bluuebunny/crossref_metadata_2025_split huggingface dataset:
LysSYL: a broad-spectrum phage endolysin targeting Staphylococcus species and eradicating S. aureus biofilms
Authors: Liu He , Wei Xuemei , Wang Zhefen , Huang Xiaonan , Li Mengyang , Hu Zhen , Zhang Kexin , Hu Qiwen , Peng Huagang , Shang Weilong , Yang Yi , Wang Yuting , Lu Shuguang , Rao Xiancai 
Published: March 2024

Abstract
Background
Staphylococcus aureus and its single or mixed biofilm infections seriously threaten global public health. Phage therapy, which uses active phage particles or phage-derived endolysins, has emerged as a promising alternative strategy to antibiotic treatment. However, high-efficient phage therapeutic regimens have yet to be established.

Results
In this study, we used an enrichment procedure to isolate phages against methicillin-resistant S. aureus (MRSA) XN108. We characterized phage SYL, a new member of the Kayvirus genus, Herelleviridae family. The phage endolysin LysSYL was expressed. LysSYL demonstrated stability under various conditions and exhibited a broader range of efficacy against staphylococcal strains than its parent phage (100% vs. 41.7%). Moreover, dynamic live/dead bacterial observation demonstrated that LysSYL could completely lyse MRSA USA300 within 10 min. Scan and transmission electron microscopy revealed evident bacterial cell perforation and deformation. In addition, LysSYL displayed strong eradication activity against single- and mixed-species biofilms associated with S. aureus. It also had the ability to kill bacterial persisters, and proved highly effective in eliminating persistent S. aureus when combined with vancomycin. Furthermore, LysSYL protected BALB/c mice from lethal S. aureus infections. A single-dose treatment with 50 mg/kg of LysSYL resulted in a dramatic reduction in bacterial loads in the blood, liver, spleen, lungs, and kidneys of a peritonitis mouse model, which resulted in rescuing 100% of mice challenged with 108 colony forming units of S. aureus USA300.

Conclusions
Overall, the data provided in this study highlight the strong therapeutic potential of endolysin LysSYL in combating staphylococcal infections, including mono- and mixed-species biofilms related to S. aureus.
The upregulation of VGF enhances the progression of oral squamous carcinoma
Authors: Chou Chung-Hsien , Yen Chun-Han , Liu Chung-Ji , Tu Hsi-Feng , Lin Shu-Chun , Chang Kuo-Wei 
Published: March 2024

Abstract
Background
Oral squamous cell carcinoma (OSCC) is a prevalent neoplasm worldwide, necessitating a deeper understanding of its pathogenesis. VGF nerve growth factor inducible (VGF), a neuropeptide, plays critical roles in nerve and endocrine cell regulation.

Methods
In this study, the TCGA datasets were initially screened, identifying the upregulation of VGF in various malignancies. We focused on OSCC cell lines, identifying the suppressor mRNA miR-432-5p as a negative regulator of VGF. Additionally, we examined the prognostic value of VGF expression in OSCC tumors and its impact on cellular functions.

Results
VGF expression was found to be an independent prognostic predictor in OSCC tumors. Cells expressing VGF exhibited increased oncogenicity, influencing the proliferation and migration of oral mucosal fibroblast. Transcriptome analysis revealed associations between VGF and various pathological processes, including malignancies, exosome release, fibrosis, cell cycle disruption, and tumor immune suppression. Moreover, IL23R expression, a favorable OSCC prognostic factor, was inversely correlated with VGF expression. Exogenous IL23R expression was found to suppress VGF-associated mobility phenotypes.

