bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of mulch films with different thicknesses on the microbial community of tobacco rhizosphere soil in Yunnan laterite
Authors: Wang Shuaibing , Li Qiuping , Ye Changbing , Ma Wenqing , Sun Yandong , Zhao Bin , Zeng Weiqing , Yue Zhiqiang , Li Lan , Li Dandan
Published: September 2024

The mulch film (MF) management model of the agricultural field affects the physical and chemical properties of soil (PCPS) and the structure of the microorganism community; however, studies on the relationship between the rhizosphere microorganism community structure and the thickness of MF are still limited. To understand the interactions among the MF thickness, PCPS, and rhizosphere microorganism, a study was conducted by using an integrated metagenomic strategy, where tobacco rhizosphere soil was treated with four commonly representative and used thicknesses of MFs (0.004, 0.006, 0.008, and 0.010 mm) in Yunnan laterite. The results showed that agronomic traits such as the tobacco plant height (TPH), leaf number (LN), fresh leaf weight (FLW), and dry leaf weight (DLW) were significantly (p < 0.01) improved in the field mulched with the thickest film (0.010 mm) compared with the exposed field (CK), and there was a 6.81 and 5.54% increase in the FLW and TPH, separately. The correlation analyses revealed a significant positive correlation of the MF thickness with the soil water content (SWC), soil organic matter (SOM), total nitrogen (TN), available nitrogen (AN), total phosphorus (TP), and available phosphorus (AP; all p < 0.01), while the MF thickness was negatively correlated with the soil temperature (ST; p < 0.01). In addition, the community structure of the rhizosphere soil bacteria was significantly changed overall by the MF thickness, which also interfered with the function of the rhizosphere soil bacteria. The correlation analyses also showed that the abundance of Bradyrhizobium and Nitrospira was positively correlated with the MF thickness, while the abundance of Sphinsinomonas and Massilia was negatively correlated with it. This indicated that with the increase of the MF thickness, the ability of the rhizosphere soil to utilize N and remove harmful molecules was strengthened, while the capacity of the rhizosphere soil to degrade pollutants was greatly reduced. These findings provide additional insights into the potential risks of the application of different thicknesses of MFs, particularly concerning the PCPS and soil microbial communities.
A “love match” score to compare root exudate attraction and feeding of the plant growth-promoting rhizobacteria Bacillus subtilis, Pseudomonas fluorescens, and Azospirillum brasilense
Authors: Fourneau Eulalie , Pannier Mélissa , Riah Wassila , Personeni Emmanuelle , Morvan-Bertrand Annette , Bodilis Josselin , Pawlak Barbara
Published: September 2024

Introduction

The rhizosphere is the zone of soil surrounding plant roots that is directly influenced by root exudates released by the plant, which select soil microorganisms. The resulting rhizosphere microbiota plays a key role in plant health and development by enhancing its nutrition or immune response and protecting it from biotic or abiotic stresses. In particular, plant growth-promoting rhizobacteria (PGPR) are beneficial members of this microbiota that represent a great hope for agroecology, since they could be used as bioinoculants for sustainable crop production. Therefore, it is necessary to decipher the molecular dialog between roots and PGPR in order to promote the establishment of bioinoculants in the rhizosphere, which is required for their beneficial functions.

Methods

Here, the ability of root exudates from rapeseed (Brassica napus), pea (Pisum sativum), and ryegrass (Lolium perenne) to attract and feed three PGPR (Bacillus subtilis, Pseudomonas fluorescens, and Azospirillum brasilense) was measured and compared, as these responses are directly involved in the establishment of the rhizosphere microbiota.

Results

Our results showed that root exudates differentially attracted and fed the three PGPR. For all beneficial bacteria, rapeseed exudates were the most attractive and induced the fastest growth, while pea exudates allowed the highest biomass production. The performance of ryegrass exudates was generally lower, and variable responses were observed between bacteria. In addition, P. fluorescens and A. brasilense appeared to respond more efficiently to root exudates than B. subtilis. Finally, we proposed to evaluate the compatibility of each plant–PGPR couple by assigning them a “love match” score, which reflects the ability of root exudates to enhance bacterial rhizocompetence.

Discussion

Taken together, our results provide new insights into the specific selection of PGPR by the plant through their root exudates and may help to select the most effective exudates to promote bioinoculant establishment in the rhizosphere.
Novel aspect of oxytocin neurons mediating parental behavior and aversive burying behavior under the control of melanin-concentrating hormone neurons
Authors: Xiong Tingbi , Tsuchida Lena , Inutsuka Ayumu , Onaka Tatsushi , Yamada Kazuo , Orikasa Chitose
Published: September 2024

Parental behavior comprises a set of crucial actions essential for offspring survival. In this study, a double transgenic mouse model engineered to specifically express channelrhodopsin-2 (ChR2) in paraventricular hypothalamic nucleus (PVN)–oxytocin neurons and ablate lateral hypothalamic area (LHA)–melanin-concentrating hormone (MCH) neurons was used to determine the relationship between PVN–oxytocin neurons and LHA–MCH neurons associated with parental behavior. Optogenetic stimulation of ChR2-expressing PVN–oxytocin neurons induces typical parental behavior with intact LHA–MCH neurons. However, after the partial ablation of LHA–MCH neurons, even optogenetic stimulation of PVN–oxytocin neurons failed to induce parental behavior in virgin male mice, resulting in neglect rather than parental behavior. Furthermore, approximately half of the subjects exhibited burying behavior toward pups, suggesting that pups became aversive stimuli, and male mice actively performed burying behavior to avoid these aversive stimuli. This study emphasizes the novel aspect of oxytocin neurons that could result in neglect in the absence of LHA–MCH neurons regulation.
Analyzing top-down visual attention in the context of gamma oscillations: a layer- dependent network-of- networks approach
Authors: Zheng Tianyi , Sugino Masato , Jimbo Yasuhiko , Ermentrout G. Bard , Kotani Kiyoshi
Published: September 2024

