bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding iron homeostasis in MDS: the role of erythroferrone
Authors: Abba Mohammed L. , Riabov Vladimir , Nowak Daniel , Hofmann Wolf-Karsten , Boch Tobias
Published: May 2024

Myelodysplastic neoplasms (MDS) are a heterogenous group of clonal stem cell disorders characterized by dysplasia and cytopenia in one or more cell lineages. Anemia is a very common symptom that is often treated with blood transfusions and/or erythropoiesis stimulating factors. Iron overload results from a combination of these factors together with the disease-associated ineffective erythropoiesis, that is seen especially in MDS cases with SF3B1 mutations. A growing body of research has shown that erythroferrone is an important regulator of hepcidin, the master regulator of systemic iron homeostasis. Consequently, it is of interest to understand how this molecule contributes to regulating the iron balance in MDS patients. This short review evaluates our current understanding of erythroferrone in general, but more specifically in MDS and seeks to place in context how the current knowledge could be utilized for prognostication and therapy.
Mushroom-derived bioactive components with definite structures in alleviating the pathogenesis of Alzheimer’s disease
Authors: Jiang Xue , Song Yu , Lv Changshun , Li Yinghui , Feng Xiangru , Zhang Hao , Chen Yujuan , Wang Qingshuang
Published: May 2024

Alzheimer’s disease (AD) is a complicated neurodegenerative condition with two forms: familial and sporadic. The familial presentation is marked by autosomal dominance, typically occurring early in individuals under 65 years of age, while the sporadic presentation is late-onset, occurring in individuals over the age of 65. The majority of AD cases are characterized by late-onset and sporadic. Despite extensive research conducted over several decades, there is a scarcity of effective therapies and strategies. Considering the lack of a cure for AD, it is essential to explore alternative natural substances with higher efficacy and fewer side effects for AD treatment. Bioactive compounds derived from mushrooms have demonstrated significant potential in AD prevention and treatment by different mechanisms such as targeting amyloid formation, tau, cholinesterase dysfunction, oxidative stress, neuroinflammation, neuronal apoptosis, neurotrophic factors, ER stress, excitotoxicity, and mitochondrial dysfunction. These compounds have garnered considerable interest from the academic community owing to their advantages of multi-channel, multi-target, high safety and low toxicity. This review focuses on the various mechanisms involved in the development and progression of AD, presents the regulatory effects of bioactive components with definite structure from mushroom on AD in recent years, highlights the possible intervention pathways of mushroom bioactive components targeting different mechanisms, and discusses the clinical studies, limitations, and future perspectives of mushroom bioactive components in AD prevention and treatment.
Protein and metabolic profiles of tyrosine kinase inhibitors co-resistant liver cancer cells
Authors: Wang Zengbin , Wu Linqing , Zhou Yu , Chen Zhong , Zhang Tao , Wei Hong , Wang Zhihong
Published: May 2024

Hepatocellular Carcinoma (HCC) patients often develop resistance to tyrosine kinase inhibitors (TKIs) like sorafenib (SR) and lenvatinib (RR). We established HCC cell lines resistant to these drugs and analyzed the correlation between protein and metabolite profiles using bioinformatics. Our analysis revealed overexpression of MISP, CHMP2B, IL-18, TMSB4X, and EFEMP1, and downregulation of IFITM3, CA4, AGR2, and SLC51B in drug-resistant cells. Differential signals are mainly enriched in steroid hormone biosynthesis, cell adhesion, and immune synapses, with metabolic pathways including cytochrome P450 drug metabolism, amino acid metabolism, and glycolysis. Proteomics and metabolomics analysis showed co-enrichment signals in drug metabolism, amino acids, glucose metabolism, ferroptosis, and other biological processes. Knocking down MISP, CHMP2B, IL-18, TMSB4X, and EFEMP1 significantly reduced drug resistance, indicating their potential as therapeutic response biomarkers. This study characterizes protein and metabolic profiles of drug-resistant HCC cells, exploring metabolite-protein relationships to enhance understanding of drug resistance mechanisms and clinical treatment.
MPASL: multi-perspective learning knowledge graph attention network for synthetic lethality prediction in human cancer
Authors: Zhang Ge , Chen Yitong , Yan Chaokun , Wang Jianlin , Liang Wenjuan , Luo Junwei , Luo Huimin
Published: May 2024

Synthetic lethality (SL) is widely used to discover the anti-cancer drug targets. However, the identification of SL interactions through wet experiments is costly and inefficient. Hence, the development of efficient and high-accuracy computational methods for SL interactions prediction is of great significance. In this study, we propose MPASL, a multi-perspective learning knowledge graph attention network to enhance synthetic lethality prediction. MPASL utilizes knowledge graph hierarchy propagation to explore multi-source neighbor nodes related to genes. The knowledge graph ripple propagation expands gene representations through existing gene SL preference sets. MPASL can learn the gene representations from both gene-entity perspective and entity-entity perspective. Specifically, based on the aggregation method, we learn to obtain gene-oriented entity embeddings. Then, the gene representations are refined by comparing the various layer-wise neighborhood features of entities using the discrepancy contrastive technique. Finally, the learned gene representation is applied in SL prediction. Experimental results demonstrated that MPASL outperforms several state-of-the-art methods. Additionally, case studies have validated the effectiveness of MPASL in identifying SL interactions between genes.
Importance of cardiac-synchronized vagus nerve stimulation parameters on the provoked chronotropic response for different levels of cardiac innervation
Authors: Haberbusch Max , Kronsteiner Bettina , Aigner Philipp , Kiss Attila , Podesser Bruno Karl , Moscato Francesco
Published: May 2024

Introduction

The influence of vagus nerve stimulation (VNS) parameters on provoked cardiac effects in different levels of cardiac innervation is not well understood yet. This study examines the effects of VNS on heart rate (HR) modulation across a spectrum of cardiac innervation states, providing data for the potential optimization of VNS in cardiac therapies.

