bluuebunny/crossref_metadata_2025 huggingface dataset:
The attenuated Pseudorabies virus vaccine Bartha K61 induces a weak cellular immunity: implications for the development of PRV-vectored vaccines
Authors: Xing Gang , Li Hui , Lu Chenhe , Li Haimin , Jin Yulan , Yan Yan , Shang Shaobin , Zhou Jiyong
Published: December 2024

Pseudorabies virus (PRV), causing Aujeszky’s disease in swine, has important economic impact on the pig industry in China and even poses a threat to public health. Although this disease has been controlled by vaccination with PRV live attenuated vaccines (LAVs), the potency of PRV LAVs in inducing cellular immunity has not been well characterized. In this study, using PRV Bartha K61 strain (BK61), the most-used PRV LAVs, as a model, we re-examined the cellular immune response elicited by the BK61 in mice and pigs by multicolor flow cytometry. We found that phenotypic activation of T cells, NK cells and B cells was hardly detected after vaccination. However, antigen-specific IFN-γ-producing CD4 T cells rather than CD8 T cells were dominantly detected but at low frequency upon restimulation with live BK61 virus. These BK61-specific CD4 T cells are also able to simultaneously produce TNF-α and IL-2, showing characteristics of multifunctional T cells. However, BK61-specific CD4 T cells showed weak secondary response upon challenge with PRV DX strain. Further vaccination with PRV-infected dendritic cells (DCs) transiently increased the percentage of IFN-γ-positive CD4 and CD8 T cells but eventually restored to low frequency and did not improve the protective efficacy of BK61 against challenge, suggesting that PRV BK61 induced a relatively weak cellular immunity that could not be overcome by the DC vaccination. Similar immune responses were also observed following vaccination with another PRV LAV HD/c in mice and pigs, suggesting that this may be an intrinsic drawback of PRV LAVs in inducing cellular immunity. Our results demonstrated that PRV LAVs elicited a CD4 Th1-biased weak cellular immunity which is implicative for the development of PRV-vectored vaccine.
Tacrolimus to belatacept conversion in proteinuric kidney transplant recipients
Authors: Efe Orhan , Al Jurdi Ayman , Eiting Morgan Mabey , Marks Christine Rogers , Cote Mariesa Ann , Wojciechowski David , Safa Kassem , Gilligan Hannah , Azzi Jamil , Goyal Nitender , Raynaud Marc , Loupy Alexandre , Weins Astrid , Riella Leonardo V.
Published: December 2024

Background

Proteinuria is associated with worse allograft outcomes in kidney transplant recipients (KTRs) and treatment strategies are limited. We examined the outcomes of calcineurin inhibitor (CNI) to belatacept conversion in proteinuric KTRs.

Methods

In a pilot phase II single-arm multicenter prospective trial, we recruited adult KTRs >6 months post-kidney transplantation with an estimated glomerular filtration rate (eGFR) ≥30 ml/min/1.73m2 and proteinuria >1 g/day. Patients were converted from CNI to belatacept. The primary outcome was a 25% reduction in proteinuria at 12 months.

Results

A total of 15 KTRs were recruited who had pre-conversion median (interquartile range) proteinuria of 1.8 (IQR 1.4 – 3.5) g/g and estimated glomerular filtration rate (eGFR) of 48 (IQR 32 – 52.5) ml/min/1.73m2. At 12 months post-conversion, median proteinuria was 1.4 (IQR 0.4 – 2.2) g/g (P = 0.068) and eGFR was maintained at 43 (34 – 54.5) ml/min/1.73m2. The primary outcome of at least a 25% reduction in proteinuria occurred in 53% (8/15) at 12 months. Abbreviated IBOX scores predicting 7-year graft survival were also stable at 1-year post-conversion compared to baseline. At extended follow-up at 5 years, both proteinuria and eGFR remained stable at 0.69 (0.24 – 2.15) g/g and 39 (31 – 57) ml/min/1.73m2, respectively.

Conclusions

CNI to belatacept conversion was associated with preserved allograft function in KTRs with significant proteinuria. These findings need to be confirmed in a larger randomized clinical trial.

Clinical trial registration

https://clinicaltrials.gov/, identifier NCT0232740.
Cutoffs on severity metrics for minimal manifestations or better status in patients with generalized myasthenia gravis
Authors: Watanabe Genya , Takai Yoshiki , Nagane Yuriko , Kubota Tomoya , Yasuda Manato , Akamine Hiroyuki , Onishi Yosuke , Uzawa Akiyuki , Kawaguchi Naoki , Masuda Masayuki , Konno Shingo , Amino Itaru , Minami Naoya , Kimura Takashi , Samukawa Makoto , Sugimoto Takamichi , Suzuki Yasushi , Takahashi Masanori P. , Suzuki Shigeaki , Murai Hiroyuki , Aoki Masashi , Utsugisawa Kimiaki
Published: December 2024

