extreme marine weather on the marine economy. After considering different industries for marine economic development and heterogeneity, we found that extreme marine weather and marine scientific and technological innovation have a great impact on marine economic development in the tertiary industry and the areas with high development concerning marine economy level, while deliver a small impact on the marine economic development in the primary industry and the areas low development level. This paper empirically studies the relationship between the two variables of marine extreme weather and marine science and technology innovation and its impact on marine economic development, enriches the research perspective of extreme weather on marine economic development, and provides new method evidence for improving the level of marine scientific and technological innovation and promoting the development of marine economy.
Larvae of an invasive scarab increase greenhouse gas emissions from soils and recruit gut mycobiota involved in C and N transformations
Authors: Avila-Arias Helena , Turco Ronald F. , Scharf Michael E. , Groves Russell L. , Richmond Douglas S.
Published: March 2023

Background

Soil-derived prokaryotic gut communities of the Japanese beetle Popillia japonica Newman (JB) larval gut include heterotrophic, ammonia-oxidizing, and methanogenic microbes potentially capable of promoting greenhouse gas (GHG) emissions. However, no research has directly explored GHG emissions or the eukaryotic microbiota associated with the larval gut of this invasive species. In particular, fungi are frequently associated with the insect gut where they produce digestive enzymes and aid in nutrient acquisition. Using a series of laboratory and field experiments, this study aimed to (1) assess the impact of JB larvae on soil GHG emissions; (2) characterize gut mycobiota associated with these larvae; and (3) examine how soil biological and physicochemical characteristics influence variation in both GHG emissions and the composition of larval gut mycobiota.

Methods

Manipulative laboratory experiments consisted of microcosms containing increasing densities of JB larvae alone or in clean (uninfested) soil. Field experiments included 10 locations across Indiana and Wisconsin where gas samples from soils, as well as JB and their associated soil were collected to analyze soil GHG emissions, and mycobiota (ITS survey), respectively.

Results

In laboratory trials, emission rates of CO2, CH4, and N2O from infested soil were ≥ 6.3× higher per larva than emissions from JB larvae alone whereas CO2 emission rates from soils previously infested by JB larvae were 1.3× higher than emissions from JB larvae alone. In the field, JB larval density was a significant predictor of CO2 emissions from infested soils, and both CO2 and CH4 emissions were higher in previously infested soils. We found that geographic location had the greatest influence on variation in larval gut mycobiota, although the effects of compartment (i.e., soil, midgut and hindgut) were also significant. There was substantial overlap in the composition and prevalence of the core fungal mycobiota across compartments with prominent fungal taxa being associated with cellulose degradation and prokaryotic methane production/consumption. Soil physicochemical characteristics such as organic matter, cation exchange capacity, sand, and water holding capacity, were also correlated with both soil GHG emission, and fungal a-diversity within the JB larval gut. Conclusions: Results indicate JB larvae promote GHG emissions from the soil directly through metabolic activities, and indirectly by creating soil conditions that favor GHG-associated microbial activity. Fungal communities associated with the JB larval gut are primarily influenced by adaptation to local soils, with many prominent members of that consortium potentially contributing to C and N transformations capable of influencing GHG emissions from infested soil.
Soil texture and microorganisms dominantly determine the subsoil carbonate content in the permafrost-affected area of the Tibetan Plateau
Authors: Shao Ming , Zhang Shengyin , Pei Yu , Song Sen , Lei Tianzhu , Yun Hanbo
Published: March 2023

Under climate warming conditions, storage and conversion of soil inorganic carbon (SIC) play an important role in regulating soil carbon (C) dynamics and atmospheric CO2 content in arid and semi-arid areas. Carbonate formation in alkaline soil can fix a large amount of C in the form of inorganic C, resulting in soil C sink and potentially slowing global warming trends. Therefore, understanding the driving factors affecting carbonate mineral formation can help better predict future climate change. Till date, most studies have focused on abiotic drivers (climate and soil), whereas a few examined the effects of biotic drivers on carbonate formation and SIC stock. In this study, SIC, calcite content, and soil microbial communities were analyzed in three soil layers (0–5 cm, 20–30 cm, and 50–60 cm) on the Beiluhe Basin of Tibetan Plateau. Results revealed that in arid and semi-arid areas, SIC and soil calcite content did not exhibit significant differences among the three soil layers; however, the main factors affecting the calcite content in different soil layers are different. In the topsoil (0–5 cm), the most important predictor of calcite content was soil water content. In the subsoil layers 20–30 cm and 50–60 cm, the ratio of bacterial biomass to fungal biomass (B/F) and soil silt content, respectively, had larger contributions to the variation of calcite content than the other factors. Plagioclase provided a site for microbial colonization, whereas Ca2+ contributed in bacteria-mediated calcite formation. This study aims to highlight the importance of soil microorganisms in managing soil calcite content and reveals preliminary results on bacteria-mediated conversion of organic to inorganic C.
A novel Toxoplasma gondii TGGT1_316290 mRNA-LNP vaccine elicits protective immune response against toxoplasmosis in mice
Authors: Li Dan , Zhang Yizhuo , Li Shiyu , Zheng Bin
Published: March 2023

