bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between nontraditional lipid parameters and the risk of type 2 diabetes and prediabetes in patients with nonalcoholic fatty liver disease: from the national health and nutrition examination survey 2017–2020
Authors: Liu Jierui , Fu Qingan , Su Ruolin , Liu Rixiang , Wu Shisheng , Li Ke , Wu Jianhua , Zhang Nuobei
Published: August 2024

Background

Nonalcoholic fatty liver disease (NAFLD) is a prevalent metabolic disorder strongly linked to type 2 diabetes mellitus (T2DM). Understanding the predictive value of lipid parameters in identifying abnormal glucose metabolism in NAFLD patients is crucial for early intervention.

Methods

This study analyzed data from the National Health and Nutrition Examination Survey(NHANES) database (2017-2020) involving 1066 NAFLD patients. Participants were categorized into three groups: T2DM (n=414), prediabetes mellitus (pre-DM) (n=507), and normoglycemia (NG) (n=145). Traditional lipid parameters [triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C)] and nontraditional lipid parameters [atherogenic index of plasma (AIP), residual cholesterol (RC), and non-high-density lipoprotein cholesterol (non-HDL-C)] were evaluated for their association with T2DM and pre-DM.

Results

Elevated TG levels were significantly associated with an increased risk of T2DM and pre-DM, whereas high HDL-C demonstrated a protective effect. Among nontraditional lipid parameters, increased AIP and RC were most strongly associated with T2DM risk, while high non-HDL-C was best associated with the development of pre-DM. Stratified analyses revealed that these associations were stronger in younger, non-obese, smoking, and female NAFLD patients.

Conclusion

Nontraditional lipid parameters, particularly AIP and RC, show superior predictive value over traditional lipid parameters in identifying abnormal glucose metabolism in NAFLD patients. Incorporating these novel biomarkers into clinical practice could enhance early detection and prevention strategies for T2DM and pre-DM in this high-risk population.
AC/DC optimal power flow and techno-economic assessment for hybrid microgrids: TIGON CEDER demonstrator
Authors: Martín-Crespo Alejandro , Hernández-Serrano Alejandro , Izquierdo-Monge Óscar , Peña-Carro Paula , Hernández-Jiménez Ángel , Frechoso-Escudero Fernando , Baeyens Enrique
Published: August 2024

In recent years, the interest in electric direct current (DC) technologies (such as converters, batteries, and electric vehicles) has increased due to their potential in energy efficiency and sustainability. However, the vast majority of electric systems and networks are based on alternating current (AC) as they also have certain advantages regarding cost-effective transport and robustness. In this paper, an AC/DC optimal power flow method for hybrid microgrids and several key performance indicators (KPIs) for its techno-economic assessment are presented. The combination of both calculations allows users to determine the viability of their hybrid microgrids. AC/DC networks have been modeled considering their most common elements. For the power flow method, polynomial optimization is formulated considering four different objective functions: the minimization of energy losses, voltage deviation, and operational costs and the maximization of the microgrid generation. The power flow method and the techno–economic analysis are implemented in Python and validated in the Centro de Desarrollo de Energías Renovables (CEDER) demonstrator for TIGON. The results show that the calculated power flow variables and those measured at CEDER are practically the same. In addition, the KPIs are obtained and compared for four operating scenarios: baseline, no battery, battery flexibility, and virtual battery (VB) flexibility. The last scenario results in the most profitable option.
Policy deficiencies and contingency plans: groundwater management implications for baseflow contributions to the Colorado River
Authors: Perry Denielle , Swanson Riley K. , Springer Abraham E.
Published: August 2024

The Colorado River is a vital water source for the western United States, yet the river is governed by disjointed and outdated policies that have left water management fragmented and water quantities overallocated. Groundwater is an overlooked component of Colorado River Basin (CRB) water supplies, making it vulnerable to overuse from disparities in uncoordinated protective management strategies. In this study, we analyzed state level groundwater policies to reveal the diversity and efficacy of groundwater governance mechanisms. The existing groundwater management plans for each state throughout the basin are fragmented and limited in scope. We found that with policies only covering 22% of the basin, they do not provide adequate protection at the basin scale for the sustainable use of groundwater resources in the face of increasing demands, creating a positive feedback loop that reinforces the scarcity issue. We conclude that a comprehensive management plan that can fully address resource use throughout the CRB is necessary for the sustainable use of groundwater and its contribution to base flow in the Colorado River. We suggest that such a plan could be derived through an interstate compact like the Colorado River Compact that is used for surface water management.
Causal role of gut microbiota, serum metabolites, immunophenotypes in myocarditis: a mendelian randomization study
Authors: Li Kaiyuan , Liu Peng , Wang Xiuqi , Zheng Zhipeng , Liu Miao , Ye Jun , Zhu Li
Published: August 2024

Background

The intricate relationship among gut microbiota, serum metabolites, and immunophenotypes may significantly impact myocarditis. However, direct causal links between these domains and myocarditis are not well understood.

Methods

The study performed Mendelian randomization (MR) analysis using genetic data from public sources. Exposure data included 211 gut microbiota, 486 serum metabolites, and 731 immunophenotypes from Mibiogen, the Metabolomics GWAS server, and GWAS catalog databases. Single nucleotide polymorphisms (SNPs) were selected as instrumental variables based on established criteria. Myocarditis data from GWAS (427,911 participants, 24, 180, 570 SNPs) were used as the outcome variable. MR analysis was conducted using Inverse Variance Weighting (IVW), with Cochran’s Q test for heterogeneity and Egger’s intercept to assess horizontal pleiotropy.

