bluuebunny/crossref_metadata_2025 huggingface dataset:
Unveiling the regulatory mechanism of poly-γ-glutamic acid on soil characteristics under drought stress through integrated metagenomics and metabolomics analysis
Authors: Hong Li , Wei Li , Fanglan Ge , Jiao Li , Shiheng Tu , Hong Yang , Yao Ren , Xinyue Gong , Can Yao
Published: May 2024

It is of utmost importance to understand the characteristics and regulatory mechanisms of soil in order to optimize soil management and enhance crop yield. Poly-γ-glutamic acid (γ-PGA), a stress-resistant amino acid polymer, plays a crucial role in plant drought stress resistance. However, little is known about the effects of γ-PGA on soil characteristics during drought treatments. In this study, the effects of different forms of γ-PGA on soil texture and basic physical and chemical properties under short-term drought conditions were investigated. Furthermore, the impact of γ-PGA on the microbial community and metabolic function of maize was analyzed. Under drought conditions, the introduction of γ-PGA into the soil resulted in notable improvements in the mechanical composition ratio and infiltration capacity of the soil. Concurrently, this led to a reduction in soil bulk density and improved soil organic matter content and fertility. Additionally, metagenomic analysis revealed that under drought conditions, the incorporation of γ-PGA into the soil enhanced the soil microbiota structure. This shift led to the predominance of bacteria that are crucial for carbon, nitrogen, and phosphorus cycles in the soil. Metabolomics analysis revealed that under drought treatment, γ-PGA affected soil metabolic patterns, with a particular focus on alterations in amino acid and vitamin metabolism pathways. Correlation analysis between the soil metagenome and metabolites showed that microorganisms played a significant role in metabolite accumulation. These results demonstrated that γ-PGA could improve soil characteristics under drought conditions and play an important role in soil microorganisms and microbial metabolism, providing further insights into the changes in soil characteristics under drought conditions.
“A second birthday”? Experiences of persons with multiple sclerosis treated with autologous hematopoietic stem cell transplantation—a qualitative interview study
Authors: Volz Timo , Sippel Anna , Fischbach Felix , Richter Johanna , Willison Alice Grizzel , Häußler Vivien , Heesen Christoph
Published: May 2024

Introduction and objective

Autologous hematopoietic stem cell transplantation (aHSCT) is a promising treatment option for persons with multiple sclerosis (pwMS). Patients undergoing aHSCT face unique challenges in all aspects of life. In this study, we explored the lived experiences of pwMS undergoing aHSCT.

Methods

Semi-structured interviews of 12 pwMS treated with aHSCT were conducted using a maximum variation sampling strategy. Interviews were transcribed verbatim and analyzed thematically using inductive and deductive categories.

Results

Three major themes were identified: (1) preparing for aHSCT, (2) experiencing the procedure, and (3) post-treatment time. A difficult decision-making process, organizational effort, and funding difficulties characterized the preparation for transplantation. AHSCT was seen as a life-changing event accompanied by both psychological and physical stress, with an associated feeling of regaining control. The transplantation had a lasting positive effect on the lives of the interviewed pwMS. However, the early post-treatment time was characterized by successes and failures alike. Particularly the independently organized medical aftercare was perceived as challenging. Retrospective revaluation has led most pwMS to wish for earlier information provision about the treatment option of aHSCT during their treatment history.

Conclusion

AHSCT had a clear impact on patients’ physical and psycho-social health, influencing their perception of life and its quality. Assessing and attending to unmet needs of patients before, during, and after transplantation may positively influence their experience of aHSCT.
Assessing brain microstructural changes in chronic kidney disease: a diffusion imaging study using multiple models
Authors: Han Limei , Yang Jie , Yuan Chao , Zhang Wei , Huang Yantao , Zeng Lingli , Zhong Jianquan
Published: May 2024

Objectives

To explore the effectiveness of diffusion quantitative parameters derived from advanced diffusion models in detecting brain microstructural changes in patients with chronic kidney disease (CKD).

Methods

The study comprised 44 CKD patients (eGFR<59 mL/min/1.73 m2) and 35 age-and sex-matched healthy controls. All patients underwent diffusion spectrum imaging (DSI) and conventional magnetic resonance imaging. Reconstructed to obtain diffusion MRI models, including diffusion tensor imaging (DTI), neurite orientation dispersion and density imaging (NODDI) and Mean Apparent Propagator (MAP)-MRI, were processed to obtain multi-parameter maps. The Tract-Based Spatial Statistics (TBSS) analysis was utilized for detecting microstructural differences and Pearson correlation analysis assessed the relationship between renal metabolism markers and diffusion parameters in the brain regions of CKD patients. Receiver operating characteristic (ROC) curve analysis assessed the diagnostic performance of diffusion models, with AUC comparisons made using DeLong’s method.

Results

Significant differences were noted in DTI, NODDI, and MAP-MRI parameters between CKD patients and controls (p < 0.05). DTI indicated a decrease in Fractional Anisotropy(FA) and an increase in Mean and Radial Diffusivity (MD and RD) in CKD patients. NODDI indicated decreased Intracellular and increased Extracellular Volume Fractions (ICVF and ECVF). MAP-MRI identified extensive microstructural changes, with elevated Mean Squared Displacement (MSD) and Q-space Inverse Variance (QIV) values, and reduced Non-Gaussianity (NG), Axial Non-Gaussianity (NGAx), Radial Non-Gaussianity (NGRad), Return-to-Origin Probability (RTOP), Return-to-Axis Probability (RTAP), and Return-to-Plane Probability (RTPP). There was a moderate correlation between serum uric acid (SUA) and diffusion parameters in six brain regions (p < 0.05). ROC analysis showed the AUC values of DTI_FA ranged from 0.70 to 0.793. MAP_NGAx in the Retrolenticular part of the internal capsule R reported a high AUC value of 0.843 (p < 0.05), which was not significantly different from other diffusion parameters (p > 0.05).

