bluuebunny/crossref_metadata_2025 huggingface dataset:
Alpha-hederin reprograms multi-miRNAs activity and overcome small extracellular vesicles-mediated paclitaxel resistance in NSCLC
Authors: Chang Yuzhen , Gao Xinyu , Jiang Yuchen , Wang Jingyi , Liu Liu , Yan Jun , Huang Gang , Yang Hao
Published: February 2024

Background: Small extracellular vesicles (sEVs) mediate intercellular communication in the tumor microenvironment (TME) and contribute to the malignant transformation of tumors, including unrestricted growth, metastasis, or therapeutic resistance. However, there is a lack of agents targeting sEVs to overcome or reverse tumor chemotherapy resistance through sEVs-mediated TME reprogramming.

Methods: The paclitaxel (PTX)-resistant A549T cell line was used to explore the inhibitory effect of alpha-hederin on impeding the transmission of chemoresistance in non-small cell lung cancer (NSCLC) through the small extracellular vesicles (sEVs) pathway. This investigation utilized the CCK-8 assay and flow cytometry. Transcriptomics, Western blot, oil red O staining, and targeted metabolomics were utilized to evaluate the impact of alpha-hederin on the expression of signaling pathways associated with chemoresistance transmission in NSCLC cells before and after treatment. In vivo molecular imaging and immunohistochemistry were conducted to assess how alpha-hederin influences the transmission of chemoresistance through the sEVs pathway. RT-PCR was employed to examine the expression of miRNA and lncRNA in response to alpha-hederin treatment.

Results: The resistance to PTX chemotherapy in A549T cells was overcome by alpha-hederin through its dependence on sEV secretion. However, the effectiveness of alpha-hederin was compromised when vesicle secretion was blocked by the GW4869 inhibitor. Transcriptomic analysis for 463 upregulated genes in recipient cells exposed to A549T-derived sEVs revealed that these sEVs enhanced TGFβ signaling and unsaturated fatty acid synthesis pathways. Alpha-hederin inhibited 15 types of unsaturated fatty acid synthesis by reducing the signaling activity of the sEVs-mediated TGFβ/SMAD2 pathway. Further, we observed that alpha-hederin promoted the production of three microRNAs (miRNAs, including miR-21-5p, miR-23a-3p, and miR-125b-5p) and the sorting to sEVs in A549T cells. These miRNAs targeted the TGFβ/SMADs signaling activity in sEVs-recipient cells and sensitized them to the PTX therapy.

Conclusion: Our finding demonstrated that alpha-hederin could sensitize PTX-resistant NSCLC cells by sEV-mediated multiple miRNAs accumulation, and inhibiting TGFβ/SMAD2 pathways in recipient cells.
Favorable response to PD-1 inhibitor plus chemotherapy as first-line treatment for metastatic gastric mixed neuroendocrine-non-neuroendocrine tumor: a case report
Authors: Zheng Lingnan , Sun Lingqi , Ma Ji
Published: February 2024

Gastric mixed neuroendocrine-non-neuroendocrine tumor (MiNEN), a rare malignancy, currently has no standard treatment. Here, we report a patient with pathologically confirmed gastric MiNEN following radical surgery with rapid postoperative distant tumor recurrence. Immunofluorescence results suggested intensive lymphocyte infiltration in the tumor. The programmed death receptor ligand 1 (PD-L1) immunohistochemistry 22C3 pharmDx assay showed tumor proportion score was 5% and combined positive score was 10. After 6 cycles of treatment with etoposide and cisplatin in combination with toripalimab, efficacy was assessed as a complete response. Our report shows that for gastric MiNEN patients with high expression of PD-L1, chemotherapy combined with immune checkpoint inhibitors may achieve more significant efficacy.
Exploring the impact of seasonal variations on the chemical composition, antinociceptive, and anti-inflammatory properties of Pogostemon heyneanus Benth. essential oil
Authors: Santos Paulo Vinicius Lima , Jerônimo Lucas Botelho , Ribeiro Weyda Suyane Campos , Lopes Gustavo Moraes , Leão Neto João Henrique de Castro , da Silva Hugo Borges Oliveira , da Silva Pedro Iuri C. , Silva Renata Cunha , da Silva Joyce Kelly , Freitas Jofre Jacob S. , Mourão Rosa Helena V. , Setzer William N. , Maia José Guilherme S. , Figueiredo Pablo Luis B.
Published: February 2024

Background:Pogostemon heyneanus leaves infusions are relevant in ethnopharmacology for treating colds, coughs, headaches, and asthma.

Purpose: The essential oil chemical composition of a Pogostemon heyneanus specimen was monthly monitored from October 2021 to July 2022 to evaluate the climatic influences on its yield and chemical composition and antinociceptive, andanti-inflammatory properties.

Methods: The leaves, collected monthly over a 10-month period, were submitted to hydrodistillation. The oils obtained were analyzed by gas chromatography coupled to a mass spectrometer and gas chromatography coupled to flame ionization detector. The P. heyneanus essential oil (PhEO) was tested in vivo to evaluate its peripheral analgesic actions through the abdominal writhing test induced by acetic acid, and peripheral analgesia by tail immersion. Neurogenic and inflammatory pain were evaluated by formalin test, and acute oral toxicity of the oil was also verified.