International consensus guidance and Japanese clinical guidelines for myasthenia gravis (MG) recommend achieving minimal manifestations or better status (MM-or-better) as the severity component of the treatment goal. However, the subjective nature of determining MM can result in ambiguity regarding this category in clinical practice and clinical trials. This study analyzed severity metrics in a large number of MG patients to propose criteria for MM-or-better. We utilized data obtained from 3800 MG patients who participated in nationwide cross-sectional surveys in Japan. Among these, 2784 patients with generalized MG were divided into two groups based on MG Foundation of America postintervention status: MM-or-better status (n = 1432); and improved-or-worse (I-or-worse) status (n = 1352). We compared severity metrics (MG-activities of daily living scale [MG-ADL], quantitative MG score [QMG], and MG composite scale [MGC]) between groups and calculated cutoff values to separate the two groups. Using these cutoffs, patients subjectively assigned as MM-or-better were classified into strict MM-or-better (below a cutoff) or optimistic MM-or-better (above a cutoff) groups, and clinical characteristics were then compared. Cutoff values for strict MM-or-better were MG-ADL ≤2, QMG ≤7, and MGC ≤4 (sensitivity 82.0%, 88.7%, and 87.4%; specificity 85.0%, 70.0%, and 77.9%; and accuracy 91.2%, 88.7%, and 90.7%, respectively). Mean values of the revised 15-item MG quality of life scale were significantly lower in the strict MM-or-better group than in the optimistic MM-or-better group. Quantitative criteria for MM-or-better appear likely to be useful in the context of rigorous clinical trials and also as reference information in clinical settings.
Regulation of human Th9 cell differentiation by lipid modulators targeting PPAR-γ and acetyl-CoA-carboxylase 1
Authors: Peesari Swetha , McAleer Jeremy P.
Published: December 2024

CD4 T cell activation induces dramatic changes to cellular metabolism for supporting their growth and differentiation into effector subsets. While the cytokines IL-4, TGF-β and IL-21 promote differentiation into Th9 cells, metabolic factors regulating this process remain poorly understood. To assess the role of lipid metabolism in human Th9 cell differentiation, naïve CD4 T cells were purified from blood of healthy volunteers and cultured in the presence or absence of compounds targeting PPAR-γ, acetyl-CoA-carboxylase 1 (ACC1), and AMP-activated protein kinase (AMPK) for four days. Th9 cell differentiation significantly increased PPARG expression, and the PPAR-γ agonist rosiglitazone suppressed IL-9 in a dose-dependent manner. The rosiglitazone-mediated suppression also occurred in the presence of the glucose metabolism inhibitor 2-deoxy-D-glucose, suggesting it was independent of glycolysis. On the other hand, the PPAR-γ antagonist GW9662 had no significant effect on IL-9 production. Next, the role of fatty acid synthesis was tested by treating cells with inhibitors of ACC1 (TOFA) or AMP-activated protein kinase (AMPK; dorsomorphin). We demonstrate reciprocal functions for these enzymes, as ACC1 inhibition substantially increased IL-9 production, whereas AMPK inhibition resulted in undetectable levels. TOFA also decreased expression of ACACA, the gene encoding ACC1, demonstrating regulation at the transcriptional level. Finally, combining TOFA treatment with exogenous oleic acid restored IL-9 back to the levels in control Th9 cultures, suggesting that ACC1 suppresses Th9 differentiation through fatty acid synthesis. Overall, our data demonstrate that lipid regulators associated with intracellular fatty acid accumulation suppress Th9 cell differentiation. These findings may have clinical implications for conditions associated with elevated IL-9 production.
The role of mitochondria in aging, cell death, and tumor immunity
Authors: Wang Qiang , Yuan Yixiao , Liu Jing , Li Chunhong , Jiang Xiulin
Published: December 2024

Mitochondria are essential double-membrane organelles with intricate structures and diverse functions within cells. Under normal physiological conditions, mitochondria regulate cellular metabolism and maintain energy homeostasis via the electron transport chain, mediate stem cell fate, and modulate reactive oxygen species production, playing a pivotal role in energy supply and lifespan extension. However, mitochondrial dysfunction can lead to various pathological changes, including cellular aging, necrosis, dysregulated tumor immunity, and the initiation and progression of cancer. Moreover, abnormal mitochondrial metabolism is closely associated with numerous diseases, such as neurodegenerative disorders, metabolic syndromes, and cancers. In recent years, targeting mitochondria has emerged as a promising anticancer strategy, aiming to modulate mitochondrial functions and metabolism for therapeutic benefits. Nonetheless, such approaches face limitations, including low delivery efficiency and insufficient specificity. This review systematically explores mitochondrial structure and function, their physiological and pathological roles, and the potential and challenges of mitochondria-targeted strategies in cancer therapy, providing insights for future research directions.
The role of APOE gene polymorphisms in lung adenocarcinoma susceptibility and lipid profile
Authors: Bi Huanhuan , Ren Dunqiang , Wang Ye , Wang Hongmei , Zhang Chunling
Published: December 2024

Background

APOE gene polym orphisms have been linked to Alzheimer’s disease and coronary heart diseases. However, their relationship with lung adenocarcinoma (LUAD) remains uncertain.

Methods

This study analyzed a cohort of 600 individuals comprising 200 LUAD patients in the lung cancer group and 400 healthy individuals as controls. APOE gene variants were identified through Sanger sequencing. Statistical analyses were conducted to assess intergroup differences, and comparisons of lipid profiles were performed across individuals carrying different APOE alleles.