Top-down visual attention is a fundamental cognitive process that allows individuals to selectively attend to salient visual stimuli in the environment. Recent empirical findings have revealed that gamma oscillations participate in the modulation of visual attention. However, computational studies face challenges when analyzing the attentional process in the context of gamma oscillation due to the unstable nature of gamma oscillations and the complexity induced by the layered fashion in the visual cortex. In this study, we propose a layer-dependent network-of-networks approach to analyze such attention with gamma oscillations. The model is validated by reproducing empirical findings on orientation preference and the enhancement of neuronal response due to top-down attention. We perform parameter plane analysis to classify neuronal responses into several patterns and find that the neuronal response to sensory and attention signals was modulated by the heterogeneity of the neuronal population. Furthermore, we revealed a counter-intuitive scenario that the excitatory populations in layer 2/3 and layer 5 exhibit opposite responses to the attentional input. By modification of the original model, we confirmed layer 6 plays an indispensable role in such cases. Our findings uncover the layer-dependent dynamics in the cortical processing of visual attention and open up new possibilities for further research on layer-dependent properties in the cerebral cortex.
Increased incidence of weight-loss-associated humane endpoints in rats administered buprenorphine slow-release LAB formulation following traumatic brain injury: a retrospective study
Authors: Lilova Radina L. , Hernandez Martina , Kelliher Corrina , Lafrenaye Audrey
Published: September 2024

Traumatic brain injury (TBI) remains a significant global public health epidemic with adverse health and cost implications. Due to its complex, heterogeneous nature and wide-ranging impacts, definitive TBI treatments remain elusive. As such, continued laboratory research using animal models is warranted. In accordance with guidelines set forth for the humane treatment of research animals, TBI animal models are often administered analgesics for pain management. The choice of drug, timing, dose, and formulation of analgesic can vary depending on the study’s unique needs and can potentially and unintentionally influence experimental results. In TBI studies utilizing rats as animal models, buprenorphine is a common analgesic administered. In addition to pain management in such studies, investigators must also monitor the research animals post-operatively and make the decision for humane euthanasia before intended experimental survival timepoint if the animals are assessed to be excessively suffering. This study investigated the differences in adult, male Sprague Dawley rats used for various TBI studies that reached weight-loss-induced humane endpoints following a single administration of buprenorphine slow-release LAB (bup-SR-LAB) or buprenorphine slow-release HCl (bup-SR-HCl). Our findings indicate that TBI-induced rats receiving bup-SR-LAB in conjunction with a secondary surgical insult such as artificial intracranial pressure elevation and/or osmotic pump implantation reach a weight-loss-induced humane euthanasia endpoint more often compared to sham-injured rats. When stratifying into the same groups, we did not find this pattern to hold true for rats administered bup-SR-HCl. Overall, this study contributes to the limited body of literature addressing different analgesic formulations’ effects on laboratory animals.
Energy-aware bio-inspired spiking reinforcement learning system architecture for real-time autonomous edge applications
Authors: Okonkwo Joshua Ifeanyi , Abdelfattah Mohamed S. , Mirtaheri Peyman , Muhtaroglu Ali
Published: September 2024

Mobile, low-cost, and energy-aware operation of Artificial Intelligence (AI) computations in smart circuits and autonomous robots will play an important role in the next industrial leap in intelligent automation and assistive devices. Neuromorphic hardware with spiking neural network (SNN) architecture utilizes insights from biological phenomena to offer encouraging solutions. Previous studies have proposed reinforcement learning (RL) models for SNN responses in the rat hippocampus to an environment where rewards depend on the context. The scale of these models matches the scope and capacity of small embedded systems in the framework of Internet-of-Bodies (IoB), autonomous sensor nodes, and other edge applications. Addressing energy-efficient artificial learning problems in such systems enables smart micro-systems with edge intelligence. A novel bio-inspired RL system architecture is presented in this work, leading to significant energy consumption benefits without foregoing real-time autonomous processing and accuracy requirements of the context-dependent task. The hardware architecture successfully models features analogous to synaptic tagging, changes in the exploration schemes, synapse saturation, and spatially localized task-based activation observed in the brain. The design has been synthesized, simulated, and tested on Intel MAX10 Field-Programmable Gate Array (FPGA). The problem-based bio-inspired approach to SNN edge architectural design results in 25X reduction in average power compared to the state-of-the-art for a test with real-time context learning and 30 trials. Furthermore, 940x lower energy consumption is achieved due to improvement in the execution time.
Pilot turning behavior cognitive load analysis in simulated flight
Authors: Zhou Wen-gang , Yu Pan-pan , Wu Liang-hai , Cao Yu-fei , Zhou Yue , Yuan Jia-jun
Published: September 2024

Background

To identify the cognitive load of different turning tasks in simulated flight, a flight experiment was designed based on real “preliminary screening” training modules for pilots.