Materials and Methods

Utilizing previously published data from VNS experiments on six sheep with intact innervation, and data of additional experiments in five rabbits post bilateral rostral vagotomy, and four isolated rabbit hearts with additionally removed sympathetic influences, the study explored the impact of diverse VNS parameters on HR.

Results

Significant differences in physiological threshold charges were identified across groups: 0.09 ± 0.06 μC for intact, 0.20 ± 0.04 μC for vagotomized, and 9.00 ± 0.75 μC for isolated hearts. Charge was a key determinant of HR reduction across all innervation states, with diminishing correlations from intact (r = 0.7) to isolated hearts (r = 0.44). An inverse relationship was observed for the number of pulses, with its influence growing in conditions of reduced innervation (intact r = 0.11, isolated r = 0.37). Frequency and stimulation delay showed minimal correlations (r < 0.17) in all conditions.

Conclusion

Our study highlights for the first time that VNS parameters, including stimulation intensity, pulse width, and pulse number, crucially modulate heart rate across different cardiac innervation states. Intensity and pulse width significantly influence heart rate in innervated states, while pulse number is key in denervated states. Frequency and delay have less impact impact across all innervation states. These findings suggest the importance of customizing VNS therapy based on innervation status, offering insights for optimizing cardiac neuromodulation.
Trichoderma carraovejensis: a new species from vineyard ecosystem with biocontrol abilities against grapevine trunk disease pathogens and ecological adaptation
Authors: Zanfaño Laura , Carro-Huerga Guzmán , Rodríguez-González Álvaro , Mayo-Prieto Sara , Cardoza Rosa E. , Gutiérrez Santiago , Casquero Pedro A.
Published: May 2024

Trichoderma strains used in vineyards for the control of grapevine trunk diseases (GTDs) present a promising alternative to chemical products. Therefore, the isolation and characterization of new indigenous Trichoderma strains for these purposes is a valuable strategy to favor the adaptation of these strains to the environment, thus improving their efficacy in the field. In this research, a new Trichoderma species, Trichoderma carraovejensis, isolated from vineyards in Ribera de Duero (Spain) area, has been identified and phylogenetically analyzed using 20 housekeeping genes isolated from the genome of 24 Trichoderma species. A morphological description and comparison of the new species has also been carried out. In order to corroborate the potential of T. carraovejensis as a biological control agent (BCA), confrontation tests against pathogenic fungi, causing various GTDs, have been performed in the laboratory. The compatibility of T. carraovejensis with different pesticides and biostimulants has also been assessed. This new Trichoderma species demonstrates the ability to control pathogens such as Diplodia seriata, as well as high compatibility with powdered sulfur-based pesticides. In conclusion, the autochthonous species T. carraovejensis can be an effective alternative to complement the currently used strategies for the control of wood diseases in its region of origin.
Part-set cuing effects in spatial memory: the role of interitem associations
Authors: Zhao Yufei , Hou Xiao , Sun Yurong , Gao Fengqiang , Han Lei
Published: May 2024

Part-set cuing facilitation and impairment effects are rarely found in spatial memory, which is a challenge to the theories of part-set cuing effects based on lexical stimulus. This study aims to investigate whether there part-set cuing facilitation and impairment effects are present in spatial memory by constructing two types of memory scenes with high and low degrees of interitem associations, achieved by manipulating the presentation of miniatures. This study examined the effects of different part-set cues on free recall, recognition, and reconstruction tasks. The results of two experiments revealed that matrix cues impaired the performance of three recall tasks in memory scenes with a high degree of interitem associations, and scene cues facilitated the reconstruction performance (Experiment 1). Conversely, in memory scenes with a low degree of interitem associations, the impairment effect of matrix cues was not observed in the three recall tasks, but scene cues still facilitated the reconstruction performance (Experiment 2). These findings supported the retrieval strategy disruption hypothesis, the two-mechanism and the multi-mechanism accounts, demonstrating the significance of interitem associations in spatial memory. Furthermore, the results provided direct evidence for the importance of the encoding-retrieval strategy matching principle in spatial memory tasks.
Predictive language processing: integrating comprehension and production, and what atypical populations can tell us
Authors: Gastaldon Simone , Bonfiglio Noemi , Vespignani Francesco , Peressotti Francesca
Published: May 2024

