bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of pituitary dysfunction and destructive thyroiditis is associated with better survival in non-small cell lung cancer patients treated with programmed cell death-1 inhibitors: a prospective study with immortal time bias correction
Authors: Suzuki Koji , Kobayashi Tomoko , Izuchi Tetsushi , Otake Koki , Ando Masahiko , Handa Tomoko , Miyata Takashi , Sugiyama Mariko , Onoue Takeshi , Hagiwara Daisuke , Suga Hidetaka , Banno Ryoichi , Hase Tetsunari , Inoue Megumi , Ishii Makoto , Arima Hiroshi , Iwama Shintaro
Published: November 2024

Background

Immune-related adverse events (irAEs) are reported to be associated with better overall survival (OS) in non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors. However, there may be a bias in that patients who develop irAEs must survive long enough to experience the irAEs, and no prospective studies adjusting for immortal time bias (ITB) have examined the relationship between OS and pituitary dysfunction or the two different types of thyroid dysfunction: destructive thyroiditis and hypothyroidism without prior thyrotoxicosis (isolated hypothyroidism).

Methods

Patients with NSCLC who received nivolumab or pembrolizumab at Nagoya University Hospital between November 2, 2015 and February 1, 2023 were enrolled. Endocrine irAEs were prospectively assessed during scheduled evaluations of hormone levels. The association between irAE development and survival when considering ITB was examined by time-dependent Cox regression analysis.

Results

Of the 194 patients included, 11 (5.7%), 10 (5.2%), and 5 (2.6%) developed pituitary dysfunction, destructive thyroiditis, and isolated hypothyroidism, respectively. The development of pituitary dysfunction (HR 0.36, 95% CI 0.13–0.98, p = 0.045) and destructive thyroiditis (HR 0.31, 95% CI 0.10–0.97, p = 0.044), but not isolated hypothyroidism (HR 1.15, 95% CI 0.42–3.20, p = 0.786), was significantly associated with longer OS.

Conclusion

NSCLC patients developing pituitary dysfunction and destructive thyroiditis showed better OS even after adjusting for ITB, suggesting that these irAEs indicate a better prognosis.
Pro-inflammatory macrophages suppress HIV replication in humanized mice and ex vivo co-cultures
Authors: Baroncini Luca , Muller Christina K. S. , Kadzioch Nicole P. , Wolfensberger Rebekka , Russenberger Doris , Bredl Simon , Mlambo Tafadzwa , Speck Roberto F.
Published: November 2024

Introduction

Very little is known about the role of macrophages as immune mediators during natural HIV infection. Humanized mice are an extremely valuable in vivo model for studying HIV pathogenesis. However, the presence of murine mononuclear phagocytes in these models represents a significant limitation for studying their human counterpart. Therefore, we have developed a novel humanized mouse model that allows selective depletion of human myeloid cells at a time point of our choosing.

Methods

We genetically engineered human hematopoietic stem and progenitor cells (HSPCs) to express an inducible caspase-9 (iCas9) suicide system under a synthetic myeloid promoter. Using these HSPCs, we generated humanized mice. iCasp9 induction in vivo resulted in selective human myeloid cell death in this inducible human myeloid depletion (iHMD) mouse model. In addition, we co-cultured monocyte-derived macrophages with ex vivo HIV-infected PBMCs to further mechanistically investigate the effect of macrophages on HIV replication using flow cytometry, cytokine analysis, and RNA sequencing of both macrophages and CD4+ T cells.

Results

HIV infection induced a pro-inflammatory phenotype in HIV-infected humanized NSG mice during the early and late stages of HIV infection. Myeloid cell depletion in HIV-infected iHMD-NSG mice resulted in a rapid increase in HIV RNA replication, which was accompanied by a loss of pro-inflammatory cytokines. Co-culture of macrophages with ex vivo HIV-infected PBMCs reproduced their anti-HIV effects observed in vivo. Transcriptomic data showed macrophages upregulate antiviral cytokines and chemokines in co-culture, while inducing CD4+ T cells to upregulate HIV restriction factors and downregulate pathways involved in protein expression and cell replication.

Discussion

This study describes a novel role of macrophages as effector cells, both ex vivo and in vivo, acting against HIV replication and limiting disease progression.
Case report: Unveiling the silent threat in the ICU – a case of disseminated invasive aspergillosis in a patient with fulminant myocarditis
Authors: Xue Yimin , Mo Jibin , Cheng Kun , Xue Ying , Chen Dongjie , Lin Fenghui , Chen Han
Published: November 2024