Results

9 gut microbiota, 10 serum metabolites, and 2 immunophenotypes were negatively associated with myocarditis risk. In contrast, 5 gut microbiota, 12 serum metabolites, and 7 immunophenotypes were positively associated with myocarditis risk (all, P < 0.05). Sensitivity analyses confirmed the stability of these results.

Conclusion

This MR study suggests that gut microbiota, serum metabolites, and immunophenotypes may causally influence myocarditis risk. These findings provide genetic evidence for myocarditis etiology and could inform future precision prevention and treatment strategies.
Exome sequence analysis identifies a homozygous, pathogenic, frameshift variant in the MAN2B1 gene underlying clinical variant of α-mannosidosis
Authors: Hashmi Jamil Amjad , Latif Muhammad , Balahmar Reham M. , Ali Muhammad Zeeshan , Alfadhli Fatima , Khan Muzammil Ahmad , Basit Sulman
Published: August 2024

Background

α-mannosidosis (MAN) is a rare genetic condition that segregates in an autosomal recessive manner. Lack of lysosomal alpha-mannosidase is the underlying cause of the disease. Symptoms of the disease gradually worsen with the age. Newborns are usually asymptomatic, however, some cases are reported with either congenital ankle equinus or hydrocephalus during the first year. Primary symptoms are characterized by immune deficiency, hearing loss, skeletal abnormalities, progressive mental, motor and speech functions’ impairment followed by facial asymmetry.

Methods

We studied two Saudi families (A and B) with bilateral moderate hearing loss (family A) and clubfoot with glaucoma (family B). Clinical diagnosis was not reached based on phenotype of patients. Therefore, hypothesis-free whole exome sequencing (WES) was performed on DNA samples from affected individuals of both the families, followed by Sanger sequencing and segregation analysis to validate the segregation of the identified variant. Furthermore, 3D protein modelling was performed to determine the in silico effects of the identified variant on the protein structure and function.

Results

Re-examination of clinical features revealed that the patients in family A have speech delay and hearing impairment along with craniostenosis, whereas the patients from family B have only clubfoot and glaucoma. WES identified a well known pathogenic homozygous frameshift variant (NM_000528.4: c.2402dupG; p.S802fs*129) in MAN2B1 in both the families. Sanger sequencing confirmed the segregation of the variant with the disease phenotype in both the families. 3D structural modeling of the MAN2B1 protein revealed significant changes in the tertiary structure of the mutant protein, which would affect enzyme function. This report presents a new case where partial and novel α-mannosidosis phenotypes are associated with a MAN2B1 gene pathogenic variant.

Conclusion

Patients in both the families have manifested peculiar set of clinical symptoms associated with α-mannosidosis. Family A manifested partial clinical symptoms missing several characteristic features like intellectual disability, dysmorphic features, neurological and abdominal manifestations, whereas family B has no reported clinical symptoms related to α-mannosidosis except the novel symptoms including club foot and glaucoma which has never been reported earlier The current findings support the evidence that biallelic variants of MAN2B1 are associated with new clinical variants of α-mannosidosis.
Identification and expression analysis of bZIP transcription factors in Setaria italica in response to dehydration stress
Authors: Yang Xuefei , Gao Changyong , Hu Yaqian , Ma Qianru , Li Zejun , Wang Jing , Li Zhaoqun , Zhang Li , Li Dongming
Published: August 2024

Among the largest transcription factor families in plants, bZIPs are crucial for various developmental and physiological processes, particularly abiotic stress resistance. Setaria italica has become a model for understanding stress resistance mechanisms. In this study, we identified 90 bZIP transcription factors in the Setaria italica genome. SibZIPs were classified into 13 groups based on references to Arabidopsis bZIPs. Members in the same group shared similar motifs and gene structure pattern. In addition, gene duplication analysis indenfied 37 pairs of segmental duplicated genes and none tandem duplicated genes in S. italica suggesting segmental duplication contributed to the expansion of the S. italica bZIP gene family. Moreover, the number of SibZIPs genes (39) exhibiting higher expression in roots was significantly more than that in other organs. Twelve SibZIP genes were upregulated in response to dehydration stress. In conclusion, our study advances the current understanding of SibZIP genes and provide a number of candidates for functional analysis of drought tolerance in S. italica.
TGF-β1 overexpression in severe COVID-19 survivors and its implications for early-phase fibrotic abnormalities and long-term functional impairment
Authors: Alfaro Enrique , Casitas Raquel , Díaz-García Elena , García-Tovar Sara , Galera Raúl , Torres-Vargas María , Fernández-Velilla María , López-Fernández Cristina , Añón José M. , Quintana-Díaz Manuel , García-Río Francisco , Cubillos-Zapata Carolina
Published: August 2024

Introduction

In post-COVID survivors, transforming growth factor-beta-1 (TGF-β1) might mediate fibroblast activation, resulting in persistent fibrosis.

Methods

In this study, 82 survivors of COVID-19-associated ARDS were examined at 6- and 24-months post-ICU discharge. At 6-months, quantitative CT analysis of lung attenuation was performed and active TGF-β1 was measured in blood and exhaled breath condensate (EBC).