Toxoplasma gondii (T. gondii) can infect almost all warm-blooded animals and is a major threat to global public health. Currently, there is no effective drug or vaccine for T. gondii. In this study, bioinformatics analysis on B and T cell epitopes revealed that TGGT1_316290 (TG290) had superior effects compared with the surface antigen 1 (SAG1). TG290 mRNA-LNP was constructed through the Lipid Nanoparticle (LNP) technology and intramuscularly injected into the BALB/c mice, and its immunogenicity and efficacy were explored. Analysis of antibodies, cytokines (IFN-γ, IL-12, IL-4, and IL-10), lymphocytes proliferation, cytotoxic T lymphocyte activity, dendritic cell (DC) maturation, as well as CD4+ and CD8+ T lymphocytes revealed that TG290 mRNA-LNP induced humoral and cellular immune responses in vaccinated mice. Furthermore, T-Box 21 (T-bet), nuclear factor kappa B (NF-kB) p65, and interferon regulatory factor 8 (IRF8) subunit were over-expressed in the TG290 mRNA-LNP-immunized group. The survival time of mice injected with TG290 mRNA-LNP was significantly longer (18.7 ± 3 days) compared with the survival of mice of the control groups (p < 0.0001). In addition, adoptive immunization using 300 μl serum and lymphocytes (5*107) of mice immunized with TG290 mRNA-LNP significantly prolonged the survival time of these mice. This study demonstrates that TG290 mRNA-LNP induces specific immune response against T. gondii and may be a potential toxoplasmosis vaccine candidate for this infection.
On gaps of clinical diagnosis of dementia subtypes: A study of Alzheimer’s disease and Lewy body disease
Authors: Wei Hui , Masurkar Arjun V. , Razavian Narges
Published: March 2023

Introduction

Alzheimer’s disease (AD) and Lewy body disease (LBD) are the two most common neurodegenerative dementias and can occur in combination (AD+LBD). Due to overlapping biomarkers and symptoms, clinical differentiation of these subtypes could be difficult. However, it is unclear how the magnitude of diagnostic uncertainty varies across dementia spectra and demographic variables. We aimed to compare clinical diagnosis and post-mortem autopsy-confirmed pathological results to assess the clinical subtype diagnosis quality across these factors.

Methods

We studied data of 1,920 participants recorded by the National Alzheimer’s Coordinating Center from 2005 to 2019. Selection criteria included autopsy-based neuropathological assessments for AD and LBD, and the initial visit with Clinical Dementia Rating (CDR) stage of normal, mild cognitive impairment, or mild dementia. Longitudinally, we analyzed the first visit at each subsequent CDR stage. This analysis included positive predictive values, specificity, sensitivity and false negative rates of clinical diagnosis, as well as disparities by sex, race, age, and education. If autopsy-confirmed AD and/or LBD was missed in the clinic, the alternative clinical diagnosis was analyzed.

Findings

In our findings, clinical diagnosis of AD+LBD had poor sensitivities. Over 61% of participants with autopsy-confirmed AD+LBD were diagnosed clinically as AD. Clinical diagnosis of AD had a low sensitivity at the early dementia stage and low specificities at all stages. Among participants diagnosed as AD in the clinic, over 32% had concurrent LBD neuropathology at autopsy. Among participants diagnosed as LBD, 32% to 54% revealed concurrent autopsy-confirmed AD pathology. When three subtypes were missed by clinicians, “No cognitive impairment” and “primary progressive aphasia or behavioral variant frontotemporal dementia” were the leading primary etiologic clinical diagnoses. With increasing dementia stages, the clinical diagnosis accuracy of black participants became significantly worse than other races, and diagnosis quality significantly improved for males but not females.

Discussion

These findings demonstrate that clinical diagnosis of AD, LBD, and AD+LBD are inaccurate and suffer from significant disparities on race and sex. They provide important implications for clinical management, anticipatory guidance, trial enrollment and applicability of potential therapies for AD, and promote research into better biomarker-based assessment of LBD pathology.
Critical closing pressure as a new hemodynamic marker of cerebral small vessel diseases burden
Authors: Fu Xian , Zhang Weijin , Li Xianliang , Liu Hongying , Zhang Yin , Gao Qingchun
Published: March 2023

Purpose

To investigate cerebrovascular hemodynamics, including critical closing pressure (CrCP) and pulsatility index (PI), and their independent relationship with cerebral small vessel disease (CSVD) burden in patients with small-vessel occlusion (SVO).