Predictive processing, a crucial aspect of human cognition, is also relevant for language comprehension. In everyday situations, we exploit various sources of information to anticipate and therefore facilitate processing of upcoming linguistic input. In the literature, there are a variety of models that aim at accounting for such ability. One group of models propose a strict relationship between prediction and language production mechanisms. In this review, we first introduce very briefly the concept of predictive processing during language comprehension. Secondly, we focus on models that attribute a prominent role to language production and sensorimotor processing in language prediction (“prediction-by-production” models). Contextually, we provide a summary of studies that investigated the role of speech production and auditory perception on language comprehension/prediction tasks in healthy, typical participants. Then, we provide an overview of the limited existing literature on specific atypical/clinical populations that may represent suitable testing ground for such models–i.e., populations with impaired speech production and auditory perception mechanisms. Ultimately, we suggest a more widely and in-depth testing of prediction-by-production accounts, and the involvement of atypical populations both for model testing and as targets for possible novel speech/language treatment approaches.
Self-regulation and conflict goals management capabilities of ecosystem entrepreneurs: a case study of Haier ecosystem
Authors: Qin Wenting , Zhang Song , Lu Baozhou
Published: May 2024

The inherent dual roles of “follower” and “leader” among ecosystem entrepreneurs inevitably introduce challenges in managing conflicting dependent and independent goals. Ecosystem entrepreneurs’ capabilities in conflict goals management directly influence new venture survival and development. This single-case qualitative study explores how ecosystem entrepreneurs develop conflict goals management capabilities through self-regulation, which is not only a unique practical challenge in ecosystem entrepreneurship, but also a cutting-edge topic in current theoretical research. Through research of entrepreneurs in Haier Entrepreneurship Ecosystem, the paper finds: (1) strategic corresponding and mechanism adapting emerge as the two trigger factors enabling ecosystem entrepreneurs to recognize the equilibrium or disequilibrium between conflicting goals; (2) by leveraging self-control, grit, and metacognition, ecosystem entrepreneurs construct decoupling mechanisms for antagonistic goal recognition and coupling mechanisms for synergistic goal recognition; (3) ecosystem entrepreneurs enhance their conflict goals management capabilities by developing both segregative and synergistic management capabilities. Furthermore, this research explores the self-regulation process underlying ecosystem entrepreneurs’ conflict goals management behaviors, including environmental interaction perception, conflict goals analysis, and delineation of goal relationships. Findings provide insights for ecosystem entrepreneurs on improving their conflict goals management capabilities through self-assessment and skill development.
A randomized controlled trial of Eye Movement Desensitization and Reprocessing (EMDR) Therapy in the treatment of fibromyalgia
Authors: Zat Çiftçi Zeynep , Delibaş Dursun Hakan , Kaya Taciser , Külcü Duygu Geler , Sarı Aylin , Nazlıkul Hüseyin , Coşkun Topsakal İlkem , Aydın Yunus Emre , Kavakçı Önder , Savran Canan , Konuk Emre
Published: May 2024

Background

In addition to pharmacological treatment, psychotherapeutic approaches are recommended for the treatment of fibromyalgia. There is a suggestion that eye movement desensitization and reprocessing (EMDR) therapy may be effective. This study aimed to investigate the impact of EMDR therapy on fibromyalgia symptoms, depression, sleep quality, and traumatic stress in fibromyalgia patients through a randomized controlled study (RCT).

Materials and methods

The sample for this study comprised 79 individuals diagnosed with fibromyalgia. Participants were randomly assigned to two groups: the “Treatment as Usual” (TAU) group and the TAU + EMDR group. Prior to the study and at six different time points (before starting the study, at the end of the 5th, 10th, and 15th sessions, 1 month later, and 3 months later), participants completed assessments, including the Fibromyalgia Impact Questionnaire (FIQ), Visual Analog Scale (VAS), Fibromyalgia ACR 2010 Diagnostic Criteria [Widespread Pain Index (WPI) and Symptom Severity Scale (SSS)], Beck Depression Inventory (BDI), Pittsburgh Sleep Quality Index (PSQI), and Trauma Symptom Checklist-40 (TSC-40).

Results

There were no differences in the sociodemographic variables between the study and experimental groups. Analysis of variance revealed a statistically significant group effect on VAS (p = 0.019), WPI (p = 0.018), BDI (p = 0.019), and TSC-40 (p = 0.21). After applying Bonferroni correction, EMDR was found to be effective for VAS, WPI, SSS, BDI, PSQI, and TSC-40 (p <0.05).

Conclusion

The results of the current study suggest that EMDR therapy is a viable alternative treatment for fibromyalgia. We believe these findings offer robust evidence supporting the efficacy of EMDR therapy in treating fibromyalgia, particularly in the context of a randomized controlled trial (RCT). The application of EMDR therapy for the treatment of patients with fibromyalgia is likely to be beneficial.

Clinical trial registration

ClinicalTrials.gov, identifier NCT06265194.
Coping strategies and adherence in people with mood disorder: a cross-sectional study
Authors: Jeżuchowska Alicja , Schneider-Matyka Daria , Rachubińska Kamila , Reginia Artur , Panczyk Mariusz , Ćwiek Dorota , Grochans Elżbieta , Cybulska Anna Maria
Published: May 2024

Introduction

Non-adherence to treatment recommendations is a significant problem, as it contributes to the progression of the disease and to the exacerbation of distressing symptoms. Failure to cope with the disease and elevated levels of stress, in turn, influence the choice of strategy for coping with a difficult situation, and thus adherence to recommendations.

Objectives

The purpose of our study was to evaluate the impact of the subjects’ stress coping styles on therapeutic adherence, life satisfaction, disease acceptance and quality of life (QoL) in people with mood disorders.