Invasive aspergillosis (IA) significantly increases mortality in critically ill patients in the ICU and its occurrence is closely related to immunocompromise. Dissemination of IA is easily misdiagnosed and mistreated due to its ability to invade multiple systems throughout the body and lack of typical clinical manifestations. In this case, a 25-year-old previously healthy woman was hospitalized with fulminant myocarditis and treated with veno-arterial extracorporeal membrane pulmonary oxygenation (VA-ECMO) support and intravenous acyclovir, high-dose methylprednisolone, and immunoglobulin. 6 days later, she was successfully weaned from VA-ECMO and underwent cardiac rehabilitation. On day 10, she developed a fever (Tmax 38.3°C) and an irritating cough and began to experience reduced vision over the right eye with eye pain, redness, photophobia, and tearing 2 days later. Administration of levofloxacin eye drops and tobramycin/dexamethasone eye ointment was ineffective. The patient was positive for serum Aspergillus galactomannan antigen. Positron emission tomography/computed tomography (PET/CT) scan showed multiple hypermetabolic cavitary nodules in both lungs (SUVmax3.6) and thickening of the ocular ring wall with hypermetabolism in the right eye (SUVmax3.2). Ophthalmologic examination revealed that her best-corrected visual acuity in the right eye was reduced to light perception with an intraocular pressure of 21 mmHg, and B-scan ultrasonography showed vitreous opacity and retinal edema with mild detachment in the right eye. Metagenomic next-generation sequencing (mNGS) identified a large number of Aspergillus fumigatus sequences in bronchoalveolar lavage fluid, blood, and aqueous humor from the right eye, supporting the diagnosis of pulmonary and ocular involvement due to disseminated IA. Vitrectomy, anterior chamber irrigation, combined with intravenous and intravitreal injections of voriconazole and liposomal amphotericin B eventually cured the patient. This case highlights the importance of early identification and intervention regarding disseminated IA in immunocompromised critically ill patients, especially in the presence of multiple organ involvement.
Effects of COVID-19 on bone fragility: a new perspective from osteoimmunological biomarkers
Authors: Galliera Emanuela , Massaccesi Luca , Mangiavini Laura , De Vecchi Elena , Villa Francesca , Corsi Romanelli Massimiliano Marco , Peretti Giuseppe
Published: November 2024

Introduction

While there is an increasing understanding of COVID-19's effect on different organs, little is known about the effect of the disease on bone turnover and remodeling so far. Osteoimmunological biomarkers have been described as potential indicators of bone remodeling in inflammatory conditions, but their potential role in evaluating the effect of COVID-19 on bone fragility has not been explored so far.

Methods

The present study aims to measure the osteoimmunological biomarkers in elderly patients undergoing orthopedic surgery, to evaluate the potential effect of COVID-19 on the bone response to the surgery.

Results

In our patients, the RANKL/OPG ratio indicated an increase of bone resorption in COVID-19-positive patients, confirming a strong diagnostic and prognostic value. RANKL/OPG displays a good correlation with the bone fragility maker FGF23, indicating that this parameter is a reliable maker of bone fragility in COVID-19 patients and could provide useful and comprehensive information about inflammation-induced bone loss. Consistently, the RANKL/OPG ratio showed a good correlation also with the two inflammatory markers IL-6 and sRAGE.

Discussion

Taken together these results indicate that the use of an osteoimmunological biomarker like the RANKL/OPG ratio could provide a significant improvement in the clinical evaluation of the COVID-19 effect on bone loss. This aspect is extremely important in elderly patients undergoing orthopedic surgery, which can manifest more severe effects of COVID-19 and present an increased level of age-induced bone fragility.
Association of inflammatory cytokines with type 2 diabetes mellitus and diabetic nephropathy: a bidirectional Mendelian randomization study
Authors: Song Siyuan , Ni Jing , Sun Yuqing , Pu Qiang , Zhang Li , Yan Qianhua , Yu Jiangyi
Published: November 2024

Objective

Previous observational studies have suggested associations between various inflammatory cytokines with type 2 diabetes mellitus and diabetic nephropathy. However, the causal association remains uncertain.

Method

Summary statistics for type 2 diabetes mellitus and diabetic nephropathy were obtained from a publicly available genome-wide association study. Data on inflammatory cytokines were sourced from a genome-wide association study on protein quantitative trait loci. The inverse variance-weighted method was applied as the primary method for causal inference. MR-Egger, weighted mode, and weighted median method were employed as supplementary analyses. Sensitivity analyses were performed to detect heterogeneity and potential horizontal pleiotropy in the study.

Result

Genetic evidence indicated that elevated levels of fibroblast growth factor 19 levels promoted the occurrence of type 2 diabetes mellitus, and increased concentrations of fibroblast growth factor 21 levels, C-C motif chemokine 19 levels, eotaxin levels, and interleukin-10 mitigated the risk of developing type 2 diabetes mellitus, while type 2 diabetes mellitus did not exert a significant influence on said proteins. Elevated levels of tumor necrosis factor ligand superfamily member 14 and TNF-related activation-induced cytokine were associated with an increased risk of diabetic nephropathy, and increased concentrations of interleukin-1-alpha and transforming growth factor-alpha were potentially correlated with a diminished risk of diabetic nephropathy. Sensitivity analyses further ensure the robustness of our findings.

Conclusion

Mendelian randomization analysis highlights a causal association between inflammatory cytokines with type 2 diabetes mellitus and diabetic nephropathy, offering valuable evidence and reference for future research.
Genetic and immunologic features associated with thrombocytopenia progression and poor prognosis in patients with myelofibrosis
Authors: Kim Tong Yoon , Eom Ki-Seong , Lee Ji Yoon , Lee Jong-Mi , Kim Myungshin , Lee Sung-Eun
Published: November 2024

Introduction

Myelofibrosis, which includes primary myelofibrosis (PMF) and secondary myelofibrosis (SMF), can exhibit cytopenic features associated with poor outcomes; however, the underlying mechanisms are unclear. Moreover, characterized by its aggressive nature and limited therapeutic options, myelofibrosis poses a major clinical challenge in hematology. Therefore, in this study, we aimed to identify genetic and immunologic features associated with thrombocytopenia progression and poor prognosis.

