Genetics Changes Research Articles

High frequency of silent mutations in gyrA gene of Mycobacterium tuberculosis in Indian isolates.

Reporting any uncommon or untapped changes in bacterial genetics or physiology would be of great importance to support the drug development process. We studied 120 Mycobacterium tuberculosis clinical isolates with different geographical origin within India and their resistance profile and found a significant number of isolates (109) harboring the polymorphism at nucleotide positions 61 and 284 of the gyrA gene. Bioinformatics analysis of these changes for drug binding suggested no significant change in the binding of the drug but have lower binding energies as compared with the wild-type proteins. Although functionally silent for the gyrA gene, these changes are indicating a silent geographical and evolutionary change that needs to be further studied for drug discovery and bacterial fitness.

Physiological, genetical changes and cdc2 gene expression for osmotic stressed Vicia faba reveal the alleviation effect of gamma radiation and putrescine

Climate change caused increasing in soil salinity worldwide. Therefore, it is critical to enhance the capability of plant to tolerate salinity stress. For this goal, putrescine and irradiation by gamma radiation were used to improve the salt tolerance of Vicia faba (the most important human crop). The results indicated depression in mitotic division and all growth parameters associated with the induction of micronucleus (MN) when salinity increased to 100mM, while there was increase in mitotic aberrations. NaCl decreased total soluble sugar, while total N%, total free amino acid, proline and protein contents showed slight increase with increasing salinity stress. Putrescine and gamma radiation mitigated the effect of salinity on cell division and growth parameters. Salt stress decreased the expression of gene encoding cyclin-dependent kinase 2 (cdc2). Both putrescine and gamma radiation increased cdc2 expression. The genetic diversity has been detected among control and treated V. faba using ISSR and SCoT markers. Ten primers had successfully generated 129 reproducible polymorphic amplicons that were suitable for studying the genetic diversity between studied genotypes. ISSR markers provided more discriminating data and were more informative than SCoT markers. Besides, cluster analysis using UPGMA and PAC successfully explained the genetic diversity within studied genotypes. These findings emphasize the efficiency of putrescine and gamma radiation for alleviating the negative impact of salt stress. Moreover, prove the importance of assessing mitotic activity, chromosomes behavior, physiological parameters, the expression level of cdc2 and molecular diversity in V. faba under stress to improve the salt tolerance of it.

The Correlation of Paternal Age on Semen Parameters in Assisted Reproduction: A Retrospective Study in Qassim, Saudi Arabia.

In the past, fertility concerns have predominantly revolved around the effect of a woman's age on the quality of her eggs and the success of her pregnancy. While men generally retain their ability to father children throughout their lives, there is evidence suggesting a decline in natural conception rates as paternal age increases. A growing body of research indicates a potential link between advanced paternal age (APA) and various adverse outcomes, including changes in sperm genetics, reduced conception rates, higher rates of miscarriage, lower live birth rates, and even long-term health consequences in offspring. However, it remains unclear whether there is an association between APA and the effectiveness of assisted reproductive technology (ART). This study aims to shed light on the relationship between APA and semen parameters. This is a retrospective, descriptive study analyzing data from electronic medical records of men undergoing ART at a fertility clinic in Saudia Arabia(2017-2022). Men aged 21-60 with at least one semen analysis and no missing data/hormonal treatment were included. Data on age and semen parameters (count, motility, and morphology) were extracted and analyzed using Jeffreys's Amazing Statistics Program (JASP; University of Amsterdam, Amsterdam, Netherlands) (descriptive statistics, Spearman's rank correlation). Analysis of 1506 men undergoing ART revealed a mean age of 37 years (SD=6.94) and a mean sperm count of 55.0 million/mL (SD=46.05). The correlation between age and sperm count indicates a minimal association (r=0.075, p<0.01); moderate positive correlations were observed between sperm count and motility (r=0.406); count and morphology (r=0.543); and motility and morphology (r=0.458). Age may not be a major factor in overall sperm parametersfor this population, but a strong positive correlation was observed between sperm count, motility, and normal morphology. These findings suggest that these semen parameters are interconnected, with higher sperm counts potentially indicating better overall sperm quality.

Musculoskeletal Failure.