Results

The APOE ϵ2 allele had been significantly more frequently occurring in the LUAD group than in the control group (15.5% vs. 7%, P <0.001). APOE ϵ2/ϵ2 and ϵ2/ϵ3 genotypes increased susceptibility to LUAD by 3.78-fold and 3.22-fold. The APOE ϵ2/ϵ3 genotype increased the risk of early-stage LUAD by 2.36-fold and advanced-stage LUAD by 4.05-fold. Individuals with the APOE ϵ2/ϵ2 genotype had a 3.22-fold higher susceptibility to moderately differentiated and a 6.8-fold higher susceptibility to poorly differentiated LUAD. Patients with the ϵ2 allele in LUAD exhibited disrupted lipid metabolism, characterized by reduced HDL, TC, and FFA levels, along with increased ApoB, particularly in advanced and poorly differentiated cancer stages.

Conclusion

Individuals carrying the ϵ2 allele have an increased susceptibility to developing LUAD, accompanied by disrupted lipid metabolism. Additionally, the APOE ϵ2/ϵ2 and ϵ2/ϵ3 genotypes are associated with an increased risk of developing advanced and poorly differentiated LUAD.
Bridging the protein gap with single-cell protein use in aquafeeds
Authors: Buttle Louise , Noorman Henk , Roa Engel Carol , Santigosa Ester
Published: December 2024

Blue foods from aquaculture are essential in bridging the protein gap to feed the human population in the future. However, for aquaculture production to be sustainable, production must be within planetary boundaries, and sourcing of sustainable raw materials is a key driver in sustainable production. This article explores the role of single-cell proteins (SCPs) derived from microorganisms in aquafeeds. Three main aspects are discussed: sustainability, scalability of fermentation technology, and fish performance. In addition, and through a comprehensive proof-of-concept trial with rainbow trout (Oncorhynchus mykiss), this article demonstrates SCP’s efficacy in replacing traditional feed ingredients without compromising fish growth and health. The trial’s findings demonstrate a high protein digestibility and a balanced amino acid profile, as well as health benefits measured through oxidative burst response. To date, commercial adoption of SCP has been hindered by high production costs and the need for substantial investments to scale fermentation technologies. However, the sustainability landscape is changing as large industry players openly commit to sustainability targets and realize that longer-term and investment thinking into the future is needed. In conclusion, SCP emerges as a promising avenue for sustainable aquafeeds, offering a solution to the protein supply challenge within planetary boundaries. In addition, in terms of environmental benefit, SCP shows clear advantages regarding land use, carbon emissions, biodiversity impact, and water consumption. Ultimately, the successful integration of SCP into aquafeeds could significantly contribute to the industry’s sustainability goals and play an essential role in securing the future supply of raw material proteins.
Predictors of response to bDMARDs and tsDMARDs in psoriatic arthritis: a pilot study on the role of musculoskeletal ultrasound
Authors: Cozzi Giacomo , Scagnellato Laura , Lorenzin Mariagrazia , Collesei Antonio , Oliviero Francesca , Damasco Amelia , Cosma Chiara , Basso Daniela , Doria Andrea , Ramonda Roberta
Published: December 2024

Objectives

This pilot study aimed to identify early predictors of drug retention in patients with clinically active peripheral psoriatic arthritis who initiated or switched to therapy with biologic and targeted synthetic disease-modifying antirheumatic drugs (bDMARDs and tsDMARDs).

Methods

Clinical and ultrasound assessments were conducted at baseline (t0) and subsequently at 1 (t1), 3 (t3), and 6 (t6) months. Ultrasound evaluations targeted joints/entheses according to PsASon-Score13 and the most clinically involved joint/enthesis/tendon or the two most clinically involved joints/entheses/tendons (MIJET and 2MIJET). After 6 months of follow-up, patients were divided into two groups based on drug retention, determined by the clinician's assessment of treatment efficacy (cResponder vs. non-cResponder). Main endpoints were ultrasound changes in MIJET, 2MIJET, and GUIS (Global US Inflammation Subscore) derived from PsASon-13.

Results

Twenty-nine patients were enrolled, 22 cResponders and 7 non-cResponders at t6. In the comparison between cResponders and non-cResponders, GUIS variation significantly differed in Δt6-t0, while MIJET and 2MIJET variations were significant as early as Δt3-t0 and confirmed in Δt6-t0. The ultrasound response of MIJET and 2MIJET was faster in cResponders treated with JAKi vs. those treated with TNFi and IL-17/12-23i, significant in Δt1-t0.

Conclusions

Ultrasound imaging of clinically involved joint sites may be a valuable early predictor of therapy response for predicting drug retention at 6 months in patients with psoriatic arthritis.
Overcoming tet(X)-harboring tigecycline resistance: a study on the efficacy of tigecycline-apramycin combinations
Authors: Liu Juan , Zheng Si-Lin , Wu Jing-Jing , Zheng Mei , Cai Da-Tong , Zhang Yan , Sun Jian , Liao Xiao-Ping , Yu Yang
Published: December 2024

Introduction

The emergence of the wide variety of novel tigecycline resistance tet(X) variants, including tet(X3), tet(X4), tet(X5), and tet(X6), has raised a serious threat to global public health and posed a significant challenge to the clinical treatment of multidrug-resistant bacterial infections.

Methods

In this study, we evaluated the synergism of tigecycline combining with other antibiotics as a means of overcoming the tet(X)-mediated resistance in Acinetobacter spp. Antibiotic synergistic efficacy was evaluated through in vitro chequerboard experiments, time-kill assays and dose–response curves. The in vivo synergistic effect of the combination was confirmed in a mouse model of thigh with neutrophilic granulocyte reduction. Additionally, combinations were tested for their ability to prevent high-level tigecycline-resistant mutants.

