bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between night eating frequency and thyroid function and sensitivity: a cross-sectional study from the NHANES database
Authors: Zhang Yanhao , Zhou Songbai , Liu Shiguang , Wang Youlin , Zhou Houyong , Wang Jiao , Wang Ling , Wang Xiaosong
Published: December 2024

Thyroid function is closely linked to circadian rhythms, but the relationship between the frequency of night eating and thyroid function remains unclear. Our study aimed to investigate the association between night eating frequency and its impact on thyroid function and sensitivity. This study included 6093 participants from the U.S. National Health and Nutrition Examination Survey (2007–2012). Night eating behavior was assessed through 24-hour dietary recall, with night eating frequency calculated on the basis of food intake between 10:00 PM and 4:00 AM. The thyroid hormone indices examined included T3, T4, FT3, FT4, TSH, TGA, Tg, and TPOAb, whereas thyroid hormone sensitivity was assessed via indices such as the FT3/FT4, TSHI, TT4RI, and TFQI. The associations between night eating frequency and thyroid function were analyzed via weighted univariate and multivariate linear regression analyses. Subgroup analyses and interaction test analyses were also employed to test this correlation. Compared with individuals who did not eat at night, those who ate more frequently at night had higher levels of Tg (OR 1.223 [95% CI 1.048, 1.429], p trend=0.015) but lower levels of T3 (OR 0.728 [95% CI 0.611, 0.868], p trend=0.235) and TPOAb (OR 0.728 [95% CI 0.611, 0.868], p trend=0.235). Subgroup analysis indicated that this association between Tg and night eating was stronger in the DM group (Tg: OR 1.49 [95% CI 1.15, 1.93]), p interaction=0.022) and that the association between TPOAb and night eating was stronger in the group without DM (TPOAb: OR 0.9 [95% CI 0.82, 0.97]), p interaction=0.003). Our findings suggest a significant association between night eating frequency and thyroid function. However, no statistically significant differences were found in thyroid sensitivity based on night eating frequency. Despite these findings, the hormone fluctuations observed were within normal clinical ranges. Further rigorously designed studies are needed to establish a causal relationship between night eating frequency and thyroid function.
Metabolic adaptation of myeloid cells in the glioblastoma microenvironment
Authors: Essakhi Nora , Bertucci Alexandre , Baeza-Kallee Nathalie , Colin Carole , Lavignolle-Heguy Rosario , Garcia-Gonzalez Paulina , Argüello Rafael J. , Tchoghandjian Aurélie , Tabouret Emeline
Published: December 2024

In recent decades, immunometabolism in cancers has emerged as an interesting target for treatment development. Indeed, the tumor microenvironment (TME) unique characteristics such as hypoxia and limitation of nutrients availability lead to a switch in metabolic pathways in both tumor and TME cells in order to support their adaptation and grow. Glioblastoma (GBM), the most frequent and aggressive primary brain tumor in adults, has been extensively studied in multiple aspects regarding its immune population, but research focused on immunometabolism remains limited. Here, we provide an overview of immunometabolism adaptation of myeloid cells in cancers with a specific focus on GBM and other brain tumors, before describing current therapeutic strategies targeting metabolic pathways. The main myeloid cells composing the GBM TME include tumor-associated macrophages (TAMs), which comprise both peripheral macrophages and local microglia, as well as myeloid-derived suppressor cells. The metabolic pathways involved in myeloid cell remodeling encompass the tricarboxylic acid cycle (TCA cycle), the lipid, glucose and amino acid metabolism and hypoxia. Developing treatments that target these metabolic pathways in tumor growth and its TME is a promising and increasing field. It includes both drug-repurposing and the development of innovative metabolic therapies. We finally provide an overview of all clinical trials in neuro-oncology involving treatments modifying cell metabolism and provide the preclinical rationale for both drugs already evaluated within clinical trials and potential candidates for future trials.
The role of PPAR in fungal keratitis
Authors: Zhou Hongyan , Zhang Hong , Bi Miaomiao , Zhang Wensong
Published: December 2024

The treatment of fungal keratitis(FK) remains challenging due to delayed fungal detection and the limited effectiveness of antifungal drugs. Fungal infection can activate both innate and adaptive immune responses in the cornea. Fungi stimulate the production of oxidative stress-related biomarkers and mediate the infiltration of neutrophils, macrophages, and T cells. These cells can induce infiltration of cytokines, chemokines, and matrix metalloproteinases (MMPs), leading to corneal tissue damage and even corneal perforation. The signaling pathway regulates the expression of inflammatory cytokines in fungal keratitis. Immune inflammatory damage is the main mechanism of FK, and oxidative stress damage is also involved in this infection process. Peroxisome proliferator-activated receptor (PPAR) is a member of the nuclear hormone receptor superfamily, with different subtypes of PPAR a, PPAR β/δ, and PPARγ. PPARs play important roles in the antioxidant response, anti-inflammatory, lipid metabolism, neuroprotection, and immune regulation processes. PPAR γ can promote macrophage polarization and reduce oxidative stress damage by regulating ROS production. PPAR has made some progress in the treatment of eye diseases: PPARa agonists can inhibit diabetes keratopathy and corneal neuropathy. PPARa agonists inhibit early immature angiogenesis in corneal alkali burns and have potential therapeutic effects on inflammatory corneal angiogenesis. PPARs can control the progression of dry eye disease and improve the condition of meibomian gland dysfunction. Based on this, we explored the potential roles of PPARs in the treatment of FK.
Inflammatory pathology in depression and suicide: a mechanistic distillation of clinical correlates
Authors: Costanza Alessandra , Amerio Andrea , Aguglia Andrea , Magnani Luca , Parise Alberto , Nguyen Khoa D. , Berardelli Isabella , Pompili Maurizio , Amore Mario , Serafini Gianluca
Published: December 2024