Results

At 6-months of ICU-discharge, patients with reduced DmCO/alveolar volume ratio exhibited higher plasma and EBC levels of active TGF-β1. Plasma TGF-β1 levels were elevated in dyspneic survivors and directly related to the high-attenuation lung volume. In vitro, plasma and EBC from survivors induced profibrotic changes in human primary fibroblasts in a TGF-β receptor-dependent manner. Finally, at 6-months, plasma and EBC active TGF-β1 levels discriminated patients who, 24-months post-ICU-discharge, developed gas exchange impairment.

Discussion

TGF-β1 pathway plays a pivotal role in the early-phase fibrotic abnormalities in COVID-19-induced ARDS survivors, with significant implications for long-term functional impairment.
Identification of immune-related biomarkers for intracerebral hemorrhage diagnosis based on RNA sequencing and machine learning
Authors: Bai Congxia , Liu Xinran , Wang Fengjuan , Sun Yingying , Wang Jing , Liu Jing , Hao Xiaoyan , Zhou Lei , Yuan Yu , Liu Jiayun
Published: August 2024

Background

Intracerebral hemorrhage (ICH) is a severe stroke subtype with high morbidity, disability, and mortality rates. Currently, no biomarkers for ICH are available for use in clinical practice. We aimed to explore the roles of RNAs in ICH pathogenesis and identify potential diagnostic biomarkers.

Methods

We collected 233 individual blood samples from two independent cohorts, including 64 patients with ICH, 59 patients with ischemic stroke (IS), 60 patients with hypertension (HTN) and 50 healthy controls (CTRL) for RNA sequencing. Differentially expressed genes (DEGs) analysis, gene set enrichment analysis (GSEA), and weighted correlation network analysis (WGCNA) were performed to identify ICH-specific modules. The immune cell composition was evaluated with ImmuneCellAI. Multiple machine learning algorithms to select potential biomarkers for ICH diagnosis, and further validated by quantitative real-time polymerase chain reaction (RT−PCR). Receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA) were performed to evaluate the diagnostic value of the signature for ICH. Finally, we generated M1 and M2 macrophages to investigate the expression of candidate genes.

Results

In both cohorts, 519 mRNAs and 131 lncRNAs were consistently significantly differentially expressed between ICH patients and HTN controls. Gene function analysis suggested that immune system processes may be involved in ICH pathology. ImmuneCellAI analysis revealed that the abundances of 11 immune cell types were altered after ICH in both cohorts. WGCNA and GSEA identified 18 immune-related DEGs. Multiple algorithms identified an RNA panel (CKAP4, BCL6, TLR8) with high diagnostic value for discriminating ICH patients from HTN controls, CTRLs and IS patients (AUCs: 0.93, 0.95 and 0.82; sensitivities: 81.3%, 84.4% and 75%; specificities: 100%, 96% and 79.7%, respectively). Additionally, CKAP4 and TLR8 mRNA and protein levels decreased in RAW264.7 M1 macrophages and increased in RAW264.7 M2 macrophages, while BCL6 expression increased in M1 macrophages but not in M2 macrophages, which may provide potential therapeutic targets for ICH.

Conclusions

This study demonstrated that the expression levels of lncRNAs and mRNAs are associated with ICH, and an RNA panel (CKAP4, BCL6, TLR8) was developed as a potential diagnostic tool for distinguishing ICH from IS and controls, which could provide useful insight into ICH diagnosis and pathogenesis.
hFcγRIIa: a double-edged sword in osteoclastogenesis and bone balance in transgenic mice
Authors: Miao Jie , Wang Hong-Min , Pan Xiao-Hua , Gong Zheng , Gao Xiao-Ming , Gong Fang-Yuan
Published: August 2024

Rheumatoid arthritis (RA) is a chronic autoimmune disease accompanied by local and systemic bone loss. FcγRs, especially FcγRIIa (hFcγRIIa), have been implicated in the pathogenesis of RA. However, the contribution of hFcγRIIa to bone loss has not been fully elucidated. In the present study, we demonstrated the double-edged sword role of hFcγRIIa on osteoclast differentiation through investigations involving hFcγRIIa-transgenic (hFcγRIIa-Tg) mice. Our findings reveal that hFcγRIIa-Tg mice, previously shown to exhibit heightened susceptibility to collagen-induced arthritis (CIA), displayed increased osteoporosis during CIA or at advanced ages (40 weeks), accompanied by heightened in vivo osteoclast differentiation. Notably, bone marrow cells from hFcγRIIa-Tg mice exhibited enhanced efficiency in differentiating into osteoclasts and bone resorption in vitro compared to wild-type mice when stimulated with receptor activators of NF-κB ligand (RANKL). Additionally, hFcγRIIa-Tg mice exhibited augmented sensitivity to RANKL-induced bone loss in vivo, highlighting the osteoclast-promoting role of hFcγRIIa. Mechanistically, bone marrow cells from hFcγRIIa-Tg mice displayed heightened Syk self-activation, leading to mTOR-pS6 pathway activation, thereby promoting RANKL-driven osteoclast differentiation. Intriguingly, while hFcγRIIa crosslinking hindered RANKL-induced osteoclast differentiation, it activated the kinase cAbl, subsequently triggering STAT5 activation and inhibiting the expression of osteoclast-associated genes. This study provides novel insights into hFcγRIIa-mediated osteoclast biology, suggesting promising therapeutic targets for managing bone remodeling disorders.
Territorial and occupancy behavior of black sea bass on oyster aquaculture gear and boulder habitat
Authors: Armbruster Adam D. , Mercaldo-Allen Renee , Rose Julie M. , Seda Kristen , Clark Paul , Phillips Gillian , Redman Dylan , Conroy Christian W.
Published: August 2024