Osteoarthritis, osteoporosis, and sarcopenia are prevalent musculoskeletal disorders that significantly impact the aging population's health and quality of life. Osteoarthritis, characterized by joint inflammation, leads to pain, stiffness, and reduced mobility. Osteoporosis, a condition marked by bone density loss, increases fracture susceptibility, especially in postmenopausal women and older adults. Sarcopenia, the age-related loss of muscle mass and function, contributes to frailty and an increased risk of falls. Combined, osteoarthritis, osteoporosis and sarcopenia constitute "Musculoskeletal Failure." These 3 conditions share common risk factors like aging, genetics, and hormonal changes, as well as unhealthy lifestyle behaviors resulting in systemic chronic inflammation. Healthy lifestyle behaviors, including regular physical activity and a nutritious diet across the lifespan play a crucial role in the prevention and management of musculoskeletal failure. Awareness of the relationship between lifestyle behaviors, systemic chronic inflammation and the development and progression of these 3 common conditions is a key step in prevention, early detection and are essential for addressing the complex interplay of these musculoskeletal disorders. As the global population ages, understanding and effectively preventing and managing osteoarthritis, osteoporosis, and sarcopenia become paramount for promoting healthy aging and mitigating the societal and economic burden associated with these conditions.

Ranking genotype, environment, management effects on the optimum nitrogen rate for maize: A cropping system modeling analysis

AbstractRanking the contribution of genotype, environment, and management (G × E × M) on maize's economic optimum nitrogen fertilizer rate (EONR) variability could improve understanding and predictability of EONR. We performed a simulation experiment using the Agricultural Production Systems sIMulator model with the objectives to (1) rank the effects of 24 individual G × E × M factors on the magnitude and interannual variability of the EONR across the US Midwest and (2) investigate the impact of G × M factors on the EONR variability under present and future climate scenarios. Results indicate that genetics (27%), management (31%), and environmental conditions (41%) each influence the EONR variability. Within these broad categories, the top three individual factors impacting the EONR were interannual weather variability, crop radiation use efficiency, and the soil inorganic N carryover from the previous year. The G × E × M factors influenced the yield response to N fertilizer in different ways. Soil‐related factors (e.g., organic matter and residual nitrate) influenced grain yields at the low N rates, while management factors (e.g., planting date and density) influenced yield at all N rates. Combining increases in plant density and changes in genetics synergistically increased the EONR by 15% from baseline. Future climate scenarios without adaptation decreased the EONR and yield loss, but crop adaptation was buffered against the negative climate change impacts. We concluded that 59% of the annual EONR variability is manageable (due to genetics and management) and that G × M factors could buffer climate change's negative effects on crop production. Present results can inform experimental research on N fertilizer and N rate decisions.

Toxic Effects of Rare Earth Elements on Human Health: A Review.

Rare earth elements (REEs) are a new type of material resource which have attracted significant attention in recent years. REEs have emerged as essential metals in modern-day technology due to their unique functions. The long-term, large-scale mining and utilization of rare earths has caused serious environmental pollution and constitutes a global health issue, which has raised concerns regarding the safety of human health. However, the toxicity profile of suspended particulate matter in REEs in the environment, which interacts with the human body, remains largely unknown. Studies have shown that REEs can enter the human body through a variety of pathways, leading to a variety of organ and system dysfunctions through changes in genetics, epigenetics, and signaling pathways. Through an extensive literature search and critical analysis, we provide a comprehensive overview of the available evidence, identify knowledge gaps, and make recommendations for future research directions.

Kegiatan Penapisan Pemeriksaan Kadar Asam Urat terhadap Hiperurisemia pada Populasi Lanjut Usia

Hyperuricemia, characterized by increased serum uric acid levels, occurs due to an imbalance between uric acid production and excretion. The prevalence in adults and the elderly in China is 12.69% and is higher in men (17.7%) than women (8.5%). Contributing factors such as genetics, diet, and lifestyle changes, lead to an increased risk of gout, kidney stones, and cardiovascular disease. Chronic hyperuricemia can cause joint damage and deformity due to the deposition of urate crystals. This activity uses the PDCA (Plan-Do-Check-Action) methodology to screen for hyperuricemia in the elderly at St. Mary's Church. Francis of Assisi. The screening results showed that 12 people (33.33%) of the 36 participants had hyperuricemia. Early detection of hyperuricemia is very important in preventing complications such as gout and cardiovascular disease. Regular check-ups and lifestyle changes can significantly improve health outcomes and quality of life for seniors.

The biomarkers for maintenance Cancer stem cell features can be applicable in precision medicine of head and neck squamous cell carcinoma

Cancer stem cells (CSCs) play a crucial role in tumor relapse, proliferation, invasion, and drug resistance in head and neck squamous cell carcinoma (HNSCC). This narrative review aims to synthesize data from articles published between 2019 and 2023 on biomarkers for detecting CSCs in HNSCC and changes in molecular pathways, genetics, epigenetics, and non-coding RNAs (ncRNAs) in CSCs relevant to precision medicine approaches in HNSCC management. The search encompassed 41 in vitro studies and 22 clinical studies. CSCs exhibit diverse molecular profiles and unique biomarker expression patterns, offering significant potential for HNSCC diagnosis, treatment, and prognosis, thereby enhancing patient survival. Their remarkable self-renewal ability and adaptability are closely linked to tumorigenicity development and maintenance. Assessing biomarkers before and after therapy can aid in identifying various cell types associated with cancer progression and relapse. Screening for CSCs, senescent tumor cells, and cells correlated with the senescence process post-treatment has proven highly beneficial. However, the clinical application of precision medicine in HNSCC management is hindered by the lack of specific and definitive CSC biomarkers. Furthermore, our limited understanding of CSC plasticity, governed by genomic, transcriptomic, and epigenomic alterations during tumorigenesis, as well as the bidirectional interaction of CSCs with the tumor microenvironment, underscores the need for further research. Well-designed studies involving large patient cohorts are, therefore, essential to establish a standardized protocol and address these unresolved queries.