Methods

The study involved 226 patients with PMF or SMF, who were categorized into three groups: platelet count ≥ 100 × 109/L (PLT ≥ 100 group; n = 131), progression to thrombocytopenia (PROG group; n = 64), and platelet count < 100 × 109/L (PLT < 100 group; n = 31).

Results

Survival analysis revealed 4-year overall survival rate of 57.7%, 89.4%, and 93.9% for the PLT < 100, PROG, and PLT ≥ 100 groups, respectively. Time-dependent covariate analysis of the PLT ≥ 100 and PROG groups revealed inferior overall survival rate of the PROG group. Multivariate analysis indicated that progression to thrombocytopenia and ASXL1 and IDH1 mutations were associated with poor overall survival. Flow cytometry revealed fewer CD45RA+CD4+ T cells in the PROG group than in the PLT ≥ 100 group. ASXL1 mutations were more prevalent in the PROG group than in the other groups, correlating with a reduced number of CD45RA+CD4+ T cells.

Discussion

ASXL1 mutation and low CD45RA+CD4+ T-cell counts correlated with progression to thrombocytopenia. Our findings underscore the clinical significance of thrombocytopenia dynamics in MF progression and prognosis, with implications for patient management and therapeutic interventions.
The relationship between pain duration characteristics and pain intensity in herpes zoster-related pain: a single-center retrospective study
Authors: Wang Liu , Lan Xiaoxiao , Lan Zhixuan , Xu Shengrong , He Ruilin , Jiang Zongbin
Published: November 2024

Background

The varicella-zoster virus (VZV) can cause herpes zoster (HZ), which may progress to postherpetic neuralgia (PHN), leading to severe inflammatory responses and pain.

Objective

This study investigates the relationship between pain duration characteristics and pain intensity in patients with herpes zoster-related pain, hypothesizing that persistent pain correlates with higher pain intensity compared to intermittent pain.

Methods

A retrospective study was conducted at the Second Affiliated Hospital of Guangxi Medical University, China. Data from patients treated for herpes zoster-related pain between January 2019 and February 2024 were analyzed. Pain intensity was measured using the Numerical Rating Scale (NRS-11), and pain duration was categorized as intermittent or persistent. Multivariate regression models were used to assess the association between pain duration and intensity, adjusting for potential confounders.

Results

A total of 840 patients were included. Persistent pain was significantly associated with higher NRS-11 scores compared to intermittent pain (β = 0.71, 95% CI 0.50–0.91, p < 0.001). Subgroup analyses showed that persistent pain was associated with higher pain intensity in both acute HZ and PHN patients (HZ: β = 0.71, 95% CI 0.45–0.96, p < 0.001; PHN: β = 0.76, 95% CI 0.40–1.13, p < 0.001). Inflammatory markers, such as C-reactive protein (CRP) and white blood cell count, were positively correlated with pain intensity.

Conclusion

Pain duration significantly impacts pain intensity in HZ patients. Considering pain duration is crucial for effective pain management. Further research should explore the mechanisms underlying persistent pain to develop better treatment strategies.
Elevated metabolic score for visceral fat was associated with increased prevalence of gallstones in American adults: a cross-sectional study
Authors: Lin Hao , Shi Kexuan , Luo Shuang , Ye Wu , Cai Xiaoniao
Published: November 2024

Background

Metabolic Visceral Fat Score (METS-VF) recently introduced is posited to be a superior metric for assessing visceral adipose tissues (VAT) compared to traditional obesity indexes. This study aims to elucidate the correlation between METS-VF and the incidence of gallstones.

Methods

In this cross-sectional study, the data from the National Health and Nutrition Examination Survey (NHANES) during the period from 2013 to 2020 were analyzed. And the correlation between METS-VF and the incidence of gallstones was explored through multivariate logistic regression analysis, receiver operating characteristic (ROC) curve, subgroup analysis and restricted cubic spline (RCS) regression.

Results

This study included 5,975 participants, of whom 645 (10.8%) were gallstone formers. As the quartile range of METS-VF increased, a notable rise in the prevalence of gallstones was observed (3.2% vs. 7.4% vs. 12.1% vs. 20.6%, p < 0.001). Logistic regression analyses indicated a significant positive correlation between METS-VF and the risk of gallstones (OR = 3.075, 95% CI: 2.158, 4.381). Subgroup analyses further revealed a stronger correlation between gallstones and METS-VF in subjects over 50 years old. RCS regression identified a non-linear positive correlation, with an inflection point at 6.698. Finally, the area under the ROC curve (AUC) of METS-VF was significantly larger (AUC = 0.705, 95%: 0.685, 0.725) than those of traditional obesity indexes and other VAT surrogate markers.

