bluuebunny/crossref_metadata_2025 huggingface dataset:
Probing archaeal cell biology: exploring the use of dyes in the imaging of Sulfolobus cells
Authors: Cezanne Alice , Hoogenberg Baukje , Baum Buzz
Published: September 2023

Archaea are key players in many critical ecological processes. In comparison to eukaryotes and bacteria, however, our understanding of both the cell biology and diversity of archaea remains limited. While archaea inhabit a wide range of environmental conditions, many species are extremophiles, surviving in extreme temperature, salt or pH conditions, making their cell biology hard to study. Recently, our understanding of archaeal cell biology has been advanced significantly by the advent of live cell imaging in extremis as well as the development of genetic tools to exogenously express fluorescent proteins in some mesophilic archaeal model systems, e.g., Haloferax volcanii. However, for most archaeal species, especially thermophilic species or emerging model systems without well characterized genetic tools, live cell imaging remains dependent on fluorescent chemical probes to label and track the dynamics of living cells. While a wide range of fluorescent stains and markers that label different components of the cell are available commercially, their use has usually been optimized for use in a small number of eukaryotic cell systems. Here we report the successes and failures of the application of membrane, DNA, S-layer and cytoplasm markers in live cell imaging of archaea, as well as the optimization of fixation and immunolabelling approaches. We have applied these markers to the thermoacidophilic archaeon Sulfolobus acidocaldarius, but expect some to work in other archaeal species. Furthermore, those procedures that failed in S. acidocaldarius may still prove useful for imaging archaea that grow at a more neutral pH and/or at a less extreme temperature.
Anti-Pseudomonas aeruginosa activity of natural antimicrobial peptides when used alone or in combination with antibiotics
Authors: Chen Xueqi , Su Shan , Yan Yan , Yin Limei , Liu Lihong
Published: September 2023

The World Health Organization has recently published a list of 12 drug-resistant bacteria that posed a significant threat to human health, and Pseudomonas aeruginosa (P. aeruginosa) was among them. In China, P. aeruginosa is a common pathogen in hospital acquired pneumonia, accounting for 16.9–22.0%. It is a ubiquitous opportunistic pathogen that can infect individuals with weakened immune systems, leading to hospital-acquired acute and systemic infections. The excessive use of antibiotics has led to the development of various mechanisms in P. aeruginosa to resist conventional drugs. Thus, there is an emergence of multidrug-resistant strains, posing a major challenge to conventional antibiotics and therapeutic approaches. Antimicrobial peptides are an integral component of host defense and have been found in many living organisms. Most antimicrobial peptides are characterized by negligible host toxicity and low resistance rates, making them become promising for use as antimicrobial products. This review particularly focuses on summarizing the inhibitory activity of natural antimicrobial peptides against P. aeruginosa planktonic cells and biofilms, as well as the drug interactions when these peptides used in combination with conventional antibiotics. Moreover, the underlying mechanism of these antimicrobial peptides against P. aeruginosa strains was mainly related to destroy the membrane structure through interacting with LPS or increasing ROS levels, or targeting cellular components, leaded to cell lysis. Hopefully, this analysis will provide valuable experimental data on developing novel compounds to combat P. aeruginosa.
Global trends and prospects about synaptic plasticity in Alzheimer’s disease: a bibliometric analysis
Authors: Zhang Yingying , Zhang Junyao , Wang Yinuo , Yao Junyan
Published: September 2023

Background and purpose

In recent years, synaptic plasticity disorders have been identified as one of the key pathogenic factors and the early pathological characteristics of Alzheimer’s disease (AD). In this study, we tried to use bibliometric analysis to gain a systematic understanding about synaptic plasticity in Alzheimer’s disease.

Methods

We extracted relevant publications from the Web of Science Core Collection (WoSCC) on August 29th, 2022. Then, we used CiteSpace, VOSviewer and other online bibliometric platforms1 to further analyze the obtained data.

Results

A total of 2,348 published articles and reviews about synaptic plasticity in AD from 2002 to 2022 were identified. During the past two decades, the overall trends of the numbers and citations of manuscripts were on the rise. The United States was the leading country with the largest number of publications which showed its crucial role in this field. The collaboration network analysis showed that the United States and China had the most frequent collaboration. In addition, Harvard University was the institution with the greatest number of publications and cited times. Among all authors, Selkoe DJ was the most influential author with the greatest cited times. The journal of Alzheimer’s disease published the maximum number of documents in the field of synaptic plasticity in AD within 20 years. Furthermore, the results of keywords burst detection showed that the hot topics have shifted from the synaptic transmission, precursor protein and plaque formation to neuroinflammation, microglia and alpha synuclein.

Conclusion

This study analyzed 2,348 publications with 82,025 references covering the topic of synaptic plasticity in AD and presented the research trends. The results indicated that neuroinflammation, microglia and alpha synuclein were the current research hotspots, which implied the potential clinical applications to AD.
Biomarkers associated with functional improvement after stroke rehabilitation: a systematic review and meta-analysis of randomized controlled trials
Authors: Chen Gengbin , Wu Manfeng , Chen Jialin , Zhang Cailing , Liu Quan , Zhao Yinchun , Xu Guangqing , Lan Yue
Published: September 2023

Objective

This study aims to identify blood and cerebrospinal fluid biomarkers that are correlated to the functional improvement of stroke patients after rehabilitation therapy, and provide ideas for the treatment and evaluation of stroke patients.