Observations of fish behavior can provide insights into habitat preferences and use. Black sea bass, Centropristis striata, are a territorial temperate reef finfish species known for their high commercial and recreational value and association with structured habitat. We used underwater action cameras to record video of black sea bass to assess territorial (agonistic, ambush, displacement) and occupancy (station-keeping) behaviors on shelf and bag style oyster aquaculture cages at a shellfish farm, and on boulders at a natural rock reef near Milford, Connecticut in Long Island Sound, Northwest Atlantic. Black sea bass at a variety of life stages were highly associated with cages, including young-of-the-year, and age 1+ fish. The high abundance of black sea bass observed on cages relative to boulders suggests this species has an affinity for the vertical structure created by aquaculture gear. When behaviors were normalized to the total fish sightings, black sea bass showed no significant difference in frequency of behaviors between habitats, indicating that per-fish rates of behavior were similar on cages and boulders. Demonstration of territorial and occupancy behaviors by black sea bass on, and around cages suggests that aquaculture gear provides structured habitat and ecosystem services for this species similar to natural reefs.These results suggest that essential fish habitat descriptions of manmade structures used by black sea bass could be broadened to include aquaculture gear. Our study provides novel information on behavioral interactions of black sea bass with oyster cages that may support aquaculture permitting and consultation processes.
Unveiling the structuring effects of eutrophication on macrobenthic biological traits in Hangzhou Bay and adjacent waters
Authors: Zhou Weiwei , Wang Xiaobo , Han Qingxi
Published: August 2024

The ecological effects of eutrophication on estuaries and coastal ecosystems are significant worldwide. Based on data collected in 2019 from Hangzhou Bay and adjacent waters, this study employed biological traits analysis and RLQ/fourth-corner analysis methods to investigate the distribution patterns of macrobenthic assemblages along a eutrophication gradient and reveal the response patterns of their biological traits to eutrophication stress. The results showed that eutrophication had a significant structuring effect on the spatial distribution of macrobenthic community structure. As the level of eutrophication increased, the community abundance and number of macrobenthic biological traits decreased. The composition of macrobenthic community biological traits changed in response to eutrophication. In areas with high levels of eutrophication, larger body sizes became more dominant, reflecting a shift in dominant traits similar to the eutrophication gradient. Furthermore, the predominant species in this region were burrowers and tube dwellers, which preferred muddy sand and sandy mud substrates. The AMBI ecological group accurately reflects the degree of eutrophication disturbance, with tolerant species and second-order opportunistic species being common in eutrophic areas.
Unraveling the association of bacteria and urinary stones in patients with urolithiasis: an update review article
Authors: Razi Abdolah , Ghiaei Azita , Dolatabadi Fahimeh Kamali , Haghighi Ramin
Published: August 2024

Urinary stone disease (USD) is a prevalent urological condition, ranking as one of the most common urinary tract disorders globally. Various risk factors influence the formation of kidney stones, and recent research indicates a rising prevalence of urolithiasis worldwide, particularly in developing countries. While the morbidity associated with urinary stones has decreased in recent years, long-term complications such as stone recurrence, kidney failure, and uremia continue to burden patients. Understanding the etiologies of urolithiasis, including the role of bacteria, is crucial as they can contribute to stone recurrence. The incidence of urinary tract infection (UTI) stones can be attributed to specific infectious risk factors, socio-demographic factors, and comorbid metabolic disorders. This review article explores the emerging evidence suggesting the involvement of bacteria in USD. It discusses the potential role of microorganisms in non-infection stones and highlights the association between UTIs and urolithiasis. Furthermore, it surveys the relationship between kidney stones and recurrent UTIs and the formation of bacterial biofilms in UTIs. Considering various risk factors, including biochemical stone analysis and the presence of bacteria, is essential for treating patients with infectious stones optimally. This review aims to provide an updated understanding of the association between bacteria and urinary stones in patients with urolithiasis, shedding light on the pathophysiology of urinary stone formation, urinary stone characteristics, and the urinary microbiome in urinary stones.
Associations of primiparous pre-pregnancy body mass index and gestational weight gain with cesarean delivery after induction: a prospective cohort study
Authors: Lin Shi , Xie Chunzhi , Teng Anyi , Chen Xiaotian , Li Yan , Zhang Yangyang , Zhang Hui , Sun Ting
Published: August 2024

Objective

The effects of Pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) in primiparas remain unclear. This study examines the associations of pre-pregnancy BMI and GWG with cesarean delivery after induction (CDaI) in primiparous women.

Methods

This prospective cohort study included 3,054 primiparous women. We recorded pre-pregnancy BMI, first, second, and third trimester weight values, as well as instances of CDaI and other pregnancy outcomes. We analyzed the associations of pre-pregnancy BMI and GWG with CDaI by conducting a multivariate logistic regression analysis after adjusting for covariates, and adjusted risk ratios (aRR) and 95% confidence intervals were reported.