Results: PhEO presented 27 chemical constituents with the highest predominance of patchoulol (43.6%–76.9%), α-bulnesene (0.2%–12.7%), α-guaiene (0.4%–8.9%), seychellene (3.8%–5.1%) and pogostol (0.0%–8.2%). The climatic parameters insolation, humidity, rainfall, and temperature did not influence the essential oil yield or the main chemical constituents, except for pogostol, which presented a strong (r = 0.73) and statistically significant (p < 0.05) correlation with temperature. PhEO did not display toxicity at the maximum 300 mg/kg dosage. The oil showed low peripheral and central analgesic action at 100 mg/kg, while in the neurogenic and inflammatory pain inhibition tests, no actions related to PhEO were observed. In the carrageenan-induced peritonitis test, PhEO did not reduce the migration of leukocytes to the peritoneal cavity compared to the control group.

Conclusion:Pogostemon heyneanus is a resistant plant to seasonal influences and a source of patchoulol. Despite ethnopharmacological indications, no in-vivo biological activities such as neurogenic or inflammatory pain were identified in the present work. So, the low influence of the climatic parameters on chemical composition can infer that the low pharmacological activity is also not subject to climatic variations, that is, it does not change due to the climate.
Sesamin ameliorates nonalcoholic steatohepatitis through inhibiting hepatocyte pyroptosis in vivo and in vitro
Authors: Zhang Teng , Zhou Yong , Zhang Yan , Wang De-Guo , Lv Qiu-Yue , Wang Wen , Bai Ya-Ping , Hua Qiang , Guo Li-Qun
Published: February 2024

Sesamin (Ses) is a natural lignan abundantly present in sesame and sesame oil. Pyroptosis, a newly identified type of pro-inflammatory programmed necrosis, contributes to the development of non-alcoholic steatohepatitis (NASH) when hepatocyte pyroptosis is excessive. In this study, Ses treatment demonstrated an improvement in hepatic damage in mice with high-fat, high-cholesterol diet-induced NASH and palmitate (PA)-treated mouse primary hepatocytes. Notably, we discovered, for the first time, that Ses could alleviate hepatocyte pyroptosis both in vivo and in vitro. Furthermore, treatment with phorbol myristate acetate, a protein kinase Cδ (PKCδ) agonist, increased PKCδ phosphorylation and attenuated the protective effects of Ses against pyroptosis in PA-treated mouse primary hepatocytes. Mechanistically, Ses treatment alleviated hepatocyte pyroptosis in NASH, which was associated with the regulation of the PKCδ/nod-like receptor family CARD domain-containing protein 4/caspase-1 axis. This study introduces a novel concept and target, suggesting the potential use of functional factors in food to alleviate liver damage caused by NASH.
Will wealth inequality decrease happiness?—Empirical evidence from China
Authors: Wang Jingtao
Published: February 2024

Introduction

This article delves into the broad social and economic impacts of wealth inequality, specifically focusing on its effects on happiness, as analyzed using micro survey data from the China Family Panel Studies (CFPS).

Methods

This article employs the panel OLS regression method with time and province fixed effects for the main result and heterogeneity analysis, then uses the mediating effect and moderating effect test for the mechanisms.

Results and discussion

The article presents several key findings: 1. Impact of Wealth Inequality on Happiness. The study confirms that wealth inequality significantly reduces happiness, a conclusion reinforced by a range of consistency tests and endogeneity checks. 2. Heterogeneity Analysis. Three areas of heterogeneity are examined: Hukou status, education level, and family members’ average income. The results indicate that the happiness of families with a family head holding an urban Hukou, higher education, or a higher per-member income level is less affected by wealth inequality. 3. Mechanisms Affecting Happiness. At the micro-level, the article identifies two mediating pathways—health and marital status—through which wealth inequality negatively influences happiness. At the macro-level, it is found that social security expenditure and economic development can moderate these effects and enhance subjective happiness under the same conditions of wealth inequality. The contributions of this study are specific as: 1. This study addresses some of the existing gaps in the research regarding the relationship between wealth inequality and happiness. 2. The article utilizes relative deprivation as a measure of wealth inequality, considered a more apt metric for studying happiness compared to absolute inequality. 3. This research offers insights into the mechanisms behind the observed effects, considering both micro-level (individual and family) and macro-level (societal and economic) factors.
Multimodal measurements enhance insights into emotional responses to immediate feedback
Authors: Horvers Anne , Molenaar Inge , Van Der West Heleen , Bosse Tibor , Lazonder Ard W.
Published: February 2024

Adaptive learning technologies often provide students with immediate feedback on task performance. This feedback can elicit various emotional responses, which, in turn, influence learning. Most recent studies capture these emotions by single data streams, contradicting the multi-componential nature of emotion. Therefore, this study investigated 32 university students solving mathematical problems using an adaptive learning technology. Students received immediate feedback on every step in the solution process, after which their physiological, experiential and behavioral responses to this feedback were recorded. Physiological arousal was measured by electrodermal activity, valence was measured by self-reports (experiential), and emotion types were measured by observations of facial expressions (behavioral). Results showed more peaks in electrodermal activity after feedback than was expected based on chance. These responses were comparable in strength after feedback on failure and success. Students’ experiential responses conveyed mostly positive valence after feedback on success and mostly negative valence after feedback on failure. Behavioral observations showed more negative than positive emotion types after feedback on failure and more positive than negative emotion types after feedback on success. These results show that physiological arousal is a valuable objective indicator of emotional responses after immediate feedback but should be accompanied by other data streams in order to understand students’ emotional responses. Both valence and emotion types can be used for this purpose. These outcomes pave the way for designing adaptive learning technologies that take students’ emotions into account.
Ketamine-assisted psychotherapy, psychedelic methodologies, and the impregnable value of the subjective—a new and evolving approach
Authors: Wolfson Phil , Vaid Gita
Published: February 2024