Methods

The PubMed, Web of Science, and Embase databases were searched for articles published in the English language, from inception to December 8, 2022.

Results

A total of 9,810 independent records generated 50 high-quality randomized controlled trials on 119 biomarkers. Among these records, 37 articles were included for the meta-analysis (with a total of 2,567 stroke patients), and 101 peripheral blood and cerebrospinal fluid biomarkers were included for the qualitative analysis. The quantitative analysis results revealed a moderate quality evidence that stroke rehabilitation significantly increased the level of brain-derived neurotrophic factor (BDNF) in serum. Furthermore, the low-quality evidence revealed that stroke rehabilitation significantly increased the concentration of serum noradrenaline (NE), peripheral blood superoxide dismutase (SOD), peripheral blood albumin (ALB), peripheral blood hemoglobin (HB), and peripheral blood catalase (CAT), but significantly decreased the concentration of serum endothelin (ET) and glutamate. In addition, the changes in concentration of these biomarkers were associated with significant improvements in post-stroke function. The serum BNDF suggests that this can be used as a biomarker for non-invasive brain stimulation (NIBS) therapy, and to predict the improvement of stroke patients.

Conclusion

The concentration of serum BNDF, NE, ET and glutamate, and peripheral blood SOD, ALB, HB and CAT may suggest the function improvement of stroke patients.
Reversible splenial lesion syndrome in children: a retrospective study of 130 cases
Authors: Chen Hui , Yu Xiongying , Chen Yong , Wu Huaping , Wu Zhuqiang , Zhong Jianmin , Tang Zhenyu
Published: September 2023

Background

Reversible splenial lesion syndrome (RESLES) is a new clinico-radiological syndrome. We retrospectively analyzed the clinical features of 130 children with RESLES in China, which is the largest case series available in the literature.

Methods

The clinical data of children diagnosed as RESLES in Jiangxi Provincial Children's Hospital between 2017 and 2023 were retrospectively analyzed. The 130 cases were divided into two groups: ≤ 3 years old group (group A) (n = 83) and > 3 years old group (group B) (n = 47). The chi-squared test or Fisher's test was used to evaluate the data.

Results

The vast majority of patients (127/130 cases, 97.7%) had prodromal symptoms of infection. Preceding infections of the gastrointestinal tract were statistically more significant in group A (60/83, 72.3%) than in group B (11/47, 23.4%) (P < 0.05). Preceding infections of the respiratory tract were statistically more significant in group B (33/47, 70.2%) than in group A (17/83, 20.5%) (P < 0.05). Seizures were statistically more significant in group A (82/83, 98.8%) than in group B (24/47,51.1%) (P < 0.05). The disturbance of consciousness and headache/dizziness were statistically more significant in group B (27/47, 57.4%; 37/47, 78.7%) than in group A (3/83, 3.6%; 1/83, 1.2%), respectively (P < 0.05). Convulsions with mild gastroenteritis (CwG) were statistically more significant in group A (50/83, 60.2%) than in group B (8/47, 17.0%) (P < 0.05). However, encephalitis/encephalopathy was statistically more significant in group B (20/47, 42.6%) than in group A (10/83, 12.0%) (P < 0.05). MRI showed cytotoxic edema in typical locations (RESLES type-1 limited to the splenium of the corpus callosum and RESLES type-2 spread to the entire corpus callosum, adjacent white matter, or both). There was full recovery of the lesions of MRI in all cases from 3 days to 50 days after the initial examinations. All the children showed normal neurodevelopment.

Conclusion

Infection was the most common cause of RESLES. Infections of the gastrointestinal tract are common in ≤ 3 years old children, while infections of the respiratory tract are common in >3 years old children. Younger patients are more likely to develop convulsions, and older children were more likely to have symptoms with disturbance of consciousness and headache/dizziness. RESLES has characteristic MRI manifestations and a good prognosis.
Associations between perioperative sleep patterns and clinical outcomes in patients with intracranial tumors: a correlation study
Authors: Liu Yang , Wu Fan , Zhang Xiaoyu , Jiang Mengyang , Zhang Yiqiang , Wang Chenhui , Sun Yongxing , Wang Baoguo
Published: September 2023

Objective

Although the quality of perioperative sleep is gaining increasing attention in clinical recovery, its impact role remains unknown and may deserve further exploration. This study aimed to investigate the associations between perioperative sleep patterns and clinical outcomes among patients with intracranial tumors.

Methods

A correlation study was conducted in patients with intracranial tumors. Perioperative sleep patterns were assessed using a dedicated sleep monitor for 6 consecutive days. Clinical outcomes were gained through medical records and follow-up. Spearman's correlation coefficient and multiple linear regression analysis were applied to evaluate the associations between perioperative sleep patterns and clinical outcomes.