Methods

Heart Rate Variability (HRV) and flight data were collected during the experiments using a flight simulator and a heart rate sensor bracelet. The turning behaviors in flight were classified into climbing turns, descending turns, and level flight turns. A recognition model for the cognitive load associated with these turning behaviors was developed using machine learning and deep learning algorithms.

Results

pnni_20, range_nni, rmssd, sdsd, nni_20, sd1, triangular_index indicators are negatively correlated with different turning load. The LSTM-Attention model excelled in recognizing turning tasks with varying cognitive load, achieving an F1 score of 0.9491.

Conclusion

Specific HRV characteristics can be used to analyze cognitive load in different turn-ing tasks, and the LSTM-Attention model can provide references for future studies on the selection characteristics of pilot cognitive load, and offer guidance for pilot training, thus having significant implications for pilot training and flight safety.
Expression of p16 and Ki67 in laryngeal squamous cell carcinoma and their clinical significance
Authors: Liu Xue-Ying , Hanjing Shangguan , Zhang Bing-huang , Luo Xian-Yang
Published: September 2024

Objective

The objective of this study is to assess the prognostic value of Ki67 and p16 proteins in laryngeal cancer.

Materials and methods

This retrospective cohort analysis comprised 260 patients diagnosed with laryngeal cancer. Immunohistochemistry (IHC) was employed to assess the expression levels of p16 and Ki67, and their correlation with the survival time of laryngeal cancer patients was analyzed.

Results

The Ki67 index level exhibited a significant association with the prognosis of laryngeal cancer. Patients with higher Ki67 index levels demonstrated shorter survival times, more severe pathological classification, and higher tumor stages (P < 0.05). Conversely, no significant differences in prognostic characteristics of laryngeal cancer were observed in the p16 (-/+) population (P > 0.05). The median survival times for patients with Ki67 index levels of 0-35%, 36-70%, and 70-100% were 3.54 years, 2.10 years, and 1.92 years, respectively. After adjusting for age, smoking, alcohol consumption, pathological classification, surgical intervention, recurrence, and metastasis, the risk of death for patients with Ki67 index levels of 70-100% was 2.0504 times higher than that of patients with Ki67 index levels of 0-35% (95% CI: 1.2997-3.2345, P = 0.0020).

Conclusion

The Ki67 index level is strongly associated with survival time and the risk of death in laryngeal cancer, making it a valuable prognostic indicator. However, the prognostic value of p16 levels in laryngeal cancer is limited. These findings provide important insights for prognosis evaluation and treatment decision-making in patients with laryngeal cancer.
Molecular profiling of pre- and post- 5-azacytidine myelodysplastic syndrome samples identifies predictors of response
Authors: González Mónica del Rey , Chakraborty Sohini , Hernández-Sánchez Jesús María , Diez Campelo María , Park Christopher Y. , Hernández Rivas Jesús María
Published: September 2024

Treatment with the hypomethylating agent 5-azacytidine (AZA) increases survival in high-risk (HR) myelodysplastic syndrome (MDS) patients, but predicting patient response and overall survival remains challenging. To address these issues, we analyzed mutational and transcriptional profiles in CD34+ hematopoietic stem/progenitor cells (HSPCs) before and following AZA therapy in MDS patients. AZA treatment led to a greater reduction in the mutational burden in both blast and hematological responders than non-responders. Blast and hematological responders showed transcriptional evidence of pre-treatment enrichment for pathways such as oxidative phosphorylation, MYC targets, and mTORC1 signaling. While blast non-response was associated with TNFa signaling and leukemia stem cell signature, hematological non-response was associated with cell-cycle related pathways. AZA induced similar transcriptional responses in MDS patients regardless of response type. Comparison of blast responders and non-responders to normal controls, allowed us to generate a transcriptional classifier that could predict AZA response and survival. This classifier outperformed a previously developed gene signature in a second MDS patient cohort, but signatures of hematological responses were unable to predict survival. Overall, these studies characterize the molecular consequences of AZA treatment in MDS HSPCs and identify a potential tool for predicting AZA therapy responses and overall survival prior to initiation of therapy.
Systemic immune-inflammation index is associated with high risk for prostate cancer among the U.S. elderly: Evidence from NHANES 2001-2010
Authors: He Ran , Ye Youjun , Zhu Qilei , Xie Changsheng
Published: September 2024

Purpose

The Systemic Immuno-Inflammation Index (SII) is a crucial clinical measure of inflammation, and there is currently no solid evidence linking SII to an increased risk of prostate cancer (PCa). Through the analysis of serum total prostate-specific antigen (tPSA), free prostate-specific antigen (fPSA), and the tPSA/fPSA (fPSA%) ratio, this study sought to investigate the relationship between SII and PCa risk among the U.S. elderly.

Methods

Elderly male participants were gathered from the NHANES database between 2001 and 2010.SII was calculated by platelet count * neutrophil count/lymphocyte count. High risk individuals for prostate cancer were defined as those with tPSA > 4 ng/ml and fPSA% < 16%. Multivariate logistic regression models, restricted cubic spline curves, and subgroup analyses were used to assess the relationship between SII and PCa risk.

Results

This research comprised 2664 people in total, 137 (5.14%) of whom were deemed to be at high risk of developing PCa. Multivariate logistic regression analysis, after controlling for variables, revealed a significant positive correlation between high PCa risk and an increase in SII (p = 0.009). The RCS suggested a turning point at 9.01. Restricted cubic spline curves revealed a non-linear U-shaped association between SII and high PCa risk (p for nonlinear = 0.028). Education level, marital status, PIR, alcohol status, smoking status, rheumatoid arthritis status, and heart problem were not significantly correlated with this positive connection, according to subgroup analyses and interaction tests.