Conclusions
This study highlights the multifaceted role of VGF in OSCC pathogenesis and introduces the miR-432-5p-VGF-IL23R regulatory axis as a critical mediator. The combined expression of VGF and IL23R emerges as a potent predictor of survival in oral carcinoma cases, suggesting potential implications for future therapeutic strategies.
Clinical efficiency of three-port inflatable robot-assisted thoracoscopic surgery in mediastinal tumor resection
Authors: Peng Hao , He YuanPeng , Sheng Siqi , Maitiyasen Maierhaba , Li Jingfeng , Liu Yvxuan , Chen Jing , Hou Xinyu , Song Haizhu , Yi Jun 
Published: March 2024

Abstract
Background
Aimed to assess clinical effect of three-port inflatable robot-assisted thoracoscopic surgery in mediastinal tumor resection by comparing results of the robot group with the video group.

Methods
Retrospectively analyze 179 patients diagnosed with anterior mediastinal tumor from May 2017 to August 2021. Two groups were divided according to the surgical approach, including 92 cases in the RATS group and 87 cases in the VATS group. The results were analyzed between two groups with variables of age, sex, BMI, tumor size, and diagnosis. Perioperative clinical data was gathered to compare.

Result
There were no significant differences between the 2 groups with regards to demographic data and clinical features. There were no significant differences inoperative time and duration of chest tube via RATS vs. VATS. The intraoperative blood loss was statistically significantly different among the RATS and VATS groups (75.9 ± 39.6 vs. 97.4 ± 35.8 ml p = 0.042). The postoperative stay of patients in RATS group were significantly shorter than that in VATS group (2.3 ± 1.0 vs. 3.4 ± 1.4 day p = 0.035),

Conclusion
Three-port inflatable robot-assisted thoracoscopic surgery for mediastinal tumor is feasible and reliable it is more advantageous, and it provides the surgeon with advice on treatment choice.
Endothelial CXCR2 deficiency attenuates renal inflammation and glycocalyx shedding through NF-κB signaling in diabetic kidney disease
Authors: Cui Siyuan , Chen Xin , Li Jiayu , Wang Wei , Meng Deqi , Zhu Shenglong , Shen Shiwei 
Published: March 2024

Abstract
Background
The incidence of diabetic kidney disease (DKD) continues to rapidly increase, with limited available treatment options. One of the hallmarks of DKD is persistent inflammation, but the underlying molecular mechanisms of early diabetic kidney injury remain poorly understood. C-X-C chemokine receptor 2 (CXCR2), plays an important role in the progression of inflammation-related vascular diseases and may bridge between glomerular endothelium and persistent inflammation in DKD.

Methods
Multiple methods were employed to assess the expression levels of CXCR2 and its ligands, as well as renal inflammatory response and endothelial glycocalyx shedding in patients with DKD. The effects of CXCR2 on glycocalyx shedding, and persistent renal inflammation was examined in a type 2 diabetic mouse model with Cxcr2 knockout specifically in endothelial cells (DKD-Cxcr2eCKO mice), as well as in glomerular endothelial cells (GECs), cultured in high glucose conditions.

Results
CXCR2 was associated with early renal decline in DKD patients, and endothelial-specific knockout of CXCR2 significantly improved renal function in DKD mice, reduced inflammatory cell infiltration, and simultaneously decreased the expression of proinflammatory factors and chemokines in renal tissue. In DKD conditions, glycocalyx shedding was suppressed in endothelial Cxcr2 knockout mice compared to Cxcr2L/L mice. Modulating CXCR2 expression also affected high glucose-induced inflammation and glycocalyx shedding in GECs. Mechanistically, CXCR2 deficiency inhibited the activation of NF-κB signaling, thereby regulating inflammation, restoring the endothelial glycocalyx, and alleviating DKD.