Results

We found that the combinations of tigecycline with apramycin exhibited synergistic activity against tet(X)-harboring Acinetobacter spp. with FICI of 0.088. The MICTGC decreased more than 5 times in the presence of subinhibitory levels of apramycin. The combination showed in vitro synergism in time-kill assays and in vivo therapeutic effectiveness in the mouse thigh infection model.

Discussion

This study shed light on the synergism of tigecycline in combination with apramycin which offers a viable therapeutic alternative for infections caused by tet(X)-harboring Acinetobacter spp.
A human monoclonal antibody isolated from Japanese encephalitis virus vaccine-vaccinated volunteer neutralizing various flaviviruses
Authors: Chen Dong , Zhang Jiayi , Liu Yusha , Zhu Jiayang , Chen Jie , Ni Hongxia , Wen Jinsheng
Published: December 2024

Introduction

Japanese encephalitis virus (JEV) and Zika virus (ZIKV) are prevalent in over 80 countries or territories worldwide, causing hundreds of thousands of cases annually. But currently there is a lack of specific antiviral agents and effective vaccines.

Methods

In the present study, to identify human neutralizing monoclonal antibody (mAb) against JEV or/and ZIKV, we isolated ZIKV-E protein-binding B cells from the peripheral venous blood of a healthy volunteer who had received the JEV live-attenuated vaccine and performed 10× Genomics transcriptome sequencing and BCR sequencing analysis, we then obtained the V region amino acid sequences of a novel mAb LZY3412. We expressed mAb LZY3412 and evaluated its ability to bind to E proteins of dengue virus, JEV and ZIKV, neutralize JEV and ZIKV infections in vitro, protect mice against lethal JEV or ZIKV attack. The epitopes on E proteins of JEV/ZIKV recognized by mAb LZY3412 were analyzed using molecular docking and constructing E protein mutants.

Results

Our results show that recombinant mAb LZY3412 has high-affinity with the E proteins of three viruses, with the kinetically derived binding affinity (KD) values of 440 and 482.5 nM against JEV-E protein and ZIKV-E protein, respectively; recombinant mAb LZY3412 can efficiently neutralize JEV and ZIKV infections in vitro, with the NT50 values of 19.9 ng/mL and 631 ng/mL, respectively; application of recombinant mAb LZY3412 can significantly improve the percentage survival and reduce the serum viral loads of neonatal mice infected with JEV or ZIKV. Finally, two amino acid residues (Ala399 and Gly400) located in EDIII of JEV-E protein were potentially recognized by LZY3412 whereas two amino acid residues (Met15 and Thr406) out of EDIII of ZIKV-E proteins were recognized by LZY3412.

Discussion

Considering mAb LZY3412 has neutralizing effects on various flaviviruses, this mAb is expected to be developed as therapeutic or preventive drug for these flaviviruses, and can also be used to guide the development of vaccines against these flaviviruses.
Case report: A pregnant woman with recurrent craniopharyngioma: surgical decision-making and doctor-patient bond
Authors: Shen Ao , Min Yue , He Shuanghong , Zhou Dongjie , Jiang Shu , Zhou Peizhi
Published: December 2024

Craniopharyngioma is a rare, benign tumor that originates from the pituitary stalk and extends along the pituitary-hypothalamic axis. It can have serious effects due to its location, affecting hormone regulation, vision, and other neurological functions. It is particularly rare and challenging to manage it during pregnancy due to the potential impacts on both maternal and fetal health, requiring careful, individualized treatment. We reported a 26-year-old pregnant woman at 27 weeks with recurrent craniopharyngioma who presented with worsening consciousness and hydrocephalus. Despite recommendations to terminate the pregnancy for tumor resection, she chose to continue. We performed an endoscopic endonasal tumor resection with pituitary transposition to preserve pituitary function, and at 32 weeks, she delivered a healthy baby via cesarean section. We provided a detailed account of the perioperative complications and their management, addressing endocrine, temperature, and fluid regulation challenges. Throughout the process, the medical team maintained open communication with the patient and her family, respecting their desire to continue the pregnancy and exemplifying patient-centered, compassionate care.
Severe postherpetic neuralgia and facial paralysis in the oral and periauricular regions managed with acupuncture and electroacupuncture: a case report
Authors: Li Junlong , Wang Jing , Li Guiping , Zhang Jieying , Zhang Boru , Wang Shu
Published: December 2024

Postherpetic neuralgia (PHN) is a severe and persistent pain condition following herpes zoster infection. This case report details the analgesic effects of acupuncture combined with electroacupuncture in a 66-year-old male patient presenting with PHN and peripheral facial paralysis, who showed limited response to conventional treatment with corticosteroids and antiviral medications. Following a comprehensive treatment protocol, including pricking-cupping bloodletting, and targeted acupuncture, the patient experienced significant pain relief and improved facial nerve function. This report highlights the potential of traditional Chinese medicine (TCM) in managing PHN, with sustained improvement observed over a one-year follow-up period.
Clinical profile and molecular genetic analysis of alport syndrome in children: a single center experience
Authors: Ahmad Aqsa , Lijun Liang , Yan Zhang , Yan Ma , Shuai Zhao , Wangnan Du
Published: December 2024

Background

Alport syndrome (AS) is a multifaceted condition that primarily affects the basement membranes of the kidneys, ears, and eyes. AS is considered the second most common cause of hereditary renal failure, exhibiting varied clinical manifestations across different lifespans. The aim of this study is to investigate the clinical features and genetic profile of AS and to elucidate the genotype-phenotype correlation of AS.