Conclusion

The results of this study suggest that inflammation represented by SII is associated with high PCa risk.
Lifestyle and risk factors associated with elevated prostate-specific antigen levels in rural men: implications for health counseling
Authors: Hsieh Kun-Lu , Chang Chia-Hao , Lin Yu-Chih , Huang Tung-Jung , Chen Mei-Yen
Published: September 2024

Background

The use of prostate-specific antigen (PSA) for early detection of prostate cancer (PCa) is common but controversial. In rural areas, PSA is widely used for screening because it is convenient and early-stage PCa often shows no symptoms. Studies suggest that PSA levels are linked to factors like unhealthy lifestyles, obesity, lack of exercise, inflammation, and aging. Proper use and interpretation of PSA are crucial for healthcare providers, especially in primary care settings. This study aims to explore the prevalence and factors linked to higher PSA levels in rural men.

Methods

We conducted a community-based cross-sectional study from March to December 2023 in the western coastal region of Taiwan. Men aged 40-75 years participated, completing a lifestyle questionnaire and providing blood samples for cardiometabolic biomarkers and PSA levels. PSA levels of ≥ 4.0 ng/mL were considered elevated. We used propensity score matching (PSM) and genetic matching (GM) for analysis, followed by regression analysis.

Results

In total, 3347 male adults with a mean age of 56.3 years (SD=11.8, range 40-75), and without cancer-related diseases, were enrolled. Findings indicated that 3.9% (n=130) of men aged 40-75 years had a PSA ≥ 4 ng/mL. and many of them did not adopt health-related behaviors, including inadequate servings of vegetables, water intake, and engaging in regular exercise. Furthermore, more than half of the participants had high blood pressure, and over one-quarter exhibited a higher waist-hip ratio and cardiometabolic diseases. After employing propensity score matching (PSM) and genetic matching (GM) with respect to age and education, the multivariate logistic regression model indicated that less water intake (p<0.01), higher waist-hip ratio (> 0.95) (p<0.05), and being diagnosed with cardiometabolic diseases (p<0.05) were significantly associated with a higher serum PSA level.

Conclusion

This study revealed that inadequate water intake and obesity related diseases are significant risk factors associated with elevated PSA levels among male adults living in rural areas. It is important for frontline healthcare providers to carefully interpret the meaning of a high PSA level. Additionally, launching a longitudinal study is necessary to further investigate its relation to PCa.
Application of different CO2 pneumoperitoneum pressure in laparoscopic pyeloplasty for infants with ureteropelvic junction obstruction
Authors: Peng Yan , Zhu Min , Chen Chunmei
Published: September 2024

Background

Laparoscopic pyeloplasty is a minimally invasive approach for the therapy of infant ureteropelvic junction obstruction (UPJO), reliant on CO2 pneumoperitoneum insufflation. While the impact of CO2 insufflation on adult and older pediatric populations has been studied, its effects on infants remain less explored.

Methods

This prospective randomized controlled trial included infants with UPJO undergoing laparoscopic pyeloplasty. Patients were allocated to low pneumoperitoneum pressure (LPP, 5 mmHg) or high pneumoperitoneum pressure (HPP, 8 mmHg) groups. Surgical parameters, postoperative complications, acid-base balance, stress markers, inflammatory cytokines, and oxidative stress markers were evaluated and compared.

Results

A total of 116 infants were analyzed. Preoperative characteristics were comparable between LPP and HPP groups. No significant differences in blood loss, operation time, or hospitalization time were observed. Postoperative complications were similar between groups. Acid-base balance analysis revealed a decrease in pH after pneumoperitoneum in both groups, with greater reductions in actual base excess and standard base excess in the HPP group. Stress markers, cytokines, and oxidative stress markers increased postoperatively in both groups, with higher levels in the HPP group.

Conclusion

HPP leads to more pronounced physiological responses, including acid-base alterations, stress reactions, and inflammatory cytokine elevations.
α-Arbutin ameliorates UVA-induced photoaging through regulation of the SIRT3/PGC-1α pathway
Authors: Lu Fang , Zhou Qi , Liang Mengdi , Liang Huicong , Yu Yiwei , Li Yang , Zhang Yan , Lu Ling , Zheng Yan , Hao Jiejie , Shu Peng , Liu Jiankang
Published: September 2024

Owing to its tyrosinase inhibitory activity, α-arbutin has been added to several skin care products as a skin-lightening agent. However, the protective effect of α-arbutin against ultraviolet A (UVA)-induced photoaging has not been well investigated. The present study was designed to investigate the photoprotective effect and mechanism of α-arbutin against UVA-induced photoaging. In vitro experiments, HaCaT cells were treated with UVA at a dose of 3 J/cm2 to evaluate the anti-photoaging effect of α-arbutin. α-Arbutin was found to exhibit a strong antioxidant effect by increasing glutathione (GSH) level and inhibiting reactive oxygen species (ROS) production. Meanwhile, α-arbutin markedly improved the expression of sirtuin 3 (SIRT3) and peroxisome proliferator-activated receptor γ coactivator 1 α (PGC-1α) proteins, initiating downstream signaling to increase mitochondrial membrane potential and mediate mitochondrial biogenesis, and improve mitochondrial structure significantly. In vivo analysis, the mice with shaved back hair were irradiated with a cumulative UVA dose of 10 J/cm2 and a cumulative ultraviolet B (UVB) dose of 0.63 J/cm2. The animal experiments demonstrated that α-arbutin increased the expression of SIRT3 and PGC-1α proteins in the back skin of mice, thereby reducing UV-induced skin damage. In conclusion, α-arbutin protects HaCaT cells and mice from UVA damage by regulating SIRT3/PGC-1α signaling pathway.
Lactation-promoting ingredients of Hemerocallis citrina Borani and the corresponding mechanisms
Authors: Fang Jinpeng , Xu Mengtao , Qiu ZhengYue , Ye Tian , Jiang HongLing , Qin FengYi , Hu Yuan , Jiang Faying , Zhong JuHua , Zhu Yishuo , Zhao Lewei , Liu Xiubin , Zeng Jianguo , Xu Yuqin , Qing Zhixing
Published: September 2024