Methods

We recruited consecutive patients with SVO of acute cerebral infarction who underwent brain magnetic resonance imaging (MRI), transcranial Doppler (TCD) and CrCP during admission. Cerebrovascular hemodynamics were assessed using TCD. We used the CSVD score to rate the total MRI burden of CSVD. Multiple regression analysis was used to determine parameters related to CSVD burden or CrCP.

Results

Ninety-seven of 120 patients (mean age, 64.51 ± 9.99 years; 76% male) completed the full evaluations in this study. We observed that CrCP was an independent determinant of CSVD burden in four models [odds ratio, 1.41; 95% confidence interval (CI), 1.17–1.71; P < 0.001] and correlated with CSVD burden [β (95% CI): 0.05 (0.04–0.06); P < 0.001]. In ROC analysis, CrCP was considered as a predictor of CSVD burden, and AUC was 86.2% (95% CI, 78.6–93.9%; P < 0.001). Multiple linear regression analysis showed that CrCP was significantly correlated with age [β (95% CI): 0.27 (0.06 to 0.47); P = 0.012], BMI [β (95% CI): 0.61 (0.00–1.22)] and systolic BP [β (95% CI): 0.16 (0.09–0.23); P < 0.001].

Conclusions

CrCP representing cerebrovascular tension is an independent determinant and predictor of CSVD burden. It was significantly correlated with age, BMI and systolic blood pressure. These results provide new insights in the mechanism of CSVD development.
Association between serologically confirmed COVID-19 infection and cognitive functioning in community dwelling older adults
Authors: Serena Sabatini , Deborah Pacifico , Anja Frei , Gwendolyn Graf , Puhan Milo A. , Albanese Emiliano
Published: March 2023

Introduction

COVID-19 infection can impact the central nervous system, and is often associated with cognitive decline. However, there are no studies linking serologically confirmed COVID-19 infection with objectively assessed cognitive functioning. We explored whether presence of SARS-CoV-2 antibodies account for variability in participants’ scores on a neuropsychological assessment.

Methods

In this cross-sectional study participants were 657 (mean age = 72.97; SD = 6.07 years; women = 47.7%) individuals randomly selected from the general population of the canton of Zurich and included in the Corona Immunitas study. We conducted serological tests between October 2020 and May 2021 to detect and quantify SARS-CoV-2 antibodies in peripheral venous blood samples. We assessed cognitive function, vaccination status (vaccinated; not vaccinated), number of health conditions, and demographic variables between January and August 2021. We studied the association between seropositivity and global cognitive function and five cognitive domains (language expression, language comprehension, temporal orientation, spatial orientation, and memory) with linear regression models. Based on SARS-CoV-2 antibodies and vaccination status, we stratified participants into three groups: No SARS-CoV-2 antibodies (N = 402); SARS-CoV-2 antibodies due to vaccination (N = 218); history of SARS-CoV-2 infection and no vaccination (N = 37).

Results

In the regression model adjusted for age, sex, educational level, and number of health conditions, compared to those without SARS-CoV-2 antibodies, those with SARS-CoV-2 antibodies due to vaccination had better global cognitive functioning (Standardized beta = 0.10; 95% CI = 0.02; 0.17), and those with SARS-CoV-2 antibodies due to infection had poorer cognitive functioning (Standardized beta = −0.10; 95% CI = −0.18; −0.03). Regarding cognitive domains, compared to those without SARS-CoV-2 antibodies, those with SARS-CoV-2 antibodies due to infection scored more poorly on language comprehension and temporal orientation, and those with SARS-CoV-2 antibodies due to vaccination scored better on memory.

Discussion

By linking serologically confirmed presence of SARS-CoV-2 antibodies to poorer global cognitive functioning in community dwelling older adults we strengthen existing evidence in support of cognitive decline related to COVID-19. Given the large number of infected older adults, and the endurance of the pandemic, our results highlight the need to address COVID-19 related cognitive decline in the clinical and public health areas of prevention, diagnosis, and treatment.
Prolonged exposure of neonatal mice to sevoflurane leads to hyper-ramification in microglia, reduced contacts between microglia and synapses, and defects in adult behavior
Authors: Li Hong , Zhou Bin , Liao Ping , Liao Daqing , Yang Linghui , Wang Jing , Liu Jin , Jiang Ruotian , Chen Lingmin
Published: March 2023

Background

Prolonged exposure to general anesthetics during development is known to cause neurobehavioral abnormalities, but the cellular and molecular mechanisms involved are unclear. Microglia are the resident immune cells in the central nervous system and play essential roles in normal brain development.