Conclusion

This study is the first to reveal a significant positive correlation between the prevalence of gallstones and METS-VF, with METS-VF outperforming other VAT surrogate markers in the diagnosis of gallstones.
Dynamic succession of the quantity and composition of epiphytic microorganisms at different growth stages on rice surface
Authors: Huang Lijuan , Zhang Zhifei , Mu Lin , Liu Xiong , Sun Rongji , Gao Wenjing , Chen Guihua
Published: November 2024

The quality of silage is uneven, which is due to the difference of epiphytic microorganisms of raw materials. To improve the quality of fermentation, the quantity and composition of epiphytic microorganisms are usually analyzed to better prepare silage. In this research, plate coating method and 16S high-throughput sequencing were used to analyze the differences in the quantity and composition of rice epiphytic microorganisms during different growth stages. The Lactic acid bacteria (LAB) and aerobic bacteria were the highest at the flowering stage, the yeast was the highest at the milk ripening stage, and the mould was the highest at the full ripening stage. And the growth stage also had a great influence on the composition of epiphytic bacterial community, at the phylum level, it was mainly composed of Proteobacteria. And at the genus level, Pantoea, Acinetobacter, Pseudomonas and Chryseobacterium were dominanted at the flowering stage; Pantoea, Stenotrophomonas and Sphingobacterium were dominanted at the milk ripening stage; Acinetobacter, Pantoea, Chryseobacterium and Lactococcus were dominanted at the dough stage; Acinetobacter and Klebsiella were dominated at the full ripening stage. Overall, the growth stage significantly affected the quantity and composition of rice epiphytic microorganisms. Therefore, rice silage can be modulated reasonably according to the number and composition of epiphytic microorganisms in different growth stages.
Panaroma of microglia in traumatic brain injury: a bibliometric analysis and visualization study during 2000–2023
Authors: Zhang Yuhang , Deng Tingzhen , Ding Xiao , Ma Xingyuan , Wang Yatao , Yang Haijun , Ding Ruiwen , Wang Dawen , Li Haotian , Zheng Maohua
Published: November 2024

Background

Traumatic brain injury (TBI) is a critical global health concern characterized by elevated rates of both morbidity and mortality. The pathological and physiological changes after TBI are closely related to microglia. Microglia, the primary immune cells in the brain, are closely linked to the mechanisms and treatment of TBI. With increasing research in this area, this study employs bibliometric analysis to identify current research hotspots and predict future trends.

Objective

We decided to perform a bibliometric analysis to provide a comprehensive overview of the advancements in microglia research related to traumatic brain injury. We aim to offer researchers insights into current trends and future research directions.

Method

We collected all articles and reviews related to microglia and traumatic brain injury published between 2000 and 2023 from the Web of Science Core Collection. These records were analyzed using VOSviewer, CiteSpace, and the R package “bibliometrix”.

Results

We retrieved 665 publications from 25 countries, with the majority contributed by the United States and China. The number of publications on traumatic brain injury and microglia has been steadily increasing each year. Our analysis highlighted the Journal of Neurotrauma and the Journal of Neuroinflammation as the most influential journals in this field. Alan I. Faden and David J. Loane are recognized as leading contributors. Keyword analysis indicates that neuroinflammation, microglial polarization, and neurodegenerative diseases are pivotal areas for future research.

Conclusion

In recent years, research on TBI-related microglia has proliferated, with current studies primarily focusing on microglial involvement in neuroinflammation, neurodegenerative changes, and microglial polarization following TBI. Since neuroinflammation and neurodegeneration are two hallmark features of TBI, targeting microglia in TBI treatment may become a central focus for future research.
Investigating neural markers of Alzheimer's disease in posttraumatic stress disorder using machine learning algorithms and magnetic resonance imaging
Authors: Yakemow Gabriella , Kolesar Tiffany A. , Wright Natalie , Beheshti Iman , Choi Eun Hyung , Ryner Lawrence , Chaulk Sarah , Patel Ronak , Ko Ji Hyun
Published: November 2024

Introduction

Posttraumatic stress disorder (PTSD) is a mental health disorder caused by experiencing or witnessing traumatic events. Recent studies show that patients with PTSD have an increased risk of developing dementia, including Alzheimer's disease (AD), but there is currently no way to predict which patients will go on to develop AD. The objective of this study was to identify structural and functional neural changes in patients with PTSD that may contribute to the future development of AD.

Methods

Neuroimaging (pseudo-continuous arterial spin labeling [pCASL] and structural magnetic resonance imaging [MRI]) and behavioral data for the current study (n = 67) were taken from our non-randomized open label clinical trial (ClinicalTrials.gov Identifier: NCT03229915) for treatment-seeking individuals with PTSD (n = 40) and age-matched healthy controls (HC; n = 27). Only the baseline measures were utilized for this study. Mean cerebral blood flow (CBF) and gray matter (GM) volume were compared between groups. Additionally, we utilized two previously established machine learning-based algorithms, one representing AD-like brain activity (Machine learning-based AD Designation [MAD]) and the other focused on AD-like brain structural changes (AD-like Brain Structure [ABS]). MAD scores were calculated from pCASL data and ABS scores were calculated from structural T1-MRI images. Correlations between neuroimaging data (regional CBF, GM volume, MAD scores, ABS scores) and PTSD symptom severity scores measured by the clinician-administered PTSD scale for DSM-5 (CAPS-5) were assessed.

Results

Decreased CBF was observed in two brain regions (left caudate/striatum and left inferior parietal lobule/middle temporal lobe) in the PTSD group, compared to the HC group. Decreased GM volume was also observed in the PTSD group in the right temporal lobe (parahippocampal gyrus, middle temporal lobe), compared to the HC group. GM volume within the right temporal lobe cluster negatively correlated with CAPS-5 scores and MAD scores in the PTSD group.