Conclusions
Taken together, under DKD conditions, activation of CXCR2 exacerbates inflammation through regulation of the NF-κB pathway, leading to endothelial glycocalyx shedding and deteriorating renal function. Endothelial CXCR2 deficiency has a protective role in inflammation and glycocalyx dysfunction, suggesting its potential as a promising therapeutic target for DKD treatment.
Transcriptome and open chromatin analysis reveals the process of myocardial cell development and key pathogenic target proteins in Long QT syndrome type 7
Authors: Chen Peipei , Long Junyu , Hua Tianrui , Zheng Zhifa , Xiao Ying , Chen Lianfeng , Yu Kang , Wu Wei , Zhang Shuyang 
Published: March 2024

Abstract
Objective
Long QT syndrome type 7 (Andersen–Tawil syndrome, ATS), which is caused by KCNJ2 gene mutation, often leads to ventricular arrhythmia, periodic paralysis and skeletal malformations. The development, differentiation and electrophysiological maturation of cardiomyocytes (CMs) changes promote the pathophysiology of Long QT syndrome type 7(LQT7). We aimed to specifically reproduce the ATS disease phenotype and study the pathogenic mechanism.

Methods and results
We established a cardiac cell model derived from human induced pluripotent stem cells (hiPSCs) to the phenotypes and electrophysiological function, and the establishment of a human myocardial cell model that specifically reproduces the symptoms of ATS provides a reliable platform for exploring the mechanism of this disease or potential drugs. The spontaneous pulsation rate of myocardial cells in the mutation group was significantly lower than that in the repair CRISPR group, the action potential duration was prolonged, and the Kir2.1 current of the inward rectifier potassium ion channel was decreased, which is consistent with the clinical symptoms of ATS patients. Only ZNF528, a chromatin-accessible TF related to pathogenicity, was continuously regulated beginning from the cardiac mesodermal precursor cell stage (day 4), and continued to be expressed at low levels, which was identified by WGCNA method and verified with ATAC-seq data in the mutation group. Subsequently, it indicated that seven pathways were downregulated (all p < 0.05) by used single sample Gene Set Enrichment Analysis to evaluate the overall regulation of potassium-related pathways enriched in the transcriptome and proteome of late mature CMs. Among them, the three pathways (GO: 0008076, GO: 1990573 and GO: 0030007) containing the mutated gene KCNJ2 is involved that are related to the whole process by which a potassium ion enters the cell via the inward rectifier potassium channel to exert its effect were inhibited. The other four pathways are related to regulation of the potassium transmembrane pathway and sodium:potassium exchange ATPase (p < 0.05). ZNF528 small interfering (si)-RNA was applied to hiPSC-derived cardiomyocytes for CRISPR group to explore changes in potassium ion currents and growth and development related target protein levels that affect disease phenotype. Three consistently downregulated proteins (KCNJ2, CTTN and ATP1B1) associated with pathogenicity were verificated through correlation and intersection analysis.

Conclusion
This study uncovers TFs and target proteins related to electrophysiology and developmental pathogenicity in ATS myocardial cells, obtaining novel targets for potential therapeutic candidate development that does not rely on gene editing.

Graphical Abstract
Where should “Humans” be in “One Health”? Lessons from COVID-19 for One Health
Authors: Su Zhaohui , McDonnell Dean , Cheshmehzangi Ali , Bentley Barry L. , Šegalo Sabina , da Veiga Claudimar Pereira , Xiang Yu-Tao 
Published: March 2024

AbstractThe culling of animals that are infected, or suspected to be infected, with COVID-19 has fuelled outcry. What might have contributed to the ongoing debates and discussions about animal rights protection amid global health crises is the lack of a unified understanding and internationally agreed-upon definition of “One Health”. The term One Health is often utilised to describe the imperative to protect the health of humans, animals, and plants, along with the overarching ecosystem in an increasingly connected and globalized world. However, to date, there is a dearth of research on how to balance public health decisions that could impact all key stakeholders under the umbrella of One Health, particularly in contexts where human suffering has been immense. To shed light on the issue, this paper discusses whether One Health means “human-centred connected health” in a largely human-dominated planet, particularly amid crises like COVID-19. The insights of this study could help policymakers make more informed decisions that could effectively and efficiently protect human health while balancing the health and well-being of the rest of the inhabitants of our shared planet Earth.
Recovery pattern after decompression of central lumbar spinal stenosis: a prospective observational cohort study
Authors: Hareni Niyaz , Ebrahimnia Soheil , Rosengren Björn E. , Karlsson Magnus K. 
Published: March 2024

Abstract
Background
Detailed preoperative information is associated with superior outcomes. We aimed to describe the recovery pattern after decompression of central lumbar spinal stenosis (CLSS).