Materials and methods

In the study, postnatal day 7 (P7) C57BL/6 mice were randomly assigned to two groups. In the sevoflurane (SEVO), mice were exposed to 2.5% sevoflurane for 4 h. In the control group, mice were exposed to carrier gas (30% O2/70% N2) for 4 h. Fixed brain slices from P14 to P21 mice were immunolabeled for ionized calcium-binding adapter molecule 1 (IBA-1) to visualize microglia. The morphological analysis of microglia in the somatosensory cortex was performed using ImageJ and Imaris software. Serial block face scanning electron microscopy (SBF-SEM) was performed to assess the ultrastructure of the microglia and the contacts between microglia and synapse in P14 and P21 mice. The confocal imaging of brain slices was performed to assess microglia surveillance in resting and activated states in P14 and P21 mice. Behavioral tests were used to assess the effect of microglia depletion and repopulation on neurobehavioral abnormalities caused by sevoflurane exposure.

Results

The prolonged exposure of neonatal mice to sevoflurane induced microglia hyper-ramification with an increase in total branch length, arborization area, and branch complexity 14  days after exposure. Prolonged neonatal sevoflurane exposure reduced contacts between microglia and synapses, without affecting the surveillance of microglia in the resting state or responding to laser-induced focal brain injury. These neonatal changes in microglia were associated with anxiety-like behaviors in adult mice. Furthermore, microglial depletion before sevoflurane exposure and subsequent repopulation in the neonatal brain mitigated anxiety-like behaviors caused by sevoflurane exposure.

Conclusion

Our experiments indicate that general anesthetics may harm the developing brain, and microglia may be an essential target of general anesthetic-related developmental neurotoxicity.
The influence of high worry on static and dynamic insular functional connectivity
Authors: Zhang Youxue , Cai Xueli , Duan Mingjun , He Hui
Published: March 2023

Worry is a form of repetitive negative thought. High worry-proneness is one risk factor leading to anxiety disorder. Several types of research indicated that anxiety disorder was highly associated with disrupted interoception. The insula is consistently considered to play a key role in interoception. However, the relationship between worry and the interoception network is poorly investigated in worry-prone individuals. Thus, it is essential to identify the neural characteristic of high worry-proneness subjects. A total of 32 high worry-proneness (HWP) subjects and 25 low worry-proneness (LWP) subjects were recruited and underwent magnetic resonance imaging scanning. Six subregions of insula were chosen as regions of interest. Then, seed-based static and dynamic functional connectivity were calculated. Increased static functional connectivity was observed between the ventral anterior insula and inferior parietal lobule in HWP compared to LWP. Decreased static functional connectivity was found between the left ventral anterior insula and the pregenual anterior cingulate cortex. Decreased dynamic functional connectivity was also shown between the right posterior insula and the inferior parietal lobule in HWP. Moreover, a post-hoc test exploring the effect of changed function within the insular region confirmed that a significant positive relationship between static functional connectivity (ventral anterior insula–inferior parietal lobule) and dynamic functional connectivity (posterior insula–inferior parietal lobule) in LWP but not in HWP. Our results might suggest that deficient insular function may be an essential factor related to high worry in healthy subjects.
Sexual dysfunction precedes motor defects, dopaminergic neuronal degeneration, and impaired dopamine metabolism: Insights from Drosophila model of Parkinson’s disease
Authors: Koza Zevelou , Ayajuddin Mohamad , Das Abhik , Chaurasia Rahul , Phom Limamanen , Yenisetti Sarat Chandra
Published: March 2023