Psychiatry is in a growth phase in which several psychedelic medicines have entered its arena with great promise. Of these, presently, ketamine is the only medicine that may be legally prescribed. We hypothesize that at subanesthetic doses, ketamine produces a unique spectrum of altered states, ranging from psychoactive to deep ego-dissolving experiences, that are intrinsic to ketamine’s therapeutic effects. When these experiences are embedded in a therapeutic relationship—a setting—that fosters an amplification of the recipient’s subjective consciousness, personal growth, inner healing, greater clarity, and better relationships may well ensue. While much of the literature on ketamine labels its dissociative effects as ‘side effects’, alteration of consciousness is a component and unavoidable ‘effect’ of its therapeutic impact. From its inception in the clinical trials of the 1960s, ketamine was recognized for producing dissociative, psychedelic effects on consciousness in subjects as they emerged from ketamine-induced anesthesia. Unanticipated and unintegrated, these experiences of ‘emergence phenomena’ were felt to be disturbing. Accordingly, such experiences have been typically labeled as dissociative side effects. However, in a conducive set and settings, these experiences have been demonstrated to be of positive use in psychiatry and psychotherapy, providing a time-out from usual states of mind to facilitate a reshaping of self-experience along with symptomatic relief. In this way, ketamine-assisted psychotherapy (KAP) offers a new potential in psychiatry and psychotherapy that is powerfully valanced toward recognizing experience, individuality, and imagination. Essential to a successful therapeutic experience and outcome with KAP is close attention to the subjective experience, its expression by the recipient and integration of the ketamine experience as a healing opportunity.
Gut microbial diversity moderates polygenic risk of schizophrenia
Authors: Zhang Liyuan , Yuan Xiuxia , Li Xue , Zhang Xiaoyun , Mao Yiqiao , Hu Shaohua , Andreassen Ole A. , Wang Yunpeng , Song Xueqin
Published: February 2024

Background

Schizophrenia (SCZ) is a heritable disorder with a polygenic architecture, and the gut microbiota seems to be involved in its development and outcome. In this study, we investigate the interplay between genetic risk and gut microbial markers.

Methods

We included 159 first-episode, drug-naïve SCZ patients and 86 healthy controls. The microbial composition of feces was characterized using the 16S rRNA sequencing platform, and five microbial α-diversity indices were estimated [Shannon, Simpson, Chao1, the Abundance-based Eoverage Estimator (ACE), and a phylogenetic diversity-based estimate (PD)]. Polygenic risk scores (PRS) for SCZ were constructed using data from large-scale genome-wide association studies. Effects of microbial α-diversity, microbial abundance, and PRS on SCZ were evaluated via generalized linear models.

Results

We confirmed that PRS was associated with SCZ (OR = 2.08, p = 1.22×10−5) and that scores on the Shannon (OR = 0.29, p = 1.15×10−8) and Simpson (OR = 0.29, p = 1.25×10−8) indices were inversely associated with SCZ risk. We found significant interactions (p < 0.05) between PRS and α-diversity indices (Shannon, Simpson, and PD), with the effects of PRS being larger in those exhibiting higher diversity compared to those with lower diversity. Moreover, the PRS effects were larger in individuals with a high abundance of the genera Romboutsia, Streptococcus, and Anaerostipes than in those with low abundance (p < 0.05). All three of these genera showed protective effects against SCZ.

Conclusion

The current findings suggest an interplay between the gut microbiota and polygenic risk of SCZ that warrants replication in independent samples. Experimental studies are needed to determine the underpinning mechanisms.
In constant search of the good: a qualitative study into insiders’ perspectives on living well with dementia
Authors: Yaron Gili , Bakker Franka , de Bruin Simone
Published: February 2024

Introduction

The new concept of ‘living well with dementia’ is currently gaining traction in practice, policy, and research. However, people with dementia and their carers’ own understanding of this concept has not received much scholarly attention. This is because empirical studies into living well with dementia are predominantly quantitative; there are only a few qualitative studies on this topic. This study therefore sets out to investigate what living well means for ‘insiders’ in an everyday context.

Methods

To explore insiders’ own perspectives on living well with dementia, we conducted interviews and focus group discussions with 21 dementia stakeholders. The study included ten individuals with mild-to-moderate dementia living at home, five family carers who are or have been involved in the care for a person with dementia, and six health and social care professionals.

Results

Living well with dementia, for our study participants, revolves around shaping their daily lives according to their values. In this sense, living well with dementia is no different than without. As it involves the values of the person with dementia and those of their social network, living well is both an individual and a collective concern. Having dementia undermines people with dementia's ability to substantiate their values, but it is still possible to live well. As they attempt to shape living well with dementia, respondents encounter tensions within the social network and within the person with dementia. To handle these tensions, they work for mutual attunement by using sensitivity and switching between leading and following in social interactions.