Results

Of 110 patients, 48 (43.6%) were men, with a median age of 57 years. A total of 618 days of data on perioperative sleep patterns were collected and analyzed. Multiple linear regression models revealed that the preoperative blood glucose was positively related to the preoperative frequency of awakenings (β = 0.125; 95% CI = 0.029–0.221; P = 0.011). The level of post-operative nausea and vomiting was negatively related to perioperative deep sleep time (β = −0.015; 95% CI = −0.027–−0.003; P = 0.015). The level of anxiety and depression was negatively related to perioperative deep sleep time, respectively (β = −0.048; 95% CI = −0.089–0.008; P = 0.020, β = −0.041; 95% CI = −0.076–0.006; P = 0.021). The comprehensive complication index was positively related to the perioperative frequency of awakenings (β = 3.075; 95% CI = 1.080–5.070; P = 0.003). The post-operative length of stay was negatively related to perioperative deep sleep time (β = −0.067; 95% CI = −0.113–0.021; P = 0.005). The Pittsburgh Sleep Quality Index was positively related to perioperative sleep onset latency (β = 0.097; 95% CI = 0.044–0.150; P < 0.001) and negatively related to perioperative deep sleep time (β = −0.079; 95% CI = −0.122–0.035; P < 0.001).

Conclusion

Perioperative sleep patterns are associated with different clinical outcomes. Poor perioperative sleep quality, especially reduced deep sleep time, has a negative impact on clinical outcomes. Clinicians should, therefore, pay more attention to sleep quality and improve it during the perioperative period.

Clinical trial registration

http://www.chictr.org.cn, identifier: ChiCTR2200059425.
Development of circadian neurovascular function and its implications
Authors: Mitchell Jennifer W. , Gillette Martha U.
Published: September 2023

The neurovascular system forms the interface between the tissue of the central nervous system (CNS) and circulating blood. It plays a critical role in regulating movement of ions, small molecules, and cellular regulators into and out of brain tissue and in sustaining brain health. The neurovascular unit (NVU), the cells that form the structural and functional link between cells of the brain and the vasculature, maintains the blood–brain interface (BBI), controls cerebral blood flow, and surveils for injury. The neurovascular system is dynamic; it undergoes tight regulation of biochemical and cellular interactions to balance and support brain function. Development of an intrinsic circadian clock enables the NVU to anticipate rhythmic changes in brain activity and body physiology that occur over the day-night cycle. The development of circadian neurovascular function involves multiple cell types. We address the functional aspects of the circadian clock in the components of the NVU and their effects in regulating neurovascular physiology, including BBI permeability, cerebral blood flow, and inflammation. Disrupting the circadian clock impairs a number of physiological processes associated with the NVU, many of which are correlated with an increased risk of dysfunction and disease. Consequently, understanding the cell biology and physiology of the NVU is critical to diminishing consequences of impaired neurovascular function, including cerebral bleeding and neurodegeneration.
Accounting for multiscale processing in adaptive real-world decision-making via the hippocampus
Authors: Mehrotra Dhruv , Dubé Laurette
Published: September 2023

For adaptive real-time behavior in real-world contexts, the brain needs to allow past information over multiple timescales to influence current processing for making choices that create the best outcome as a person goes about making choices in their everyday life. The neuroeconomics literature on value-based decision-making has formalized such choice through reinforcement learning models for two extreme strategies. These strategies are model-free (MF), which is an automatic, stimulus–response type of action, and model-based (MB), which bases choice on cognitive representations of the world and causal inference on environment-behavior structure. The emphasis of examining the neural substrates of value-based decision making has been on the striatum and prefrontal regions, especially with regards to the “here and now” decision-making. Yet, such a dichotomy does not embrace all the dynamic complexity involved. In addition, despite robust research on the role of the hippocampus in memory and spatial learning, its contribution to value-based decision making is just starting to be explored. This paper aims to better appreciate the role of the hippocampus in decision-making and advance the successor representation (SR) as a candidate mechanism for encoding state representations in the hippocampus, separate from reward representations. To this end, we review research that relates hippocampal sequences to SR models showing that the implementation of such sequences in reinforcement learning agents improves their performance. This also enables the agents to perform multiscale temporal processing in a biologically plausible manner. Altogether, we articulate a framework to advance current striatal and prefrontal-focused decision making to better account for multiscale mechanisms underlying various real-world time-related concepts such as the self that cumulates over a person’s life course.
Precise sound characteristics drive plasticity in the primary auditory cortex with VNS-sound pairing
Authors: Borland Michael S. , Buell Elizabeth P. , Riley Jonathan R. , Carroll Alan M. , Moreno Nicole A. , Sharma Pryanka , Grasse Katelyn M. , Buell John M. , Kilgard Michael P. , Engineer Crystal T.
Published: September 2023

Introduction

Repeatedly pairing a tone with vagus nerve stimulation (VNS) alters frequency tuning across the auditory pathway. Pairing VNS with speech sounds selectively enhances the primary auditory cortex response to the paired sounds. It is not yet known how altering the speech sounds paired with VNS alters responses. In this study, we test the hypothesis that the sounds that are presented and paired with VNS will influence the neural plasticity observed following VNS-sound pairing.

Methods

To explore the relationship between acoustic experience and neural plasticity, responses were recorded from primary auditory cortex (A1) after VNS was repeatedly paired with the speech sounds ‘rad’ and ‘lad’ or paired with only the speech sound ‘rad’ while ‘lad’ was an unpaired background sound.