Methods

This survey-based study included 102 respondents diagnosed with mood disorders, living in the West Pomeranian Voivodeship. It was performed using the sociodemographic questionnaire and standardized tools: The Coping Inventory for Stressful Situations (CISS), The Satisfaction with Life Scale (SWLS), The Short Form-36 (SF-36) Health Survey, The Adherence to Refills and Medication Scale (ARMS), and The Acceptance of Illness Scale (AIS).

Results

Some 47.06% of the respondents suffered from depressive disorders, while 34.31% had depression or mixed anxiety disorder. Patients who made greater use of an emotion-focused style were found to have significantly lower life satisfaction than other patients. Moreover, this style was related to such SF-36 domains as general health, social functioning, role emotional, vitality, and mental health, as well as to physical component summary (PCS) and mental component summary (MCS).

Conclusion

Treatment non-adherence is a serious challenge in the treatment of patients with mood disorders. Individuals who do not adequately follow treatment recommendations often resort to alternative activities as a mechanism for coping with difficult situations. Patients who predominantly adopt an emotion-oriented coping style tend to experience lower life satisfaction and greater difficulty accepting their condition compared to their peers. Conversely, patients who adopt a task-oriented coping style report better quality of life than those who rely on emotion-oriented coping or alternative activities.
Lower back pain and associated factors among weavers working in Bahir Dar City, Northwest Ethiopia: A cross-sectional study
Authors: Zinabu Fiseha Sefiwu , Getie Kefale , Takele Mihret Dejen , Chanie Samuel Teferi , Abich Yohannes , Shibabaw Yadelew Yimer , Kibret Alemu Kassaw
Published: May 2024

Background

Work-related musculoskeletal disorders are widespread among workers of informal small-scale enterprises. Specifically, lower back pain is a prevalent occupational health problem across various industries, including weaving factories. Lower back pain significantly impairs the functioning, performance, and productivity of weavers. However, information on the prevalence and associated factors of low back pain among weavers of Bahir Dar City and nationwide is scarce. Therefore, this study aimed to assess the prevalence and associated factors of lower back pain among weavers working in Bahir Dar City.

Method

A multicentered institutional-based cross-sectional study was conducted on 403 weavers in Bahir Dar City, Ethiopia, from April to May 2023 using a structured face-to-face interview questionnaire. Samples were proportionally allocated to each institution, and study participants were selected using a simple random sampling technique. Variables with a P-value < 0.25 in the bivariate logistic regression were adopted for the multivariate logistic regression analysis after verifying the model fitness. In the multivariate logistic regression analysis, the adjusted odds ratio (AOR) with a 95% confidence interval (CI) and a P-value < 0.05 were considered to identify the associated factors of lower back pain among weavers.

Result

The results revealed that the overall annual prevalence of lower back pain was 63.5% (95% CI = 58.8–68.5). Longer working hours [AOR = 2.580 (CI = 1.517–4.384)], lack of back support [AOR = 1.938 (CI = 2.089–3.449)], repetitive movement of the back during weaving [AOR = 5.940 (CI = 2.709–13.02)], awkward posture [AOR = 2.915 (CI = 1.677–5.065), static working posture [AOR = 4.505 (CI = 2.298–8.831)], and job stress [AOR = 3.306 (CI = 1.896–5.765)] were significantly associated with lower back pain among weavers.

Conclusions

Lower back pain among weavers was found to be highly prevalent. Working longer hours, lack of back support, repetitive movement of the back, awkward posture, static posture, and job stress were significantly associated with lower back among weavers. The study recommends prompt interventions on weavers to ensure that they use sitting support, weave for <8 h per day, change positions every 2 h, reduce job-related stress, and minimize task repetition, thereby enhancing their working conditions and minimizing the occurrence of lower back pain.
Evaluating the effects of two different kinesiology taping techniques on shoulder range of motion and proprioception in patients with hypermobile Ehlers–Danlos syndrome: a randomized controlled trial
Authors: Tudini Frank , Jordon Max , Levine David , Healy Michael , Cathey Sarah , Chui Kevin
Published: May 2024

Background

Ehlers–Danlos syndrome (EDS) is a common group of inherited connective tissue disorders with a prevalence as high as 0.75%–2% of the population. Physical manifestations include pain and decreased proprioception, especially in more mobile joints, such as the shoulder. The kinesiology tape (K-Tape) is often used to treat patients with shoulder dysfunction. The effectiveness of the K-Tape is uncertain, and there is a lack of studies specifically studying the K-Tape in an EDS population.

Purpose

The purpose of this study was to compare the short-term effects of two different K-Tape procedures on shoulder active joint reposition (AJR) and active range of motion (AROM) in patients with hypermobile EDS (hEDS) and shoulder pain.

Methods

All participants were recruited from the EDS support groups and presented with shoulder pain. Baseline demographic information was obtained for each participant, after which AROM and AJR were assessed. The participants were randomized to receive one of two K-Tape procedures. Testing was repeated immediately post-taping and 48 h post-taping.

Results

Significant improvements in shoulder external (F = 10.917, p < 0.001) and internal (F = 11.736, p < 0.001) rotations were seen from baseline to immediately post-taping and baseline to 48 h post-taping in the experimental K-Tape group. There were no significant differences in the shoulder rotation in the control K-Tape group and no significant differences in either group for shoulder flexion or AJR at any time point (p > 0.05).