Discussion

Living well with dementia in a daily context is a dynamic process in which people with dementia, family carers, and professionals constantly seek the good together. This insight contributes to a better understanding of stakeholders’ ongoing, invisible efforts to mutually attune. It may also help bypass dichotomizing approaches to dementia. Finally, it opens up new venues for research into reciprocity in the care collective. The article closes with recommendations to improve dementia care and support in light of these findings.
Evolutionary conservation of putative suicidality-related risk genes that produce diminished motivation corrected by clozapine, lithium and antidepressants
Authors: Ajayi Titilade , Thomas Alicia , Nikolic Marko , Henderson Lauryn , Zaheri Alexa , Dwyer Donard S.
Published: February 2024

Background

Genome wide association studies (GWAS) and candidate gene analyses have identified genetic variants and genes that may increase the risk for suicidal thoughts and behaviors (STBs). Important unresolved issues surround these tentative risk variants such as the characteristics of the associated genes and how they might elicit STBs.

Methods

Putative suicidality-related risk genes (PSRGs) were identified by comprehensive literature search and were characterized with respect to evolutionary conservation, participation in gene interaction networks and associated phenotypes. Evolutionary conservation was established with database searches and BLASTP queries, whereas gene-gene interactions were ascertained with GeneMANIA. We then examined whether mutations in risk-gene counterparts in C. elegans produced a diminished motivation phenotype previously connected to suicide risk factors.

Results and conclusions

From the analysis, 105 risk-gene candidates were identified and found to be: 1) highly conserved during evolution, 2) enriched for essential genes, 3) involved in significant gene-gene interactions, and 4) associated with psychiatric disorders, metabolic disturbances and asthma/allergy. Evaluation of 17 mutant strains with loss-of-function/deletion mutations in PSRG orthologs revealed that 11 mutants showed significant evidence of diminished motivation that manifested as immobility in a foraging assay. Immobility was corrected in some or all of the mutants with clozapine, lithium and tricyclic antidepressant drugs. In addition, 5-HT2 receptor and muscarinic receptor antagonists restored goal-directed behavior in most or all of the mutants. These studies increase confidence in the validity of the PSRGs and provide initial clues about possible mechanisms that mediate STBs.
Locked down-locked in: experiences of families of young children with autism spectrum disorders in Delhi, India
Authors: Kaur Abhipreet , Lall Gitanjali , Abhilashi Minal , Naithani Lavangi , Verma Mamta , Roy Reetabrata , Juneja Monica , Gulati Sheffali , Taylor Carol , Leadbitter Kathy , Patel Vikram , Green Jonathan , Divan Gauri
Published: February 2024

Introduction

The onset of the COVID-19 pandemic and subsequent lockdowns in March 2020 disrupted the lives of families across India. The lockdown related restrictions brought forth a multitude of challenges including loss of employment, social isolation, school closures and financial burdens. Specifically, it also resulted in the restriction of health-care services for children with neurodevelopmental disabilities.

Methods

This qualitative study was conducted as a part of a larger trial in India to understand the experiences of families of young children with autism during the pandemic. In-depth interviews were carried out with 14 caregivers residing in New Delhi, India.

Results

Our findings identified pandemic and lockdown’s universal impacts on family life and financial stability stemming from job loss, business closure, and salary deductions, affecting quality of life of families. Furthermore, COVID-19 pandemic’s impact on autistic children was evident through limited access to essential services and financial challenges related service interruptions even after resumption of services. The lockdown’s novelty also affected children’s behavior, with both challenging behavioral changes and positive impacts. Primary caregivers, predominantly mothers, assumed additional responsibilities in household tasks, schooling, and therapy administration. While some these experiences were universally experienced, a few of these improved outcomes for autistic children. Despite challenges, parents expressed gratitude for their family’s safety and well-being during the difficult time.

Discussions

These findings inform service provision for vulnerable families and offer implications for designing interventions such as credit schemes for families, guidance and resources for establishing and maintaining routines of children with autism, adopting flexible and adaptable approaches to service delivery, and special provisions for children with autism to be able to maintain their routines outside of home. Furthermore, the study highlights the need for comprehensive support, including educational resources and stress management counselling to empower parents in supporting essential care and routines for their children during such unprecedented times.
Bone union and mobility outcomes for reconstructed open tibial fractures: a plastic surgical experience from a major trauma center
Authors: Sreedharan Sadhishaan , Bruscino-Raiola Frank , Lew Philip , Ling Yuan , Ferris Scott
Published: February 2024

Introduction

The goal in open tibial fracture management is to achieve a united tibia in an extremity that allows pain free mobilization. The objective of this study was to assess factors that lead to this functional outcome in lower limb reconstruction, from a plastic surgical perspective.

Materials and methods

The Plastic and Reconstructive Surgery lower limb database at a tertiary trauma hospital was searched for open tibial injuries from February 2015 to March 2020. The nature and severity of injury, timing and details of all operations including reconstructions were collected prospectively. Mobility including gait aids, pain, and complications were retrospectively collected. Union was assessed in two ways, depending on fracture location. Metaphyseal and diaphyseal tibial fractures were provided mRUST scores (union defined as RUST > 13) and epiphyseal tibial fractures were categorically classified as “united” or “non-union” by two independent radiologists.