Sexual dysfunction (SD) is one of the most common non-motor symptoms of Parkinson’s disease (PD) and remains the most neglected, under-reported, and under-recognized aspect of PD. Studies have shown that Dopamine (DA) in the hypothalamus plays a role in regulating sexual behavior. But the detailed mechanism of SD in PD is not known. Drosophila melanogaster shares several genes and signaling pathways with humans which makes it an ideal model for the study of a neurodegenerative disorder such as PD. Courtship behavior of Drosophila is one such behavior that is closely related to human sexual behavior and so plays an important role in understanding sexual behavior in diseased conditions as well. In the present study, a sporadic SD model of PD using Drosophila was developed and SD phenotype was observed based on abnormalities in courtship behavior markers. The Drosophila SD model was developed in such a way that at the window of neurotoxin paraquat (PQ) treatment [PQ is considered a crucial risk factor for PD due to its structural similarity with 1-methyl-4-phenyl pyridinium (MPP+), the active form of PD-inducing agent, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)], it does not exhibit mobility defects but shows SD. The whole brain tyrosine hydroxylase immunostaining showed no observable dopaminergic (DAergic) degeneration (number of DA neurons and fluorescence intensity of fluorescently labeled secondary antibodies that target anti-TH primary antibody) of the SD model. Similarly, there was no significant depletion of brain DA and its metabolite levels (HVA and DOPAC) as determined using HPLC-ECD (High-Performance Liquid Chromatography using Electrochemical Detector). The present study illustrates that the traits associated with courtship and sexual activity provide sensitive markers at the earlier stage of PD onset. This PQ-induced SD fly model throws an opportunity to decipher the molecular basis of SD under PD conditions and to screen nutraceuticals/potential therapeutic molecules to rescue SD phenotype and further to DAergic neuroprotection.
Activation of POMC neurons to adiponectin participating in EA-mediated improvement of high-fat diet IR mice
Authors: Xu Wanling , Li Junfeng , Ji Chang , Fang Danwei , Yao Lulu , Xu Nenggui , Yi Wei
Published: March 2023

Background

Insulin resistance (IR) is one of the common pathological manifestations of metabolic-related diseases, and the prevalence of relevant diseases is high. Acupuncture is beneficial to IR patients, but the central mechanism underlying this treatment remains unclear. This study provides mechanistic insights into how electroacupuncture (EA) improves IR through the response of Pro-opiomelanocortin (POMC) neurons to adiponectin (Adipo).

Methods

Glucose tolerance tests (GTT), Insulin tolerance tests (ITT) and fasting blood glucose (FBG) were detected by glucometer. Serum insulin, Adipo and skeletal muscle adiponectin receptor 1 (AdipoR1) protein levels were examined by ELISA. Homeostasis model assessment estimated insulin resistance (HOMA-IR) was calculated using the following formula: HOMA-IR = fasting insulin (FINS) (mU/L) × FBG (mmol/L)/22.5. The expression levels of AdipoR1 and Adipo mRNA in skeletal muscle were detected by real-time PCR quantification. The co-marking of c-Fos/AdipoR1 and POMC neurons were investigated using immunofluorescence. Spontaneous excitatory postsynaptic currents (sEPSCs) of POMC neurons and the response of POMC neurons to Adipo were detected via electrophysiology.

Results

EA significantly ameliorated HFD-induced impairment of GTT, ITT, FBG, and HOMA-IR which was correlated with recovery of the expression level of AdipoR1 and Adipo in skeletal muscle. The improved response of POMC neurons to Adipo in the hypothalamus may be a key factor in correcting abnormal glucose tolerance and improving IR.

Conclusion

This study demonstrates that EA can ameliorate HFD-induced impaired glucose tolerance through improved response of POMC neurons to Adipo in the hypothalamus, providing insight into the central mechanism of improving IR through EA.
Osteoid cell-derived chemokines drive bone-metastatic prostate cancer
Authors: Johnson Catherine S. , Cook Leah M.
Published: March 2023

One of the greatest challenges in improving prostate cancer (PCa) survival is in designing new therapies to effectively target bone metastases. PCa regulation of the bone environment has been well characterized; however, bone-targeted therapies have little impact on patient survival, demonstrating a need for understanding the complexities of the tumor-bone environment. Many factors contribute to creating a favorable microenvironment for prostate tumors in bone, including cell signaling proteins produced by osteoid cells. Specifically, there has been extensive evidence from both past and recent studies that emphasize the importance of chemokine signaling in promoting PCa progression in the bone environment. Chemokine-focused strategies present promising therapeutic options for treating bone metastasis. These signaling pathways are complex, with many being produced by (and exerting effects on) a plethora of different cell types, including stromal and tumor cells of the prostate tumor-bone microenvironment. ​This review highlights an underappreciated molecular family that should be interrogated for treatment of bone metastatic prostate cancer (BM-PCa).
Identification of endothelial-related molecular subtypes for bladder cancer patients
Authors: Li Deng-xiong , Feng De-chao , Shi Xu , Wu Rui-cheng , Chen Kai , Han Ping
Published: March 2023

Background

Bladder cancer (BC) is a disease with significant heterogeneity and poor prognosis. The prognosis and therapeutic response of BC patients are significantly influenced by endothelial cells in the tumor microenvironment. In order to understand BC from the perspective of endothelial cells, we orchestrated molecular subtypes and identified key genes.

Methods

Single-cell and bulk RNA sequencing data were extracted from online databases. R and its relative packages were used to analyze these data. Cluster analysis, prognostic value analysis, function analysis, immune checkpoints, tumor immune environment and immune prediction were conducted.