Conclusion

K-Tape may offer short-term improvements in shoulder rotation AROM in patients with hEDS and shoulder pain.
Vascularization of kidney organoids: different strategies and perspectives
Authors: Raykhel Irina , Nishikawa Masaki , Sakai Yasuyuki , Vainio Seppo J. , Skovorodkin Ilya
Published: May 2024

Kidney diseases such as glomerulopathy and nephron dysfunction are estimated to grow to more than 900 million cases by 2030, in 45% of which kidney transplantation will be required, representing a major challenge for biomedicine. A wealth of progress has been made to model human diseases using induced pluripotent stem cells (iPSCs) in vitro differentiated to a variety of organoids, including kidney organoids, and in developing various microfluidics-based organ-on-a-chip (OoC) systems based on them. With the combination of targeted gene editing capacities, relevant polymorphic genetic variants can be established in such organoid models to advance evidence-based medicine. However, the major drawback of the current organoid disease models is the lack of functional endothelial vasculature, which especially concerns the kidney, the function of which is strongly associated with blood flow. The design of novel medical devices using tissue engineering approaches such as kidney organoids is also strongly dependent on the understanding of the fundamental principles of nephrogenesis and the vascularization of organs and tissues. Developmental vascularization of the kidney has been an area of intense research for decades. However, there is still no consensus among researchers on how exactly the vascularization of the kidney occurs in normal and pathological conditions. This lack of consensus is partly due to the lack of an appropriate model system to study renal vascularization during nephrogenesis. In this review, we will describe recent progress in the areas of kidney vasculature development, kidney organoids in general and assembled on microfluidic devices in particular. We will focus on the in vitro vasculature of kidney organoids in microfluidic OoC model systems to study kidney diseases and on the perspectives of tissue engineering for the modeling of kidney diseases and the design of bioartificial medical devices. We also aim to summarize the information related to the key mechanisms of intercellular communication during nephrogenesis and the formation of the renal vasculature in an OoC setup.
Moderate intensity intermittent lifestyle physical activity is associated with better executive function in older adults
Authors: MacDonald Emily , Morrison Elisabeth G. , Shivgulam Madeline E. , Pellerine Liam P. , Kimmerly Derek S. , Bray Nick W. , Mekari Said , O’Brien Myles W.
Published: May 2024

Executive functions are among the first cognitive abilities to decline with age and age-related executive function slowing predisposes older adults to cognitive disorders and disease. Intermittent Lifestyle Physical Activity (ILPA) reflects brief, unplanned activity that occurs during routine daily activities and is operationalized as activity bouts <60s. Our understanding of short bouts of habitual physical activity and executive functions is limited. We tested the hypothesis that greater amounts of ILPA in moderate and vigorous intensity domains would be associated with better executive function in older adults. Forty older adults (26 females, 68 ± 6, >55 years; body mass index: 26.6 ± 4.3 kg/m2) completed a Trail-Making-Task and wore an activPAL 24-hr/day for 6.2 ± 1.8-days. For each intensity, total time and time spent in bouts <60 s were determined. Trail A (processing speed) and Trail B (cognitive flexibility) were completed in 25.8 ± 8.2 s and 63.2 ± 26.2 s, respectively. Non-parametric Spearman's rank correlations report that moderate ILPA (3.2 ± 3.2 min/day) and total-moderate physical activity (20.1 ± 16.0 min/day) were associated with faster Trail A (total-moderate physical activity: ρ=−0.48; moderate-ILPA: ρ = −0.50; both, p < 0.003) and Trail B time (total-moderate physical activity: ρ = 0.36; moderate-ILPA: ρ = −0.46; both, p < 0.020). However, the results show no evidence of an association with either vigorous physical activity or light physical activity (total time or ILPA bouts: all, p > 0.180). Moderate physical activity accumulated in longer bouts (>60 s) was not associated with Trail B time (p = 0.201). Therefore, more total moderate physical activity and shorter bouts (<60 s) may result in better executive functions in older adults.
Agricultural socialized services and Chinese food security: examining the threshold effect of land tenure change
Authors: Cai Baozhong , Wangda Liao , Shi Fang , Abate Meseret Chanie , Geremew Betelhemabraham , Addis Amsalu K.
Published: May 2024

Revolutionary agricultural structural reforms in the supply chain and cutting-edge institutional mechanisms are pivotal in catalyzing a quantum leap in food production. China’s focus on achieving self-sufficiency in grain production for domestic security necessitates structural reforms in the agricultural supply chain and innovative institutional mechanisms. The emergence of socialized agricultural institutions plays a pivotal role in providing essential services to smallholder farmers. However, a dearth of studies evaluating the efficacy of these services in enhancing grain production exists. This study aims to fill this gap by analyzing provincial panel data from China spanning 2011 to 2020 to evaluate the impact of Agricultural Socialized Services (ASS) development levels on grain production. Employing panel and panel threshold models for empirical analysis, the research investigates how this impact varies between major grain-producing regions and non-major grain-producing regions. Findings indicate a significant positive effect of ASS on grain production, with a correlation coefficient of 1.3555. While its impact is less pronounced in grain-producing regions, it proves beneficial in non-grain regions. Moreover, the transfer of farmland use rights amplifies ASS’s influence on grain production, with a threshold value of 33.18%. The study concludes by outlining policy implications from various perspectives, providing practical recommendations for policymakers and stakeholders in the agricultural sector.
Midterm survival and risk factor analysis in patients with pyogenic vertebral osteomyelitis: a retrospective study of 155 cases
Authors: Schindler Melanie , Walter Nike , Reinhard Jan , Pagano Stefano , Szymski Dominik , Alt Volker , Rupp Markus , Lang Siegmund
Published: May 2024

Background

Pyogenic vertebral osteomyelitis (VO) represents a clinical challenge and is linked to substantial morbidity and mortality. This study aimed to examine mortality as well as potential risk factors contributing to in-hospital mortality among patients with VO.