Results

During the five-year study period there were 148 open leg injuries in the database. Twenty-one patients underwent a primary amputation due to severity of their initial injury. One hundred patients underwent primary limb salvage. Sixty-one patients in the limb salvage group achieved primary tibial union with a mean follow-up time of 19.4 months post injury. Twenty-three additional patients were confirmed to subsequently unite. Patient who achieved union were more likely to mobilise without gait aids.

Discussion

In this study definitive external fixation and soft tissue infection were both associated with higher rates of non-union. Longer times to soft tissue reconstruction was not associated with an increase in acute soft tissue complications. More importantly bone union, pain and mobility did not decline. After undertaking a primary limb salvage pathway for 100 patients, the ultimate tibial fracture union rate was 84% and the confirmed ambulation rate was 96%.
Self-Reported Health as Predictor of Allostatic Load and All-Cause Mortality: Findings From the Lolland-Falster Health Study
Authors: Bruun-Rasmussen Neda Esmailzadeh , Napolitano George , Bojesen Stig Egil , Ellervik Christina , Rasmussen Knud , Lynge Elsebeth
Published: February 2024

Objectives: The aim was to determine the association between self-reported health (SRH), allostatic load (AL) and mortality.

Methods: Data derived from the Lolland-Falster Health Study undertaken in Denmark from 2016–2020 (n = 14,104). Median follow-up time for death was 4.6 years where 456 participants died. SRH was assessed with a single question and AL by an index of ten biomarkers. Multinomial regression analysis were used to examine the association between SRH and AL, and Cox regression to explore the association between SRH, AL and mortality.

Results: The risk of high AL increased by decreasing level of SRH. The ratio of relative risk (RRR) of having medium vs. low AL was 1.58 (1.11–2.23) in women reporting poor/very poor SRH as compared with very good SRH. For men it was 1.84 (1.20–2.81). For high vs. low AL, the RRR was 2.43 (1.66–3.56) in women and 2.96 (1.87–4.70) in men. The hazard ratio (HR) for all-cause mortality increased by decreasing SRH. For poor/very poor vs. very good SRH, the HR was 6.31 (2.84–13.99) in women and 3.92 (2.12–7.25) in men.

Conclusion: Single-item SRH was able to predict risk of high AL and all-cause mortality.
Mapping Research on Natural Capital Accounting: A Strategic Challenge for Multinational Firms
Authors: García-López María-Jose , Pérez-Hernández Francisco
Published: February 2024

In the contemporary context, characterized by the paramount importance of sustainability, both governments and companies, particularly multinational enterprises (MNEs), play an important role in fostering and overseeing the transformative processes necessary to establish a robust accounting framework for natural capital. The objective of this paper is twofold: firstly, to conduct a comprehensive review of the existing body of literature on this subject and to highlight the importance of avoiding intangible liabilities in MNE from bad practices based on Natural Capital bad practices, and secondly, to outline prospective directions for further research in this domain. To achieve these objectives, we pose two fundamental research questions: (1) What is the current state of knowledge regarding the intangible liabilities and accounting practices of MNEs concerning Natural Capital? (2) How can future research in the field of Natural Capital Accounting be oriented to assist MNEs in accounting for their interactions with Natural Capital? A mixed-method approach is used to address these inquiries. Initially, we substantiate the intrinsic connection between MNEs and the natural environment, utilizing bibliometric techniques to identify the primary themes and areas of focus in the realm of natural capital accounting. Subsequently, we employ in-depth analysis and logical reasoning to propose potential avenues for future research. Additionally, we present a comprehensive model designed to guide forthcoming research endeavors in the domain of natural capital accounting. Among the salient findings derived from our model analysis, it is evident that the inclusion of other environmental factors, such as ecosystem services and biodiversity, should be integral to the overall framework of natural capital accounting. Furthermore, the incorporation of such accounting practices into the day-to-day operations of companies is essential to preserving the natural capital and the reputation of the firms.
Do Animal Welfare Education Campaigns Really Work? An Evaluation of the RSPCA’s #DogKind Campaign in Raising Awareness of Separation-Related Behaviours in UK Dog Owners
Authors: Philpotts Izzie , Blackwell Emily J. , Dillon Justin , Rooney Nicola J.
Published: February 2024

One of the main aims of companion animal welfare charities is to educate the public about the needs of animals. This is frequently performed through campaigns focusing on specific aspects of welfare. The Royal Society for the Prevention of Cruelty to Animals (RSPCA), Britain’s biggest animal welfare charity, launched the nationwide #DogKind campaign in March 2019. Targeted mainly at 25–34-year-olds, the campaign aimed to increase awareness of separation-related behaviour (SRB) among dog owners and encourage them to seek help for SRB from reliable sources. This research involved a quasi-experimental, non-equivalent control group design evaluating the campaign’s effectiveness. It was conducted through a series of online surveys at three different time points: before the launch of the campaign (n = 2002), six months after (n = 2423), and, again, two months later (n = 269), during which we asked the same questions regarding knowledge of SRB. An experimental trial of 269 participants tested whether accessing a video alongside the campaign web pages increased the effectiveness of the campaign objectives. Overall, the campaign appeared to be effective in reaching its target audience but not at raising awareness of SRB or increasing the number of owners intending to seek help. The inclusion of a video in the campaign made no difference to its effectiveness. This study shows that this campaign had limited success in achieving its targets and highlights the importance of thorough evaluations of education interventions that aim to improve the welfare of companion animals.
Characterisation of Dry-Salted Violino and Bresaola from Grass-Fed Bergamasca Sheep
Authors: Lopez Annalaura , Mainardi Edda , Beretta Ernesto , Ratti Sabrina , Bellagamba Federica , Corino Carlo , Moretti Vittorio Maria , Rossi Raffaella
Published: February 2024