Method

The clinical and genetic data of ten children with AS treated at the General Hospital of Ningxia Medical University between January 2021 and May 2024 were retrospectively analyzed.

Results

Ten children with AS, six male and four female patients, with a mean age of 9 years (ranging from 3 to 15 years) were reported. Hematuria was observed in all individuals, with six cases exhibiting microscopic hematuria and four cases exhibiting macroscopic hematuria. Furthermore, extra-renal manifestations were noted in five cases, encompassing ocular abnormalities (n = 2) and hearing impairment (n = 3). In total, eight cases displayed mutations in COL4A5 indicating XLAS, while two cases manifested mutations in COL4A4 indicating ADAS. Nine different variants were detected, with 3 mutations identified as novel. Two cases underwent histopathological analysis, revealing a thin basement membrane and mild to moderate mesangial proliferation. Three cases were lost to follow-up, while the remaining seven maintained regular visits to our hospital. As of August 1st, 2024, the median follow-up time was 30 (range 24–36) months, and the renal function of the children under observation remained within normal parameters.

Conclusion

In this study, the most commonly observed mutation was glycine substitution. Additionally, patients exhibiting severe mutations showed an increased vulnerability to complications, including proteinuria, ocular lesions, and hearing impairment. Genetic testing emerged as a critical resource for diagnosing AS. Furthermore, early diagnosis is crucial for implementing an appropriate management plan and assessing the prognosis.
Platelets as crucial players in the dynamic interplay of inflammation, immunity, and cancer: unveiling new strategies for cancer prevention
Authors: Contursi Annalisa , Tacconelli Stefania , Di Berardino Sara , De Michele Alessandra , Patrignani Paola
Published: December 2024

Inflammation plays a critical role in the pathogenesis of various diseases by promoting the acquisition of new functional traits by different cell types. Shared risk factors between cardiovascular disease and cancer, including smoking, obesity, diabetes, high-fat diet, low physical activity, and alcohol consumption, contribute to inflammation linked to platelet activation. Platelets contribute to an inflammatory state by activating various normal cells, such as fibroblasts, immune cells, and vascular cells. This activation is achieved by releasing diverse molecules from platelets, including lipids (eicosanoids), growth and angiogenic factors, and extracellular vesicles (EVs) rich in various RNA species. Antiplatelet agents like low-dose aspirin can prevent cardiovascular disease and cancer by inhibiting platelet functions beyond the antithrombotic action. Throughout the initial phases of tumorigenesis, the activation of platelets induces the overexpression of cyclooxygenase (COX)-2 in stromal cells, leading to increased biosynthesis of prostaglandin (PG)E2. This prostanoid can contribute to tumor development by inhibiting apoptosis, promoting cancer cell proliferation and migration, and immune evasion. Notably, platelets induce the epithelial-mesenchymal transition (EMT) in tumor cells, enhancing their metastatic potential. Two platelet eicosanoids, PGE2 (generated as a minor product of COX-1) and 12S-hydroxyeicosatetraenoic acid (HETE) [derived from the platelet-type 12-lipoxygenase (LOX)], contribute to EMT. In addition to the pharmacological inhibition of eicosanoid biosynthesis, a potential strategy for mitigating platelet-induced metastasis might encompass the inhibition of direct interactions between platelets and cancer cells. For example, there is promise in utilizing revacept to inhibit the interaction between platelet collagen receptors (particularly GPVI) and galectin-3 in cancer cells. Identifying these novel platelet functions suggests the potential application of antiplatelet agents, such as low-dose aspirin, in mitigating cancer risk, particularly in the case of colorectal cancer. It is necessary to investigate the effectiveness of other antiplatelet drugs, such as ADP P2Y12 receptor antagonists, in cancer prevention. Other new antiplatelet drugs, such as revacept and selective 12-LOX inhibitors, currently under clinical development, are of interest due to their low risk of bleeding. Platelets and EVs carry important clinical information because they contain specific proteins and RNAs associated with disease conditions. Their analysis can improve the accuracy of liquid biopsies for early cancer detection, monitoring progression, and assessing drug response.
Biocompatible nanoparticles self-assembled by PEGylated polyphosphoesters for combination of photodynamic therapy and hypoxia-activated chemotherapy against breast cancer
Authors: Wang Fengyu , Zou Xiaojing , Sun Chunyang
Published: December 2024

Introduction

Although photodynamic therapy (PDT) shows considerable potential for cancer treatment due to its precise spatial control and reduced toxicity, effectively eliminating residual cells under hypoxic conditions remains challenging because of the resistance conferred by these cells.

Methods

Herein, we synthesize an amphiphilic PEGylated polyphosphoester and present a nanocarrier (NPCT) specifically designed for the codelivery of hydrophobic photosensitizer (chlorin e6, Ce6) and hypoxia-activated prodrugs (tirapazamine, TPZ). We investigate the antitumor effect of NPCT on both cellular and animal level.