Methods

This retrospective analysis involved patients receiving treatment for VO at University Regensburg in Germany from January 1, 2000, to December 3, 2020. It included in-hospital mortality rate, comorbidities and pathogens. Patients were identified using ICD-10 diagnosis codes: M46.2, M46.3, M46.4, and M46.5. Kaplan–Meier probability plots and odds ratios (OR) for mortality were calculated.

Results

Out of the total cohort of 155 patients with VO, 53 patients (34.1%) died during a mean follow-up time of 87.8 ± 70.8 months. The overall mortality was 17.2% at one year, 19.9% at two years and 28.3% at five years. Patients with congestive heart failure (p = 0.005), renal disease (p < 0.001), symptoms of paraplegia (p = 0.029), and sepsis (p = 0.006) demonstrated significantly higher overall mortality rates. In 56.1% of cases, pathogens were identified, with Staphylococcus aureus (S. aureus) and other unidentified pathogens being the most common. Renal disease (OR 1.85) and congestive heart failure (OR 1.52) were identified as significant risk factors.

Conclusion

Early assessment of the specific risk factors for each patient may prove beneficial in the management and treatment of VO to reduce the risk of mortality. These findings demonstrate the importance of close monitoring of VO patients with underlying chronic organ disease and early identification and treatment of sepsis. Prioritizing identification of the exact pathogens and antibiotic sensitivity testing can improve outcomes for patients in this high-risk group.
Identifying differentially expressed genes in goat mammary epithelial cells induced by overexpression of SOCS3 gene using RNA sequencing
Authors: Song Ning , Ma Cunxia , Guo Yuzhu , Cui Shuangshuang , Chen Shihao , Chen Zhi , Ling Yinghui , Zhang Yunhai , Liu Hongyu
Published: May 2024

The suppressor of cytokine signaling 3 (SOCS3) is a key signaling molecule that regulates milk synthesis in dairy livestock. However, the molecular mechanism by which SOCS3 regulates lipid synthesis in goat milk remains unclear. This study aimed to screen for key downstream genes associated with lipid synthesis regulated by SOCS3 in goat mammary epithelial cells (GMECs) using RNA sequencing (RNA-seq). Goat SOCS3 overexpression vector (PC-SOCS3) and negative control (PCDNA3.1) were transfected into GMECs. Total RNA from cells after SOCS3 overexpression was used for RNA-seq, followed by differentially expressed gene (DEG) analysis, functional enrichment analysis, and network prediction. SOCS3 overexpression significantly inhibited the synthesis of triacylglycerol, total cholesterol, non-esterified fatty acids, and accumulated lipid droplets. In total, 430 DEGs were identified, including 226 downregulated and 204 upregulated genes, following SOCS3 overexpression. Functional annotation revealed that the DEGs were mainly associated with lipid metabolism, cell proliferation, and apoptosis. We found that the lipid synthesis-related genes, STAT2 and FOXO6, were downregulated. In addition, the proliferation-related genes BCL2, MMP11, and MMP13 were upregulated, and the apoptosis-related gene CD40 was downregulated. In conclusion, six DEGs were identified as key regulators of milk lipid synthesis following SOCS3 overexpression in GMECs. Our results provide new candidate genes and insights into the molecular mechanisms involved in milk lipid synthesis regulated by SOCS3 in goats.
Minimizing Incision in Living Donor Liver Transplantation: Initial Experience and Comparative Analysis of Upper Midline Incision in 115 Recipients
Authors: Rastogi Amit , Gupta Ankur A. , Bansal Raghav , Kollanta Valappil Fysal , Yadav Kamal S. , Chaudhary Suchet , Bhangui Prashant , Dhampalvar Swapnil , Choudhary Narendra S. , Saraf Neeraj , Soin Arvinder S.
Published: May 2024

Living donor liver transplantation (LDLT) needs “Mercedes Benz” or “J-shaped” incision, causing short and long-term complications. An upper midline incision (UMI) is less invasive alternative but technically challenging. Reporting UMI for recipients in LDLT vs. conventional J-shaped incision. Retrospective analysis, July 2021 to December 2022. Peri-operative details and post-transplant outcomes of 115 consecutive adult LDLT recipients transplanted with UMI compared with 140 recipients with J-shaped incision. Cohorts had similar preoperative and intraoperative variables. The UMI group had significant shorter time to ambulation (3 ± 1.6 vs. 3.6 ± 1.3 days, p = 0.001), ICU stay (3.8 ± 1.3 vs. 4.4 ± 1.5 days, p = 0.001), but a similar hospital stay (15.6±7.6 vs. 16.1±10.9 days, p = 0.677), lower incidence of pleural effusion (11.3% vs. 27.1% p = 0.002), and post-operative ileus (1.7% vs. 9.3% p = 0.011). The rates of graft dysfunction (4.3% vs. 8.5% p = 0.412), biliary complications (6.1% vs. 12.1% p = 0.099), 90-day mortality (7.8% vs. 12.1% p = 0.598) were similar. UMI-LDLT afforded benefits such as reduced pleuropulmonary complications, better early post-operative recovery and reduction in scar-related complaints in the medium-term. This is a safe, non-inferior and reproducible technique for LDLT.
Coupling Coordination between Agricultural Eco-Efficiency and Urbanization in China Considering Food Security
Authors: He Xiuli , Liu Wenxin
Published: May 2024