The association between inflammation with depression and suicide has prompted many investigations of the potential contributors to inflammatory pathology in these psychiatric illnesses. However, a distillation of diverse clinical findings into an integrated framework of the possible involvement of major physiological processes in the elicitation of pathological inflammation in depression and suicide has not yet been explored. Therefore, this review aims to provide a concise synthesis of notable clinical correlates of inflammatory pathology in subjects with various depressive and suicidal clinical subtypes into a mechanistic framework, which includes aberrant immune activation, deregulated neuroendocrine signaling, and impaired host-microbe interaction. These issues are of significant research interest as their possible interplays might be involved in the development of distinct subtypes of depression and suicide. We conclude the review with discussion of a pathway-focused therapeutic approach to address inflammatory pathology in these psychiatric illnesses within the realm of personalized care for affected patients.
Enhancing cell-mediated immunity through dendritic cell activation: the role of Tri-GalNAc-modified PLGA-PEG nanoparticles encapsulating SR717
Authors: Gong Yang , Jia Hongbin , Dang Wenrui , Zhou Ting , He Pu , Wang Xiaolei , Zhu Bingdong
Published: December 2024

Introduction

Vaccines against intracellular pathogens like Mycobacterium tuberculosis (M. tuberculosis) require the induction of effective cell-mediated immunity. Adjuvants primarily enhance antigen-induced adaptive immunity by promoting the activation of antigen-presenting cells (APCs).This study is to develop an adjuvant targeted to dendritic cells (DCs), one of the main APCs, so as to assist in inducing a long-term cellular immune response to M. tuberculosis protein antigens.

Methods

Polylactic-co-glycolic acid-polyethylene glycol (PLGA-PEG) nanoparticles (NPs) modified with Triantennary N-Acetylgalactosamine (Tri-GalNAc) were prepared to target DCs. Additionally, the stimulator of interferon genes (STING) agonist SR717 was encapsulated within PLGA-PEG NPs to activate DCs. Meanwhile, M. tuberculosis fusion protein (TP) was encapsulated in PLGA-PEG NPs to construct vaccine candidates: TP/Tri-GalNAc-PLGA-PEG-SR717 (TP/GPS in short) and TP/ Tri-GalNAc-PLGA-PEG (TP/GP in short). The targeting and activation effects of these NPs were assessed in vitro and in vivo, and their immunogenicity were evaluated in mice.

Results

Tri-GalNAc modification significantly enhanced the targeting of NPs to DCs, and encapsulated SR717 effectively promoted the maturation and activation of DCs. TP/GPS elicited a potent antigen-specific T cell immune response and successfully induced long-term immune memory in mice. Moreover, after the mice were infected with H37Ra via nasal instillation, TP/GPS significantly reduced the bacterial load in their lungs.

Discussion

Tri-GalNAc-modified PLGA-PEG NPs in combination with SR717 targeted and activated DCs, effectively assisting M. tuberculosis antigen in inducing long-term T cell-mediated immunity. This approach offers an innovative and effective adjuvant strategy for the development of subunit vaccine against intracellular pathogen.
Connexin 43 and Pannexin 1 hemichannels as endogenous regulators of innate immunity in sepsis
Authors: Li Jianhua , Lou Li , Chen Weiqiang , Qiang Xiaoling , Zhu Cassie , Wang Haichao
Published: December 2024

Sepsis is a life-threatening organ dysfunction resulting from a dysregulated host response to infections that is initiated by the body’s innate immune system. Nearly a decade ago, we discovered that bacterial lipopolysaccharide (LPS) and serum amyloid A (SAA) upregulated Connexin 43 (Cx43) and Pannexin 1 (Panx1) hemichannels in macrophages. When overexpressed, these hemichannels contribute to sepsis pathogenesis by promoting ATP efflux, which intensifies the double-stranded RNA-activated protein kinase R (PKR)-dependent inflammasome activation, pyroptosis, and the release of pathogenic damage-associated molecular pattern (DAMP) molecules, such as HMGB1. Mimetic peptides targeting specific regions of Cx43 and Panx1 can distinctly modulate hemichannel activity in vitro, and diversely impact sepsis-induced lethality in vivo. Along with extensive supporting evidence from others, we now propose that hemichannel molecules play critical roles as endogenous regulators of innate immunity in sepsis.
Too hot to handle? The impact of the 2023 marine heatwave on Florida Keys coral
Authors: Neely Karen L. , Nowicki Robert J. , Dobler Michelle A. , Chaparro Arelys A. , Miller Samantha M. , Toth Kathryn A.
Published: December 2024