Hemerocallis citrina Borani is a traditional folk food used to promote the lactation of postpartum mothers in China; however, the active ingredients and corresponding mechanisms are still unknown. In this study, the lactogenic effect of alcoholic and aqueous extracts of H. citrina was primarily evaluated, and the aqueous extract (1,000 and 2,000 mg/kg) displayed significant lactation-promoting effects. Three eluates of the aqueous extract (0%, 30%, and 50%HCW) were further evaluated for their lactogenic effect, and 30% and 50% HCW showed significant lactation-promoting activity. Nineteen ingredients, including those with a high content of rutin and isoquercetin, were then identified from 30% and 50%HCW using the ultra-performance liquid chromatography-quadrupole-time-of-flight-mass spectrometry (UPLC-Q-TOF-MS) method. Finally, the lactogenic effect of rutin and isoquercetin was evaluated, and both compounds displayed significant lactation-promoting activity. The mechanisms relative to the lactation-promoting active ingredients for H. citrina extracts and compounds are to stimulate the release of prolactin (PRL) and progesterone (P), as well as to induce the expression of prolactin receptor (PRLR) and improve the morphology of mammary tissue. This study first clarified the lactation-promoting active ingredients of H. citrina and the corresponding mechanisms, which provide a new insight into the new lactation-promoting drug and promote the high-value utilization of H. citrina resources.
3D cell culture models in research: applications to lung cancer pharmacology
Authors: Vella Nathan , Fenech Anthony G. , Petroni Magri Vanessa
Published: September 2024

Lung cancer remains one of the leading causes of cancer-related mortality worldwide, necessitating innovative research methodologies to improve treatment outcomes and develop novel strategies. The advent of three-dimensional (3D) cell cultures has marked a significant advancement in lung cancer research, offering a more physiologically relevant model compared to traditional two-dimensional (2D) cultures. This review elucidates the various types of 3D cell culture models currently used in lung cancer pharmacology, including spheroids, organoids and engineered tissue models, having pivotal roles in enhancing our understanding of lung cancer biology, facilitating drug development, and advancing precision medicine. 3D cell culture systems mimic the complex spatial architecture and microenvironment of lung tumours, providing critical insights into the cellular and molecular mechanisms of tumour progression, metastasis and drug responses. Spheroids, derived from commercialized cell lines, effectively model the tumour microenvironment (TME), including the formation of hypoxic and nutrient gradients, crucial for evaluating the penetration and efficacy of anti-cancer therapeutics. Organoids and tumouroids, derived from primary tissues, recapitulate the heterogeneity of lung cancers and are instrumental in personalized medicine approaches, supporting the simulation of in vivo pharmacological responses in a patient-specific context. Moreover, these models have been co-cultured with various cell types and biomimicry extracellular matrix (ECM) components to further recapitulate the heterotypic cell-cell and cell-ECM interactions present within the lung TME. 3D cultures have been significantly contributing to the identification of novel therapeutic targets and the understanding of resistance mechanisms against conventional therapies. Therefore, this review summarizes the latest findings in drug research involving lung cancer 3D models, together with the common laboratory-based assays used to study drug effects. Additionally, the integration of 3D cell cultures into lung cancer drug development workflows and precision medicine is discussed. This integration is pivotal in accelerating the translation of laboratory findings into clinical applications, thereby advancing the landscape of lung cancer treatment. By closely mirroring human lung tumours, these models not only enhance our understanding of the disease but also pave the way for the development of more effective and personalized therapeutic strategies.
Case report: A case of severe capecitabine toxicity due to confirmed in trans compound heterozygosity of a common and rare DPYD variant
Authors: de Haar-Holleman Amy , Cortoos Pieter-Jan , Vlaeminck Jelle , Van Landuyt Paulien , Steurbaut Stephane , Vaeyens Freya , Haufroid Vincent
Published: September 2024