When studying the coupling coordination relationship between agricultural eco-efficiency and urbanization, it is crucial to consider food security, especially in a populous country like China. This paper focuses on 31 provinces in China as the research units, covering the time period from 2000 to 2020. Based on the concept of agricultural eco-efficiency, an evaluation index system was developed to include undesirable outputs (carbon emissions), and agricultural eco-efficiency scores were calculated using the SBM–DEA model. An urbanization evaluation index system, covering six dimensions and twelve indexes, was constructed. A comprehensive index of urbanization is measured using the entropy method. On this basis, a coupling coordination model was applied to quantify the relationship between agricultural eco-efficiency and urbanization at the provincial scale in China. The results showed that the agricultural eco-efficiency of all provincial units in China exhibited an overall trend of improvement. Average efficiency followed a spatial pattern of majority grain-consuming areas > grain production–consumption balance areas > majority grain-producing areas. The level of coupling between agricultural eco-efficiency and urbanization is generally low. Currently, no regions have reached the stage of synergy or high-level coupling. Most regions are currently in an antagonistic stage with a coupling degree of 0.3 < C ≤ 0.5. The classification of coupling coordination levels changed from four levels of “severe imbalance”, “moderate imbalance”, “mild imbalance”, and “primary coordination” to “moderate imbalance”, “mild imbalance”, “primary coordination”, and “intermediate coordination”. The level of “severe imbalance” disappeared, the level of “intermediate coordination” appeared, and the level of “mild imbalance” became the largest scale level. From the perspective of food security, the proportion of grain production in the categories of “primary coordination” and “intermediate coordination” was less than 10%, and these provinces never achieved self-sufficiency in food production. The proportion of grain production at the “mild imbalance” level reached 62.4%, while the per capita grain production at the “moderate imbalance” level reached 846.7 kg. Provinces with lower levels of coupling coordination have stronger food security capabilities. It can be observed that the weaker the coupling coordination between agricultural eco-efficiency and urbanization, the higher the food self-sufficiency. Based on the research results above, we discussed strategies to enhance agricultural eco-efficiency in majority grain-producing regions by focusing on technological progress and technical efficiency. Additionally, we analyzed approaches to achieve grain self-sufficiency in regions characterized by a high level of coordination between agricultural eco-efficiency and urbanization, considering both production and trade dimensions.
The City as an Evolutionary Hothouse—The Search for Rapid Evolution in Urban Settings
Authors: Perry Gad , Göttert Thomas
Published: May 2024

Cities are ubiquitous and, though a novel phenomenon by evolutionary standards, provide a home for many species and exert particularly strong and novel selection pressures on them. They thus offer a unique opportunity to study rapid evolutionary processes. We conducted a scoping review of published studies documenting evolutionary processes in urban environments, focusing primarily on more recent work. Unfortunately, cities have not been attractive environments for biological research and thus remain poorly studied, despite slowly growing interest in recent years. Nonetheless, we found studies documenting the effects of mutation, genetic drift, and selection in cities. However, studies show some geographic bias and were not always as conclusive as might be desired. There is even support for incipient urban speciation. Evidence across the board is less abundant and less conclusive than desirable, suggesting the need for more data collection. The urban setting, with its stronger selection, more common intermixing, and abundance of both human and widespread potential non-human zoonosis hosts and human-associated species offers great opportunities to further document evolution in action and explore its conservation implications.
Variability and Number of Circulating Complementary Sex Determiner (Csd) Alleles in a Breeding Population of Italian Honeybees under Controlled Mating
Authors: De Iorio Maria Grazia , Lazzari Barbara , Colli Licia , Pagnacco Giulio , Minozzi Giulietta
Published: May 2024

In Apis mellifera, csd is the primary gene involved in sex determination: haploid hemizygous eggs develop as drones, while females develop from eggs heterozygous for the csd gene. If diploid eggs are homozygous for the csd gene, diploid drones will develop, but will be eaten by worker bees before they are born. Therefore, high csd allelic diversity is a priority for colony survival and breeding. This study aims to investigate the variability of the hypervariable region (HVR) of the csd gene in bees sampled in an apiary under a selection scheme. To this end, an existing dataset of 100 whole-genome sequences was analyzed with a validated pipeline based on de novo assembly of sequences within the HVR region. In total, 102 allelic sequences were reconstructed and translated into amino acid sequences. Among these, 47 different alleles were identified, 44 of which had previously been observed, while 3 are novel alleles. The results show a high variability in the csd region in this breeding population of honeybees.
A Testis-Specific DMRT1 (Double Sex and Mab-3-Related Transcription Factor 1) Plays a Role in Spermatogenesis and Gonadal Development in the Hermaphrodite Boring Giant Clam Tridacna crocea
Authors: Noor Zohaib , Zhao Zhen , Guo Shuming , Wei Zonglu , Cai Borui , Qin Yanping , Ma Haitao , Yu Ziniu , Li Jun , Zhang Yuehuan
Published: May 2024