Methods
50 patients aged 51–85 years who underwent decompression without fusion due to CLSS were followed from before to after surgery (post-op day 1, 7, and 14). Back and leg pain were evaluated using the Numeric Rating Scale (NRS; 0 = no pain 0, 10 = worst pain) and quality of life using the EuroQol-5D index (0 = death, 1 = best), and EQ-5D-visual analogue scale (VAS; 0 = worst, 100 = best).

Results
NRS leg pain was reduced from preoperative to first postoperative day by 5.2 (6.1, 4.3) (mean (95%CI)], and NRS back pain from postoperative day 1–7 by 0.6 (1.2, 0.03) and from day 7 to 14 by 0.7 (1.3, 0.2)]. In contrast, EQ-5D index increased from preoperative to first postoperative day by 0.09 (0.06, 0.13) and from day 1 to 7 by 0.05 (0.02,0.08), and EQ-5D VAS from preoperative to first postoperative day by 13.7 (9.1, 18.3) and from day 1 to 7 by 6.0 (2.0, 10.0). After two weeks, 51% of the patients had improved above the minimal clinically important difference (MCID) in back pain and 71% in leg pain.

Conclusions
Patients scheduled for decompression due to CLSS should be informed that improvement in leg pain and quality of life in general can be expected within one day of surgery, that quality of life improves a little further in the first postoperative week, and that back pain improves in the first 2 postoperative weeks. In most patients, decompression without fusion due to CLSS seems to achieve clinically relevant improvement within 2 weeks.
Cordyceps sinensis relieves non-small cell lung cancer by inhibiting the MAPK pathway
Authors: Lu Tianming , Zhou Lirun , Chu Zheng , Song Yang , Wang Qixin , Zhao Minghong , Dai Chuanhao , Chen Lin , Cheng Guangqing , Wang Jigang , Guo Qiuyan 
Published: March 2024

Abstract
Objective
To determine the pharmacodynamic mechanism underlying Cordyceps sinensis relief in a murine model of non-small cell lung cancer (NSCLC).

Methods
We created a murine model of NSCLC and studied the potential molecular mechanism by which C. sinensis relieved NSCLC using a combination of transcriptomics, proteomics, and experimental validation.

Results
C. sinensis markedly suppressed the fluorescence values in mice with NSCLC, improved the pathologic morphology of lung tissue, ameliorated inflammatory cytokines (tumor necrosis factor-alpha, interleukin-6, interleukin-10, and the oxidative stress indicators superoxide dismutase, malondialdehyde, and glutathione peroxidase). Transcriptomics results showed that the therapeutic effect of C. sinensis was primarily involved in the differentiation and activation of T cells. Based on the proteomic results, C. sinensis likely exerted a protective effect by recruiting immune cells and suppressing tumor cell proliferation via the MAPK pathway. Finally, the experimental validation results indicated that C. sinensis significantly decreased the VEGF and Ki67 expression, downregulated RhoA, Raf-1, and c-fos expression, which are related to cell migration and invasion, increased the serum concentration of hematopoietic factors (EPO and GM-CSF), and improved the percentage of immune cells (natural killer cells, dendritic cells, and CD4+ and CD8+ lymphocytes), which enhanced immune function.