Results

Pairing both sounds with VNS increased the response strength and neural discriminability of the paired sounds in the primary auditory cortex. Surprisingly, pairing only ‘rad’ with VNS did not alter A1 responses.

Discussion

These results suggest that the specific acoustic contrasts associated with VNS can powerfully shape neural activity in the auditory pathway. Methods to promote plasticity in the central auditory system represent a new therapeutic avenue to treat auditory processing disorders. Understanding how different sound contrasts and neural activity patterns shape plasticity could have important clinical implications.
Argon-helium knife cryoablation plus programmed cell death protein 1 inhibitor in the treatment of advanced soft tissue sarcomas: there is no evidence of the synergistic effects of this combination therapy
Authors: Wang Jiaqiang , Zong Dengwei , Dong Shuping , Gao Shilei , Yang Yonghao , Zhang Peng , Wang Xin , Yao Weitao , Tian Zhichao
Published: September 2023

Background

Effective treatment for advanced soft tissue sarcomas (STSs) is necessary for improved outcomes. Previous studies have suggested that cryoablation can have a synergistic effect with programmed cell death protein-1 (PD-1) inhibitor in the treatment of malignancy. This study aimed to clarify the efficacy and safety of argon-helium knife cryoablation in combination with PD-1 inhibitor in the treatment of STSs.

Methods

Retrospectively collected and analyzed the clinical data of patients with advanced STS who underwent cryoablation and PD-1 inhibitor between March 2018 and December 2021.

Results

This study included 27 patients with advanced STS. In terms of target lesions treated with cryoablation, 1 patient achieved complete response, 15 patients had partial response (PR), 10 patients had stable disease, and 1 patient had progressive disease. This corresponded to an overall response rate of 59.3% and a disease control rate of 96.3%. In terms of distant target lesions untreated with cryoablation, only two patients had a PR compared to the diameter of the lesion before ablation. The combination therapy was relatively well tolerated. None of the patients experienced treatment-related death or delayed treatment due to adverse events.

Conclusion

Cryoablation combined with PD-1 inhibitors in the therapy of advanced STS is safe and can effectively shrink the cryoablation-target lesion. However, there is no evidence of the synergistic effects of this combination therapy.
Neoadjuvant chemoimmunotherapy cycle number selection for non-small cell lung cancer and clinical outcomes: a real-world analysis
Authors: Zhang Baihua , Guo Xiaotong , Jia Ran , Wang Zhan , Wu Jie , Chen Xiaoyan , Li Jigang , Yang Desong , Li Xu , Wang Wenxiang , Xiao Qin
Published: September 2023

Objectives

Neoadjuvant chemoimmunotherapy is the optimal choice in the treatment of NSCLC; however, the optimal number of therapeutic cycles remains unclear. The primary aim of this study was to determine the optimal number of neoadjuvant therapeutic cycles in NSCLC.

Methods

This study was a real-world clinical analysis that included patients who received neoadjuvant chemoimmunotherapy followed by surgery from January 2020 to August 2022. Patients were divided into two groups based on the number of therapeutic cycles: 2-cycle group and 3-4-cycles group. The primary endpoint was the major pathological response (MPR) rate.

Results

A total of 251 patients were included: 150 in the 2-cycle group and 101 in the 3-4-cycles group. Baseline characteristics were well-balanced between the groups. The MPR in the 2-cycle group was 57.3% and not significantly different from that of 57.4% in the 3-4-cycles group (p=0.529). Thirty-two patients (31.7%) in the 3-4-cycles group underwent surgery > 42 days after the final cycle of neoadjuvant therapy, significantly more than the 24 patients (16.0%) in the 2-cycle group (p=0.003). The incidence of adverse events related to neoadjuvant therapy was higher in the 3-4-cycles vs 2-cycle groups (72.3% versus 58.0%, respectively; p=0.021), while the 2-cycle group had a higher rate of postoperative morbidities (28.0% versus 12.9%, respectively; p=0.004). Additionally, for patients with ≤ 44.2% regression in diameter on computed tomography after two cycles of treatment, the MPR rate was higher in the 3-4-cycles vs 2-cycle group (47.3% versus 29.9%, respectively; p=0.048). For cases with programmed death-ligand 1 expression, regarding tumor proportion score ≤ 10%, 3-4 cycles of neoadjuvant treatment increased the MPR rate compared with 2 cycles (37.5% versus 9.5%, respectively; p=0.041).

Conclusion

Our data support the positive role of chemoimmunotherapy in the neoadjuvant treatment of NSCLC. Extending to 3–4 cycles instead of 2 cycles of neoadjuvant chemoimmunotherapy may improve the safety of surgery and result in a lower incidence of postoperative morbidities; however, the MPR rate may not increase significantly. CT re-evaluation during treatment and PD-L1 expression at initial diagnosis are potential indicators to guide the choice of the number of therapeutic cycles.
Size and depth of residual tumor after neoadjuvant chemoradiotherapy in rectal cancer – implications for the development of new imaging modalities for response assessment
Authors: van der Stel Stefan D. , van den Berg Jose G. , Snaebjornsson Petur , Seignette Iris M. , Witteveen Mark , Grotenhuis Brechtje A. , Beets Geerard L. , Post Anouk L. , Ruers Theo J. M.
Published: September 2023