The summer 2023 marine heatwave was the most severe on record for Florida’s Coral Reef, with unprecedented water temperatures and cumulative heat stress leading to 100% coral bleaching. An existing fate-tracking program of over 4200 brain and boulder coral colonies across five offshore and four inshore reefs allowed for analyses of bleaching-related mortality and diseases through the event. Across the vast majority of assessed corals, there was no partial or full mortality as a result of the 2023 bleaching event. At seven of the nine sites, only 0 – 2% of fate-tracked colonies experienced any mortality. The other two sites, both inshore, had the highest cumulative heat stress and did experience substantial bleaching-related mortality. However, acute mortality at one of them began at relatively low cumulative heat stress, suggesting death was the result of exceeding thermal maxima rather than bleaching-related resource depletion. At the two most impacted sites, 43% and 30% of all monitored corals died, but mortality varied among species: brain corals fared worse than boulder corals. The health status of corals before the bleaching event had little impact on whether they exhibited mortality during the event. At three sites, we observed unusual lesions on Orbicella faveolata colonies shortly after color returned to the corals; these were only present for a few months, but on some colonies led to substantial tissue loss. Though not part of the monitoring program, we also observed local extinctions of Acroporid corals at most sites, as well as local extinctions of octocorals at three inshore reefs. Though most reef-building corals survived the 2023 marine heatwave in the Florida Keys, continually rising temperatures are likely to make these temperature regimes more common. We encourage future research on why the brain and boulder corals fared differently at highly-impacted sites, and on what the unusual O. faveolata lesions are. Our results also provide perspective on how restoration strategies, particularly those focused on species likely to die under current and future climate regimes, might prioritize species likely to survive. Finally, these results highlight the importance of fate-tracking individuals of different species and in different geographies and habitat types through disturbance events.
Physiological and intestinal microbiota responses of sea cucumber Apostichopus japonicus to various stress and signatures of intestinal microbiota dysbiosis
Authors: Cui Liang , Xie Yumeng , Luo Kai , Wang Mingyang , Liu Longzhen , Li Changlin , Tian Xiangli
Published: December 2024

Identifying the signatures of intestinal dysbiosis caused by common stresses is fundamental to establishing efficient health monitoring strategies for sea cucumber. This study investigated the impact of six common stress experienced frequently in aquaculture on the growth performance, intestinal homeostasis and microbiota of sea cucumber, including thermal (23°C), hypoosmotic (22‰ salinity), ammonium (0.5 mg/L NH4+-N), and nitrite (0.25 mg/L NO2−-N) stress exposure for 30 days, as well as starvation and crowding (6 kg/m3 density) stress exposure for 60 days. Results demonstrated that all stress led to reduced growth performance and digestive capacity of sea cucumber, along with varying degrees of oxidative stress and immune responses. Various stresses significantly altered the diversity, community structure (except for crowding stress), and composition of intestinal microbiota. The ratios of Bacteroidota: Proteobacteria (B: P) and Firmicutes: Proteobacteria (F: P) declined markedly compared to the control. Potentially pathogenic bacteria of Shewanellaceae, Vibrionaceae, and Moraxellaceae significantly increased under crowding, ammonium, and nitrite stress, respectively, whereas beneficial microbes of Achromobacter and Rhodobacteraceae were, respectively, enriched under hypoosmotic and starvation stresses. The complexity and stability of microbial ecological networks were further altered by these stresses. KEGG predictions revealed the reduced functional pathways of intestinal microbiota involved in host immunity under different stresses. Correlation analysis further confirmed a strong link between microbiota response and host immunity under different stresses. The increased abundance of Verrucomicrobia species could also be identified as the sensitive indicator for diagnosing whether the host was under stressful pressure by random forest analysis.
Prediction of preoperative peritoneal cancer index for pseudomyxoma peritonei by multiple linear regression analysis
Authors: Bai Mingjian , Feng Jing , Liu Jie , Li Yunxiang , Xu Yueming , Ma Fucun , Ma Ruiqing , Liang Guowei , Liu Xuekai , Zhao Na
Published: December 2024

Background

The aim of the present study was to establish a predictive model to predict the peritoneal cancer index (PCI) preoperatively in patients with pseudomyxoma peritonei (PMP).

Methods

A total of 372 PMP patients were consecutively included from a prospective follow-up database between 1 June 2013 and 1 June 2023. Nine potential variables, namely, gender, age, Barthel Index (BAI), hemoglobin (Hb), albumin (Alb), D-dimer, carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA 125), and CA 19-9, were estimated using multiple linear regression (MLR) analysis with a stepwise selection procedure. The established MLR model was internally validated using K-fold cross-validation. The agreement between the predicted and surgical PCI was assessed using Bland–Altman plots and intraclass correlation (ICC). A p-value of less than 0.05 was considered statistically significant.

Results

Six independent predictors were confirmed by the stepwise MLR analysis with an R2 value of 0.570. The predicted PCI formula was represented as follows: PCI = 19.567 + 2.091 * Gender (male = 1, female = 0) − 0.643 * Alb +4.201 * Lg (D-dimer) + 2.938 * Lg (CEA) + 5.441 * Lg (CA 125) + 1.802 * Lg (CA 19-9). The agreement between predicted and surgical PCI was assessed using Bland–Altman plots, showing a limit of agreement (LoA) between −15.847 (95%CI: −17.2646 to −14.4292) and +15.847 (95%CI: 14.4292–17.2646).

Conclusion

This study represents the first attempt to use an MLR model for the preoperative prediction of PCI in PMP patients. Nevertheless, the MLR model did not perform well enough in predicting preoperative PCI. In the future, more advanced statistical techniques and a radiomics-based CT-PCI-participated MLR model will be developed, which may enhance the predictive ability of PCI.
Dynamic changes and prognostic value of glutathione S-transferase alpha in mild cognitive impairment and Alzheimer’s disease
Authors: Tang Yangyang , Li Ni , Dai Linyan , Wang Xingsheng , Lai Xia
Published: December 2024

Objectives

Glutathione S-transferase alpha (GSTα) is an important antioxidant enzyme closely associated with the onset and progression of neurodegenerative diseases. The alterations in GSTα protein levels associated with Alzheimer’s disease and their impact on cognitive abilities remain unclear. Thus, investigating the fluctuations of GSTα protein levels in mild cognitive impairment (MCI) and Alzheimer’s disease (AD) is essential.