Results

Five endothelial-related genes (CYTL1, FAM43A, HSPG2, RBP7, and TCF4) divided BC patients in the TCGA, GSE13507, and GSE32894 datasets into two clusters, respectively. In prognostic value analysis, patients in the cluster 2 were substantially associated with worse overall survival than those in the cluster 1 according to the results of TCGA, GSE13507 and GSE32894 datasets. In the results of functional analysis, the endothelial-related clusters was enriched in immune-related, endothelial-related and metabolism-related pathways. Samples in the cluster 1 had a statistically significant increase in CD4+ T cells and NK-cell infiltration. Cluster 1 was positively correlated with the cancer stem score and tumor mutational burden score. The results of immune prediction analysis indicated that 50.6% (119/235) of patients in the cluster 1 responded to immunotherapy, while the response rate in the cluster 2 decreased to 16.7% (26/155).

Conclusion

In this study, we categorized and discovered distinctive prognosis-related molecular subtypes and key genes from the perspective of endothelial cells at the genetic level by integrating single-cell and bulk RNA sequencing data, primarily to provide a roadmap for precision medicine.
A novel BRCA1 splicing variant detected in an early onset triple-negative breast cancer patient additionally carrying a pathogenic variant in ATM: A case report
Authors: Colombo Mara , Mondini Patrizia , Minenza Elisa , Foglia Claudia , Mosconi Annamaria , Molica Carmen , Pistola Lorenza , Ludovini Vienna , Radice Paolo
Published: March 2023

The widespread adoption of gene panel testing for cancer predisposition is leading to the identification of an increasing number of individuals with clinically relevant allelic variants in two or more genes. The potential combined effect of these variants on cancer risks is mostly unknown, posing a serious problem for genetic counseling in these individuals and their relatives, in whom the variants may segregate singly or in combination. We report a female patient who developed triple-negative high grade carcinoma in the right breast at the age of 36 years. The patient underwent bilateral mastectomy followed by combined immunotherapy and chemotherapy (IMpassion030 clinical trial). Two years later she developed a skin recurrence on the right anterior chest wall. Despite intensive treatment, the patient died at 40-year-old due to disease progression. Gene panel testing of patient’s DNA revealed the presence of a protein truncating variant in ATM [c.1672G>T; p.(Gly558Ter)] and of a not previously reported variant in the BRCA1 exon 22 donor splice site [c.5406+6T>G], whose clinical significance was unknown. The analysis of patient’s RNA revealed the up-regulation of two alternative BRCA1 mRNA isoforms derived from skipping of exon 22 and of exons 22-23. The corresponding predicted protein products, p.(Asp1778GlyfsTer27) and p.(Asp1778_His1822del) are both expected to affect the BRCA1 C Terminus (BRCT) domain. The two variants were observed to co-occur also in the proband’s brother who, in addition, was heterozygous for a common variant (c.4837A>G) mapped to BRCA1 exon 16. This allowed to ascertain, by transcript-specific amplification, the lack of functional mRNA isoforms expressed by the c.5406+6T>G allele and provided evidence to classify the BRCA1 variant as pathogenic, according to the guidelines of the Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) consortium. To our knowledge, excluding two cases detected following the screening of population specific recurrent variants, only one ATM/BRCA1 double heterozygote has been reported in the literature, being the case here described the one with the youngest age at cancer onset. The systematic collection of cases with pathogenic variants in more than one cancer predisposition gene is needed to verify if they deserve ad hoc counseling and clinical management.
Treatment strategies for clear cell renal cell carcinoma: Past, present and future
Authors: Yang Junwei , Wang Kuansong , Yang Zhichun
Published: March 2023

Clear cell renal cell carcinoma (ccRCC) is the most prevalent histological subtype of kidney cancer, which is prone to metastasis, recurrence, and resistance to radiotherapy and chemotherapy. The burden it places on human health due to its refractory nature and rising incidence rate is substantial. Researchers have recently determined the ccRCC risk factors and optimized the clinical therapy based on the disease’s underlying molecular mechanisms. In this paper, we review the established clinical therapies and novel potential therapeutic approaches for ccRCC, and we support the importance of investigating novel therapeutic options in the context of combining established therapies as a research hotspot, with the goal of providing diversified therapeutic options that promise to address the issue of drug resistance, with a view to the early realization of precision medicine and individualized treatment.
An immune infiltration-related prognostic model of kidney renal clear cell carcinoma with two valuable markers: CAPN12 and MSC
Authors: Xia Guang , Wu Song , Cui Xiaoyu
Published: March 2023

Background

Since its discovery, clear cell renal cell carcinoma (ccRCC) has been the most prevalent and lethal kidney malignancy. Our research aims to identify possible prognostic genes of ccRCC and to develop efficient prognostic models for ccRCC patients based on multi-omics investigations to shed light on the treatment and prognosis of ccRCC.