Conclusion

The advanced diffusion models (DTI, NODDI, and MAP-MRI) are promising for detecting brain microstructural changes in CKD patients, offering significant insights into CKD-affected brain areas.
Peripheral cutaneous synucleinopathy characteristics in genetic Parkinson’s disease
Authors: Yuan Yanpeng , Wang Yangyang , Liu Minglei , Luo Haiyang , Liu Xiaojing , Li Lanjun , Mao Chengyuan , Yang Ting , Li Shuo , Zhang Xiaoyun , Gao Yuan , Xu Yuming , Yang Jing
Published: May 2024

Background

Cutaneous phosphorylated alpha-synuclein (p-α-syn) deposition is an important biomarker of idiopathic Parkinson’s disease (iPD). Recent studies have reported synucleinopathies in patients with common genetic forms of PD.

Objective

This study aimed to detect p-α-syn deposition characteristic in rare genetic PD patients with CHCHD2 or RAB39B mutations. Moreover, this study also aimed to describe peripheral alpha-synuclein prion-like activity in genetic PD patients, and acquire whether the cutaneous synucleinopathy characteristics of genetic PD are consistent with central neuropathologies.

Methods

We performed four skin biopsy samples from the distal leg (DL) and proximal neck (C7) of 161 participants, including four patients with CHCHD2 mutations, two patients with RAB39B mutations, 16 patients with PRKN mutations, 14 patients with LRRK2 mutations, five patients with GBA mutations, 100 iPD patients, and 20 healthy controls. We detected cutaneous synucleinopathies using immunofluorescence staining and a seeding amplification assay (SAA). A systematic literature review was also conducted, involving 64 skin biopsies and 205 autopsies of genetic PD patients with synucleinopathy.

Results

P-α-syn was deposited in the peripheral cutaneous nerves of PD patients with CHCHD2, LRRK2, or GBA mutations but not in those with RAB39B or PRKN mutations. There were no significant differences in the location or rate of α-syn-positive deposits between genetic PD and iPD patients. Peripheral cutaneous synucleinopathy appears to well represent brain synucleinopathy of genetic PD, especially autosomal dominant PD (AD-PD). Cutaneous α-synuclein SAA analysis of iPD and LRRK2 and GBA mutation patients revealed prion-like activity.

Conclusion

P-α-syn deposition in peripheral cutaneous nerves, detected using SAA and immunofluorescence staining, may serve as an accurate biomarker for genetic PD and iPD in the future.
Static and dynamic brain morphological changes in isolated REM sleep behavior disorder compared to normal aging
Authors: Park Gilsoon , Jo Hyunjin , Chai Yaqiong , Park Hea Ree , Lee Hanul , Joo Eun Yeon , Kim Hosung
Published: May 2024

Objective/background

To assess whether cerebral structural alterations in isolated rapid eye movement sleep behavior disorder (iRBD) are progressive and differ from those of normal aging and whether they are related to clinical symptoms.

Patients/methods

In a longitudinal study of 18 patients with iRBD (age, 66.1 ± 5.7 years; 13 males; follow-up, 1.6 ± 0.6 years) and 24 age-matched healthy controls (age, 67.0 ± 4.9 years; 12 males; follow-up, 2.0 ± 0.9 years), all participants underwent multiple extensive clinical examinations, neuropsychological tests, and magnetic resonance imaging at baseline and follow-up. Surface-based cortical reconstruction and automated subcortical structural segmentation were performed on T1-weighted images. We used mixed-effects models to examine the differences between the groups and the differences in anatomical changes over time.

Results

None of the patients with iRBD demonstrated phenoconversion during the follow-up. Patients with iRBD had thinner cortices in the frontal, occipital, and temporal regions, and more caudate atrophy, compared to that in controls. In similar regions, group-by-age interaction analysis revealed that patients with iRBD demonstrated significantly slower decreases in cortical thickness and caudate volume with aging than that observed in controls. Patients with iRBD had lower scores on the Korean version of the Mini-Mental Status Examination (p = 0.037) and frontal and executive functions (p = 0.049) at baseline than those in controls; however, no significant group-by-age interaction was identified.

Conclusion

Patients with iRBD show brain atrophy in the regions that are overlapped with the areas that have been documented to be affected in early stages of Parkinson’s disease. Such atrophy in iRBD may not be progressive but may be slower than that in normal aging. Cognitive impairment in iRBD is not progressive.
Controlling the nutritional status score: a new tool for predicting postoperative mortality in patients with infrarenal abdominal aortic aneurysm treated with endovascular aneurysm repair
Authors: Ye Sheng-Lin , Xu Tian-Ze , Wang Chuang , Han Kang , Jiang Xu-Dong , Tang Tao , Song Bin , Du Xiao-Long , Hu Nan , Li Xiao-Qiang
Published: May 2024

Background

AAA is a fatal condition that commonly occurs during vascular surgery. Nutritional status exerts a significant influence on the prognosis of various pathological conditions Scores from the CONUT screening tool have been shown to predict outcomes of certain malignancies and chronic diseases. However, the ramifications of nutritional status on AAA patients undergoing EVAR have not been elucidated in prior studies. In this study, we aimed to elucidate the correlation between CONUT scores and postoperative prognostic outcomes in patients with AAA undergoing EVAR.