Variations in the activity of the enzyme dihydropyrimidine dehydrogenase (DPD) are associated with toxicity to fluoropyrimidine-containing chemotherapy. Testing of DPD deficiency either by targeted genotyping of the corresponding DPYD gene or by quantification of plasma concentration of uracil and dihydrouracil (phenotyping approach) are the two main methods capable of predicting reduced enzymatic activity in order to reduce adverse reactions after fluoropyrimidine treatment. In this paper, we describe a patient with locally advanced colon carcinoma with severe toxicity following capecitabine therapy. Whereas targeted genotyping for the 4 most common DPYD variants analysis revealed heterozygous presence of the c.2846A>T variant, which is a relatively common variant associated with a partial deficiency, additional phenotyping was compatible with a complete DPD deficiency. Subsequent sequencing of the whole DPYD gene revealed the additional presence of the rare c.2872A>G variant, which is associated with a total loss of DPD activity. A clinical case of in trans compound heterozygosity of a common and a rare DPYD variant (c.2846A>T and c.2872A>G) has, to the best of our knowledge, not been previously described. Our case report shows the importance of performing either preemptive phenotyping or preemptive complete genetic analysis of the DPYD gene for patients planned for systemic fluoropyrimidines to identify rare and low frequency variants responsible for potentially life-threatening toxic reactions.
Efficacy and safety of PARP inhibitor maintenance therapy for ovarian cancer: a meta-analysis and trial sequential analysis of randomized controlled trials
Authors: Sun Guojuan , Liu Yi
Published: September 2024

Background

The landscape of poly (ADP-ribose) polymerase (PARP) inhibitor treatment for ovarian cancer (OC) is continually evolving. This research aimed to evaluate the efficacy and safety of PARP inhibitors compared to placebo as a maintenance therapy for OC patients.

Methods

We conducted a search of PubMed, Embase, Web of Science, and the Cochrane Library databases for randomized controlled trials (RCTs) involving the use of PARP inhibitors as maintenance therapy in OC patients, up to 16 June 2024. Data regarding progression-free survival (PFS), overall survival (OS), chemotherapy-free interval (CFI), time to first subsequent therapy or death (TFST), time to second subsequent therapy or death (TSST), and treatment-emergent adverse events (TEAEs) were aggregated. Pooled hazard ratio (HR) and their corresponding 95% confidence intervals (CI) were calculated for PFS, OS, CFI, TFST, and TSST. Additionally, the relative risk (RR) and 95% CI for TEAEs were determined.

Results

This meta-analysis encompassed 20 RCTs involving 7,832 participants. The overall analysis demonstrated that maintenance therapy with PARP inhibitors led to significant improvements in PFS (HR: 0.398, 95% CI = 0.339–0.467, 95% PI = 0.219–0.724), OS (HR: 0.677, 95% CI = 0.582–0.788, 95% PI = 0.546–0.839), CFI (HR: 0.417, 95% CI = 0.368–0.472, 95% PI = 0.265–0.627), TFST (HR: 0.441, 95% CI = 0.391–0.498, 95% PI = 0.308–0.632), and TSST (HR: 0.574, 95% CI = 0.507–0.649, 95% PI = 0.488–0.674) compared with placebo. Subgroup analyses further indicated that PARP inhibitor maintenance treatment significantly improved PFS, regardless of homologous recombination status (all p < 0.05). However, the risks of any grade (RR = 1.046, 95% CI = 1.032–1.059, 95% PI = 1.028–1.055) and grade ≥3 TEAEs (RR = 2.931, 95% CI = 2.641–3.253, 95% PI = 2.128–3.792) were increased by PARP inhibitor maintenance therapy compared to placebo.

Conclusion

Our research elucidated the benefits of maintenance therapy with PARP inhibitors in patients with OC, showing improvements in PFS, OS, CFI, TFST, and TSST. Vigilance regarding TEAEs is paramount for clinicians implementing PARP inhibitor maintenance therapy in clinical practice.

Systematic Review Registration

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024560286.
Analysis of chromatin accessibility in peripheral blood mononuclear cells from patients with early-stage breast cancer
Authors: Xia Longjie , Lu Jiamin , Qin Yixuan , Huang Runchun , Kong Fanbiao , Deng Yu
Published: September 2024

Objective: This study was aimed at exploring a specific open region of chromatin in the peripheral blood mononuclear cells (PBMCs) of patients with breast cancer and evaluating its feasibility as a biomarker for diagnosing and predicting breast cancer prognosis.

Methods: We obtained PBMCs from breast cancer patients and healthy people for the assay for transposase-accessible chromatin (ATAC) sequencing (n = 3) and obtained the GSE27562 chip sequencing data for secondary analyses. Through bioinformatics analysis, we mined the pattern changes for chromatin accessibility in the PBMCs of breast cancer patients.

Results: A total of 1,906 differentially accessible regions (DARs) and 1,632 differentially expressed genes (DEGs) were identified via ATAC sequencing. The upregulated DEGs in the disease group were mainly distributed in the cells, organelles, and cell-intima-related structures and were mainly responsible for biological functions such as cell nitrogen complex metabolism, macromolecular metabolism, and cell communication, in addition to functions such as nucleic acid binding, enzyme binding, hydrolase reaction, and transferase activity. Combined with microarray data analysis, the following set of nine DEGs showed intersection between the ATAC and microarray data: JUN, MSL2, CDC42, TRIB1, SERTAD3, RAB14, RHOB, RAB40B, and PRKDC. HOMER predicted and identified five transcription factors that could potentially bind to these peak sites, namely NFY, Sp 2, GFY, NRF, and ELK 1.