MiRNA on the Battlefield of Cancer: Significance in Cancer Stem Cells, WNT Pathway, and Treatment.

Carcinogenesis is a complex process characterized by intricate changes in organ histology, biochemistry, epigenetics, and genetics. Within this intricate landscape, cancer stem cells (CSCs) have emerged as distinct cell types possessing unique attributes that significantly contribute to the pathogenesis of cancer. The WNT signaling pathway plays a critical role in maintaining somatic stem cell pluripotency. However, in cancer, overexpression of WNT mediators enhances the activity of β-catenin, resulting in phenomena such as recurrence and unfavorable survival outcomes. Notably, CSCs exhibit heightened WNT signaling compared to bulk cancer cells, providing intriguing insights into their functional characteristics. MicroRNAs (miRNAs), as post-transcriptional gene expression regulators, modulate various physiological processes in numerous diseases including cancer. Upregulation or downregulation of miRNAs can affect the production of pro-oncogenic or anti-oncogenic proteins, influencing cellular processes that maintain tissue homeostasis and promote either apoptosis or differentiation, even in cancer cells. In order to understand the dysregulation of miRNAs, it is essential to examine miRNA biogenesis and any possible alterations at each step. The potential of a miRNA as a biomarker in prognosis, diagnosis, and detection is being assessed using technologies such as next-generation sequencing. Extensive research has explored miRNA expression profiles in cancer, leading to their utilization as diagnostic tools and the development of personalized and targeted cancer therapies. This review delves into the role of miRNAs in carcinogenesis in relation to the WNT signaling pathway along with their potential as druggable compounds.

Nanomaterial-Induced Modifications in Plant Physiology and Genetics for Optimal Crop Production Strategies

Nanotechnology has ushered in a new era in agriculture, offering transformative solutions to address the pressing challenges of feeding a burgeoning global population while adapting to a changing climate. At the forefront of this revolution are nanomaterials, characterized by their unique properties at the nanoscale. This article explores the intricate and dynamic relationship between nanomaterials and plants, unveiling how they induce profound changes in plant physiology and genetics. These changes, while complex, hold the key to unlocking novel approaches for crop improvement and sustainable agriculture. However, the core of this study delves into understanding how nanomaterials are taken up by plants and transported within their intricate biological systems. The mechanisms underlying nanomaterial uptake and distribution within plants are unveiled, offering possibilities for precise nutrient targeting and enhanced uptake efficiency. Subsequent sections meticulously dissect the consequences of nanomaterial exposure on plant physiology, including growth, development, and stress responses. The intricate genetic modifications and epigenetic changes that nanomaterials induce in plants are explored, revealing the potential for tailored crop improvement strategies. Notably, we demonstrate the practical implications of these nanomaterial-induced changes, showcasing their relevance for optimizing crop yields, resilience to environmental stressors, and nutritional quality. This article also takes a holistic approach by addressing the environmental and safety considerations that accompany the use of nanomaterials in agriculture. It emphasizes the necessity of responsible application, ecological impact assessment, and the establishment of regulatory frameworks to guide safe utilization. In conclusion, this article serves as an illuminating exploration of the nascent field where nanomaterials meet plant physiology and genetics, with implications that could reshape the future of agriculture.

Association of ABO/Rh Blood Group with Hypertension in Pre and Postmenopausal Libyan women