Methods

This was a retrospective review of 177 AAA patients treated with EVAR from June 2018 to November 2019 in a single center. Patient characteristics, CONUT scores, and postoperative status were collected. These patients were stratified into groups A and B according to CONUT scores. Subsequently, a comparative analysis of the baseline characteristics between the two cohorts was conducted. Cox proportional hazards and logistic regression analyses were employed to identify the autonomous predictors of mid-term mortality and complications, respectively.

Results

Compared with group A, patients in group B had higher midterm mortality (p < 0.001). Univariate analysis showed that CONUT scores; respiratory diseases; stent types; preoperative Hb, CRP, PT, and Fb levels were risk factors for death. Multivariate analysis confirmed that CONUT score [HR, 1.276; 95% CI, 1.029–1.584; p = 0.027] was an independent risk factor for mortality. Logistic regression analysis showed that prior arterial disease, smoking, and D-dimer levels were risk factors, although multivariate analysis showed smoking (OR, 3.492; 95% CI, 1.426–8.553; p = 0.006) was an independent risk factor. Kaplan–Meier curves showed that patients in group B had shorter mid-term survival than those in group A (log-rank p < 0.001).

Conclusion

Malnutrition was strongly associated with mid-term mortality in patients with infrarenal AAA treated with EVAR.
Electrochemical DNA-nano biosensor for the detection of Goserelin as anticancer drug using modified pencil graphite electrode
Authors: Laylani Layla Abd-Al-Sattar Sadiq , Al-dolaimy F. , Altharawi Ali , Sulaman Ghasen M. , Mustafa Mohammed Ahmed , Alkhafaji Adnan Taan , Alkhatami Ali G.
Published: May 2024

Goserelin is an effective anticancer drug, but naturally causes several side effects. Hence the determination of this drug in biological samples, plays a key role in evaluating its effects and side effects. The current studies have concentrated on monitoring Goserelin using an easy and quick DNA biosensor for the first time. In this study, copper(II) oxide nanoparticles were created upon the surface of multiwalled carbon nanotubes (CuO/MWCNTs) as a conducting mediator. The modified pencil graphite electrode (ds-DNA/PA/CuO/MWCNTs/PGE) has been modified with the help of polyaniline (PA), ds-DNA, and CuO/MWCNTs nanocomposite. Additionally, the issue with the bio-electroanalytical guanine oxidation signal in relation to ds-DNA at the surface of PA/CuO/MWCNTs/PGE has been examined to determination Goserelin for the first time. It also, established a strong conductive condition to determination Goserelin in nanomolar concentration. Thus, Goserelin’s determining, however, has a 0.21 nM detection limit and a 1.0 nM-110.0 µM linear dynamic range according to differential pulse voltammograms (DPV) of ds-DNA/PA/CuO/MWCNTs/PGE. Furthermore, the molecular docking investigation highlighted that Goserelin is able to bind ds-DNA preferentially and supported the findings of the experiments. The determining of Goserelin in real samples has been effectively accomplished in the last phase using ds-DNA/PA/CuO/MWCNTs/PGE.
High immune cell infiltration predicts improved survival in cholangiocarcinoma
Authors: Wirta Erkki-Ville , Szeto Säde , Koppatz Hanna , Nordin Arno , Mäkisalo Heikki , Arola Johanna , Sirén Jukka , Ahtiainen Maarit , Böhm Jan , Mecklin Jukka-Pekka , Sallinen Ville , Seppälä Toni T.
Published: May 2024

Background

Antitumoral immune response has a crucial role in constraining cancer. However, previous studies on cholangiocarcinoma (CCA), a rare and aggressive cancer, have reported contradictory findings on the prognostic impact of tumor-infiltrating T-lymphocytes. We aimed to clarify the effect of tumor-infiltrating CD3+ and CD8+ lymphocytes and PD-1/PD-L1 expression on CCA prognosis.

Methods

CD3+, CD8+, and PD-1+ lymphocyte densities, as well as PD-L1 expression rate were analyzed from stained tissue microarray samples from the tumor center and invasive margin of 47 cholangiocarcinomas. The association of CD3+ and CD8+ based Immune cell score (ICS) and its components with overall survival was evaluated, adjusting for age, sex, TNM stage, radicality of surgery, tumor location, and PD-L1 expression on immune cells.

Results

Low ICS was a strong independent prognostic factor for worse overall survival (Hazard ratio 9.27, 95% confidence interval 2.72-31.64, P<0.001). Among the ICS components, high CD8+ lymphocyte infiltration at the tumor center had the most evident impact on patient outcome. PD-1 and PD-L1 expression on immune cells did not have a significant impact on overall survival alone; however, PD-L1 positivity seemed to impair survival for ICSlow subgroup.