Results

The efficient encapsulation of Ce6 and TPZ by NPCT enables the prolonged blood circulation and improved tumor distribution of both agents. Upon internalization by tumoral cells, 660 nm laser irradiation activates Ce6, leading to the generation of reactive oxygen species (ROS) that effectively kill murine 4T1 breast cancer cells. Meanwhile, the PDT process consumes a large amount of oxygen to generate the hypoxic microenvironment that activates the liberated TPZ from NPCT. The resulting highly cytotoxic radicals specifically target and induce cytotoxicity in remaining hypoxic cancer cells. Compared to other groups, the combination of NPCT and 660 nm laser irradiation resulted in the most substantial tumor growth inhibition.

Discussion

This innovative approach provides new avenues for the development of advanced delivery systems based on polyphosphoesters and combination therapeutic strategies.
The effects of aerobic exercise on 24-hour mean blood glucose levels measured by continuous glucose monitoring in type 2 diabetes: a meta-analysis
Authors: Wang Chou , Tang Shaokai
Published: December 2024

Purpose

To examine the effects of structured aerobic exercise on 24-hour mean blood glucose outcomes assessed by continuous glucose monitors in adults with type 2 diabetes.

Methods

The study established specific inclusion and exclusion criteria and conducted a comprehensive search across five databases, including PubMed, Web of Science, Embase, Cochrane Library, and EBSCOhost from the start year of each database’s coverage to 22 July 2024. The quality of the included studies was evaluated using the Cochrane Handbook 5.1 guidelines. Data analysis was performed using Review Manager 5.4 to determine effect sizes, conduct sensitivity analyses, assess potential biases, and perform subgroup analyses.

Results

A total of 1,034 articles were retrieved, and after 4 rounds of screening, 13 articles were finally selected for meta-analysis. The study included 626 participants (30% female; mean ± SD: age, 59.4 ± 6.4 years; BMI, 29.61 ± 2.24 kg/m2), including 330 in the experimental group and 296 in the control group. The results of the meta-analysis showed that aerobic exercise can improve the 24-hour mean blood glucose in patients with T2DM (d = −0.65, 95% CI: −0.75 to −0.55, p < 0.05). Subgroup analysis showed that moderate-intensity and high-intensity aerobic exercise can improve the 24-hour mean blood glucose in patients with T2DM (d = −0.71, 95% CI: −0.81 to −0.60, p < 0.05), (d = −0.60, 95% CI: −0.98 to −0.22, p < 0.05). Also, 20–40 min and 40–60 min of aerobic exercise per session can improve the 24-hour average blood glucose in patients with T2DM (d = −0.75, 95% CI: −0.91 to −0.59, p < 0.05), (d = −0.59, 95% CI: −0.71 to −0.46, p < 0.05). Aerobic exercise can improve the 24-hour mean blood glucose in patients with T2DM who have a body mass index (BMI) between 29 and 30 kg/m2, as well as those with a BMI greater than 30 kg/m2 (d = −0.65, 95% CI: −0.94 to −0.36, p < 0.05), (d = −0.76, 95% CI: −0.87 to −0.64, p < 0.05).

Conclusion

Aerobic exercise can improve the 24-hour mean blood glucose in patients with T2DM. Additionally, 20–60 min of aerobic exercise with moderate intensity, and high intensity can improve the 24-hour mean blood glucose in patients with T2DM who have a BMI greater than 29 kg/m2.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/, identifer PROSPERO CRD42024590812
Microalgae-based biofertilizers improve fertility and microbial community structures in the soil of potted tomato
Authors: Song Xiaotong , Liu Jiayi , Feng Yanzhang , Zhou Chengxu , Li Xiaohui , Yan Xiaojun , Ruan Roger , Cheng Pengfei
Published: December 2024

Continuous cropping decreases soil nutrients and destroys microbial community structure, so the development of eco-friendly and effective biofertilizers is necessary under present conditions. In this study, the preserving microalgal strain Tribonema sp. (H) was firstly selected to be combined with agroforestry waste (shell powder, straw fermentation liquid) and the agroforestry microorganism Bacillus sp. to form microalgae-based fertilizers for the continuous cropping soil of potted tomato. Compared to the control (CK), microalgae-based fertilizers (concentration: 4.45 × 106 cells/ml, dosage: 20 ml/day) improved soil nutrients and salinization indicators. Specifically, the combination of Tribonema sp. and shell powder (HB) reduced electrical conductivity (EC) by 33.7% and significantly increased the Ca2+ content by 59.4%; Tribonema sp. and Bacillus sp. (HY) improved the effects of available phosphorous (AP), DOC, DON, NH4+-N, NO3−-N, and Mg2+ in the soil by 27.4%, 231.3%, 403.4%, 125.2%, 215.6%, and 73.4%, respectively. Microalgae-based fertilizers alter the abundance of soil bacteria and fungi, causing beneficial bacteria such as Thermonaerobaculia, Subgroup_10, Sordariomycetes, and Microascaceae to increase, while pathogenic bacteria like Pseudomonas, Togniniaceae, and Phaeoacremonium decreased. Combining microalgae with agroforestry wastes as a biofertilizer is promising to improve the microbial community structure of the soil with continuous cropping, which will aid in the increase of tomato production and promote green agricultural development.
tRNA gene content, structure, and organization in the flowering plant lineage
Authors: Monloy Kim Carlo , Planta Jose
Published: December 2024