Conclusions
Based on our preclinical study, C. sinensis was shown to exert a protective effect on NSCLC, primarily by inhibiting the MAPK pathway.
Formononetin reverses Treg/Th17 imbalance in immune-mediated bone marrow failure mice by regulating the PI3K/Akt signaling pathway
Authors: Lan Huixuan , Qiu Wei , Wu Jie , Hu Zhijing , Zhang Xiaomin , Zhu Lingling 
Published: March 2024

Abstract
Background
Severe aplastic anemia (SAA) is a syndrome of bone marrow failure which is life-threatening. Recent studies have demonstrated that CD4 + T cell subsets, including T regulatory (Treg) and T helper 17 (Th17) cells, play a pivotal role in the pathogenesis of SAA. Formononetin (FMN) is a natural compound extracted from the traditional Chinese medicine Huangqi, which has the ability to regulate the imbalance of Treg/Th17 cells in some inflammatory diseases. Nevertheless, the therapeutic effect of FMN in SAA has yet to be definitively established. Therefore, the objective of this research was to investigate the effect of FMN on SAA and elucidate its underlying mechanism.

Methods
In vivo experiments, the mice were divided into the following five groups: control, model, low-dose FMN, high-dose FMN, and positive control cyclosporine A group. The immune-mediated bone marrow failure (BMF) mouse model was established by the total body X-ray radiation and lymphocyte infusion. After 10 days of continuous administration of FMN, the numbers of Treg/Th17 cells in the bone marrow and spleen were assessed by flow cytometry. The protein expressions of PI3K/Akt pathway in the bone marrow and spleen was assessed by immunohistochemistry and western blotting. In vitro, the impact of FMN on the differentiation of naive CD4 + T cells into Treg cells was investigated by flow cytometry and ELISA.

Results
In comparison with the control group, the model group showed a reduction in bone marrow nucleated cells, a significant decrease in peripheral blood cells, and an altered CD8 + /CD4 + T cell ratio. These findings indicate the successful establishment of a mouse model of immune-mediated BMF. After FMN treatment, there were the increased levels of red blood cells and hemoglobin. In addition, FMN mitigated the bone marrow destruction and restored the CD8 + /CD4 + T cell ratio. Furthermore, in comparison with the control group, the model group showed the decreased levels of Treg cells and the increased levels of Th17 cells. After FMN treatment, there was a significantly increased number of Treg cells and a decreased number of Th17 cells. Additionally, FMN remarkably down-regulated the expression levels of PI3K and Akt proteins in immune-mediated BMF mice.

Conclusions
FMN alleviates immune-mediated BMF by modulating the balance of Treg/Th17 cells through the PI3K/Akt signaling pathway.
CT-based radiomics combined with hematologic parameters for survival prediction in locally advanced esophageal cancer patients receiving definitive chemoradiotherapy
Authors: Cui Jinfeng , Zhang Dexian , Gao Yongsheng , Duan Jinghao , Wang Lulu , Li Li , Yuan Shuanghu 
Published: March 2024

Abstract
Objectives
The purpose of this study was to investigate the prognostic significance of radiomics in conjunction with hematological parameters in relation to the overall survival (OS) of individuals diagnosed with esophageal squamous cell carcinoma (ESCC) following definitive chemoradiotherapy (dCRT).

Methods
In this retrospective analysis, a total of 122 patients with locally advanced ESCC were included. These patients were randomly assigned to either the training cohort (n = 85) or the validation cohort (n = 37). In the training group, the least absolute shrinkage and selection operator (LASSO) regression was utilized to choose the best radiomic features for calculating the Rad-score. To develop a nomogram model, both univariate and multivariate analyses were conducted to identify the clinical factors and hematologic parameters that could predict the OS. The performance of the predictive model was evaluated using the C-index, while the accuracy was assessed through the calibration curve.