Conclusion

Identifying patient subgroups that could benefit from immunotherapy with PD-1/PD-L1 pathway blockade may help improve treatment strategies for this aggressive cancer. Our findings highlight the importance of evaluating the immune contexture in cholangiocarcinoma, as ICS serves as a strong independent prognostic and selective factor for patients who might benefit from immunotherapy.
Comparison between single-muscle evaluation and cross-sectional area muscle evaluation for predicting the prognosis in patients with oral squamous cell carcinoma: a retrospective cohort study
Authors: Takayama Hirotaka , Yoshimura Takuya , Suzuki Hajime , Hirano Yuka , Tezuka Masahiro , Ishida Takayuki , Ishihata Kiyohide , Amitani Marie , Amitani Haruka , Nakamura Yasunori , Imamura Yasushi , Inui Akio , Nakamura Norifumi
Published: May 2024

Introduction

The most effective method of assessing sarcopenia has yet to be determined, whether by single muscle or by whole muscle segmentation. The purpose of this study was to compare the prognostic value of these two methods using computed tomography (CT) images in patients with oral squamous cell carcinoma (OSCC).

Materials and methods

Sex- and age-adjusted Cox proportional hazards models were employed for each parameter of sarcopenia related to overall survival, disease-free survival, and disease-specific survival. Harrell’s concordance index was calculated for each model to assess discriminatory power.

Results

In this study including 165 patients, a significant correlation was found between the CT-based assessment of individual muscles and their cross-sectional area. Single muscle assessments showed slightly higher discriminatory power in survival outcomes compared to whole muscle assessments, but the difference was not statistically significant, as indicated by overlapping confidence intervals for the C-index between assessments. To further validate our measurements, we classified patients into two groups based on intramuscular adipose tissue content (P-IMAC) of the spinous process muscle. Analysis showed that the higher the P-IMAC value, the poorer the survival outcome.

Conclusion

Our findings indicate a slight advantage of single-muscle over whole-muscle assessment in prognostic evaluation, but the difference between the two methods is not conclusive. Both assessment methods provide valuable prognostic information for patients with OSCC, and further studies involving larger, independent cohorts are needed to clarify the potential advantage of one method over the other in the prognostic assessment of sarcopenia in OSCC.
Conditional survival of patients with primary bone lymphoma of the spine: how survival changes after initial diagnosis
Authors: Zheng Gang , Yang Zhihao , Qian Hui , Huang Hua , Gu Zhiwei
Published: May 2024

Background

The current survival prediction methodologies for primary bone lymphoma (PBL) of the spine are deficient. This study represents the inaugural utilization of conditional survival (CS) to assess the outcome of this disease. Moreover, our objective was to devise a CS-based nomogram for predicting overall survival (OS) in real-time for spinal PBL.

Methods

Patients with PBL of the spine diagnosed between January 2000 and December 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. The OS was determined through the Kaplan–Meier method. The CS characteristic of patients with spinal PBL was delineated, with the CS being estimated utilizing the formula: CS(α|β) = OS(α+β)/OS(β). CS(α|β) denotes the probability of additional α-year survivorship, assuming the patient has already survived β years after the time of observation. Three methods including univariate Cox regression, best subset regression (BSR) and the least absolute shrinkage and selection operator (LASSO) regression were used to identify predictors for CS-based nomogram construction.

Results

Kaplan-Meier analysis was executed to determine the OS rate for these patients, revealing a survival rate of 68% and subsequently 63% at the 3-year and 5-year mark respectively. We then investigated the CS patterning exhibited by these patients and discovered the survival of PBL in the spine progressively improved with time. Meanwhile, through three different prognostic factor selection methods, we identified the best predicter subset including age, tumor histology, tumor stage, chemotherapy and marital status, for survival prediction model construction. Finally, we successfully established and validated a novel CS-based nomogram model for real-time and dynamic survival estimation. Moreover, we further designed a risk stratification system to facilitate the identification of high-risk patients.

Conclusions

This is the first study to analyze the CS pattern of PBL of the spine. And we have also developed a CS-based nomogram that provide dynamic prognostic data in real-time, thereby aiding in the formulation of personalized treatment strategies in clinical practice.
Natural products’ antiangiogenic roles in gynecological cancer
Authors: Jia Shangmei , Li Ling , Yu Chenghao , Peng Fu
Published: May 2024

Gynecological cancers pose a significant threat to women’s health. Although the pathogenesis of gynecological cancer remains incompletely understood, angiogenesis is widely acknowledged as a fundamental pathological mechanism driving tumor cell growth, invasion, and metastasis. Targeting angiogenesis through natural products has emerged as a crucial strategy for treating gynecological cancer. In this review, we conducted comprehensive searches in PubMed, Embase, Web of Science, Science Direct, and CNKI databases from the first publication until May 2023 to identify natural products that target angiogenesis in gynecologic tumors. Our findings revealed 63 natural products with anti-angiogenic activity against gynecological cancer. These results underscore the significance of these natural products in augmenting their anticancer effects by modulating other factors within the tumor microenvironment via their impact on angiogenesis. This article focuses on exploring the potential of natural products in targeting blood vessels within gynecological cancer to provide novel research perspectives for targeted vascular therapy while laying a solid theoretical foundation for new drug development.
Phytic acid attenuates acetaminophen-induced hepatotoxicity via modulating iron-mediated oxidative stress and SIRT-1 expression in mice
Authors: Hassan Hend M. , Abdel-Halim Nehal H. M. , El-Shenbaby Ibrahim , Helmy Manar A. , Hammad Maha O. , Habotta Ola A. , El Nashar Eman M. , Alghamdi Mansour A. , Aldahhan Rashid A. , Al-Khater Khulood M. , Almohaywi Basmah , Farrag Eman A. E.
Published: May 2024

Introduction: Administration of high doses of acetaminophen (APAP) results in liver injury. Oxidative stress and iron overload play roles in the pathogenesis of APAP-induced hepatotoxicity. The present study assessed the potential hepatoprotective effects of phytic acid (PA), a natural antioxidant and iron chelator, on APAP-induced hepatotoxicity and the possible underlying mechanism through its effects on CYP2E1 gene expression, iron homeostasis, oxidative stress, and SIRT-1 expression levels.