Results

We recorded 969 CDaIs. In the vaginal delivery group, each increase of 1 standard deviation in the pre-pregnancy BMI was correlated with a 6% increase in the CDaI risk [aRR (95% CI), 1.06 (1.01–1.11)]. Each increase of 1 standard deviation in the rate of weight gain during the entire pregnancy was correlated with a 21% increase in the CDaI risk [aRR (95% CI), 1.21 (1.14–1.29)]. Compared to women with a normal weekly GWG in the second and third trimester, those with slow GWG had a 19% increased risk of CDaI [aRR (95% CI), 1.19 (1.01–1.37)]. The subgroup analysis results showed that increases in pre-pregnancy BMI could increase the CDaI risk regardless of the induction method.

Conclusion

High pre-pregnancy BMI, excessive GWG, and rapid first trimester weight gain are risk factors for CDaI in primiparous women. Excessive first trimester weight gain, may associated with increased risks of CDaI in primiparous women.
Plant microRNAs regulate the defense response against pathogens
Authors: Luo Changxin , Bashir Nawaz Haider , Li Zhumei , Liu Chao , Shi Yumei , Chu Honglong
Published: August 2024

MicroRNAs (miRNAs) are a class of small non-coding RNAs, typically 20–25 nucleotides in length, that play a crucial role in regulating gene expression post-transcriptionally. They are involved in various biological processes such as plant growth, development, stress response, and hormone signaling pathways. Plants interact with microbes through multiple mechanisms, including mutually beneficial symbiotic relationships and complex defense strategies against pathogen invasions. These defense strategies encompass physical barriers, biochemical defenses, signal recognition and transduction, as well as systemic acquired resistance. MiRNAs play a central role in regulating the plant’s innate immune response, activating or suppressing the transcription of specific genes that are directly involved in the plant’s defense mechanisms against pathogens. Notably, miRNAs respond to pathogen attacks by modulating the balance of plant hormones such as salicylic acid, jasmonic acid, and ethylene, which are key in activating plant defense mechanisms. Moreover, miRNAs can cross boundaries into fungal and bacterial cells, performing cross-kingdom RNA silencing that enhances the plant’s disease resistance. Despite the complex and diverse roles of miRNAs in plant defense, further research into their function in plant-pathogen interactions is essential. This review summarizes the critical role of miRNAs in plant defense against pathogens, which is crucial for elucidating how miRNAs control plant defense mechanisms.
Essential oils as capsule disruptors: enhancing antibiotic efficacy against multidrug-resistant Klebsiella pneumoniae
Authors: El-Demerdash Azza SalahEldin , Alfaraj Rihaf , Farid Faten A. , Yassin Mohamed H. , Saleh Abdulrahman M. , Dawwam Ghada E.
Published: August 2024

Background

Multidrug-resistant Klebsiella pneumoniae (MDR-KP) poses a significant global health threat due to its involvement in severe infections and high mortality rates. The emergence of MDR strains necessitates the exploration of alternative therapeutic strategies.

Methods

K. pneumoniae isolates were obtained from human and animal sources. Antibacterial susceptibility testing was performed, followed by the evaluation of essential oil activity through inhibition zone, MIC, and MBC determinations. Checkerboard assays were conducted to assess synergistic effects with amikacin. Gene expression analysis and transmission electron microscopy were employed to elucidate the mechanisms of action. Molecular docking studies were performed to identify potential binding targets of bioactive compounds.

Results

Klebsiella pneumoniae was isolated from 25 of the100 samples examined, representing a prevalence rate of 25%. All isolates were found to be multidrug-resistant. Tea tree and thyme essential oils exhibited potent antibacterial activity and synergistic effects with amikacin. Notably, these combinations significantly downregulated the expression of key capsule virulence genes (wcaG, rmpA, magA, uge, and wabG), suggesting a novel mechanism for enhancing amikacin efficacy. Transmission electron microscopy revealed disrupted cell integrity in MDR-KP cells treated with the combinations. Molecular docking analysis identified Terpinen-4-ol, Farnesol, 1,4-Dihydroxy-p-menth-2-ene, and 7-Oxabicyclo [4.1.0] heptane as potential bioactive compounds responsible for the observed effects.

Conclusion

By effectively combating MDR-KP, this research holds promise for reducing antibiotic resistance, improving treatment outcomes, and ultimately enhancing potential care.
Neuropathology and neuroinflammation in Alzheimer’s disease via bidirectional lung–brain axis
Authors: Lu Jie , Li Cheng-Jun , Wang Jing , Wang Yang
Published: August 2024

Alzheimer’s disease (AD) is the most common form of age-related dementia worldwide. Although the neuropathology of AD is clear, its pathogenesis remains unclear. Recently, conceptualising AD as brain-centred has reoriented many scientists because the close functional relationship between the peripheral and central nerves is increasingly recognised. Recently, various studies have focused on the crosstalk between peripherals and centrals. A new hotspot of research and new therapeutic strategies have emerged from this great progress. This mini-review is an overview of the potential molecular mechanism in AD via the bidirectional lung-brain axis, providing a new perspective for the systemic understanding of AD onset.
Mediation effect of stroke recurrence in the association between post-stroke lactate dehydrogenase and functional disability
Authors: He Qian , Wang Miaoran , Zhu Haoyue , Xiao Ying , Wen Rui , Liu Xiaoqing , Shi Yangdi , Zhang Linzhi , Wang Yu , Xu Bing
Published: August 2024

Background

We aimed to use lactate dehydrogenase (LDH) as a marker of inflammation burden and quantify post-stroke inflammation’s direct and indirect effect on functional disability.