Results
The Rad-score was calculated by selecting 10 radiomic features through LASSO regression. OS was predicted independently by neutrophil-to-monocyte ratio (NMR) and Rad-score according to the results of multivariate analysis. Patients who had a Rad-score > 0.47 and an NMR > 9.76 were at a significant risk of mortality. A nomogram was constructed using the findings from the multivariate analysis. In the training cohort, the nomogram had a C-index of 0.619, while in the validation cohort, it was 0.573. The model’s accuracy was demonstrated by the calibration curve, which was excellent.

Conclusion
A prognostic model utilizing radiomics and hematologic parameters was developed, enabling the prediction of OS in patients with ESCC following dCRT.

Critical relevance statement
Patients with esophageal cancer who underwent definitive chemoradiotherapy may benefit from including CT radiomics in the nomogram model.

Key points
• Predicting the prognosis of ESCC patients before treatment is particularly important.
• Patients with a Rad-score > 0.47 and neutrophil-to-monocyte ratio > 9.76 had a high risk of mortality.
• CT-based radiomics nomogram model could be used to predict the survival of patients.

Graphical Abstract
Gradient estimates for a class of elliptic equations with logarithmic terms
Authors: Gao Ze , Guo Qiming 
Published: March 2024

AbstractWe obtain the gradient estimates of the positive solutions to a nonlinear elliptic equation on an n-dimensional complete Riemannian manifold $(M, g)$
(
M
,
g
)
$$ \Delta u +au(\ln{u})^{p}+bu\ln{u}=0, $$
Δ
u
+
a
u

(
ln
u
)

p

+
b
u
ln
u
=
0
,
where $a\ne 0$
a
≠
0
, b are two constants and $p=\frac{k_{1}}{2k_{2}+1}\ge 2$
p
=

k
1

2

k
2

+
1

≥
2
, here $k_{1}$

k
1

and $k_{2}$

k
2

are two positive integers. The gradient bound is independent of the bounds of the solution and the Laplacian of the distance function. As the applications of the estimates, we show the Harnack inequality and the upper bound of the solution.
Murraya koenigii (L.) Sprengel seeds and pericarps in relation to their chemical profiles: new approach for multidrug resistant Acinetobacter baumannii ventilator-associated pneumonia
Authors: El-Shiekh Riham A. , Elshimy Rana , Mandour Asmaa A. , Kassem Hanaa A. H. , Khaleel Amal E. , Alseekh Saleh , Fernie Alisdair R. , Salem Mohamed A. 
Published: March 2024

AbstractAcinetobacterbaumannii is without a doubt one of the most problematic bacteria causing hospital-acquired nosocomial infections in today's healthcare system. To solve the high prevalence of multi-drug resistant (MDR) in A.baumannii, we investigated one of the medicinal plants traditionally used as antibacterial agent; namely Murrayakoenigii (L.) Sprengel. The total methanolic extracts of seeds and pericarps were prepared and their anti-bacterial activity was assessed using the agar diffusion method and minimum inhibitory concentration (MIC) was then calculated as compared to tigecycline. Then, an in-vivo murine model was established which confirmed the promising activity of M.koenigii seeds in demonstrating anti-bacterial and anti-inflammatory actions. The histopathological study of lungs, scoring of pulmonary lesions, counting of bacterial loads after infection by multi-drug resistant A.baumannii all provided evidence to support these findings. LC–MS/MS profiling coupled to molecular networking and chemometrics detected the presence of carbazole alkaloids, and coumarins as dominate metabolites of the active seed extracts. Positively correlated metabolites to antibacterial potential were 6-(2ʹ,3ʹ-dihydroxy-3-methylbutyl)-8-prenylumbelliferone, scopoline, and 5-methoxymurrayatin. An in-silico study was also performed on the crystal structure of MurF from A.baumannii (PDB ID: 4QF5), the studied structures of the mentioned extracts revealed good docking interaction at the active site suggestive of competition with the ATP ligand. These collective findings suggest that extracts of Murrayakoenigii (L.) Sprengel seed is a novel prospective for the discovery of drug candidates against infections caused by MDR A.baumannii.