Methods: Twenty-four adult male albino mice were used in this study. Mice were divided into four groups (six mice in each group): control, APAP-treated, PA-treated and APAP + PA-treated groups. Liver function tests, serum and liver tissue iron load were evaluated in all the study groups. Hepatic tissue homogenates were used to detect oxidative stress markers, including malondialdehyde (MDA) and reduced glutathione (GSH). Histological hepatic evaluation and immunohistochemistry of SIRT-1 were performed. Quantitative real-time PCR was used for the assessment of CYP2E1 and SIRT-1 gene expressions. APAP-induced biochemical and structural hepatic changes were reported.

Results: PA administration showed beneficial effects on APAP-induced hepatotoxicity through improvements in liver functions, decreased CYP2E1 gene expression, decreased serum and liver iron load, decreased MDA, increased GSH, increased SIRT-1 expression level and improvement in hepatic architecture.

Conclusion: Conclusively, PA can be considered a potential compound that can attenuate acetaminophen-induced hepatotoxicity through its role as an iron chelator and antioxidant, as well as the up-regulation of SIRT-1 and down-regulation of CYP2E1.
Induction of ferroptosis by natural products in non-small cell lung cancer: a comprehensive systematic review
Authors: Zhang Qiang , Xia Yuting , Wang Feiyan , Yang Dongfeng , Liang Zongsuo
Published: May 2024

Lung cancer is one of the leading causes of cancer-related deaths worldwide that presents a substantial peril to human health. Non-Small Cell Lung Cancer (NSCLC) is a main subtype of lung cancer with heightened metastasis and invasion ability. The predominant treatment approaches currently comprise surgical interventions, chemotherapy regimens, and radiotherapeutic procedures. However, it poses significant clinical challenges due to its tumor heterogeneity and drug resistance, resulting in diminished patient survival rates. Therefore, the development of novel treatment strategies for NSCLC is necessary. Ferroptosis was characterized by iron-dependent lipid peroxidation and the accumulation of lipid reactive oxygen species (ROS), leading to oxidative damage of cells and eventually cell death. An increasing number of studies have found that exploiting the induction of ferroptosis may be a potential therapeutic approach in NSCLC. Recent investigations have underscored the remarkable potential of natural products in the cancer treatment, owing to their potent activity and high safety profiles. Notably, accumulating evidences have shown that targeting ferroptosis through natural compounds as a novel strategy for combating NSCLC holds considerable promise. Nevertheless, the existing literature on comprehensive reviews elucidating the role of natural products inducing the ferroptosis for NSCLC therapy remains relatively sparse. In order to furnish a valuable reference and support for the identification of natural products inducing ferroptosis in anti-NSCLC therapeutics, this article provided a comprehensive review explaining the mechanisms by which natural products selectively target ferroptosis and modulate the pathogenesis of NSCLC.
Development and therapeutic evaluation of 5D3(CC-MLN8237)3.2 antibody-theranostic conjugates for PSMA-positive prostate cancer therapy
Authors: Liatsou Ioanna , Assefa Betelhem , Liyanage Wathsala , Surasinghe Sharmane , Nováková Zora , Bařinka Cyril , Gabrielson Kathleen , Raman Venu , Artemov Dmitri , Hapuarachchige Sudath
Published: May 2024

Prostate cancer (PC) is an aggressive cancer that can progress rapidly and eventually become castrate-resistant prostate cancer (CRPC). Stage IV metastatic castrate-resistant prostate cancer (mCRPC) is an incurable late-stage cancer type with a low 5-year overall survival rate. Targeted therapeutics such as antibody-drug conjugates (ADCs) based on high-affinity monoclonal antibodies and potent drugs conjugated via smart linkers are being developed for PC management. Conjugating further with in vitro or in vivo imaging agents, ADCs can be used as antibody-theranostic conjugates (ATCs) for diagnostic and image-guided drug delivery. In this study, we have developed a novel ATC for PSMA (+) PC therapy utilizing (a) anti-PSMA 5D3 mAb, (b) Aurora A kinase inhibitor, MLN8237, and (c) for the first time using tetrazine (Tz) and trans-cyclooctene (TCO) click chemistry-based conjugation linker (CC linker) in ADC development. The resulting 5D3(CC-MLN8237)3.2 was labeled with suitable fluorophores for in vitro and in vivo imaging. The products were characterized by SDS-PAGE, MALDI-TOF, and DLS and evaluated in vitro by optical imaging, flow cytometry, and WST-8 assay for cytotoxicity in PSMA (+/−) cells. Therapeutic efficacy was determined in human PC xenograft mouse models following a designed treatment schedule. After the treatment study animals were euthanized, and toxicological studies, complete blood count (CBC), blood clinical chemistry analysis, and H&E staining of vital organs were conducted to determine side effects and systemic toxicities. The IC50 values of 5D3(CC-MLN8237)3.2-AF488 in PSMA (+) PC3-PIP and PMSA (−) PC3-Flu cells are 8.17 nM and 161.9 nM, respectively. Pure MLN8237 shows 736.9 nM and 873.4 nM IC50 values for PC3-PIP and PC3-Flu cells, respectively. In vivo study in human xenograft mouse models confirmed high therapeutic efficacy of 5D3(CC-MLN8237)3.2-CF750 with significant control of PSMA (+) tumor growth with minimal systemic toxicity in the treated group compared to PSMA (−) treated and untreated groups. Approximately 70% of PSMA (+) PC3-PIP tumors did not exceed the threshold of the tumor size in the surrogate Kaplan-Meyer analysis. The novel ATC successfully controlled the growth of PSMA (+) tumors in preclinical settings with minimal systemic toxicities. The therapeutic efficacy and favorable safety profile of novel 5D3(CC-MLN8237)3.2 ATC demonstrates their potential use as a theranostic against aggressive PC.
Periodic motion of macro- and/or micro-scale cantilevered fluid-conveying pipes with O(2) symmetry: a finite dimensional analysis
Authors: Guo Yong
Published: May 2024