With the shift towards organ preserving treatment strategies in rectal cancer it has become increasingly important to accurately discriminate between a complete and good clinical response after neoadjuvant chemoradiotherapy (CRT). Standard of care imaging techniques such as CT and MRI are well equipped for initial staging of rectal tumors, but discrimination between a good clinical and complete response remains difficult due to their limited ability to detect small residual vital tumor fragments. To identify new promising imaging techniques that could fill this gap, it is crucial to know the size and invasion depth of residual vital tumor tissue since this determines the requirements with regard to the resolution and imaging depth of potential new optical imaging techniques. We analyzed 198 pathology slides from 30 rectal cancer patients with a Mandard tumor regression grade 2 or 3 after CRT that underwent surgery. For each patient we determined response pattern, size of the largest vital tumor fragment or bulk and the shortest distance from the vital tumor to the luminal surface. The response pattern was shrinkage in 14 patients and fragmentation in 16 patients. For both groups combined, the largest vital tumor fragment per patient was smaller than 1mm for 38% of patients, below 0.2mm for 12% of patients and for one patient as small as 0.06mm. For 29% of patients the vital tumor remnant was present within the first 0.01mm from the luminal surface and for 87% within 0.5mm. Our results explain why it is difficult to differentiate between a good clinical and complete response in rectal cancer patients using endoscopy and MRI, since in many patients submillimeter tumor fragments remain below the luminal surface. To detect residual vital tumor tissue in all patients included in this study a technique with a spatial resolution of 0.06mm and an imaging depth of 8.9mm would have been required. Optical imaging techniques offer the possibility of detecting majority of these cases due to the potential of both high-resolution imaging and enhanced contrast between tissue types. These techniques could thus serve as a complimentary tool to conventional methods for rectal cancer response assessment.
Distribution pattern of medial group retropharyngeal lymph nodes and its implication in optimizing clinical target volume in nasopharyngeal carcinoma
Authors: Zong Dan , Jiang Ning , Kong Cheng , Wen Jing , Wang Li-jun , Guo Ye-song , Zhang Lan-fang , He Xia , Chen Zhen-zhang , Huang Sheng-fu
Published: September 2023

Purpose

This study aimed to determine the diagnostic value of diffusion-weighted imaging (DWI) and to elucidate the clinical characteristics of medial group retropharyngeal lymph nodes (RLNs) based on multi-modal imaging. Also, we intended to explore the feasibility of optimizing the CTV60 boundary based on the characteristics of medial group RLNs.

Methods

A total of 549 patients with nasopharyngeal carcinoma received magnetic resonance imaging (MRI), DWI, and contrast-enhanced computed tomography (CT) to detect and evaluate clinical characteristics of medial group RLNs. [18F]Fluorodeoxyglucose positron emission tomography/computed tomography was utilized to identify fluorodeoxyglucose uptaking and contrast-enhanced CT to ensure the reliability of CTV optimization during radiotherapy. The DESdC (Drinking, Eating, Swallowing Difficulties, and Coughing while Eating or Drinking) score was utilized to evaluate swallowing disability.

Results

Fourteen of 549 patients had medial group RLNs with a transverse diameter of 2.0–19.0 mm, which distributed between the upper margin of 1st cervical vertebra (C1) and the upper one-third of C3. Lasso regression and Pearson chi-square test suggested that its occurrence was associated with stage N, bilateral cervical lymph node metastases, especially when the transverse diameter of cervical lymph nodes was > 3 cm. The sensitivity of DWI, T2 STIR, and contrast-enhanced CT was 100%, 57.1%, and 21.4%, respectively. We optimized CTV60 of medial group RLNs from the base of skull to the upper edge of C2 excluding specific cases. For patients with CTV60 optimization, radiation dose and volume of swallowing structures decreased obviously. Based on our radiotherapy strategy on CTV60, acute toxicities of enrolled patients were well tolerated. Ninety-six of 549 patients had scores with DESdC score. Eighty-three patients scored 1, seven patients scored 2, one patient scored 3, and three patients scored 4. The median interval from the onset of symptoms was 72 (4–114) months. The 5-year overall survival, progression-free survival, local recurrence-free survival, and distant metastasis-free survival were 87%, 80%, 93%, and 85%, respectively. None of the patients with regional recurrence happened in the optimized region.

Conclusion

DWI possesses superiorities in displaying lymph nodes. Based on the low incidence of the medial RLNs, CTV60 of medial group RLNs from the base of skull to the upper edge of C2 is feasible and has dosimetric advantages for protecting swallowing structures.
Network pharmacology and experimental verification reveal the mechanism of safranal against glioblastoma (GBM)
Authors: Yang Xiaobing , Lu Di , Sun Yanfei , Wei Tiandi , Man Dulegeqi , Chen Anbin , Luo Tao , Zhao Feihu , Liu Xuemeng , Cheng Bo , Wang Xu , Zhao Peng , Wang Donghai , Li Xingang
Published: September 2023

Introduction

Safranal is an active component of the traditional Tibetan medicine (TTM) saffron, which has potential anticancer activity.