This study focuses on characterising two seasoned products, violino and bresaola, derived from grass-fed Bergamasca sheep monitored with a GPS system. The evaluation includes both nutritional and sensory aspects. Results reveal that both products boast a high protein content (approximately 40%) and a beneficial fatty acid profile, endorsing a healthy n-6/n-3 ratio (2.2), along with rumenic acid (92–184 mg/100 g) and branched-chain fatty acids (BCFAs) (237–621 mg/100 g). The sensory evaluation highlights distinctive ovine characteristics in aroma and flavour. Violino and bresaola from grass-fed Bergamasca sheep showcase positive attributes for human consumption. The study emphasises the potential for added value to seasoned products from Bergamasca sheep through a traceable, sustainable, and health-conscious supply chain.
Bone Marrow Mesenchymal Stem Cell-Derived Exosomes Ameliorate Aging-Induced BTB Impairment in Porcine Testes by Activating Autophagy and Inhibiting ROS/NLRP3 Inflammasomes via the AMPK/mTOR Signaling Pathway
Authors: Zhou Yi , Yan Jiale , Qiao Limin , Zeng Jiaqin , Cao Fuyu , Sheng Xihui , Qi Xiaolong , Long Cheng , Liu Bingying , Wang Xiangguo , Yao Hua , Xiao Longfei
Published: February 2024

As a pivotal player in spermatogenesis, the blood-testis barrier (BTB) made from junction apparatus coexisting in Sertoli cells (SCs) is impaired with an increase in age and ultimately induces spermatogenic dysfunction or even infertility. It has been corroborated that bone marrow mesenchymal stem cell (BMSC) transplantation can efficiently repair and regenerate the testicular function. As vital mediators of cell-to-cell communication, MSC-derived exosomes (Exos) can directly serve as therapeutic agents for tissue repair and regeneration. However, the therapeutic value of BMSC-Exos in aging-induced BTB damage remains to be confirmed. In this study, we explored that the old porcine testes had defective autophagy, which aggravated BTB disruption in SCs. BMSC-Exos could decrease ROS production and NLRP3 inflammasome activation but enhanced autophagy and tight junction (TJ) function in D-gal-triggered aging porcine SCs and mouse model testes, according to in vitro and in vivo experiments. Furthermore, rapamycin, NAC, MCC950, and IL-1Ra restored the TJ function in D-gal-stimulated aging porcine SCs, while BMSC-Exos’ stimulatory effect on TJ function was inhibited by chloroquine. Moreover, the treatment with BMSC-Exos enhanced autophagy in D-gal-induced aging porcine SCs by means of the AMPK/mTOR signal transduction pathway. These findings uncovered through the present study that BMSC-Exos can enhance the BTB function in aging testes by improving autophagy via the AMPK/mTOR signaling pathway, thereby suppressing ROS production and NLRP3 inflammasome activation.
Increased Diabetes Complications in a Mouse Model of Oxidative Stress Due to ‘Mismatched’ Mitochondrial DNA
Authors: Januszewski Andrzej S. , Blake Rachel , Zhang Michael , Ma Ben , Anand Sushma , Pinkert Carl A. , Kelly Darren J. , Jenkins Alicia J. , Trounce Ian A.
Published: February 2024

Associations between chronic diabetes complications and mitochondrial dysfunction represent a subject of major importance, given the diabetes pandemic and high personal and socioeconomic costs of diabetes and its complications. Modelling diabetes complications in inbred laboratory animals is challenging due to incomplete recapitulation of human features, but offer mechanistic insights and preclinical testing. As mitochondrial-based oxidative stress is implicated in human diabetic complications, herein we evaluate diabetes in a unique mouse model that harbors a mitochondrial DNA from a divergent mouse species (the ‘xenomitochondrial mouse’), which has mild mitochondrial dysfunction and increased oxidative stress. We use the streptozotocin-induced diabetes model with insulin supplementation, with 20-weeks diabetes. We compare C57BL/6 mice and the ‘xenomitochondrial’ mouse, with measures of heart and kidney function, histology, and skin oxidative stress markers. Compared to C57BL/6 mice, the xenomitochondrial mouse has increased diabetic heart and kidney damage, with cardiac dysfunction, and increased cardiac and renal fibrosis. Our results show that mitochondrial oxidative stress consequent to divergent mtDNA can worsen diabetes complications. This has implications for novel therapeutics to counter diabetes complications, and for genetic studies of risk, as mtDNA genotypes may contribute to clinical outcomes.
A Model of Hepatitis B Viral Dynamics with Delays
Authors: Chen-Charpentier Benito
Published: February 2024