Introduction: In this study, the spatial bending vibration of macro- and/or micro-scale cantilevered fluid-conveying pipes is investigated through finite dimensional analysis.

Methods: Firstly, the Galerkin method is employed to discretize the partial differential equations of motion of the system into a system of ordinary differential equations. Then, the projection method based on center manifold-normal form theory is adopted to derive the coefficient formula that determines the pipe’s nonlinear dynamic behaviors, i.e., the change rate of the real part of the critical eigenvalue with respect to the flow velocity and the nonlinear resonance term, thereby obtaining reduced-order equations. Compared to previous studies that relied on the numerical solution of ordinary differential equations to determine the existence and stability of periodic motion, this paper concludes the existence and stability of periodic motion by utilizing the coefficients of the Galerkin discretized equations and the reduced-order equations, significantly saving time in determining the dynamic properties of pipes.

Results and discussion: Subsequently, by investigating the reduced-order equations under specific parameters, the existence and stability of the two types of periodic motion of the pipe are studied. For macro pipes, the truncated mode numbers are set incrementally to calculate the coefficients of the reduced-order equations, investigate the distribution of the stability of the two types of periodic motions with the mass ratio, and carry out a longitudinal comparison (i.e., the comparison between the results obtained under different truncated mode numbers) as well as a horizontal comparison (i.e., the comparison of results between the finite dimensional analysis and the infinite dimensional analysis). It is found that the reasonable truncated mode number required to study this type of system is 15. Previous studies primarily focused on the convergence of frequency and amplitude when determining the truncated mode numbers. On this basis, our study further examines the convergence of motion forms with respect to the truncated mode numbers. Finally, based on the Galerkin discretization equations of 15 modes, the distribution of the stability of two types of the periodic motion of micro pipes with the mass ratio is analyzed. For macro- and micro-scale pipes, when the truncated mode number is 15, the error between the finite dimensional analysis results and the infinite dimensional analysis results is calculated to be about 7%. The above results are verified by obtaining the numerical solution to Galerkin discretization equations.
Transport capacity is uncoupled with endodormancy breaking in sweet cherry buds: physiological and molecular insights
Authors: Fouché Mathieu , Bonnet Hélène , Bonnet Diane M. V. , Wenden Bénédicte
Published: May 2024

Introduction

To avoid the negative impacts of winter unfavorable conditions for plant development, temperate trees enter a rest period called dormancy. Winter dormancy is a complex process that involves multiple signaling pathways and previous studies have suggested that transport capacity between cells and between the buds and the twig may regulate the progression throughout dormancy stages. However, the dynamics and molecular actors involved in this regulation are still poorly described in fruit trees.

Methods

Here, in order to validate the hypothesis that transport capacity regulates dormancy progression in fruit trees, we combined physiological, imaging and transcriptomic approaches to characterize molecular pathways and transport capacity during dormancy in sweet cherry (Prunus avium L.) flower buds.

Results

Our results show that transport capacity is reduced during dormancy and could be regulated by environmental signals. Moreover, we demonstrate that dormancy release is not synchronized with the transport capacity resumption but occurs when the bud is capable of growth under the influence of warmer temperatures. We highlight key genes involved in transport capacity during dormancy.

Discussion

Based on long-term observations conducted during six winter seasons, we propose hypotheses on the environmental and molecular regulation of transport capacity, in relation to dormancy and growth resumption in sweet cherry.
A density map-based method for counting wheat ears
Authors: Zhang Guangwei , Wang Zhichao , Liu Bo , Gu Limin , Zhen Wenchao , Yao Wei
Published: May 2024

Introduction

Field wheat ear counting is an important step in wheat yield estimation, and how to solve the problem of rapid and effective wheat ear counting in a field environment to ensure the stability of food supply and provide more reliable data support for agricultural management and policy making is a key concern in the current agricultural field.

Methods

There are still some bottlenecks and challenges in solving the dense wheat counting problem with the currently available methods. To address these issues, we propose a new method based on the YOLACT framework that aims to improve the accuracy and efficiency of dense wheat counting. Replacing the pooling layer in the CBAM module with a GeM pooling layer, and then introducing the density map into the FPN, these improvements together make our method better able to cope with the challenges in dense scenarios.