Methods

We analyzed 5,129 patients with acute ischemic stroke (AIS) admitted to Shenyang First People’s Hospital. Stroke recurrence and functional outcome measured by the modified Rankin Scale (mRS) were assessed at 90 days. Functional disability was defined as mRS score > 2. Receiver operating characteristic curve and restricted cubic spline (RCS) analysis were conducted to illustrate the associations between LDH levels and 90-day functional outcomes in patients with AIS. Mediation analyses were performed to examine the potential causal chain in which stroke recurrence may mediate the relationship between LDH and functional outcome. Positive correlation between LDH and hs-CRP was found and mediation effects of stroke recurrence in the association between LDH or hs-CRP and functional disability were both less than 20%. Sensitivity analyses in different subgroups showed comparable results.

Results

Among 5,129 included AIS patients, the median (IQR) level of LDH was 186 (161–204.4) U/L. Functional disability was seen in 1200 (23.4%) patients and recurrence was observed in 371(7.2%) patients at 90-day follow-up. Each standard deviation increase in the concentration of LDH was linked to an increased risk of functional disability (adjusted odds ratio[aOR], 1.07; 95%CI,1.04–1.09) and stroke recurrence (aOR,1.02; 95%CI, 1.01–1.04) within 90 days. The highest quartile of LDH (>204.2 U/L) had an elevated risk of suffering functional disability (aOR, 1.21; 95%CI, 1.00–1.47) and recurrence (aOR, 1.21; 95%CI,1.00–1.47) compared with the lowest quartile of LDH (<161 U/L). Stroke recurrence during follow-up explained 12.90% (95%CI, 6.22–21.16%) of the relationship between LDH and functional disability. Positive correlation between LDH and hs-CRP was found and mediation effects of recurrence in the association between LDH or hs-CRP and functional disability were both less than 20%. Sensitivity analyses in different subgroups showed comparable results.

Conclusion

The relationship between LDH and functional disability at 90 days among AIS patients is partially mediated by stroke recurrence, accounting for less than 20%. LDH deserves equal attention as hs-CRP in predicting recurrence and functional outcome. In addition to traditional secondary prevention measures, innovative anti-inflammatory strategies warrant further investigation.
Symptoms similar to Kleine–Levin syndrome in a patient with basilar artery occlusion: a case report and literature review
Authors: Kong Linghua , Li Chunyan
Published: August 2024

Introduction

Kleine–Levin syndrome (KLS) is a rare disorder characterized by recurrent periodic hypersomnia, cognitive disturbances, hyperphagia, and hypersexuality. Although many factors have been associated with its occurrence, little is known about treatment. Herein, we present a case of symptoms similar to KLS thought to be related to vascular occlusion disease.

Case description

An 81-year-old woman was admitted to the hospital due to recurring episodes of disturbance of consciousness, cognitive disorder, and hyperphagia for 18 years. She was diagnosed with KLS and basilar artery occlusion. Endovascular and antithrombotic therapy was initiated, and her symptoms fully resolved within 2 weeks of treatment initiation.

Conclusion

KLS has diverse clinical presentations and demonstrates variable therapeutic responses. Vascular disease or blood flow disorder may be one possible factor for this disease. This case underscores the need for further research into the etiology and pathogenesis of KLS to promote evidence-based approaches for its diagnosis and treatment.
Biologic activity and treatment resistance to gastrointestinal cancer: the role of circular RNA in autophagy regulation
Authors: Zhang Bo , Li Zhe , Ye Guoliang , Hu Kefeng
Published: August 2024

Circular RNAs (circRNAs) lack the 5’-end methylated guanine cap structure and 3’ polyadenylate tail structure, classifying it as a non-coding RNA. With the extensive investigation of circRNA, its role in regulating cell death has garnered significant attention in recent years, establishing it as a recognized participant in cancer’s biological processes. Autophagy, an essential pathway in programmed cell death (PCD), involves the formation of autophagosomes using lysosomes to degrade cellular contents under the regulation of various autophagy-related (ATG) genes. Numerous studies have demonstrated that circRNA can modulate the biological activity of cancer cells by influencing the autophagy pathway, exhibiting a dualistic role in suppressing or promoting carcinogenesis. In this review, we comprehensively analyze how autophagy-related circRNA impacts the progression of gastrointestinal cancer (GIC). Additionally, we discuss drug resistance phenomena associated with autophagy regulation in GIC. This review offers valuable insights into exploring potential biological targets for prognosis and treatment strategies related to GIC.
Comparative efficacy and hematologic safety of different dosages of JAK inhibitors in the treatment of myelofibrosis: a network meta-analysis
Authors: Chen Ke , Zhang Yanyu , Zou Jixuan , Wang Dehao , Yu Xinyue , Sun Yan , Li Yumeng , Niu Jicong , Chen Yi , Zhao Pei , Liu Weiyi , Lv Yan , Wang Mingjing , Hu Xiaomei
Published: August 2024

Background

Myelofibrosis (MF) is a myeloproliferative neoplasm characterized by bone marrow fibrosis associated with substantial morbidity and mortality. The therapeutic landscape for MF has advanced with the development of Janus kinase inhibitors (JAKis) like ruxolitinib (RUX), fedratinib (FED), pacritinib (PAC), and momelotinib (MMB), aiming to alleviate symptoms and enhance patient comfort.