Hepatitis B is a liver disease caused by the human hepatitis B virus (HBV). Mathematical models help further the understanding of the processes involved and help make predictions. The basic reproduction number, R0, is an index that predicts whether the disease will be chronic or not. This is the single most-important information that a mathematical model can give. Within-host virus processes involve delays. We study two within-host hepatitis B virus infection models without and with delay. One is a standard one, and the other considering additional processes and with two delays is new. We analyze the basic reproduction number and alternative threshold indices. The values of R0 and the alternative indices change depending on the model. All these indices predict whether the infection will persist or not, but they do not give the same rate of growth of the infection when it is starting. Therefore, the choice of the model is very important in establishing whether the infection is chronic or not and how fast it initially grows. We analyze these indices to see how to decrease their value. We study the effect of adding delays and how the threshold indices depend on how the delays are included. We do this by studying the local asymptotic stability of the disease-free equilibrium or by using an equivalent method. We show that, for some models, the indices do not change by introducing delays, but they change when the delays are introduced differently. Numerical simulations are presented to confirm the results. Finally, some conclusions are presented.
Composition, Distribution, and Biodiversity of Zooplanktons in Tropical Lentic Ecosystems with Different Environmental Conditions
Authors: Umi Wahidah Ahmad Dini , Yusoff Fatimah M. , Balia Yusof Zetty Norhana , Ramli Norulhuda Mohamed , Sinev Artem Y. , Toda Tatsuki
Published: February 2024

A study was conducted to evaluate zooplankton species composition, abundance, and diversity in both natural and artificial lakes with varying trophic levels and to determine the relationship between zooplankton community structure and lake environmental conditions. This study hypothesized that correlations exist between zooplankton community structures and environmental parameters associated with eutrophication in natural and artificial lakes. Sampling was conducted across 16 distinct freshwater lentic ecosystems in Malaysia, including natural lakes/swamps, reservoirs, constructed lakes/ponds, and old mining lakes, spanning a range of trophic levels from mesotrophic to hypereutrophic conditions. Physicochemical parameters were measured in situ, while water and zooplankton samples were collected for nutrient analyses, as well as for zooplankton identification and enumeration. Throughout this study, a total of 58 zooplankton species, consisting of 36 species of rotifers, 12 species of cladocerans, and 10 species of copepods, were recorded. The highest zooplankton density (365.7 ± 13.7 ind L−1) was recorded in constructed lakes/ponds while the lowest density was recorded in natural shallow lakes/swamps (200.5 ± 25.5 ind L−1). On the other hand, significantly higher (p < 0.05) mean species diversity was observed in natural lakes/swamps (H’ = 2.2 ± 0.0); whereas, the lowest diversity was in old mining lakes (H’ = 1.5 ± 0.1). The canonical correspondence analysis (CCA) scores indicated that Polyarthra vulgaris and Chydorus ventricosus were the discriminating species in natural shallow lakes/swamps associated with high water transparency. Meanwhile, the small-sized cladocerans (Ceriodaphnia cornuta) and rotifers (Keratella spp., Brachionus spp., and Trichocerca spp.) were the most discriminating species in lakes with high turbidity, nutrients, and chlorophyll a concentrations, which are the main features of reservoirs and constructed lakes/ponds. Low density and diversity in old mining lakes were due to a low species number and the dominance of two species, Lophocharis curvata (38.8%) and Ptygura libera (39.7%). Overall, the high dominance of a specific zooplankton species resulted in lower biodiversity in artificial ecosystems compared to natural ecosystems. This study elucidated that zooplankton community structure in lakes was significantly influenced by the environmental conditions related to the lake trophic status.
A Numerical Modeling Study on the Earth’s Surface Brightening Effect of Cirrus Thinning
Authors: Shi Xiangjun , Liu Yuxin , Liu Jiaojiao
Published: February 2024

Cirrus thinning, as one kind of geoengineering approach, not only cools our planet but also enhances the amount of sunlight reaching the Earth’s surface (brightening effect). This study delves into the brightening effect induced by cirrus thinning with a flexible seeding method. The thinning of cirrus clouds alone leads to a considerable globally averaged cooling effect (−2.46 W m−2), along with a notable globally averaged brightening effect (2.19 W m−2). Cirrus thinning also results in substantial reductions in the cloud radiative effects of the lower mixed-phase and liquid clouds. While these reductions counteract the cooling effect from cirrus clouds, they enhance the brightening effect from cirrus clouds. Consequently, the brightening effect caused by cirrus seeding (4.69 W m−2) is considerably stronger than its cooling effect (−1.21 W m−2). Furthermore, due to the more pronounced changes from the mixed-phase and liquid clouds at low and mid-latitudes, the cooling effect is primarily concentrated at high latitudes. In contrast, the brightening effect is stronger over most low- and mid-latitude regions. Overall, cirrus thinning could lead to a notable brightening effect, which can be leveraged to offset the dimming effect (the opposite of the brightening effect) of other geoengineering approaches.
Application of SWATH Mass Spectrometry and Machine Learning in the Diagnosis of Inflammatory Bowel Disease Based on the Stool Proteome
Authors: Shajari Elmira , Gagné David , Malick Mandy , Roy Patricia , Noël Jean-François , Gagnon Hugo , Brunet Marie A. , Delisle Maxime , Boisvert François-Michel , Beaulieu Jean-François
Published: February 2024