Conclusion: Chromatin accessibility analysis of the PBMCs from patients with early-stage breast cancer underscores its potential as a significant avenue for biomarker discovery in breast cancer diagnostics and treatment. By screening the transcription factors and DEGs related to breast cancer, this study provides a comprehensive theoretical foundation that is expected to guide future clinical applications and therapeutic developments.
Comparison of organelle genomes between endangered mangrove plant Dolichandrone spathacea to terrestrial relative provides insights into its origin and adaptative evolution
Authors: Zhang Ying , Zhang Jingwen , Chen Zewei , Huang Yanni , Liu Jiaxuan , Liu Yuqi , Yang Yong , Jin Xiang , Yang Yuchen , Chen Yiqing
Published: September 2024

Dolichandrone spathacea is a mangrove associate with high medicinal and ecological values. However, due to the dual-pressure of climate change and human activities, D. spathacea has become endangered in China. Moreover, misidentification between D. spathacea and its terrestrial relative D. cauda-felina poses further challenges to field protection and proper medicinal usage of D. spathacea. Thus, to address these problems, we sequenced and assembled mitochondrial (mt) and chloroplast (cp) genomes for both D. spathacea and D. cauda-felina. Comparative analysis revealed apparently different size and scaffold number between the two mt genomes, but a high similarity between the cp genomes. Eight regions with high sequence divergence were identified between the two cp genomes, which might be used for developing candidate DNA markers for distinguishing the two species. The splitting between D. spathacea and D. cauda-felina was inferred to occur at ~6.8 - 7.7 million years ago (Mya), which may be driven by the environment fluctuations in late Miocene. In the cp genome, 12 genes related to the expression of photosynthesis-associated proteins were detected with signatures of positive selection, which may contribute to the origin and evolutionary adaptation of Dolichandrone mangrove species. These new findings do not only enrich organelle genomic resources of Dolichandrone species, but also provide important genetic clues for improving the conservation and proper usage of endangered mangrove associate D. spathacea.
Recent advances of CRISPR-based genome editing for enhancing staple crops
Authors: Chen Feng , Chen Lu , Yan Zhao , Xu Jingyuan , Feng Luoluo , He Na , Guo Mingli , Zhao Jiaxiong , Chen Zhijun , Chen Huiqi , Yao Gengzhen , Liu Chunping
Published: September 2024

An increasing population, climate change, and diminishing natural resources present severe threats to global food security, with traditional breeding and genetic engineering methods often falling short in addressing these rapidly evolving challenges. CRISPR/Cas systems have emerged as revolutionary tools for precise genetic modifications in crops, offering significant advancements in resilience, yield, and nutritional value, particularly in staple crops like rice and maize. This review highlights the transformative potential of CRISPR/Cas technology, emphasizing recent innovations such as prime and base editing, and the development of novel CRISPR-associated proteins, which have significantly improved the specificity, efficiency, and scope of genome editing in agriculture. These advancements enable targeted genetic modifications that enhance tolerance to abiotic stresses as well as biotic stresses. Additionally, CRISPR/Cas plays a crucial role in improving crop yield and quality by enhancing photosynthetic efficiency, nutrient uptake, and resistance to lodging, while also improving taste, texture, shelf life, and nutritional content through biofortification. Despite challenges such as off-target effects, the need for more efficient delivery methods, and ethical and regulatory concerns, the review underscores the importance of CRISPR/Cas in addressing global food security and sustainability challenges. It calls for continued research and integration of CRISPR with other emerging technologies like nanotechnology, synthetic biology, and machine learning to fully realize its potential in developing resilient, productive, and sustainable agricultural systems.
The relationship between physical activity and mental health of middle school students: the chain mediating role of negative emotions and self-efficacy
Authors: Yan Hao-Ming , Huang Ping , Chen Rui , Wang Yi-Cheng
Published: September 2024

Objective

To explore the relationship between mental health and physical activity (PA) in middle school students, and examining the roles of negative emotions and self-efficacy in the relationship.

Methods

Data from 1,134 Chinese middle school students (50.2% females, 49.8% males; Mage = 15.18, SDage = 2.00) were collected using the Physical Activity Rating Scale (PARS-3), Positive and Negative Affect Scale (PANAS), General Self-Efficacy Scale (GSES), and Middle School Student Mental Health Scale (MSSMHS).

Results

(1) There is a significant positive correlation between PA and mental health (r = 0.16, p < 0.01), and the direct path of PA on mental health is significant (t = 2.101, p < 0.01). (2) PA negatively predicts negative emotions (r = −0.12, p < 0.01), and is significantly positively correlated with self-efficacy (r = 0.24, p < 0.01). Negative emotions negatively predict self-efficacy (r = −0.23, p < 0.01) and mental health (r = −0.67, p < 0.01). Self-efficacy positively predicts mental health (r = 0.30, p < 0.01). (3) Negative emotions and self-efficacy play a significant mediating role between PA and mental health. The mediating effect includes three paths: PA → negative emotion → mental health (effect value: 0.130); PA → self-efficacy → mental health (effect size: 0.052); PA → negative emotions → self-efficacy → mental health (effect size: 0.006).

Conclusion

PA among middle school students can indirectly affect mental health through negative emotions and self-efficacy. Middle school students should be encouraged to participate in PA to reduce their negative emotions and increase their self-efficacy, thus improving their mental health.
Psilocybin for major depressive disorder: a systematic review of randomized controlled studies
Authors: Li Li-Juan , Mo Yu , Shi Zhan-Ming , Huang Xing-Bing , Ning Yu-Ping , Wu Hua-Wang , Yang Xin-Hu , Zheng Wei
Published: September 2024

Objectives

The purpose of this systematic review of randomized controlled trials (RCTs) was to evaluate the effectiveness, safety, and tolerability of psilocybin in adult patients with major depressive disorder (MDD).