Results

Experiments show our model improves wheat ear counting performance in complex backgrounds. The improved attention mechanism reduces the RMSE from 1.75 to 1.57. Based on the improved CBAM, the R2 increases from 0.9615 to 0.9798 through pixel-level density estimation, the density map mechanism accurately discerns overlapping count targets, which can provide more granular information.

Discussion

The findings demonstrate the practical potential of our framework for intelligent agriculture applications.
Screening, identification and evaluation of an acidophilic strain of Bacillus velezensis B4-7 for the biocontrol of tobacco bacterial wilt
Authors: Meng Xiang-jia , Wang Lan-qin , Ma Bai-ge , Wei Xi-hong , Zhou Yi , Sun Zheng-xiang , Li Yan-yan
Published: May 2024

Tobacco (Nicotiana tabacum L.) bacterial wilt, caused by Ralstonia solanacearum, is indeed a highly destructive plant disease, leading to substantial damage in tobacco production. While biological control is considered an effective measure for managing bacterial wilt, related research in this area has been relatively limited compared to other control methods. In order to discover new potential antagonistic bacteria with high biocontrol efficacy against tobacco bacterial wilt, we conducted an analysis of the microbial composition differences between disease-suppressive and disease-conducive soils using Illumina sequencing. As a result, we successfully isolated six strains from the disease-suppressive soil that exhibited antibacterial activity against Ralstonia solanacearum. Among these strains, B4-7 showed the strongest antibacterial activity, even at acidic conditions with a pH of 4.0. Based on genome analysis using Average Nucleotide Identity (ANI), B4-7 was identified as Bacillus velezensis. In greenhouse and field trials, strain B4-7 significantly reduced the disease index of tobacco bacterial wilt, with control efficiencies reaching 74.03% and 46.88% respectively. Additionally, B4-7 exhibited plant-promoting abilities that led to a 35.27% increase in tobacco production in field conditions. Quantitative real-time (qPCR) analysis demonstrated that strain B4-7 effectively reduced the abundance of R. solanacearum in the rhizosphere. Genome sequencing and Liquid Chromatography-Mass Spectrometry (LC-MS) analysis revealed that strain B4-7 potentially produces various lipopeptide metabolites, such as microlactin, bacillaene, difficidin, bacilysin, and surfactin. Furthermore, B4-7 influenced the structure of the rhizosphere soil microbial community, increasing bacterial abundance and fungal diversity, while also promoting the growth of different beneficial microorganisms. In addition, B4-7 enhanced tobacco’s resistance to R. solanacearum by increasing the activities of defense enzymes, including superoxide dismutase (SOD), phenylalanine ammonia-lyase (PAL), peroxidase (POD), catalase (CAT), and polyphenol oxidase (PPO). Collectively, these findings suggest that B. velezensis B4-7 holds significant biocontrol potential and can be considered a promising candidate strain for eco-friendly management of tobacco bacterial wilt.
Tomato R-gene-mediated resistance against Fusarium wilt originates in roots and extends to shoots via xylem to limit pathogen colonization
Authors: Šimkovicová Margarita , Kramer Gertjan , Rep Martijn , Takken Frank L. W.
Published: May 2024

Vascular wilt disease, caused by the soil-borne fungus Fusarium oxysporum (Fo), poses a threat to many crop species. Four different tomato resistance (R) genes (I-1, I-2, I-3, and I-7) have been identified to confer protection against Fo f.sp. lycopersici (Fol). These I genes are root-expressed and mount an immune response upon perception of the invading fungus. Despite immune activation, Fol is still able to colonize the xylem vessels of resistant tomato lines. Yet, the fungus remains localized in the vessels and does not colonize adjacent tissues or cause disease. The molecular mechanism constraining Fol in the vascular system of the stem remains unclear. We here demonstrate that an I-2-resistant rootstock protects a susceptible scion from Fusarium wilt, notwithstanding fungal colonization of the susceptible scion. Proteomic analyses revealed the presence of fungal effectors in the xylem sap of infected plants, showing that the lack of fungal pathogenicity is not due to its inability to express its virulence genes. To identify mobile root-derived proteins, potentially involved in controlling fungal proliferation, comparative xylem sap proteomics was performed. We identified distinct pathogenesis-related (PR) protein profiles in xylem sap from Fol-inoculated I-1, I-2, I-3, and I-7 resistant lines. Despite structural diversity, all four immune receptors trigger the accumulation of a common set of four PR proteins: PR-5x, PR-P2, and two glucan endo-1,3-β-D-glucosidases. This research provides insights into Fusarium resistance mechanisms and identifies a core set of proteins whose abundance correlates with defense against Fusarium wilt.
Business culture impairs facial trustworthiness judgments
Authors: Zhang Hongchuan , Liu Yitong , Li Weiran , Nie Mengjie , Xin Ziqiang
Published: May 2024

Previous research has found that business culture has a detrimental impact on interpersonal trust. To understand whether this impact extends to rapid, automatic, bottom–up judgments of facial trustworthiness, we conducted 4 experiments involving 244 participants from economic and non-economic backgrounds. We presented participants with both trustworthy and untrustworthy faces and asked them to make judgments on trustworthiness. The results show that individuals who are engaged in studying economics, work in an economics-related occupation, or are exposed to an imagined business culture evaluate trustworthy faces to be less trustworthy. The findings shed light on why and how business culture affects the formation of interpersonal trust.
Mental health, COVID-19 burden and quality of life of kidney transplant recipients two years after the COVID-19 pandemic
Authors: De Pasquale Concetta , Pistorio Maria Luisa , Veroux Massimiliano , Barbagallo Noemi , Cottone Provvidenza Marisa , Ekser Burcin , Lorenzano Giuseppina , Giaquinta Alessia , Veroux Pierfrancesco
Published: May 2024

Introduction

Few studies have evaluated the psychological distress of COVID-19 in kidney transplantation and the psychological impact that the COVID-19 pandemic has had on kidney transplant recipients is not yet well understood. The present study aimed to investigate the change in symptom burden and health-related quality of life in the two years after initial assessment, by outlining the change over time of symptoms at 12 and 24 months of follow-up.