Methods

A network meta-analysis was conducted to assess the efficacy and safety of eleven JAKi treatment regimens across nine randomized controlled trials (RCTs) with a total of 2340 participants. Outcomes were evaluated in terms of spleen volume reduction (SVR), total symptom score reduction (TSSR), hematological safety profiles, and overall survival (OS).

Results

RUX and MMB were superior in achieving SVR and TSSR, with significant dose-response relationships observed. PAC and MMB were associated with a decreased risk of grade 3/4 anemia and thrombocytopenia compared to other JAKis. However, no substantial benefits in OS were observed with newer JAKis compared to RUX. The poorer OS outcomes with certain PAC dosages were likely influenced by baseline patient characteristics, particularly severe cytopenias.

Conclusion

The introduction of JAKis significantly changed the treatment of MF. This meta-analysis reaffirms the core role of RUX and positions MMB as a potentially powerful alternative for treating symptoms and reducing spleen size. Meanwhile, MMB and PAC have a positive effect on anemia in MF while FED is more tolerable for patients with thrombocytopenia. However, it should be noted that these results are influenced by baseline patient characteristics, particularly cytopenias, which affects both management and overall survival. Therefore, there is an urgent need for personalized dosing strategies to optimize the balance between efficacy and safety, with careful consideration of patient-specific factors.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023424179.
Development and application of a nomogram model for predicting the risk of central precocious puberty in obese girls
Authors: Huang Ren-Hao , Yang Li , Yang Yu , Xu Qing-Bo , Xie Li-Ling , Cao Lan-Fang
Published: August 2024

Objective

The purpose of this study is to develop and assess a nomogram risk prediction model for central precocious puberty (CPP) in obese girls.

Methods

We selected 154 cases of obese girls and 765 cases of non-obese girls with precocious puberty (PP) who underwent the gonadotropin-releasing hormone stimulation test at the Jiangxi Provincial Children's Hospital. Univariate analysis and multivariate analysis were conducted to identify predictors of progression to CPP in girls with PP. A predictive model was developed and its predictive ability was preliminarily evaluated. The nomogram was used to represent the risk prediction model for CPP in girls with obesity. The model was validated internally using the Bootstrap method, and its efficacy was assessed using calibration curves and clinical decision analysis curves.

Results

In obese girls with PP, basal luteinizing hormone (LH) and follicular stimulating hormone (FSH) levels, as well as uterine volume, were identified as independent risk factors for progression to CPP. In non-obese girls, the basal LH level, bone age, and uterine volume were identified as independent risk factors for progression to CPP. With an AUC of 0.896, the risk prediction model for obese girls, was found to be superior to that for non-obese girls, which had an AUC of 0.810. The model displayed strong predictive accuracy. Additionally, a nomogram was used to illustrate the CPP risk prediction model for obese girls. This model performs well in internal validation and is well calibrated, providing a substantial net benefit for clinical use.

Conclusion

A medical nomogram model of CPP risk in obese girls comprised of basal LH value, basal FSH value, and uterine volume, which can be used to identify those at high risk for progression of CPP in obese girls and develop individualized prevention programs.
A U.S. Pharmacopeia (USP) overview of Pan American botanicals used in dietary supplements and herbal medicines
Authors: Upton Roy , Agudelo Ignacio , Cabrera Yadira , Caceres Armando , Calderón Angela , Calzada Fernando , Camacho Rosa , da Costa Fernando , Dobrecky Cecilia , Enciso Roberto , Escobar Marcela , Fakhary Mina , Fletcher Edward , Gao Quanyin , Lock Olga , Mata Rachel , Parada Mirtha , Perera Wilmer , Pombo Luis Miguel , Reich Eike , Sanchez Eric , Simirgiotis Mario Juan , Sood Christian , Amiguet Virginie Treyvaud , Villar Martha , Ghelman Ricardo , Schveitzer Mariana Cabral , Portella Caio Fábio Schlechta , Wolffenbüttel Adriana , Ruppelt Bettina , Frickmann Fabiana Souza , Gavillan-Suarez Janette , Allen Kristin , Alvarado Luis Diego , Sarma Nandakumara , Marles Robin , Monagas Maria , Navarro-Hoyos Mirtha
Published: August 2024

The United States Pharmacopeial Convention (USP) is a nonprofit, scientific, standard-setting organization, and world leader in establishing quality, purity, and testing standards for medicines, foods, and dietary supplements. USP quality standards are used in more than 140 countries and are legally recognized by more than 40 countries. Currently, there is renewed interest in herbal medicines globally, and health policies are being implemented worldwide for the use of complementary and traditional medicine. In response, USP has developed a robust body of monographs that can be used to guide industry and regulators in ensuring the quality and safety of botanical ingredients used in dietary supplements and herbal medicines. Throughout the Pan American regions, there is a strong tradition of using botanicals as herbal medicines and, as in other regions, a growing desire for botanical dietary supplements. This underscores the need for public quality standards to ensure quality, reduce the flow of substandard and adulterated products, and ensure public health and safety. In April 2022, USP launched the Pan America Botanical Dietary Supplements and Herbal Medicines Expert Panel, with experts representing 12 different countries. The Expert Panel’s work focuses on developing quality control standards for the most important botanical ingredients used in the respective countries, ingredients that are also of global importance. This article provides an overview of the state of botanical dietary supplements and herbal medicines in different Pan American regions with a focus on the regulatory status of herbal products, the development of national quality and research initiatives, and policies related to agriculture conservation and sustainability, among other topics.
Investigating the therapeutic potential of hesperidin targeting CRISP2 in intervertebral disc degeneration and cancer risk mitigation
Authors: Zhang Hui , Jiang Wei , Jiang Yuqing , Xu Nanwei , Nong Luming , Li Tengfei , Liu Ruiping
Published: August 2024