Methods and results

Here, we studied the therapeutic effect and mechanism of safranal on GBM. CCK-8, GBM-brain organoid coculture experiments and 3D tumour spheroid invasion assays showed that safranal inhibited GBM cell proliferation and invasion in vitro. Network pharmacology, RNA-seq, molecular docking analysis, western blotting, apoptosis, and cell cycle assays predicted and verified that safranal could promote GBM cell apoptosis and G2/M phase arrest and inhibit the PI3K/AKT/mTOR axis. In vivo experiments showed that safranal could inhibit GBM cell growth alone and in combination with TMZ.

Conclusion

This study revealed that safranal inhibits GBM cell growth in vivo and in vitro, promotes GBM cell apoptosis and G2/M phase arrest, inhibits the PI3K/AKT/mTOR axis and cooperate with TMZ.
Using extracellular matrix derived from sugen-chronic hypoxia lung tissue to study pulmonary arterial hypertension
Authors: Link Patrick A. , Farkas Laszlo , Heise Rebecca L.
Published: September 2023

Pulmonary arterial hypertension has characteristic changes to the mechanical environment, extracellular matrix, and cellular proliferation. In order to develop a culture system to investigate extracellular matrix (ECM) compositional-dependent changes in pulmonary arterial hypertension, we decellularized and characterized protein and lipid profiles from healthy and Sugen-Chronic Hypoxia rat lungs. Significant changes in lipid profiles were observed in intact Sugen-Hypoxia lungs compared with healthy controls. Decellularized lung matrix retained lipids in measurable quantities in both healthy and Sugen-Chronic Hypoxia samples. Proteomics revealed significantly changed proteins associated with pulmonary arterial hypertension in the decellularized Sugen-Chronic Hypoxia lung ECM. We then investigated the potential role of healthy vs. Sugen-Chronic Hypoxia ECM with controlled substrate stiffness to determine if the ECM composition regulated endothelial cell morphology and phenotype. CD117+ rat lung endothelial cell clones were plated on the variable stiffness gels and cellular proliferation, morphology, and gene expression were quantified. Sugen-Chronic Hypoxia ECM on healthy stiffness gels produced significant changes in cellular gene expression levels of Bmp2, Col1α1, Col3α1 and Fn1. The signaling and cell morphology observed at low substrate stiffness suggests early changes to the ECM composition can initiate processes associated with disease progression. These data suggest that Sugen-Chronic Hypoxia ECM can be used to investigate cell-ECM interactions relevant to pulmonary arterial hypertension.
A quasi-experimental study of the volume-based procurement (VBP) effect on antiviral medications of hepatitis B virus in China
Authors: Wen Xiaotong , Xu Luxinyi , Chen Xiaoze , Wu Ruonan , Luo Jia , Wan Yuying , Mao Zongfu
Published: September 2023

Background: The Pilot Plan of National Centralized Volume-Based Procurement (NCVBP) was adopted to cope with the rapid increase in drug expenditures. This research aimed to quantitatively evaluate the impact of the NCVBP on antiviral medications for the hepatitis B virus.

Methods: Data on nucleoside analogs (NAs) medications of hepatitis B virus monthly procurement records in the pilot cities from January 2018 to December 2019 were extracted from the China Drug Supply Information Platform (CDSIP). The impacts of the NCVBP on purchased volumes, expenditures, and pre-defined daily dose costs were evaluated by interrupted time-series (ITS) analysis using Stata 16.0. We constructed two segments with one interruptive point (March 2019).

Results: Compared to the same period between pre-and post-intervention, the purchased volume of NAs medications were increased by 92.85%, and selected medications were increased by 119.09%. Analysis of changes in the level of NAs medication followed a decrease in purchased expenditure (coefficient: 5364.88, p < 0.001), meanwhile, the purchased volume was increased with statistical significance (coefficient:605.49, p < 0.001). The Defined Daily Dose cost (DDDc) of NAs medication followed a decrease (coefficient: 8.90, p < 0.001). The NCVBP reform was followed by an increase of 618.41 ten thousand Defined Daily Dose (DDD) (p < 0.001) in purchased volume and a reduction of 5273.84 ten thousand Chinese Yuan (CNY) (p < 0.001) in the purchased expenditure of selected medications in the level. The DDDc of selected medications decreased in the level (coefficient: 9.87, p < 0.001), while the DDDc of alternative medications increased in the slope (coefficient:0.07, p = 0.030). The purchased volume and expenditure of bid-winning products increased by 964.08 ten thousand DDD and 637.36 ten thousand CNY in the level (p < 0.001). An increase of 633.46 ten thousand DDD (p < 0.001) in purchased volume and a reduction of 4285.32 ten thousand CNY (p < 0.001) in the purchased expenditure of generic drugs in the level was observed.