Conclusion

Results suggest that patients with PTSD with reduced GM volume in the right temporal regions (parahippocampal gyrus) experienced greater symptom severity and showed more AD-like brain activity. These results show potential for early identification of those who may be at an increased risk for future development of dementia.
Case report: Pulmonary Ewing sarcoma disguised as non-small cell lung cancer
Authors: Carter Mary E. , Benegiamo-Chilla Alessia , Kloker Linus D. , Paulsen Nikolas , Potkrajcic Vlatko , Paulsen Frank , Nemeth Attila , Steger Volker , Schulze Martin , Biskup Saskia , Benzler Katrin , Singer Stephan , Lauer Ulrich M. , Zender Lars , Deinzer Christoph K. W.
Published: November 2024

Ewing sarcoma is the second most common primary malignant bone cancer in children and adolescents. This rare type of cancer is characterized by its high malignancy and therefore high risk of metastases. Typically, Ewing sarcomas originate from bones. However, extraosseous Ewing sarcoma such as pulmonary Ewing sarcoma can also be found. In this case report, we present a 55-year old male patient who was initially diagnosed with non-small cell lung cancer at his local district hospital. However, the diagnosis was changed to one of pulmonary Ewing sarcoma after subsequent histopathological and molecular pathological analysis performed in a reference pathology laboratory. After patient referral to a certified (according to the German Cancer Society) high-volume sarcoma center, multimodal chemotherapy was initiated based on recently published clinical data as opposed to the more commonly used treatment regimen in Europe. The patient responded well to treatment and underwent a complete surgical tumor resection followed by radiotherapy. In summary, this case report highlights the importance of a rigorous and timely histopathological examination of biopsy samples by a specialized cancer center to enable a correct diagnosis of the cancer type. Additionally, molecular pathology plays a crucial part in this analysis and allows the necessary differentiation between cancer types. Up to now, there is no international treatment guideline available for the treatment of Ewing sarcoma. Patients should be referred to specialist centers to allow the best possible treatment of the cancer type in view of current published clinical data. In the case of Ewing sarcoma, and in accordance with the most recent research, patients should be treated with vincristine, doxorubicin and cyclophosphamide plus ifosfamide and etoposide in combination with local treatment such as surgery and/or radiotherapy because this has been demonstrated to be the more effective therapy.
Partnership of I-ACT for children (US) and European pediatric clinical trial networks to facilitate pediatric clinical trials
Authors: Degraeuwe Eva , Hovinga Collin , De Maré Annelies , Fernandes Ricardo M. , Heaton Callie , Nuytinck Lieve , Persijn Laura , Raes Ann , Vande Walle Johan , Turner Mark A.
Published: November 2024

Background/aims

Due to a lack of standard pediatric prescribing information, medicines are often used in a dosage form or for an indication that has not been investigated in children. Pediatric clinical trial research networks aim to facilitate the timely availability of innovative drugs for children by developing standardized trial facilitation and conduct processes. This paper aims to assess the (pre)feasibility duration and characteristics of a US-sponsored clinical trial, in collaboration with I-ACT for Children, for distribution across European sites via European clinical research facilitation networks.

Method

A transatlantic partnership between the Belgian Pediatric Clinical Research Network (BPCRN,) and I-ACT for Children conducted feasibilities in Europe for industry-sponsored early-stage pharmacological clinical trials between 2019 and 2022. The collaboration recorded time to event for key elements of feasibility, influences on successful feasibility, and benefits of collaboration.

Results

Trials were conducted across 17 European countries with 202 participating hospital sites. The initial phase, the pre-feasibility questionnaire had a 70% response rate from 142 sites, and sites took a median 38 days (IQR 20 days) to complete the questionnaire for five trials. All responses underwent a quality control, addressing inaccuracies in site capabilities and recruitment. The first trial's CDA and feasibility questionnaire were completed in roughly 2 months for 7 countries. Time to completion was affected by precontracted sites, limited scope of studies, changes in timelines, COVID-related disruptions, and a learning curve for collaboration.

Conclusion

Collaboration between European collaborative national networks and US-network I-ACT for Children has supported site identification of global pediatric clinical trials. This illustrates one method for the importance of early engagement with sponsors and implementation of effective communication systems.
Investigation of the therapeutic effects and mechanisms of Houpo Mahuang Decoction on a mouse model of chronic obstructive pulmonary disease
Authors: Li Shanlan , Dai Ziqi , Zhang Tong , Guo Zhuoqian , Gao Feng , Cheng Xuehao , An Jin , Lin Yixuan , Xiong Xiaomin , Wang Nan , Jiang Guanghui , Xu Bing , Lei Haimin
Published: November 2024

Background

With a growing global population affected by Chronic Obstructive Pulmonary Disease (COPD), the traditional Chinese herbal formula Houpo Mahuang Decoction (HPMHD) has been used for centuries to address respiratory ailments. While studies have demonstrated the therapeutic benefits of HPMHD in COPD, the effective active ingredients, potential targets, and molecular mechanisms underlying its effectiveness remained unclear.

Methods

The mechanisms of action of certain HPMHD components, targets, and pathways for the treatment of COPD were predicted using a network pharmacology method. We induced a COPD mouse model using porcine pancreatic elastase and evaluated the pathological changes and healing processes through HE and Masson staining. Immunofluorescence was used to assess the levels of IL-6 and TNF-ɑ. RNA-Seq analysis was conducted to identify differentially expressed genes (DEGs) in the lungs of normal, control, and treated mice, revealing the biological pathways enriched by HPMHD in COPD treatment. Finally, the expression of DEGs was verified using Western blotting and RT-qPCR.