Methods

DATA were enrolled from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database, and we studied healthy individuals (as controls, a total of 54), patients with mild cognitive impairment (345), and patients with Alzheimer’s disease (96) A one-year follow-up was conducted to collect data on the dynamic changes of GSTα protein levels in plasma and primary information data, and to analyze the correlation between the changes in GSTα protein levels before and after the follow-up and cognitive function and its predictive value.

Results

Plasma GSTα protein levels were significantly lower in the AD group than in the CN group (0.94 vs1.05, p = 0.04) and the MCI group (0.94 vs1.09, p < 0.001). Plasma GSTα protein level changes were positively correlated with altered MMSE levels in MCI and AD patients (r = 0.09, p = 0.04). The AUC (95% CI) of the area under the prediction curve of plasma GSTα protein levels for MCI was 0.63 (0.54–0.71), p = 0.02, and the AUC (95% CI) of the area under the prediction curve of plasma GSTα protein levels for AD was 0.74 (0.69–0.80), p < 0.001. At the same time, we plotted ROC curves for the difference in the change of plasma GSTα protein levels after 1 year of follow-up. The results showed that the AUC (95% CI) of the area under the prediction curve of plasma GSTα protein levels change for MCI was 0.76 (0.696–0.83), p < 0.001, and the AUC (95% CI) of the area under the prediction curve of plasma GSTα protein levels change for AD was 0.75 (0.69–0.80), p < 0.001.

Conclusion

The findings of the study indicated notable differences in GSTα protein levels among patients with MCI and those with AD after a one-year follow-up period. Furthermore, a positive correlation was observed between changes in GST αprotein levels and the decline in both baseline and cognitive function. This suggests that GSTα protein could potentially act as a biomarker for both MCI and AD, offering fresh insights for early detection and intervention strategies.
Synthesis and characterization of a fluorescent magnetic molecularly imprinted polymer for enhanced adsorption and selective extraction of pesticides from agricultural waters
Authors: Ali Zeeshan , Raza Nadeem , Hayat Muhammad , Khezami Lotfi , Khairy Mohamed , Almuqri Eman Abdullah , Basher Nosiba S. , Parveen Humaira , Chaudhary Anis Ahmad
Published: December 2024

Introduction

A novel fluorescent magnetic molecularly imprinted polymer (FMMIP) was developed for the effective extraction of malathion (MLT) and chlorpyrifos (CPS) from agricultural water sources.

Methods

The FMMIP was confirmed to have a stable polymer structure with significant thermal resilience through comprehensive characterization using techniques such as TEM and TGA. The magnetic properties of the FMMIP facilitated easy separation by external magnetic fields, with a notable magnetization of 0.006 emu/g. Kinetic and isotherm studies revealed that adsorption of MLT and CPS onto the FMMIP conformed best to the pseudo-first-order model and Freundlich isotherm, suggesting a predominance of physisorption mechanisms and heterogeneous binding sites.

Results and Discussion

The FMMIP demonstrated exceptional adsorption capacities, achieving a maximum of 93 mg/g for MLT and 69 mg/g for CPS. Regeneration trials indicated that the FMMIP maintains its high adsorptive performance over multiple cycles, highlighting its potential for sustainable use. Statistical validation confirmed the method’s reliability, with RSD values for MLT and CPS at 6.5% and 7.3%, respectively, and LODs determined to be 1.26 mg/L for MLT and 1.22 mg/L for CPS. The strong R2 values of 0.992 for MLT and 0.998 for CPS from the adsorption studies substantiate the method’s effectiveness. This study demonstrates that the synthesized FMMIP is a promising material for removing MLT and CPS, supporting its application in environmental clean-up initiatives to protect and preserve ecosystems.
Prognostic significance of preoperative prognostic nutritional index in hepatocellular carcinoma after curative hepatectomy: a meta-analysis and systemic review
Authors: Zhang Haiyan , Li Dan , Li Jing
Published: December 2024

Background

The Prognostic Nutritional Index (PNI), which reflects both nutritional and immune status, has emerged as a potential predictor of survival outcomes in cancer patients. However, its role in forecasting the prognosis of hepatocellular carcinoma (HCC) following curative hepatectomy remains unclear. To further investigate the association between PNI and survival outcomes in HCC patients, we conducted a systematic review and meta-analysis.

Methods

We performed a comprehensive search across Web of Science, PubMed, Embase, Cochrane Library, and China National Knowledge Infrastructure to identify studies evaluating the prognostic value of PNI in HCC following curative hepatectomy. Overall survival (OS), recurrence-free survival (RFS), and disease-free survival (DFS) were extracted as primary outcomes. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using fixed-effect or random-effect models. Additionally, heterogeneity, publication bias, and sensitivity analyses were performed to evaluate the consistency and robustness of the obtained results.

Results

This systematic review and meta-analysis included 19 studies comprising a total of 9,830 patients. The results indicated that higher PNI was significantly associated with longer overall survival (OS) (n = 6,812; HR = 1.60; 95% CI: 1.44–1.77; p < 0.001) and recurrence-free survival (RFS) (n = 8,529; HR = 1.48; 95% CI: 1.30–1.69; p < 0.001). There was significant heterogeneity among studies for RFS (I2 = 56.0%, p = 0.004). Subgroup analysis indicated that age, variations in PNI cutoff values and follow-up periods were the primary contributors to this heterogeneity. The trim-and-fill method indicated that publication bias did not impact the OS results, and Egger’s test found no publication bias for RFS (p = 0.104). Sensitivity analysis further confirmed the stability of these results.