Graphical Abstract

The graphic abstract illustrates a study investigating the therapeutic potential of Hesperidin in targeting the CRISP2 gene to treat intervertebral disc degeneration (IDD) while mitigating cancer risks associated with estrogen. The workflow begins with differential gene expression and enriched pathway analysis in IDD, breast cancer (BRCA), and estrogen receptor (ER) pathways. An intersection analysis reveals overlapping genes, highlighting CRISP2 as a significant target. Hesperidin emerges as a promising natural metabolic regulator for treating IDD and potentially collaborating with estrogen therapy to improve spinal health while minimizing cancer risks, paving the way for innovative therapeutic approaches.
Gastrointestinal tract organoids as novel tools in drug discovery
Authors: Zhou Li , Luo Dan , Lu Wei , Han Jun , Zhao Maoyuan , Li Xueyi , Shen Tao , Jin Zhao , Zeng Jinhao , Wen Yueqiang
Published: August 2024

Organoids, characterized by their high physiological attributes, effectively preserve the genetic characteristics, physiological structure, and function of the simulated organs. Since the inception of small intestine organoids, other organoids for organs including the liver, lungs, stomach, and pancreas have subsequently been developed. However, a comprehensive summary and discussion of research findings on gastrointestinal tract (GIT) organoids as disease models and drug screening platforms is currently lacking. Herein, in this review, we address diseases related to GIT organoid simulation and highlight the notable advancements that have been made in drug screening and pharmacokinetics, as well as in disease research and treatment using GIT organoids. Organoids of GIT diseases, including inflammatory bowel disease, irritable bowel syndrome, necrotizing enterocolitis, and Helicobacter pylori infection, have been successfully constructed. These models have facilitated the study of the mechanisms and effects of various drugs, such as metformin, Schisandrin C, and prednisolone, in these diseases. Furthermore, GIT organoids have been used to investigate viruses that elicit GIT reactions, including Norovirus, SARS-CoV-2, and rotavirus. Previous studies by using GIT organoids have shown that dasabuvir, gemcitabine, and imatinib possess the capability to inhibit viral replication. Notably, GIT organoids can mimic GIT responses to therapeutic drugs at the onset of disease. The GIT toxicities of compounds like gefitinib, doxorubicin, and sunset yellow have also been evaluated. Additionally, these organoids are instrumental for the study of immune regulation, post-radiation intestinal epithelial repair, treatment for cystic fibrosis and diabetes, the development of novel drug delivery systems, and research into the GIT microbiome. The recent use of conditioned media as a culture method for replacing recombinant hepatocyte growth factor has significantly reduced the cost associated with human GIT organoid culture. This advancement paves the way for large-scale culture and compound screening of GIT organoids. Despite the ongoing challenges in GIT organoid development (e.g., their inability to exist in pairs, limited cell types, and singular drug exposure mode), these organoids hold considerable potential for drug screening. The use of GIT organoids in this context holds great promises to enhance the precision of medical treatments for patients living with GIT diseases.
Brchli1 mutation induces bright yellow leaves by disrupting magnesium chelatase I subunit function in Chinese cabbage (Brassica rapa L. ssp. pekinensis)
Authors: Liu Chuanhong , Chai Yi , Tan Chong , Shi Fengyan , Zhang Yun , Liu Zhiyong
Published: August 2024

Magnesium chelatase (MgCh) plays a pivotal role in photosynthesis, catalyzing the insertion of magnesium into protoporphyrin IX (Proto IX), a key intermediate in chlorophyll (Chl) biosynthesis. MgCh is a heteromeric complex composed of the MgCh D subunit (CHLD), the MgCh H subunit (CHLH), and the MgCh I subunit (CHLI). The bright yellow leaves (byl) mutant was obtained through ethyl methanesulfonate (EMS) mutagenesis of the ‘FT’ Chinese cabbage (Brassica rapa L. ssp. pekinensis) doubled haploid line, whose Chl content, net photosynthetic rate (Pn), and non-photochemical quenching coefficient (NPQ) were decreased, and whose chloroplast development was incomplete. byl recovered to a light green phenotype under weak light conditions. Genetic analysis revealed that the bright yellow leaves phenotype of byl was caused by a single recessive nuclear gene. Using Mutmap sequencing and Kompetitive allele-specific PCR (KASP) identification, BraA01g010040.3.5C, encoding the CHLI subunit of MgCh, was identified as the candidate gene and named Brchli1. A nonsynonymous G-to-A mutation in the Brchli1 exon resulted in the substitution of aspartic acid with asparagine. Brchli1-silenced Chinese cabbage displayed bright yellow leaves with decreased Brchli1 expression. Transiently overexpressed Brchli1 in the byl mutant restored the green leaf phenotype and significantly increased relative Brchli1 expression levels. Both BrCHLI1 and its mutated variant were localized in chloroplasts. Yeast two-hybrid and luciferase complementation imaging assays demonstrated that BrCHLI1 interacted with both BrCHLD and itself. BrCHLI1 mutations did not affect its interaction with BrCHLD. Together, Brchli1 mutations impaired the function of MgCh, providing insights into the molecular mechanism of leaf coloration.