Conclusion: The NCVBP reduced the DDDc of NAs medication, improved the utilization of the selected medications, and promoted the usage of generic products.
Development of a parallel multiscale 3D model for thrombus growth under flow
Authors: Shankar Kaushik N. , Diamond Scott L. , Sinno Talid
Published: September 2023

Thrombus growth is a complex and multiscale process involving interactions spanning length scales from individual micron-sized platelets to macroscopic clots at the millimeter scale. Here, we describe a 3D multiscale framework to simulate thrombus growth under flow comprising four individually parallelized and coupled modules: a data-driven Neural Network (NN) that accounts for platelet calcium signaling, a Lattice Kinetic Monte Carlo (LKMC) simulation for tracking platelet positions, a Finite Volume Method (FVM) simulator for solving convection-diffusion-reaction equations describing agonist release and transport, and a Lattice Boltzmann (LB) flow solver for computing the blood flow field over the growing thrombus. Parallelization was achieved by developing in-house parallel routines for NN and LKMC, while the open-source libraries OpenFOAM and Palabos were used for FVM and LB, respectively. Importantly, the parallel LKMC solver utilizes particle-based parallel decomposition allowing efficient use of cores over highly heterogeneous regions of the domain. The parallelized model was validated against a reference serial version for accuracy, demonstrating comparable results for both microfluidic and stenotic arterial clotting conditions. Moreover, the parallelized framework was shown to scale essentially linearly on up to 64 cores. Overall, the parallelized multiscale framework described here is demonstrated to be a promising approach for studying single-platelet resolved thrombosis at length scales that are sufficiently large to directly simulate coronary blood vessels.
Available cloned genes and markers for genetic improvement of biotic stress resistance in rice
Authors: Simon Eliza Vie , Hechanova Sherry Lou , Hernandez Jose E. , Li Charng-Pei , Tülek Adnan , Ahn Eok-Keun , Jairin Jirapong , Choi Il-Ryong , Sundaram Raman M. , Jena Kshirod K. , Kim Sung-Ryul
Published: September 2023

Biotic stress is one of the major threats to stable rice production. Climate change affects the shifting of pest outbreaks in time and space. Genetic improvement of biotic stress resistance in rice is a cost-effective and environment-friendly way to control diseases and pests compared to other methods such as chemical spraying. Fast deployment of the available and suitable genes/alleles in local elite varieties through marker-assisted selection (MAS) is crucial for stable high-yield rice production. In this review, we focused on consolidating all the available cloned genes/alleles conferring resistance against rice pathogens (virus, bacteria, and fungus) and insect pests, the corresponding donor materials, and the DNA markers linked to the identified genes. To date, 48 genes (independent loci) have been cloned for only major biotic stresses: seven genes for brown planthopper (BPH), 23 for blast, 13 for bacterial blight, and five for viruses. Physical locations of the 48 genes were graphically mapped on the 12 rice chromosomes so that breeders can easily find the locations of the target genes and distances among all the biotic stress resistance genes and any other target trait genes. For efficient use of the cloned genes, we collected all the publically available DNA markers (~500 markers) linked to the identified genes. In case of no available cloned genes yet for the other biotic stresses, we provided brief information such as donor germplasm, quantitative trait loci (QTLs), and the related papers. All the information described in this review can contribute to the fast genetic improvement of biotic stress resistance in rice for stable high-yield rice production.
Do yoga and meditation moderate the relationship between negative life events and depressive symptoms? Analysis of a national cross-sectional survey of Australian women
Authors: Lauche Romy , Anheyer Dennis , Uebelacker Lisa A. , Sibbritt David , Adams Jon , Cramer Holger
Published: September 2023

Objectives

This study aims to examine the role of yoga/meditation in the relationship between negative life events, stress and depression.

Methods

The Australian Longitudinal Study on Women’s Health (ALSWH) surveyed 7,186 women aged 36–43 years (mean age 39.2 years; 57.2% university degree) in 2015. Mediation and moderation analyses were conducted to examine whether yoga/meditation practice moderated those relationships.

Results

Yoga/meditation was practiced by 27.5% of participants, 33.2% reported negative life events in the past 12 months, and 24% had clinical depression. Perceived stress partially mediated the association between negative life events and depressive symptoms (B = 6.28; 95%CI 5.65; 6.92). Social support (B = −0.38; 95%CI −0.54; −0.23) and optimism (B = −0.25;95%CI −0.31; −0.18) moderated the association between stress and depressive symptoms. Yoga/meditation practice moderated the direct association between negative life events and depressive symptoms (B = −0.92; 95%CI −1.67; −0.18).

Conclusion

Yoga/meditation use was a significant moderator of the relationship between negative life events and depression. Yoga/mediation use did not act via reducing perceived stress, but instead was found to dampen the influence of negative life events on depression directly. More research on how yoga has an impact on depression is warranted.
Thinking by metaphor, fast and slow: Deliberate Metaphor Theory offers a new model for metaphor and its comprehension
Authors: Steen Gerard J.
Published: September 2023

The immense increase in metaphor theory and research over the past decades is posing a threat of fragmentation to the field, which has been responded to by calls for new and more encompassing approaches to virtually all aspects metaphorical. This article argues that the opposite response may be more productive. By focusing on a different way of theorizing metaphor and its comprehension, existing theories and data can be re-ordered in an alternative and coherent way, which moreover breaks new grounds in tying up both with a general theory for all utterance comprehension as well as a general theory for all cognition as involving fast and slow thinking. The core of the new theory highlights the differentiation between deliberate and non-deliberate metaphor use, related to how people see the use of a metaphor as a metaphor in communication, that is, as a metaphor that counts as a metaphor between language users. It shows how this distinction can be employed to make sense of many insights about metaphor and its comprehension in innovative ways. The article outlines the foundations of the new theory and discusses how existing data, old and new, can be seen as supporting the new proposals.
Who are the convoys of the happiness of Chinese urban residents? Research on social relations and subjective well-being based on the convoy model
Authors: Li Jianna , Guo Bin , Lu Mengyuan , Zhang Wen
Published: September 2023

Introduction

While the rapid advancement of urbanization has driven the improvement of material living standards, it has also brought about rapid social changes and intensified competition. In this “involutive” environment characterized by highly competitive and strong pressure, urban residents tend to fall into a state of “mental exhaustion.” Anxiety, depression, sleep disorders, and other mental illnesses have seriously threatened public health in Chinese cities. Support from social relations is crucial for enhancing residents’ subjective well-being (SWB) and promoting their mental health, especially in China’s highly contextualized collectivist culture.