Results

HPMHD effectively alleviated pathological symptoms and improved COPD in mice by modulating the IL-17 signaling pathway. Treatment with HPMHD improved lung morphology and structure, reduced inflammatory cell infiltration, and inhibited IL-6 and TNF-ɑ levels. Network pharmacology and transcriptomics further revealed the mechanism, indicating that the IL-17 signaling pathway might been instrumental in the inhibitory effect of HPMHD on mouse model of COPD. Subsequent experiments, including protein blotting and RT-qPCR analysis, confirmed the activation of the IL-17 signaling pathway by HPMHD in the COPD mouse model, further supporting the initial findings.

Conclusion

HPMHD was shown to alleviate COPD and reduce lung inflammation in mice, potentially through the activation of the IL-17 signaling pathway. This study provides a novel direction for the development of COPD drugs.
Inspired by an ancient Chinese Medicine prescription: the modern significance and potential of Yiyi Fuzi Baijiang San in treating diseases
Authors: Zhang Yuli , Zhang Lu , Chai Ni , Wan ZhiQiang , Sui Hua
Published: November 2024

Classic Formulas (Jing fang) are considered the essence and authority of Traditional Chinese Medicine (TCM) due to their long history and proven efficacy. These formulas play a pivotal role in all kinds of different disease prevention and therapeutic strategies. Yiyi Fuzi Baijiang San (YYFZBJS), one of the Classic Formulas, was originally developed for the treatment of chronic intestinal abscess. With the accumulation of clinical experience and the exploration of modern pharmacological research in recent years, YYFZBJS has been extensively employed to address a broad spectrum of conditions such as colorectal cancer. Although numerous studies have explored the clinical efficacy and underlying mechanisms of YYFZBJS, no comprehensive review summarizing these findings exists to date. This study aims to systematically review and critically assess the current clinical and mechanistic research on YYFZBJS, with the objective of providing valuable insights and guidance for TCM research in the future.
MS-YOLOv8: multi-scale adaptive recognition and counting model for peanut seedlings under salt-alkali stress from remote sensing
Authors: Zhang Fan , Zhao Longgang , Wang Dongwei , Wang Jiasheng , Smirnov Igor , Li Juan
Published: November 2024

Introduction

The emergence rate of crop seedlings is an important indicator for variety selection, evaluation, field management, and yield prediction. To address the low recognition accuracy caused by the uneven size and varying growth conditions of crop seedlings under salt-alkali stress, this research proposes a peanut seedling recognition model, MS-YOLOv8.

Methods

This research employs close-range remote sensing from unmanned aerial vehicles (UAVs) to rapidly recognize and count peanut seedlings. First, a lightweight adaptive feature fusion module (called MSModule) is constructed, which groups the channels of input feature maps and feeds them into different convolutional layers for multi-scale feature extraction. Additionally, the module automatically adjusts the channel weights of each group based on their contribution, improving the feature fusion effect. Second, the neck network structure is reconstructed to enhance recognition capabilities for small objects, and the MPDIoU loss function is introduced to effectively optimize the detection boxes for seedlings with scattered branch growth.

Results

Experimental results demonstrate that the proposed MS-YOLOv8 model achieves an AP50 of 97.5% for peanut seedling detection, which is 12.9%, 9.8%, 4.7%, 5.0%, 11.2%, 5.0%, and 3.6% higher than Faster R-CNN, EfficientDet, YOLOv5, YOLOv6, YOLOv7, YOLOv8, and RT-DETR, respectively.

Discussion

This research provides valuable insights for crop recognition under extreme environmental stress and lays a theoretical foundation for the development of intelligent production equipment.
Effect of planting methods and tillage practices on soil health and maize productivity
Authors: Gao Peng Ju , Abbas Hasnain , Li Fa Qiao , Tang Guo Rong , Lv Ju Zhi , Zhou Xun Bo
Published: November 2024

Introduction

To increase the crop yield, the amount of agrochemicals used in field has increased in recent years. Moreover, indiscriminate use of chemical fertilizers has led to soil deterioration and compaction. Inclusion of straw and tillage practices to the field could play an important role in improving the soil quality and crop yield. Therefore, we hypothesized that combination of straw return and different tillage practices would result in improvement in soil health and crop productivity.

Methods

Therefore an experiment was conducted a split plot design during 2018-2022. They were comprised of traditional planting with no straw return and straw return, accompanied by four different tillage methods: control (no tillage), rotary tillage (25 cm tillage depth), subsoiling (35 cm tillage depth), and subsoiling plus rotary tillage (35 + 25 cm tillage depth).

Results

Results showed that subsoiling along with rotary tillage enhanced soil total nitrogen (TN) by 9.0%, soil organic carbon (SOC) 7.5%, soil microbial biomass carbon (MBC) 6.8%, soil catalase (S-CAT) 9.6%, soil urease (S-UE) 4.1%, soil cellulase (S-CL) 14.5%, soil sucrase (S-SC) 10.8% and maize yield 3.0% compared to no tillage.