Methods

A systematic search (up to September 14, 2023) was conducted for RCTs that examined the efficacy, safety, and tolerability of psilocybin in physically healthy adult patients with MDD. Three independent researchers extracted data from publications where the primary outcome was a change in depressive symptoms, and key secondary outcomes were changes in anxiety symptoms and suicidal ideation, discontinuation rates for any reason, and adverse drug reactions (ADRs).

Results

Five RCTs with 472 adult patients with MDD on psilocybin (n = 274) and controls (n = 198) were included. Two of the five RCTs (40%) reported mixed results, while the other three (60%) found that psilocybin had a beneficial effect on MDD treatment. Four RCTs (80%) assessing the anxiolytic effects of psilocybin for treating MDD found that psilocybin was significantly more effective than the control group in improving anxiety symptoms. Psilocybin was more effective than the control group in improving suicidal ideation in one out of five RCTs. Discontinuation rates were similar for any reason between the psilocybin group (2–13%) and the control group (4–21%) (P > 0.05). Four RCTs (80%) reported ADRs in detail. The most common ADR in both groups was headache.

Conclusion

Psilocybin was effective in improving depressive symptoms in over half of the included studies and reduced anxiety symptoms in patients with MDD. The long-term efficacy and safety of psilocybin for MDD treatment needs to be further investigated in large RCTs.
Relationships between screen time and childhood attention deficit hyperactivity disorder: a Mendelian randomization study
Authors: Meng Zhuo , Ao Bo , Wang Wei , Niu Tongtong , Chen Yanan , Ma Xiaoqing , Huang Youliang
Published: September 2024

Background

In previous observational studies and meta-analyses, childhood attention deficit hyperactivity disorder (ADHD) is found to have a significant association with screen time. However, the causal associations between them remain unclear.

Method

This study performed a bidirectional two-sample Mendelian randomization (MR) analysis to confirm the causality between screen time and childhood ADHD. Large-scale genome-wide association studies (GWAS) datasets derived from the Psychiatric Genomics Consortium (PGC) and the UK Biobank were used to identify single nucleotide polymorphisms (SNPs) associated with exposure and outcome. Four categories of datasets were selected to represent screen time. The SNPs that are significantly associated with exposure data (P < 5e-08) and have a strong correlation with the exposure in the F-statistic (F > 10) were selected as instrumental variables. This study also used the PhenoScanner V2 database and the LDlink webtool to exclude confounding factors, and the MR-PRESSO method (p < 0.05) was employed to eliminate outliers with bias. Five commonly used methods were employed to assess the interaction and the Inverse Variance Weighted (IVW) method was utilized as the primary basis for determining the MR estimates in this study.

Results

The MR analysis revealed that the length of mobile phone use (OR, 1.848; 95% CI, 1.3360-2.5558; p=2.07e-4) and the time spent watching television (OR, 2.104; 95% CI, 1.3958-3.1703; p=3.8e-4) increased the risk of childhood ADHD. Although the causal relationships were exclusively identified through the IVW and weighted median methods, the results retained their statistical significance following correction. In the reverse analysis, no evidence was found to support an effect of childhood ADHD on screen time. The sensitivity analysis conducted on the significant findings revealed no evidence of horizontal pleiotropy or heterogeneity.

Conclusion

This study provides some evidence for the causality of screen time and childhood ADHD. Given the limitations of our study, further research is required to comprehensively investigate this relationship.
Effect of sleep quality on repetitive transcranial magnetic stimulation outcomes in depression
Authors: Kweon Jamie , Fukuda Andrew M. , Gobin Asi P. , Haq Lamaan , Carpenter Linda L. , Brown Joshua C.
Published: September 2024

Introduction

While repetitive transcranial magnetic stimulation (rTMS) is effective for 50-60% of those treatment-resistant depression, it is critical to identify predictors of response for optimal patient selection to improve therapy. Insomnia is a known symptom of depression that is both correlated with depression severity and associated with poor antidepressant response. Therefore, understanding this relationship may open new opportunities for the optimization of rTMS treatment. We aimed to explore whether baseline sleep quality, specifically insomnia, is associated with rTMS outcomes in a naturalistic sample of 975 patients (age 18-90; 63.9% F) receiving a standard course of rTMS treatment from two outpatient TMS clinics located within psychiatric hospitals in the United States. One site additionally collected information on concurrent medication use on 350 patients; among these, we examined whether pharmacological treatment of insomnia affected TMS treatment response.

Methods

Depression was measured using the 30-item Inventory of Depressive Symptomology Self Report (IDS-SR) in site one and an abbreviated 16-item Quick Inventory of Depressive Symptomology (QIDS) derived from the IDS-SR in site two. Sleep disturbances were measured using three insomnia-related questions. Multilevel logistic regression was used to determine whether baseline insomnia scores were associated with TMS treatment outcome. Upon dichotomous categorization of the sample by insomnia and sleep-medication use, depression and sleep scores were analyzed across time using mixed repeated measures ANOVA.

Results

We found that sleep quality improves after TMS (p<.001) and correlates with improvement in non-insomnia related depression symptoms (r= .318, p<.001). We found that among those who had significant insomnia at baseline, those not using sleep medications had significantly worse post-treatment IDS-SR scores compared to those using sleep medications (p=. 021) despite no difference in final insomnia score.

Discussion

Together, our results suggest that while baseline insomnia is not associated with TMS effectiveness, treating insomnia may affect the trajectory of TMS therapy. Future prospective studies are needed to examine the effect of insomnia treatment alongside TMS for depression.