Methods

According to the social structure of China’s “difference sequence pattern,” this paper constructs a theoretical framework of the relationship between social relations and SWB based on the convoy model and uses CGSS2018 data to verify the applicability of the theoretical framework.

Results

Kinship and friendship positively relate to SWB, and their interaction effect is significantly negative. There is no necessary correlation between neighborhood and SWB. The relationship between social relations and SWB of different age groups is heterogeneous. In addition, the moderating effects of relative income and social class are significantly negative.

Discussion

Kinship and friendship are Chinese urban residents’ SWB convoys, and these two factors have an obvious substitution effect. The neighborhood has withdrawn from the convoy orbit of Chinese urban residents’ SWB, which may be related to neighborhood indifference caused by China’s housing system reform. From the life course perspective, the SWB convoys of young and middle-aged groups consist of kinship and friendship, while those of elderly people include kinship and neighborhood. In addition, for poor individuals living at the bottom of society, support from kinship is the most important source of social capital. These findings provide new insights into the relationship between social relations and the welfare of Chinese urban residents.
A weapon to fight against pervasive Omicron: systematic actions transiting to pre-COVID normal
Authors: Wang Na , Xue Jia , Xu Tianjiao , Li Huijie , Liu Bo
Published: September 2023

The Coronavirus Disease-2019 (COVID-19) pandemic is not just a health crisis but also a social crisis. Confronted with the resurgence of variants with massive infections, the triggered activities from personal needs may promote the spread, which should be considered in risk management. Meanwhile, it is important to ensure that the policy responses on citizen life to a lower level. In the face of Omicron mutations, we need to sum up the control experience accumulated, adapting strategies in the dynamic coevolution process while balancing life resumption and pandemic control, to meet challenges of future crises. We collected 46 cases occurring between 2021 and 2022, mainly from China, but also including five relevant cases from other countries around the world. Based on case studies, we combine micro-view individual needs/behaviors with macro-view management measures linking Maslow’s hierarchy of needs with the transmission chain of Omicron clusters. The proposed loophole chain could help identify both individual and management loopholes in the spread of the virus. The systematic actions that were taken have effectively combated these ubiquitous vulnerabilities at lower costs and lesser time. In the dynamic coevolution process, the Chinese government has made effective and more socially acceptable prevention policies while meeting the divergent needs of the entire society at the minimum costs. Systematic actions do help maintain the balance between individuals’ satisfaction and pandemic containment. This implies that risk management policies should reasonably consider individual needs and improve the cooperation of various stakeholders with targeted flexible measures, securing both public health and life resumption.
Risk of SARS-CoV-2 transmission in the close contacts in a small rural area in the Veneto Region (NE-Italy): past evidence for future scenarios
Authors: Bassanello Marco , Geppini Ruggero , Bonsembiante Erminio , Coli Ugo , Farencena Aldo , D’Aquino Maurizio , Gambaro Andrea , Buja Alessandra , Baldovin Tatjana
Published: September 2023

Background

During the first pandemic phase of COVID-19, an epidemiological study, named First survey, was conducted on the population of a small rural area in northern Italy. In spring 2020, the results showed how a prolonged lockdown slowed down the spread of the virus.

Methods

After contacting positive First Survey subjects and their families, those who decided to join voluntarily underwent a blood test to assess the presence of qualitative lgG about 2 months after the previous one. This was to determine if IgG persisted in individuals who tested positive in the First Survey as well as to assess the antibody status of their close family members, to determine if they were unintentionally infected.

Results

Based on serological analysis, 35.1% of the samples contained blood IgG. In subjects who tested positive during the First Survey, 62.5% remained IgG positive more than 2 months later. Among family members who were exposed to a positive relative, 23.7% were infected. Linear regression analysis showed that the presence of an infected person within a household resulted in the infection spreading to the others, but not excessively. Induced isolation extinguished the infection regardless of the extent of the contagion (intra-family or extra-family). Micro-outbreaks of SARS-Cov-2 infection which arose in the same household from extra-familial infections played a decisive role on the statistical significance of IgG-positive subjects (p < 0.001).

Discussion

The study reveal 52.6% of the IgG-positive subjects in the Second Survey came from the First Survey and 47.4% were family members previously in contact with positive subjects. Data suggest that there have been undiagnosed patients feeding the spread of the virus since the beginning of the pandemic. In conclusion, for future pandemics, it will be necessary: i) to ensure the rapid isolation of symptomatic patients and the early identification of their close contacts, ii) to carry out the maximum number of tests in the shortest possible time, both on symptomatic and asymptomatic subjects, and iii) to implement information campaigns to make people aware of their risks, and implement clear, non-conflicting communication.