Conclusion

Preoperative PNI is a significant prognostic indicator in HCC patients undergoing curative hepatectomy, with higher PNI correlating with improved survival outcomes.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024530150, identifier CRD42024530150.
Prognosticating post-bariatric surgery outcomes and management of postoperative recurrent weight gain and diabetes recurrence
Authors: Xiao He , Du Yudie , Tan Yuanyuan , Ren Yixing
Published: December 2024

Bariatric surgery stands as the most potent treatment for achieving substantial weight reduction and alleviating the complications associated with obesity. However, it is not the treatment of choice for patients with obesity combined with type 2 diabetes mellitus, and the benefit of bariatric surgery varies widely among individuals. There is a noticeable inconsistency in the outcomes following these procedures. The ability to predict how an individual will respond to bariatric surgery is a valuable asset in clinical practice. And the importance of postoperative interventions should not be underestimated. Proactive measures targeting both pre- and post-operative eating habits and lifestyle adjustments are of greater significance than the investigation into pre-operative factors alone. The judicious application of medication, endoscopic intervention and conversional surgeries after bariatric surgery can yield superior outcomes in managing recurrent weight regain and the recurrence of diabetes, albeit with consideration for the associated complication rates.
An optimized support vector machine for lung cancer classification system
Authors: Oyediran Mayowa O. , Ojo Olufemi S. , Raji Ibrahim A. , Adeniyi Abidemi Emmanuel , Aroba Oluwasegun Julius
Published: December 2024

Introduction

Lung cancer is one of the main causes of the rising death rate among the expanding population. For patients with lung cancer to have a higher chance of survival and fewer deaths, early categorization is essential. The goal of thisresearch is to enhance machine learning to increase the precision and quality of lung cancer classification.

Methods

The dataset was obtained from an open-source database and was utilized for testing and training. The suggested system used a CT scan picture as its input image, and it underwent a variety of image processing operations, including segmentation, contrast enhancement, and feature extraction.

Results

The training process produces a chameleon swarm-based supportvector machine that can identify between benign, malignant, and normal nodules.

Conclusion

The performance of the system is evaluated in terms of false-positive rate (FPR), sensitivity, specificity, recognition time and recognition accuracy.
Evaluating the prognostic relevance of neutrophil-to-lymphocyte ratio in cervical cancer: a systematic review and meta-analysis
Authors: Zhuang Xieyan , Li Yan , Zheng Hongfeng , Fu Langjing
Published: December 2024

Background

Recently, the neutrophil-to-lymphocyte ratio (NLR) has emerged as a promising prognostic marker for survival outcomes in individuals affected cervical cancer. However, research specifically focusing on the prognostic relevance of NLR across different cancer stages and in cases of recurrent metastases remains scant.

Methods

We executed a systematic review of the literature from databases including PubMed, Embase, the Cochrane Library, and Web of Science, covering publications up to March 3, 2024. Studies evaluating the relationship between NLR and patient clinical outcomes were retrieved, guided by specifically defined inclusion and exclusion parameters. The key goals were to assess progression-free survival (PFS) and overall survival (OS), measured through hazard ratios (HR) and 95% confidence intervals (CI).

Results

This meta-analysis encompassed 38 retrospective cohort studies, including data from 10,246 patients. The aggregated data showed that patients with increased NLR prior to treatment exhibit reduced OS (HR = 1.58, 95% CI: 1.44-1.74; p < 0.00001) and decreased PFS (HR = 1.48, 95% CI: 1.34-1.63; p < 0.00001). Furthermore, elevated NLR significantly impacted disease-free survival (HR: 1.79, 95% CI: 1.18-2.71; p = 0.006), recurrence rates (HR: 2.18, 95% CI: 1.36-3.51; p = 0.001), recurrence-free survival (HR: 3.05, 95% CI: 1.79-5.19; p < 0.0001), and the incidence of distant metastases (HR: 1.73, 95% CI: 1.20-2.50; p = 0.003).

Conclusion

An elevated NLR prior to treatment demonstrates a strong association with decreased OS and PFS among patients with cervical cancer, underscoring the significance of NLR as a prognostic marker within this population.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=529817, identifier CRD42024529817.
Small-molecule MMRi36 induces apoptosis in p53-mutant lymphomas by targeting MDM2/MDM4/XIAP for degradation
Authors: Lama Rati , Wu Wenjie , Mavis Cory K. , Ruiz Federico M. , Querol-García Javier , Martin Diana , Chemler Sherry R. , Chandra Dhyan , Goodrich David W. , Hernandez-Ilizaliturri Francisco J. , Muñoz Inés G. , Wang Xinjiang
Published: December 2024