Transfer RNAs (tRNAs) are noncoding RNAs involved in protein biosynthesis and have noncanonical roles in cellular metabolism, such as RNA silencing and the generation of transposable elements. Extensive tRNA gene duplications, modifications to mature tRNAs, and complex secondary and tertiary structures impede tRNA sequencing. As such, a comparative genomic analysis of complete tRNA sets is an alternative to understanding the evolutionary processes that gave rise to the extant tRNA sets. Although the tRNA gene (tDNA) structure and distribution in prokaryotes and eukaryotes, specifically in vertebrates, yeasts, and flies, are well understood, there is little information regarding plants. A detailed and comprehensive analysis and annotation of tDNAs from the genomes of 44 eudicots, 20 monocots, and five other non-eudicot and non-monocot species belonging to the Ceratophyllaceae and the ANA (Amborellales, Nymphaeales, and Austrobaileyales) clade will provide a global picture of plant tDNA structure and organization. Plant genomes exhibit varying numbers of nuclear tDNAs, with only the monocots showing a strong correlation between nuclear tDNA numbers and genome sizes. In contrast, organellar tDNA numbers varied little among the different lineages. A high degree of tDNA duplication in eudicots was detected, whereby most eudicot nuclear genomes (91%) and only a modest percentage of monocot (65%) and ANA nuclear genomes (25%) contained at least one tDNA cluster. Clusters of tRNATyr–tRNASer and tRNAIle genes were found in eudicot and monocot genomes, respectively, while both eudicot and monocot genomes showed clusters of tRNAPro genes. All plant genomes had intron-containing tRNAeMet and tRNATyr genes with modest sequence conservation and a strictly conserved tRNAAla-AGC species. Regulatory elements found upstream (TATA-box and CAA motifs) and downstream (poly(T) signals) of the tDNAs were present in only a fraction of the detected tDNAs. A and B boxes within the tDNA coding region show varying consensus sequences depending on the tRNA isotype and lineage. The chloroplast genomes, but not the mitogenomes, possess relatively conserved tRNA gene organization. These findings reveal differences and patterns acquired by plant genomes throughout evolution and can serve as a foundation for further studies on plant tRNA gene function and regulation.
Fine mapping and identification of the bright green leaf gene BoBGL in Chinese kale (Brassica oleracea var. alboglabra)
Authors: Zhang Qi , Wang Chenchen , Song Jialu , Gao Liwei , Shen Wenjie , Liu Yi , Chen Daozong , Tan Chen
Published: December 2024

Introduction

Chinese kale (Brassica oleracea var. alboglabra), is an annual herb belonging to the Brassica genus of Cruciferae, and is one of the famous specialty vegetables of southern China. Some varieties show bright green leaf (BGL) traits and have better commerciality. However, the genes responsible for this trait remain unidentified.

Methods

In this study, gene mapping was measured by BSR-Seq and molecular marker analysis. Gene expression analysis was performed qRT-PCR. Cloning and sequence analysis of candidate genes were also performed.

Results

Genetic analysis revealed that the bright green leaf trait is a dominant trait governed by a single pair of genes. BSR-seq and molecular marker validation mapped the candidate interval to about 1.5 Mb on chromosome C8. After expanding the BC1 population and analyzing recombinant individuals, the interval was refined to approximately 102 kb on chromosome C8 (50,787,908- 50,890,279 bp). There are 24 genes in this region, and after annotation and expression analysis, BolC8t52930H (BoCER1.C8), associated with wax synthesis, emerged as a key candidate for BoBGL. We cloned this gene from both parents, revealing significant differences in their promoter regions. A co-segregation primer was subsequently developed and validated in a segregated population, with results consistent with expectations.

Discussion

The gene BoCER1.C8 is a potential candidate for controlling the bright green leaf trait in Chinese kale, and its function needs to be validated next. Mapping and cloning this gene is crucial to understanding wax synthesis regulation and developing new bright green leafy varieties of Chinese kale.
Motivational orientation and perception of active learning instruction by pre-service language teachers
Authors: Halimi Florentina , Tryzna Marta , Brunstein Angela
Published: December 2024

This study investigates the impact of active learning instruction on the motivational orientation of pre-service language teachers. The data were collected by using the AGQ-R and the StRIP questionnaire, and analyzed through repeated measures of MANOVAs and correlation coefficient. Pre-service language teachers reported a higher approach goal orientation emphasizing the desire to succeed rather than avoidance goal orientation, i.e., the fear of failure. In terms of classroom practices, the participants report having experienced all types of instruction (passive, active, interactive and constructive) in the language education program. Although the pre-service teachers’ perception of instruction as passive is preponderant in this study, it does not necessarily point to a higher use of traditional passive lecture and note taking practices. Regardless of the perceived instruction type, the participants’ motivation and engagement remain high, as they report high cognitive and emotional engagement, as well as very high participation and low distraction levels. Regarding correlations, motivation, engagement and active instruction are all highly correlated with each other, as highly motivated and engaged individuals tend to benefit more from active instruction than less motivated students, who chiefly rely on passive instruction for academic success. The results of the study may indicate an emergent need for a careful balance between various teaching strategies and approaches in language education programs in particular, and possibly at tertiary level pedagogy in general.
The environmental impact of religious beliefs in the East and West: evidence from China
Authors: Yang Junyan , Lu Chuntian
Published: December 2024