Methods

To determine a risk score for each patient, we screened out differentially expressed genes using data from tumor samples, and control samples mined from The Cancer Genome Atlas (TCGA) and GTEx datasets. Somatic mutation and copy number variation profiles were analyzed to look for specific genomic changes connected to risk scores. To investigate potential functional relationships of prognostic genes, gene set variation analysis (GSVA) and gene set enrichment analysis (GSEA) were carried out. We created a prognostic model by fusing risk ratings with other clinical variables. For validation, the 786-O cell line was used to carry out the dual-gRNA approach to knock down CAPN12 and MSC. This was followed by qRT-PCR to verify the knockdown of CAPN12 and MSC.

Results

For ccRCC, seven predictive genes were discovered: PVT1, MSC, ALDH6A1, TRIB3, QRFPR, CYS1, and CAPN12. The most enriched pathways in the GSVA study and GSEA analysis promote tumorigenesis and immune system modulation. The risk score derived from prognostic genes corresponds with immune infiltration cells and helps predict how well a medicine will work. The mutation of numerous oncogenes was also linked to a high-risk score. A prognostic model with a high ROC value was created for the risk score. An in vitro study demonstrates that the suppression of CAPN12 and MSC dramatically reduced the ability of 786-O cells to proliferate in the CCK-8 proliferation assay and plate clonality assays.

Conclusions

A thorough prognostic model with good performance has been developed for ccRCC patients using seven prognostic genes that were discovered to be related to ccRCC prognosis. In ccRCC, CAPN12 and MSC were significant indicators and would make good therapeutic targets.
Diagnosis of covert coarctation of the aorta in adolescents
Authors: Wei Luyao , Hu Shijun , Gong Xueyang , Ahemaiti Yiliya , Zhao Tianli
Published: March 2023

Objectives

By reviewing the diagnostic process for adolescents with coarctation of the aorta (CoA) in our institution, we analyzed the reasons for delayed diagnosis of CoA. We also proposed a diagnostic protocol to improve the detection rate of CoA.

Methods

In this retrospective study, we included 48 patients aged 12–18 years who were diagnosed with CoA in our hospital from January 2000 to November 2022. Clinical data from involved cases in local hospitals and our institution were collected.

Results

All patients had blood pressure (BP) measurements in upper and lower extremities in our institution. They all had hypertension, 29 (60.4%) of whom had known histories of the same. BP in the upper limbs of 47 (97.9%) patients was ≥20 mmHg higher than that in the lower limbs, and BP in the upper limb of 1 (2.1%) patient was greater than 0 and less than 20 mmHg than that in the lower limb. Echocardiography (ECHO) was performed in all patients, computed tomography (CT) or magnetic resonance imaging (MRI) was performed in 44 patients (91.7%). There were 38 (79.2%) patients who visited local hospitals. Among them, a total of 20 (52.6%) patients had their right upper extremity BP measured, 18 (47.4%) only had their left upper extremity BP measured, and 16 (42.1%) had their lower extremity BP measured. ECHO was performed in 27 (56.2%) patients and CT/MRI was performed in 18 (37.5%) patients. The detection rate for CT/MRI was 100%, and those of ECHO were 72.9% and 18.5% at our institution and a local hospital, respectively. Forty-eight (100%) and 23 (60.5%) patients were detected in our institution and local hospitals (P < 0.0001).

Conclusion

We recommend measuring BP in the bilateral upper extremities. Measurement of BP in the lower extremities is recommended if hypertension is diagnosed. MRI/CT is recommended when BP in the upper extremity is greater than that in the lower extremity.
Analysis of influencing factors of multiple urethrocutaneous fistula after urethroplasty in children with hypospadias
Authors: Tian Guangchao , Guo Bingtao , Zhang Lihua
Published: March 2023

Objective

The objective of this study was to investigate the influencing factors of multiple urethrocutaneous fistula (UF) after urethroplasty in children with hypospadias.

Methods

The clinical data of 195 children with UF after urethroplasty treated surgically in the Third Affiliated Hospital of Zhengzhou University from August 2015 to August 2022 were retrospectively analyzed and divided into the single UF group (n = 134) and the multiple UF group (n = 61) according to whether multiple UF occurred after urethroplasty. The possible correlated factors were collected and compared between the two groups, including hypospadias degree, length of formed urethra, time of urethroplasty, pre-urethroplasty weight, age at urethroplasty, urethroplasty style, season of urethroplasty, the first fistula repair method, season of the first fistula repair, diameter of the largest fistula of the first fistula repair, time of the first fistula repair surgery, and other 13 factors.