Inflammatory bowel disease (IBD) flare-ups exhibit symptoms that are similar to other diseases and conditions, making diagnosis and treatment complicated. Currently, the gold standard for diagnosing and monitoring IBD is colonoscopy and biopsy, which are invasive and uncomfortable procedures, and the fecal calprotectin test, which is not sufficiently accurate. Therefore, it is necessary to develop an alternative method. In this study, our aim was to provide proof of concept for the application of Sequential Window Acquisition of All Theoretical Mass Spectra-Mass spectrometry (SWATH-MS) and machine learning to develop a non-invasive and accurate predictive model using the stool proteome to distinguish between active IBD patients and symptomatic non-IBD patients. Proteome profiles of 123 samples were obtained and data processing procedures were optimized to select an appropriate pipeline. The differentially abundant analysis identified 48 proteins. Utilizing correlation-based feature selection (Cfs), 7 proteins were selected for proceeding steps. To identify the most appropriate predictive machine learning model, five of the most popular methods, including support vector machines (SVMs), random forests, logistic regression, naive Bayes, and k-nearest neighbors (KNN), were assessed. The generated model was validated by implementing the algorithm on 45 prospective unseen datasets; the results showed a sensitivity of 96% and a specificity of 76%, indicating its performance. In conclusion, this study illustrates the effectiveness of utilizing the stool proteome obtained through SWATH-MS in accurately diagnosing active IBD via a machine learning model.
Depleted-MLH1 Expression Predicts Prognosis and Immunotherapeutic Efficacy in Uterine Corpus Endometrial Cancer: An In Silico Approach
Authors: Wolde Tesfaye , Huang Jing , Huang Peng , Pandey Vijay , Qin Peiwu
Published: February 2024

Uterine corpus endometrial carcinoma (UCEC) poses significant clinical challenges due to its high incidence and poor prognosis, exacerbated by the lack of effective screening methods. The standard treatment for UCEC typically involves surgical intervention, with radiation and chemotherapy as potential adjuvant therapies. In recent years, immunotherapy has emerged as a promising avenue for the advanced treatment of UCEC. This study employs a multi-omics approach, analyzing RNA-sequencing data and clinical information from The Cancer Genome Atlas (TCGA), Gene Expression Profiling Interactive Analysis (GEPIA), and GeneMANIA databases to investigate the prognostic value of MutL Homolog 1 (MLH1) gene expression in UCEC. The dysregulation of MLH1 in UCEC is linked to adverse prognostic outcomes and suppressed immune cell infiltration. Gene Set Enrichment Analysis (GSEA) data reveal MLH1’s involvement in immune-related processes, while its expression correlates with tumor mutational burden (TMB) and microsatellite instability (MSI). Lower MLH1 expression is associated with poorer prognosis, reduced responsiveness to Programmed cell death protein 1 (PD-1)/Programmed death-ligand 1 (PD-L1) inhibitors, and heightened sensitivity to anti-cancer agents. This comprehensive analysis establishes MLH1 as a potential biomarker for predicting prognosis, immunotherapy response, and drug sensitivity in UCEC, offering crucial insights for the clinical management of patients.
Interacting with Obstacles Using a Bio-Inspired, Flexible, Underactuated Multilink Manipulator
Authors: Prigozin Amit , Degani Amir
Published: February 2024

With the increasing demand for robotic manipulators to operate in complex environments, it is important to develop designs that work in obstacle-rich environments and can navigate around obstacles. This paper aims to demonstrate the capabilities of a bio-inspired, underactuated multilink manipulator in environments with fixed and/or movable obstacles. To simplify the system design, a single rotational actuator is used at the base of the manipulator. We present a modeling method for flexible, multilink underactuated manipulators, including their interaction with obstacles. We also demonstrate how to plan a trajectory for the manipulator in environments with fixed obstacles. The robustness of the manipulator is examined by analyzing the effects of uncertainty in its initial state and the position of obstacles. Next, we demonstrate the performance of the manipulator in environments with movable obstacles and show the advantages of controlling the obstacles’ radii and positions. Lastly, we showcase the process of picking up an object in workspaces with obstacles. All the findings are supported by simulations as well as hardware experiments.
Bioinspired Design and Experimental Validation of an Aquatic Snake Robot
Authors: Bianchi Giovanni , Lanzetti Luca , Mariana Daniele , Cinquemani Simone
Published: February 2024

This article presents the design, simulation, and experimental validation of a novel modular aquatic snake robot capable of surface locomotion. The modular structure allows each unit to function independently, facilitating ease of maintenance and adaptability to diverse aquatic environments. Employing the material point method with the moving least squares (MPM-MLS) simulation technique, the robot’s dynamic behavior was analyzed, yielding reliable results. The control algorithm, integral to the robot’s autonomous navigation, was implemented to enable forward propulsion at high speed, steering, and obstacle detection and avoidance. Extensive testing of the aquatic snake robot was conducted, demonstrating its practical viability. The robot showcased promising swimming capabilities, achieving high speeds and maneuverability. Furthermore, the obstacle detection and avoidance mechanisms were proven effective, showing the robot’s ability to navigate through dynamic environments. The presented aquatic snake robot represents an advancement in the field of underwater robotics, offering a modular and versatile solution for tasks ranging from environmental monitoring to search and rescue operations.