Methods

This is a follow-up study. We performed a study published in 2021 (phase 1 of COVID-19); of the 89 kidney transplant recipients evaluated in this study, 60 completed the 12 months follow-up (March 2021 June 2021, phase 2 of COVID-19) and 57 completed the 24 months follow-up (March 2022 June 2022, post COVID-19). The same tools as in previous study were administered: the ad hoc questionnaire on emotional state and psychophysical well-being during COVID-19, the Middlesex Hospital Questionnaire (MHQ) to provide a simple and rapid quantification of the psychological and somatic symptoms and the Short Form Health Survey 36 (SF-36) was used to assess health-related quality of life.

Results

Compared to the first and second phase of COVID-19, the mean score of quality of life variables were higher in the post COVID-19 phase; thus the recipients physical health, mental health and their perception of their general health improved. Regarding the psychopathology variables the levels of Anxiety, Depression and Phobia in the Post COVID-19 phase decreased, while the Somatization score was higher. Lastly, burden of COVID-19 scores in the third phase, significantly decreased.

Discussion

Our study highlights a significant association between mental health and the burden of COVID-19 pandemic in kidney transplant recipients. This study showed, a significant worsening, over time, of some specific symptoms, such as somatization and phobias. However, the results showed that depressive symptoms improved during the study period. Long-term monitoring of kidney transplant recipients therefore remains fundamental. These results confirmed the need to provide integrated multidisciplinary services to adequately address the long-term effects of the COVID-19 pandemic on the mental health of the most vulnerable subjects.
Differential predictors of early- and delayed-onset post-traumatic stress disorder following physical injury: a two-year longitudinal study
Authors: Kang Sung-Gil , Kim Ju-Wan , Kang Hee-Ju , Jang Hyunseok , Kim Jung-Chul , Lee Ju-Yeon , Kim Sung-Wan , Shin Il-Seon , Kim Jae-Min
Published: May 2024

Objectives

This study aimed to investigate the predictors of both early- and delayed-onset PTSD over a 2-year period following physical injuries.

Methods

Patients were recruited from a trauma center at a university hospital in South Korea (June 2015 ~ January 2021). At baseline, 1142 patients underwent comprehensive assessments including socio-demographic, pre-trauma, trauma-related, and peri-trauma evaluations. Diagnoses of acute stress disorder (ASD) and subthreshold ASD were also determined using the Clinician-administered PTSD Scale (CAPS). Follow-up assessments at three months included diagnoses of PTSD and subthreshold PTSD using CAPS, and stressful life events (SLEs), with additional evaluations at 6, 12, and 24 months. The analyzed sample comprised 1014 patients followed up at least once after the baseline and 3-month evaluations. PTSD diagnoses were categorized into early-onset (within the first six months after trauma) and delayed-onset (more than six months after trauma). Logistic regression models identified predictors for each group.

Results

Early-onset and delayed-onset PTSD were diagnosed in 79 and 35 patients, respectively. Early-onset PTSD was predicted by previous psychiatric disorders, previous traumatic events, ASD and subthreshold ASD diagnoses, and higher anxiety levels. In contrast, delayed-onset PTSD was linked to higher education, higher injury severity, and subthreshold PTSD and SLEs at 3-month follow-up.

Conclusion

Distinct predictors were found for early-onset and delayed-onset PTSD. The findings underscore the heterogeneous factors influencing the temporal development of PTSD post-trauma, and may provide valuable guidance for more targeted interventions and improved patient outcomes.
Organizational support enhances nurses’ work-family enrichment: a person–context interactionist perspective
Authors: Xu Hao , Zhao Xiufang
Published: May 2024

Introduction

Attaining a favorable work-life balance is a complex and ongoing challenge in the nursing profession. According to a person–context interactionist perspective and the two-factor theory, this study investigated the underlying mechanism by which organizational support impacts work-family enrichment via protective factors (i.e., decent work) and depleting factors (i.e., burnout) among Chinese nurses.

Methods

A descriptive cross-sectional research design was utilized in this study, employing an online questionnaire as the primary method for data collection. The study included 355 nurses who completed a self-reported questionnaire designed to measure variables such as organizational support, decent work, burnout, work-family enrichment, and demographic information. The collected data were analyzed using a chain mediation model in PROCESS macro (Model 6).

Results

The findings of the analysis revealed that nurses reporting higher levels of organizational support also exhibited a greater sense of work-family enrichment. Moreover, the study identified indirect effects of organizational support on work-family enrichment, mediated by decent work and burnout.

Discussion

These findings suggest that targeted interventions aimed at promoting organizational support can contribute to the overall well-being and work-life balance of nurses.