This study explores the influence of religious beliefs on environmental attitudes and behaviors in China. Using data from the 2021 Chinese General Social Survey (CGSS), two structural equation models were constructed to examine the mediating roles of natural empathy and anthropocentrism in the relationship between environmental awareness and willingness to make sacrifices for environmental protection. The results indicated that while environmental awareness positively influenced willingness to sacrifice, natural empathy did not significantly mediate this relationship. Conversely, anthropocentrism negatively mediated the relationship, suggesting that individuals with anthropocentric tendencies were less willing to make personal sacrifices for environmental protection. Furthermore, a multi-group analysis revealed that individuals with traditional Eastern religious beliefs (Buddhism, Taoism, and folklore) exhibited higher environmental awareness and willingness to sacrifice compared to those with no religion or traditional Western (Christianity) religious beliefs. These findings highlight the influence of religious traditions, particularly the emphasis on nature reverence in Eastern religions, on shaping pro-environmental attitudes and behaviors. The study contributes to understanding the complex interplay between religious beliefs, environmental values, and sustainable behaviors in the Chinese context.
A typology of organizational readiness for change based on a latent profile analysis
Authors: Köhler Alina , Ritter Marie , Kauffeld Simone
Published: December 2024

Companies have to undergo many change processes to succeed in the transforming economy. However, many change processes fail because employees are insufficiently accompanied through the process in a targeted manner. This study of N = 427 employees from a steel industry company undergoing a transformation process examines whether the organizational readiness for change (ORC) of highly affected employees can be classified into profiles, how these profiles can be predicted by various antecedents, and whether outcome variables such as job satisfaction can be explained by profile membership. Based on five facets of ORC (i.e., individual valence and positive affect), a total of six ORC profiles were identified: Proactives, Acceptors, Opens, Neutrals, Reluctants and Deniers. Employees’ optimism and the degree of perceived interpersonal and informational fairness can predict profile membership. It was shown that profiles significantly differ in relevant outcome variables satisfaction and intention to leave. These results contribute to the basic understanding of ORC and provide an initial approach for improving ORC profiles which could increase the success rate of change processes in companies.
Can motor competence be influenced by the type of training interventions preschool children are exposed to? A randomized experimental study comparing sports games and psychomotricity activities
Authors: Guo Xiaodan , Li Chuangtao , Zhang Zhaoxiang , Silva Ana Filipa , Clemente Filipe Manuel
Published: December 2024

Introduction

This study aimed to compare the effects of structured sports games (SG) and psychomotricity activities (PCM) on the locomotor, stability, and manipulative motor competencies of preschool children.

Methods

A randomized controlled trial was conducted over an 8-week period, involving two experimental groups (SG, n = 30 and PCM, n = 30) and one control group (CG, n = 28), with participants attending two intervention sessions per week. A total of 88 5-year-old children participated in the experiment (boys n = 48; girls n = 40). They were evaluated three times (at baseline, after 4 weeks, and after 8 weeks) using the Motor Competence Assessment test to measure their locomotor, stability, and manipulative motor competencies.

Results

The scores were standardized to percentiles based on sex and age. However, significant differences were observed between groups post-intervention in the locomotor domain (p = 0.003; ηp2 = 0.128), with the SG showing significantly higher values compared to the CG (mean difference: 17.0%; p = 0.021; d = 0.783), and PCM (mean difference: 19.8%; p = 0.005; d = 0.947). Additionally, significant differences were found between groups post-intervention in the manipulative domain (p = 0.001; ηp2 = 0.142), with the SG showing significantly higher values compared to the CG (mean difference: 19.3%; p = 0.009; d = 0.845) and PCM (mean difference: 21.4%; p = 0.003; d = 0.998).

Discussion

Our study highlights the significant benefits of increased practice in developing motor competence, particularly in children’s locomotor and manipulative skills. Additionally, at this age, fun, competition, and social interaction seem to play a crucial role, as the SG group demonstrated greater improvements compared to the PCM group.
The roles of psychological needs satisfaction and impulsivity to parent-child conflict and non-suicidal self-injury
Authors: Wei Chang , Liu Bao , Wang Yu , Wang Yaping , Xu Qian
Published: December 2024

Introduction

Non-suicidal self-injury is a serious health problem among adolescents. However, the association between parent–child conflict and adolescent non-suicidal self-injury and its underlying mechanisms have not been studied sufficiently. Based on the interpersonal model of non-suicidal self-injury, we tested the relationship between parent–child conflict and adolescent non-suicidal self-injury. Furthermore, based on self-determination theory and the diathesis-stress model, we examined whether psychological needs satisfaction mediated the link between parent–child conflict and adolescent non-suicidal self-injury, and if impulsivity moderated this mediating effect.

Methods

Using cross-sectional design, we recruited 656 adolescents (Mage = 13.43; 47% female) from two junior high schools in the Hubei province of China.

Results

The results indicated a positive association between parent–child conflict and adolescent non-suicidal self-injury. Psychological needs satisfaction mediated the relationship between parent–child conflict and adolescent non-suicidal self-injury. High impulsivity strengthened the indirect effect of parent–child conflict on adolescent non-suicidal self-injury. Specifically, high impulsivity strengthened the direct relationship between psychological needs satisfaction and adolescent non-suicidal self-injury and further strengthened the indirect association between parent–child conflict and adolescent non-suicidal self-injury.

Conclusions

Our findings highlight the potential mechanisms underlining the relationship between parent–child conflict and adolescent non-suicidal self-injury. Our findings can inspire educational practitioners to focus on the interaction of family risk factors and individual risk factors when developing intervention programs for adolescent non-suicidal self-injury.