Discussion

Correlation analysis showed that (i) maize yield was significantly and positively correlated with S-SC, S-CL, S-UE, SOC, and TN. (ii) S-SC was significantly and positively correlated with TN, SOC, and MBC. (iii) TN was significantly and positively correlated with S-UE, and SOC was significantly and positively correlated with S-SC. It has been concluded that straw return coupled with subsoiling and rotary tillage is an appropriate approach to enrich soil nutrients, enzyme activities, and maize yield.
Identifying the earliest citrus responses to Candidatus Liberibacter asiaticus infection: a temporal metabolomics study
Authors: Li Jingwen , Wang Yuanzhi Zimmy , Gmitter Fred G. , Wang Yu
Published: November 2024

The global citrus industry faces a great threat from Huanglongbing (HLB), a destructive disease caused by ‘Candidatus Liberibacter asiaticus’ (CLas) that induces significant economic losses without any known cure. Understanding how citrus plants defend against HLB, particularly at the early stages of infection, is crucial for developing long-term solutions. This study investigated the earliest metabolic responses of fresh citrus leaves to CLas infection using untargeted metabolomics and machine learning models. HLB-tolerant and HLB-sensitive cultivars were compared to analyze their biochemical reactions within 48 hours post-infection. HESI/Q-Orbitrap MS analysis identified temporal differential metabolites, revealing distinct metabolic pathways activated in response to CLas infection. Both cultivars responded by increasing specific metabolite concentrations, such as flavonoids, within 2 hours post-infection, but the HLB-tolerant cultivar maintained higher levels throughout the 48-hour period. This early metabolic activity could influence long-term plant health by enhancing disease resistance and reducing pathogen impact. These findings provide potential biomarkers for breeding HLB-resistant cultivars and offer valuable insights for developing sustainable management strategies to mitigate the impact of HLB on the citrus industry, ensuring its long-term productivity and economic viability.
Transcriptome and genome-wide analysis of the potential role of SKP1 gene family in the development of floral organs of two related species of Allium fistulosum
Authors: Wang Ning , Lin Chenyi , Yang Zhongmin , Zhao Dan
Published: November 2024

Allium fistulosum is an important plant germplasm resource, rich in nutrients and possessing unique medicinal value. However, due to its small floral organs, low seed setting rate of a single flower, high cost of artificial emasculation, and artificial pollination, the use of male sterile lines to prepare Allium hybrids has become a common choice. In this study, A. fistulosum var. viviparum Makino and A. galanthum were used as materials to study the regulation mechanism of anther development, aiming to provide a reference for male sterility. Through transcriptome differential gene screening and genome-wide bioinformatics analysis, 34 SKP1 (S-phase kinase-associated protein 1) genes (AfSKP1-1 to AfSKP1-34) were identified in the whole genome of A. fistulosum. The AfSKP1 genes are unevenly distributed on eight chromosomes. Furthermore, two pairs of collinear relationships are evident among family members, and fragment replication events between AfSKP1 genes have been identified. The phylogenetic tree analysis demonstrated that the AfSKP1, AtSKP1, OsSKP1, and SlSKP1 genes were clustered into six groups, exhibiting a gene structure analogous to that observed in members of an evolutionary classification. A combination of gene structure and phylogenetic analysis revealed the presence of cis-acting elements associated with growth, hormone regulation, and stress response within the AfSKP1 genes. Furthermore, expression analysis demonstrated that the AfSKP1 genes exhibited differential expression patterns across various tissues of A. fistulosum. The tissue-specific expression of the AfSKP1 gene was verified by Real-Time PCR. A comparison of the two materials revealed significant differences in the expression of the AfSKP1-8 gene in floral buds, the AfSKP1-11 gene in inflorescence meristems, and the AfSKP1-14 gene in inflorescence meristems, scapes, and floral buds. The results indicated that the three genes may be involved in anther development, thereby providing a theoretical basis for further study of floral organ development and pollen development in AfSKP1 family members.
Exploring the impact of key physicochemical properties of rice on taste quality and instant rice processing
Authors: Yang Wen , Li Xiaoling , Zheng Xiaohang , Wang Mengyuan , Pan Wenxu , Liu Pin , Zhang Zehua , Gong Caixiong , Zheng Ling , Yuan Hua , Li Ting , Chen Weilan , Qin Peng , Wang Yuping , Li Shigui , Ma Bingtian , Tu Bin
Published: November 2024

Taste quality is one of the most important indicators for assessing the quality of rice. However, there has been a lack of systematic studies investigating the impact factors of taste quality. In this study, chromosomal segment substitution lines (CSSLs) with notable differences in physicochemical properties were obtained by screening the CSSL population. A correlation analysis between the physicochemical properties and the taste qualities of rice revealed that amylose and protein content are significantly negatively correlated with the taste value of both freshly cooked and rehydrated instant rice. The alkali spreading value (ASV) had limited impact on the taste value of rice, but low-ASV rice is more resistant to cooking. Grain chalkiness played a critical role in maintaining the integrity of freshly cooked rice and instant rice grains after rehydration. In summary, our study provides crucial insights and guidance for rice breeding, with the goal of developing excellent quality and enhancing the processing of instant rice.
Genome-wide analysis of the Cannabis sativa cytochrome P450 monooxygenase superfamily and uncovering candidate genes for improved herbicide tolerance
Authors: Kaur Navneet , Verma Awadhesh Kumar , Girdhar Madhuri , Kumar Anil , Siddiqui Maqsood A. , Al-Khedhairy Abdulaziz A. , Malik Tabarak , Mohan Anand
Published: November 2024