Results

By univariate analysis, statistically significant differences were found between the two groups in age at urethroplasty, length of the formed urethra, method of urinary drainage after urethroplasty, whether or not purulent urethral drainage after first fistula repair was present, the first fistula repair method, and diameter of the largest fistula of the first fistula repair (P < 0.05). After multifactorial analysis, the independent risk factors associated with multiple UF after urethroplasty were determined to be use of a vesicostomy tube as the urinary drainage method after urethroplasty (P < 0.05, OR = 6.574, 95% CI: 2.720–15.891) and the presence of purulent urethral drainage after first fistula repair (P < 0.05, OR = 2.723, 95% CI: 1.214–6.109).

Conclusions

A catheter as the drainage method after urethroplasty is an independent protective factor for multiple urethrocutaneous fistula, and the existence of purulent urethral secretions after the first fistula repair is an independent risk factor.
Assessment for late developmental hip dysplasia in a cohort of infants with risk factors and normal hip ultrasound
Authors: Morello Rosa , Bocchi Beatrice , Mariani Francesco , Bononi Alice , Giuli Cristina , Bonfiglio Nadia , Valentini Piero , Lazzareschi Ilaria , Rendeli Claudia , Palmacci Osvaldo , Buonsenso Danilo
Published: March 2023

Background

Developmental dysplasia of the hip (DDH) is a known orthopedic pathology of newborns that, if not diagnosed and treated, can lead to debilitating long-term consequences. Ultrasound has proven to be an effective method for the early diagnosis of this condition. Recently, reports of late DDH in populations at risk (breech presentation) and after negative ultrasound examination have emerged in the literature.

Aim

The objective of the study was to assess the possible appearance of late DDH in Italian children with risk factors but negative ultrasound screening.

Materials and methods

We selected patients with risk factors for DDH and a negative hip ultrasound from the medical records of children referred to the Hip Ultrasound Clinic (Rome, Italy) from January 2018 to November 2021. To identify possible cases of late DDH, from February 2022 to July 2022, all patients who met the inclusion criteria were submitted to orthopedic follow-up clinical evaluation. In the case of a pathological objective examination, radiography was performed.

Results

Fifty-five patients (52.7% female, 52.7% with breech presentation, and 41.8% with a positive family history) met the inclusion criteria. The median age of gait onset was 13 months. The median age of orthopedic follow-up examination was 45 months. Only three patients (5.5%) had a pathological examination, but no x-ray were pathological.

Conclusion

Our study has not documented cases of late DDH. Considering the small study population and the only clinical follow-up, further studies are needed to clarify the possible late development of this condition.
A bibliometrics analysis and visualization study of TRPV1 channel
Authors: Gao Ning , Li Meng , Wang Weiming , Liu Zhen , Guo Yufeng
Published: March 2023

Background: At the end of the 1990s, transient receptor potential vanilloid 1 (TRPV1) was first identified and cloned, serving as a key pain and heat sensor in humans. A large body of evidence have revealed its polymodal structure, complex function and wide-spread distribution, the specific mechanism of the ion channel remains unclear. Our goal here is to perform a bibliometric analysis and visualization study to present hotspots and trends in TRPV1 channel.

Materials and Methods: TRPV1-related publications from inception to 2022 were retrieved from the Web of Science database. Excel, VOSviewer, and CiteSpace software were utilized for co-authorship, co-citation and co-occurrence analysis.

Results: There were 9,113 publications included in the study, the number of publications increased rapidly after 1989, from 7 in 1990 to 373 in 2007, during which the number of citations per publication (CPP) also reached a peak in 2000 (CPP = 106.52). A total of 1,486 journals published TRPV1 articles, mainly belong to Q1 or Q2 divisions; The United States published the most articles (TP = 3,080), followed by Japan (TP = 1,221), China (TP = 1,217), and England (TP = 734); In recent years, the TRPV1-related research direction has been broaden to multiple fields related to inflammation, oxidative stress, and apoptosis; Keyword clustering refined the topic distributions and could be generalized as neuralgia, endogenous cannabinoid system, TRPV1 mediated airway hyperresponsiveness, involvement of apoptosis, TRPV1 antagonists as therapy targets.

Conclusion: By conducting an exhaustive bibliographic search, this review refined the topic distributions and generalized as neuralgia, endogenous cannabinoid system, TRPV1 mediated airway hyperresponsiveness, involvement of apoptosis, TRPV1 antagonists as therapy targets. It is currently being clarified how exactly TRPV1 works as an ion channel, and much more in-depth basic research is needed in the future.