Rituximab combined with systemic chemotherapy significantly improves the rate of complete response in B-cell lymphomas. However, acquired rituximab resistance develops in most patients leading to relapse. The mechanisms underlying rituximab resistance are not well-understood. MDM2 and MDM4 proteins are major negative regulators of p53, but they also have p53-independent activities in mouse models of lymphomagenesis. Whether MDM2 or MDM4 is involved in rituximab resistance has not been explored. Here we report that MDM2 and MDM4 are upregulated in p53-mutant rituximab-resistant cells by transcriptional and post-transcriptional mechanisms. Knockdown of MDM2 or MDM4 significantly hindered growth of rituximab-resistant cells. To explore whether targeting the RING-domain of MDM2-MDM4 heterodimers is a viable strategy for the treatment of rituximab-resistant lymphomas, we identified MMRi36 in a high throughput small-molecule screen. Here we show that MMRi36 binds and stabilizes MDM2-MDM4 RING heterodimers and acts as an activator of the MDM2-MDM4 E3 ligase complex in vitro and promotes proteasomal degradation of MDM2/MDM4 proteins in cells. MMRi36 potently induces p53-independent apoptosis in p53-mutant lymphoma cells and it exerts non-apoptotic anti-lymphoma effect in rituximab resistant cells. The pro-apoptotic mechanisms of MMRi36 involves activation of both caspase 3 and caspase 7 associated with increased polyubiquitination and degradation of XIAP. Therefore, MMRi36 is a novel prototype small-molecule for targeting MDM2/MDM4/XIAP for degradation and induction of apoptosis in p53-mutant lymphomas.
Prognostic significance of p27 in colorectal cancer: a meta-analysis and bioinformatics analysis
Authors: Zou Jing , Wang Dong , Yin Gaoping , Lu Kexiang , Chang Kaibin , Li He
Published: December 2024

Background

In the past, numerous investigations have delved into the influence of p27 (p27kip) on the prognosis and clinicopathological characteristics of colorectal cancer (CRC), yielding conclusions that are not universally statistically significant, thus rendering the discourse rather contentious.

Methods

We collected available articles published before August 2024 and extracted data to analyze the association between the expression of p27 and the prognosis and clinicopathological features of CRC. In addition, we used Gene Expression Profiling Interactive Analysis (GEPIA), University of Alabama at Birmingham’s Cancer Data Analysis Portal (UALCAN), and the Human Protein Atlas (HPA) to validate our results.

Results

Through an extensive examination of four prominent databases, a total of 21 original articles encompassing a cohort of 3,378 patients were identified. The findings indicated that a low expression of p27 could lead to shorter overall survival (OS) [hazard ratio (HR) = 0.44, 95% confidence interval (95%CI) = 0.31–0.61, Z = 4.89, p = 0.000] and disease-free survival (DFS) (HR = 0.40, 95%CI = 0.28–0.59, Z = 4.75, p = 0.000). In addition, a low expression of p27 predisposed tumors to the right colon [odds ratio (OR) = 0.61, 95%CI = 0.46–0.82, Z = 3.32, p = 0.001] and limited tumor differentiation (OR = 0.56, 95%CI = 0.41–0.77, Z = 3.62, p = 0.000), but had no effect on TNM staging (OR = 0.80, 95%CI = 0.52–1.22, Z = 1.05, p = 0.295), lymph node metastasis (OR = 0.90, 95%CI = 0.25–3.28, Z = 0.16, p = 0.876), and tumor size (OR = 0.94, 95%CI = 0.54–1.65, Z = 0.21, p = 0.835). The results from GEPIA and UALCAN showed that p27 had no effect on TNM staging, lymph node metastasis, DFS, and OS; moreover, there was no expression difference between tumor tissues and normal tissues. The findings from the HPA indicated that there was lower expression of p27 in tumor tissues compared with normal tissues.

Conclusion

Although inconsistent results were reached with the bioinformatics analysis from this meta-analysis, it was confirmed that a low expression of p27 can adversely affect the prognosis of patients with CRC and make a meaningful impact on a part of the clinicopathological features in the meta-analysis with abundant data. In the future, predicting the prognosis of patients with CRC and guiding treatment might emerge as a significant objective.
A supercritical oil extract of Schisandra chinensis seeds ameliorates Huntington’s disease-like symptoms and neuropathology: the potential role of anti-oxidant and anti-inflammatory effects
Authors: Jo Hyo-Sung , Lee Youn-Woo , Son So-Ri , Jang Dae Sik , Woo Kwon Tae , Ha Yujeong , Moon Sang-Kwan , Kim Min Soo , Cho Ik-Hyun
Published: December 2024

Background

Huntington disease (HD), a neurodegenerative autosomal dominant disorder, is characterized by involuntary choreatic movements with cognitive and behavioral disturbances. Up to now, no therapeutic strategies are available to completely ameliorate the progression of HD. Schisandra chinensis has various pharmacologic effects such as antioxidant and anti-inflammatory activities. However, the neuroprotective value of seed oil of S. chinensis (SOSC) has not been elucidated yet. The purpose of this study was to determine neuroprotective effects of SOSC by supercritical fluid extraction against 3-nitropropionic acid (3-NPA)-induced HD-like symptoms and neuropathology in an experimental mouse model.

Methods

SOSC (75, 150, and 300 mg/kg/day) was orally pre-administration once daily at 1 hour before 3-NPA intoxication.

Results

SOSC ameliorated movement dysfunction and lethality following 3-NPA intoxication in connection with reduction of lesion area, neurodegeneration/apoptosis, microglial migration/activation, and mRNA expression of pro-inflammatory cytokines/enzymes in the striatum. SOSC inhibited the activation of nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPKs) pathways but stimulated nuclear factor erythroid 2-related factor 2 (Nrf2) in the striatum after 3-NPA intoxication. Schizandrin, a main component of SOSC, reduced protein expression levels of Iba-1 and p-NF-κB in 3-NPA-induced BV2 cells (murine microglia cell line). BV2 cell’s conditioned medium inhibited cleaved caspase-3 in 3-NPA-induced SH-SY5Y cells (a neuroblastoma cell line).