The testis-specific double sex and mab-3-related transcription factor 1 (DMRT1) has long been recognized as a crucial player in sex determination across vertebrates, and its essential role in gonadal development and the regulation of spermatogenesis is well established. Here, we report the cloning of the key spermatogenesis-related DMRT1 cDNA, named Tc-DMRT1, from the gonads of Tridacna crocea (T. crocea), with a molecular weight of 41.93 kDa and an isoelectric point of 7.83 (pI). Our hypothesis is that DMRT1 machinery governs spermatogenesis and regulates gonadogenesis. RNAi-mediated Tc-DMRT1 knockdown revealed its critical role in hindering spermatogenesis and reducing expression levels in boring giant clams. A histological analysis showed structural changes, with normal sperm cell counts in the control group (ds-EGFP) but significantly lower concentrations of sperm cells in the experimental group (ds-DMRT1). DMRT1 transcripts during embryogenesis exhibited a significantly high expression pattern (p < 0.05) during the early zygote stage, and whole-embryo in-situ hybridization confirmed its expression pattern throughout embryogenesis. A qRT-PCR analysis of various reproductive stages revealed an abundant expression of Tc-DMRT1 in the gonads during the male reproductive stage. In-situ hybridization showed tissue-specific expression of DMRT1, with a positive signal detected in male-stage gonadal tissues comprising sperm cells, while no signal was detected in other stages. Our study findings provide an initial understanding of the DMRT1 molecular machinery controlling spermatogenesis and its specificity in male-stage gonads of the key bivalve species, Tridacna crocea, and suggest that DMRT1 predominantly functions as a key regulator of spermatogenesis in giant clams.
Pin1 Downregulation Is Involved in Excess Retinoic Acid-Induced Failure of Neural Tube Closure
Authors: Chen Yuwen , Pang Jiao , Ye Lu , Zhang Zhentao , Kang Junfeng , Qiu Zhuotao , Lin Na , Liu Hekun
Published: May 2024

Neural tube defects (NTDs), which are caused by impaired embryonic neural tube closure, are one of the most serious and common birth defects. Peptidyl-prolyl cis/trans isomerase 1 (Pin1) is a prolyl isomerase that uniquely regulates cell signaling by manipulating protein conformation following phosphorylation, although its involvement in neuronal development remains unknown. In this study, we explored the involvement of Pin1 in NTDs and its potential mechanisms both in vitro and in vivo. The levels of Pin1 expression were reduced in NTD models induced by all-trans retinoic acid (Atra). Pin1 plays a significant role in regulating the apoptosis, proliferation, differentiation, and migration of neurons. Moreover, Pin1 knockdown significantly was found to exacerbate oxidative stress (OS) and endoplasmic reticulum stress (ERs) in neuronal cells. Further studies showed that the Notch1-Nrf2 signaling pathway may participate in Pin1 regulation of NTDs, as evidenced by the inhibition and overexpression of the Notch1-Nrf2 pathway. In addition, immunofluorescence (IF), co-immunoprecipitation (Co-IP), and GST pull-down experiments also showed that Pin1 interacts directly with Notch1 and Nrf2. Thus, our study suggested that the knocking down of Pin1 promotes NTD progression by inhibiting the activation of the Notch1-Nrf2 signaling pathway, and it is possible that this effect is achieved by disrupting the interaction of Pin1 with Notch1 and Nrf2, affecting their proteostasis. Our research identified that the regulation of Pin1 by retinoic acid (RA) and its involvement in the development of NTDs through the Notch1-Nrf2 axis could enhance our comprehension of the mechanism behind RA-induced brain abnormalities.
Rapid Determination of Kinetic Constants for Slow-Binding Inhibitors and Inactivators of Human Histone Deacetylase 8
Authors: Kopranovic Aleksandra , Meyer-Almes Franz-Josef
Published: May 2024

The kinetics and mechanism of drug binding to its target are critical to pharmacological efficacy. A high throughput (HTS) screen often results in hundreds of hits, of which usually only simple IC50 values are determined during reconfirmation. However, kinetic parameters such as residence time for reversible inhibitors and the kinact/KI ratio, which is the critical measure for evaluating covalent inactivators, are early predictive measures to assess the chances of success of the hits in the clinic. Using the promising cancer target human histone deacetylase 8 as an example, we present a robust method that calculates concentration-dependent apparent rate constants for the inhibition or inactivation of HDAC8 from dose–response curves recorded after different pre-incubation times. With these data, hit compounds can be classified according to their mechanism of action, and the relevant kinetic parameters can be calculated in a highly parallel fashion. HDAC8 inhibitors with known modes of action were correctly assigned to their mechanism, and the binding mechanisms of some hits from an internal HDAC8 screening campaign were newly determined. The oxonitriles SVE04 and SVE27 were classified as fast reversible HDAC8 inhibitors with moderate time-constant IC50 values of 4.2 and 2.6 µM, respectively. The hit compound TJ-19-24 and SAH03 behave like slow two-step inactivators or reversible inhibitors, with a very low reverse isomerization rate.