Cannabis sativa is an economically important crop, yet weed management remains a significant challenge due to limited herbicide options. Cytochrome P450 enzymes play crucial roles in plant metabolism, including herbicide detoxification. This study aimed to identify and characterize the CYP gene family in Cannabis and investigate their potential role in herbicide metabolism. We identified 225 CYP proteins encoded by 221 genes in the Cannabis genome, classified into 9 clans and 47 families. The majority of CsCYPs were predicted to be located in endomembrane system and chromosomal mapping revealed that they were present in all the chromosomes. Motif and gene structure analysis supported the results from phylogenetic analysis. The gene duplication analysis results showed that tandem duplication plays a pivotal role in evolutionary expansion of CsCYP superfamily. Promoter analysis revealed various cis-acting elements involved in stress, light, hormone and development responses. Molecular docking simulations identified several CsCYPs with strong binding affinities to ALS-inhibiting herbicides, particularly bispyribac-sodium, propoxycarbazone-sodium, and pyriftalid. CsCYP_215, CsCYP_213, CsCYP_217 and CsCYP_14 emerged as promising candidates for herbicide metabolism. Analysis of binding site residues revealed the importance of hydrophobic and aromatic interactions in herbicide binding. This study provides the first comprehensive characterization of the CYP gene family in C. sativa and offers new insights into their potential roles in herbicide metabolism. The identification of promising herbicide-metabolizing CYP candidates opens new avenues for developing herbicide-tolerant Cannabis varieties, potentially addressing key challenges in weed management and crop productivity.
Association between stressful life events and depression, anxiety, and quality of life among urban adolescents and young adults in Latin America
Authors: Diez-Canseco Francisco , Carbonel Adriana , Bernabe-Ortiz Antonio , Olivar Natividad , Gómez-Restrepo Carlos , Toyama Mauricio , Uribe-Restrepo José Miguel , Brusco Luis Ignacio , Hidalgo-Padilla Liliana , Ramirez-Meneses Daniela , Carbonetti Fernando Luis , Ariza-Salazar Karen , Sureshkumar Diliniya Stanislaus , Fung Catherine , Priebe Stefan
Published: November 2024

Background

Latin American youth have a high prevalence of mental health disorders and face major socioeconomic and public safety problems. This study assesses the association between stressful life events (SLEs) and depression, anxiety, and quality of life among adolescents and young adults from deprived neighbourhoods of Latin America.

Methods

The sample consisted of 2,402 participants, between adolescents (15–16 years) and young adults (20–24 years), from Bogotá (Colombia), Buenos Aires (Argentina), and Lima (Peru), assessed in 2021–2022 and recruited in education and community settings and social media. We evaluated the most frequent recent and distant SLEs (occurred in the previous year and more than a year ago, respectively), the relationship between SLEs and severity of depression (PHQ-8), anxiety (GAD-7), and quality of life (MANSA), and we tested for differences by gender and age group.

Results

The most common recent and distant SLEs were related to public safety issues and financial distress. Accidents and school suspensions were more frequent among men, and sexual harassment and bullying among women. Every additional reported recent SLE increased the odds of mild, moderate, and severe depression (18, 17, and 25%, respectively) and anxiety (10, 17, and 21%, respectively) symptoms. Similar trends were found with distant SLEs and depression (8, 9, and 11% for mild, moderate, and severe symptoms, respectively) and anxiety (9, 11, and 12%, respectively). Furthermore, a higher number of recent and distant SLEs were associated with lower quality of life (β = −0.05, p < 0.001, 95% CI [−0.06, −0.04] and β = −0.04, p < 0.001, 95% CI [−0.05, −0.03], respectively). The relationship between mental distress and quality of life of recent SLEs seems stronger than the one from distant SLEs, and recent SLEs may have a higher impact on adolescents’ mental health compared with young adults.

Conclusion

Both recent and distant SLEs are related to mental distress and quality of life. Policies and programmes should aim to enhance public and health safety, as well as improve individual, family, and community protective factors that could mitigate the effect of SLEs on Latin American youth.
Analysis of willingness to use health management APP for female college students: application of UTAUT model based on Fogg theory
Authors: Wang Lanying , Zhang Yinying , Li Zhihong , Pang Xinyu , Zhang Yuanyuan , Zou Mingming
Published: November 2024

Introduction

As the development process of medical industry informatization has entered the stage of smart healthcare, health management applications (apps) have played an important role in improving people’s health and preventing diseases, especially among female college students.

Methods

This study combines the UTAUT model and the Fogg behavioral model (FBM) as a theoretical framework to investigate the factors affecting female college students’ willingness to use health management apps. A survey was conducted with 624 female college students regarding their usage of AI health management mobile applications.

Results

The analysis reveals that social influence (β = 0.497, p < 0.001), performance expectancy (β = 0.268, p < 0.001), effort expectancy (β = 0.359, p < 0.001), and facilitating conditions (β = 0.603, p < 0.001) positively predict attitude; social influence (β = 0.36, p < 0.001) and effort expectancy (β = 0.183, p < 0.001) positively predict perceived risk, while facilitating conditions negatively predict perceived risk (β = −0.108, p < 0.01). Additionally, performance expectancy (β = 0.231, p < 0.001), effort expectancy (β = 0.285, p < 0.001), facilitating conditions (β = 0.25, p < 0.01), and attitude (β = 0.291, p < 0.05) positively predict an individual’s intention to use such applications, which in turn affects actual behavior (β = 0.804, p < 0.001).

Discussion

This study develops a comprehensive theoretical framework to explore the psychological and social factors influencing female college students’ utilization of health management applications. The findings underscore the significant roles of social influence, performance expectancy, effort expectancy, and facilitating conditions in shaping user attitudes and intentions. These insights offer valuable guidance for formulating effective interventions to enhance the adoption of these applications.