Conclusion

SOSC might ameliorate movement dysfunction by inhibiting neuropathology through its anti-inflammatory and antioxidant activities in the striata of 3-NPA-intoxicated mice. These findings suggest that SOSC could serve as a promising therapeutic candidate for HD-like symptoms, providing a foundation for future treatment strategies targeting neuroinflammation and oxidative stress.
Zhili decoction ameliorates ulcerative colitis by modulating gut microbiota and related metabolite, and inhibiting the TLR4/NF-κB/NLRP3 pathway
Authors: Tan Tianying , Chen Qin , Chen Ping , Li Shuangshuang , Hu Wenting , Yang Tao , Jia Yingtian
Published: December 2024

Ethnopharmacological Importance

Zhili decoction (ZLD) is a traditional Chinese medicine prescription for ulcerative colitis (UC). However, the mechanism by which ZLD exerts its therapeutic effects in the context of UC remains unclear.

Aim of study

The aim of this study was to investigate the effects of ZLD on the gut microbiota and related fecal metabolite levels using a mouse model of UC. In addition, we examined the underlying molecular mechanisms responsible for these effects.

Materials and methods

The major components of ZLD were detected by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). An integrated approach employing 16S rRNA and fecal metabolomics was employed to assess the potential impacts of ZLD on gut flora abundance and diversity, fecal metabolite levels, and various metabolic pathways. To further investigate the potential mechanisms of ZLD in treating UC, the expression of genes and proteins were examined by RT-qPCR, immunohistochemical staining and Western blotting.

Results

ZLD markedly alleviated symptoms and inflammatory injury in mice with UC. DSS induced notable alterations in the gut microbiome, and ZLD enhanced gut microbial diversity in UC mice by augmenting the abundance of Bacteroidota, Christensenella, Lactobacillus, etc., while reducing the Firmicutes/Bacteroidota ratio. ZLD treatment significantly modified the metabolic profile of mice with UC. It significantly suppressed the arachidonic acid metabolic pathway and promoted the butyrate acid metabolic pathway. ZLD reduced inflammatory factors and inhibited TLR4/NF-κB/NLRP3 pathway expression. In addition, correlation analysis demonstrated a close relationship between gut microbes, fecal metabolites, and inflammatory factors.

Conclusion

ZLD alleviated UC by regulating gut flora, modulating related metabolite levels, and inhibiting TLR4/NF-κB/NLRP3 pathway.
Frontiers in medical physics: material classification and blood pressure measurement of wearable piezoelectric sensors
Authors: Cao Fuchen , Li Yanli
Published: December 2024

Wearable piezoelectric sensors, as an emerging tool for blood pressure measurement, have attracted much attention at the forefront of medical physics and have broad application prospects due to their portability, real-time monitoring and low interference with human activities. However, the development of piezoelectric materials is currently a key factor restricting the development of wearable piezoelectric sensors. In order to continuously improve the accuracy and speed of blood pressure measurements by wearable piezoelectric sensors, new measurement methods need to be designed in addition to the development of high-performance piezoelectric materials. We present the advantages and disadvantages of different types of piezoelectric materials for wearable piezoelectric sensors, illustrate their future development directions, and discuss the current new strategies and the latest applied research of piezoelectric sensors applied to blood pressure measurement. In addition, the challenges and future prospects of wearable piezoelectric sensors for blood pressure measurement are revealed, providing new ideas for future applications of high-performance wearable piezoelectric sensors for health monitoring.
Unveiling the immunomodulator role of plasma oxidized lipids in SA-AKI progression: a CRRT perspective
Authors: Zhou Lu , Li Huirong , Guo Wenfeng , Feng Lan , Hu Jiangtao , Liu Jing , Wang Tingting , Liu Hongbao
Published: December 2024

Background

Plasma oxidized lipids are intimately linked to immune regulation as bioactive mediators. However, it is not clear whether they are related to the progression of sepsis-associated acute kidney injury (SA-AKI) and the effect of continuous renal replacement therapy (CRRT). This study intends to explore the changes in certain oxidized lipid during CRRT treatment and their correlation with the immune microenvironment and prognosis by analyzing plasma oxidative lipidomics.

Methods

A total of 48 SA-AKI patients undergoing CRRT for more than 72 h were enrolled in this prospective cohort study. Oxidative lipidomics was analyzed by ultra performance liquid chromatography coupled with tandem mass spectrometric (UPLC-MS/MS) detection at the beginning of CRRT (T0) and 72 h later (T72), respectively.

Results

Compared with survivors, plasma EETs, EpOMEs and EpDPEs in non-survivors were significantly down-regulated at T0, while PGFs, TXB and HEPEs were up-regulated. After 72 h of CRRT, DiHETEs were significantly up-regulated and PGFs were down-regulated in non-survivors, while HEPEs and EpOMEs were up-regulated and 6keto-PGF1α was down-regulated in survivors. KEGG annotation showed that the differential lipids of survivors before and after CRRT were mainly enriched and up-regulated in metabolic pathway.

Conclusion

This study provided a comprehensive overview of plasma oxidized lipids in SA-AKI patients undergoing CRRT and further elucidated the lipids and pathways linked to patient severity and prognosis. Additionally, we unveiled the potential mechanisms by which CRRT improves the prognosis of SA-AKI patients by removing PGFs and TXs while simultaneously upregulating HEPE to ameliorate the immune microenvironment, as well as the potential significance of adjusting CRRT prescriptions based on plasma oxidized lipidomics.
Metabolomic and metagenomic analyses elucidate the role of intercropping in mitigating continuous cropping challenges in tobacco
Authors: Liu Ming , Xue Rujun , Jin Shuangzhen , Gu Kaiyuan , Zhao Jie , Guan Shuyue , Xie Xiaoyu , Su Jiaen , Wang Longchang
Published: December 2024

Introduction

Crop rotation of tobacco with other crops could effectively break the negative impact of continuous tobacco cropping, but the mechanisms of intercropping system effects on tobacco, especially on the rhizosphere, are not clear.

Methods

In this study, we investigated the impact of intercropping system on the diversity and function of tobacco metabolites and microorganisms through metabolomic and metagenomic analyses of the tobacco rhizosphere microenvironment intercropped with maize and soybean.

Results

The results showed that the contents of huperzine b, chlorobenzene, and P-chlorophenylalanine in tobacco rhizosphere soils differed significantly among soybean-tobacco and maize-tobacco intercropping system. Chlorobenzene and P-chlorophenylalanine had the highest relative abundance under the soybean-tobacco intercropping system, and huperzine b had the highest relative abundance in the maize-tobacco cropping system. At the phylum level, the three most dominant strains were the same across all treatments: Proteobacteria, Actinobacteria, and Acidobacteria, with only minor differences in their abundance, with the fourth most abundant strain in both the tobacco monoculture. KEGG enrichment analysis of the tobacco rhizosphere soil microbiome revealed that intercropping significantly increased the abundance of metabolites in the ABC transporters pathway and up-regulated the LivK, LivH, Livg, LivM, and LivF genes of the branched-chain amino acid pathway

Discussion

Collectively, our results indicate that the intercropping could enhance the activity of Livs to enhance the ABC transport pathway, and thus improve the transmembrane transport ability of tobacco roots, thus reducing the negative impact of continuous tobacco cropping. At the same time, the maize-tobacco intercropping could promote the production and transportation of phenolic acids, flavonoids, and other bioactive substances in the tobacco root system, which could enhance tobacco adaptation capacity to abiotic stress.
Effect of vapor pressure deficit on growth and yield of pearl millet germplasm originating from semi-arid, semi-humid and humid regions
Authors: Garba Hadizatou , Hamidou Falalou , Abdou Harou , Burridge James , Vadez Vincent
Published: December 2024

Introduction

The increase in vapor pressure deficit (VPD) is among the expected change in futur climate, and understanding its effect on crop growth is of much significance for breeeding programs. Three groups (G1,G2 and G3) of pearl millet germplasm, originating from regions with different rainfall intensities, were grown in the field during period of high and low VPDs. The groups G1,G2 and G3 were respectively from Guinean (rainfall above 1000 mm), Soudanian (rainfall between 600 mm and 900 mm), and Sahelian zones (rainfall between 600 and 300 mm) of Africa. The objective was to assess if there was any growth response difference among the germplasm groups.

Method

Four trials were conducted, two in the dry season of 2019 (Ds19) and 2020 (Ds20) with avarage VPDs of 3.62 kPa and 2.92 kPa, respectively, and two in the rainy season of 2019 (Rs19) and 2020 (Rs20) with avaerage VPDs of 1.14 kPa and 0.61 kPa, respectively.

Results

In order to avoid possible confounding effects of radiation on millet growth and yield, data were normalized by the quantity of light received during each season. After this normalization, leaf area and grain yield decreased in the highest-VPD seasons whereas tiller number decreased only in Ds19 (one high VPD season). The comparison of the three germplasm groups indicates that G3 the germplasm group from Sahelian regions showed greater tolerance to high VPD than G1 and G2.

Discussion

Germplasm from the G3 group could be a good material for developing tolerant germplasm to future climate that is bound to have high VPD.
Enhancement on selenium volatilization for phytoremediation: role of plant and soil microbe interaction
Authors: Karna Ranju R. , Kumara Samantha T. , McCracken Vance J. , Fowler Thomas J. , Lin Zhi-Qing
Published: December 2024

This study aimed at quantifying the potential effects of plant and soil microbial interaction on selenium (Se) volatilization, with the specific objectives of identifying soil bacteria associated with rabbitfoot grass (Polypogon monspeliensis) and demonstrating the enhancement of Se volatilization in the soil-Indian mustard (Brassica juncea) system through inoculation of the soil with the identified best Se-volatilizing bacterial strain. Soil bacteria were isolated from topsoil and rhizosphere soils of rabbitfoot grass, and the bacterial colonies were characterized via PCR-DGGE and DGGE band analysis prior to their identification using 16S rDNA sequencing technique. Bacillus cereus produced over 500-fold more volatile Se in a culture medium treated with 15 µg Se/mL (equal mixture of SeO42-, SeO32- and selenomethionine) than any of the other eight identified bacterial strains. Inoculation of Indian mustard vegetated soil with the best Se volatilizing bacterial strain B. cereus resulted in a significant (p<0.05) increase in Se volatilization during a 7-day time period, compared to the soil-plant system without inoculation of B. cereus. Thus, inoculation of the soil with B. cereus substantially enhanced Se removal via biogenic volatilization in the soil-Indian mustard system. This study evaluated the role of B. cereus in enhancing Se volatilization in soil-plant systems, and demonstrated the importance of plant and soil microbial interaction for Se phytoremediation.