BACKGROUND AND AIM: Hypertension is a prevalent and significant public health issue worldwide, affecting a substantial portion of the population. While various risk factors have been implicated in the development of hypertension, including genetics, lifestyle, and hormonal changes, the role of ABO/Rh blood groups in hypertension remains underexplored, particularly in different stages of Libyan women’s life. This research study aimed to investigate the potential association between ABO/Rh blood groups and hypertension in both pre- and post-menopausal Libyan women. METHODOLOGY: A cross sectional study was conducted over a four-month period on a diverse cohort of women aged 35 to 75 years. It involved a total of 200 hypertensive women divided into pre- (n=100) and post-menopausal (n=100) groups. It took place at Tripoli University Hospital, Tajoura Heart Centre and Total Care Clinic. Data were collected through structured interviews, clinical examinations, and blood sample analyses. Blood pressure (BP) measurements and blood group typing were performed using standard medical procedures. A statistical analysis was performed using SPSS program version 26.0. RESULTS: The distribution of ABO blood groups shows that blood group O is the most prevalent blood group among samples (58% in the pre-menopausal and 41% in post-menopausal hypertensives), whereas blood group AB is the least prevalent (only 9% in the pre-menopausal and 7% in post-menopausal hypertensives). One hundred and eighty-one (90.5%) were Rh +ve. Analysis of data revealed significant differences in age distribution as well as in the percentages of Rh +ve and Rh -ve blood groups among pre- and post-menopausal women (p&lt;0.05). However, there was no statistically significant difference in the mean values of BP indices between ABO/Rh blood groups (p&gt;0.05).CONCLUSION: This study showed that ABO/Rh blood group system does not significantly affect BP indices among the pre-menopausal and post-menopausal women. Findings of present study also illustrated that age could potentially influence the connection between blood groups and hypertension. Additionally, among ABO/Rh blood groups, the most observed type was 'O.' However, further investigation is necessary to validate these initial results and better understand the underlying mechanisms behind this relationship

An IT-supported multidimensional approach for frailty screening in community-dwelling older adults

Introduction: Frailty in older adults is characterised by a dynamic state of vulnerability with weakness and reduced physiological reserve leading to an increased risk of worsening in quality of life, falls, institutionalisation, disability and death [1]. The COVID-19 pandemic is an example of how an infectious hit can determine an increased mortality especially among older and vulnerable population subgroups [2], as well as a deterioration in their quality of life due to loneliness and limited access to health and social services. Frailty syndrome is a complex interplay between several factors, including, but not limited to, natural physiological changes in ageing, multi-morbidities, malnutrition, living environment, genetics and lifestyle [3]. Early screening for frailty risk factors in the community-dwelling older adult population allows preventive interventions on the clinical and social determinants of frailty, avoiding adverse events and contributing to improve the resilience of health care systems.&#x0D; Method: Programma Mattone Internazionale Salute (ProMIS), the Italian Ministry of Health's programme for innovation of regional health systems [4], built up a working group (WG) on Frailty, including doctors, nurses, home care professionals, physiotherapists, pharmacists, psychologists, dieticians, social workers, physical trainers and policy makers, to develop a proactive and integrated approach to detect frailty and its risk factors in community-dwelling older adult population.&#x0D; Results: The participatory activity of ProMIS’ WG led to the identification of an integrated approach aimed to connect the SUNFRAIL tool for the early identification of frailty in the over-65 population [5] to other in-depth scales for the assessment of specific dimensions of frailty, guiding subsequent diagnostic assessments for health promotion, disease prevention and intervention. An IT tool was developed for data collection, SUNFRAIL+, which includes, in addition to SUNFRAIL tools, the validated scales for screening the nine domains of frailty, which automatically generates alerts, thanks to which targeted interventions will be activated in the compromised domains. A national multi-centre observational study protocol has been designed to validate the approach by assessing the impact of early, integrated, and multi-professional care on the quality of life of the community-dwelling older adult population and the professional’s satisfaction.&#x0D; Conclusion and discussion: The study design builds on the tool developed by the SUNFRAIL EU project [6], and provides the background for bridging multidimensional interventions to prevent frailty and mitigate its consequences on quality of life and functional ability in community-dwelling older adults, exploiting available services in the different health care services. The study will also provide the information needed to design a logical model integrating coherent interventions in the framework of specific frailty domains.

The interplay between the microbiota, diet and T regulatory cells in the preservation of the gut barrier in inflammatory bowel disease.

Inflammatory bowel disease (IBD) is becoming more common in the Western world due to changes in diet-related microbial dysbiosis, genetics and lifestyle. Incidences of gut permeability can predate IBD and continued gut barrier disruptions increase the exposure of bacterial antigens to the immune system thereby perpetuating chronic inflammation. Currently, most of the approved IBD therapies target individual pro-inflammatory cytokines and pathways. However, they fail in approximately 50% of patients due to their inability to overcome the redundant pro inflammatory immune responses. There is increasing interest in the therapeutic potential of T regulatory cells (Tregs) in inflammatory conditions due to their widespread capability to dampen inflammation, promote tolerance of intestinal bacteria, facilitate healing of the mucosal barrier and ability to be engineered for more targeted therapy. Intestinal Treg populations are inherently shaped by dietary molecules and gut microbiota-derived metabolites. Thus, understanding how these molecules influence Treg-mediated preservation of the intestinal barrier will provide insights into immune tolerance-mediated mucosal homeostasis. This review comprehensively explores the interplay between diet, gut microbiota, and immune system in influencing the intestinal barrier function to attenuate the progression of colitis.

Neuronal hyperexcitability in AD

AbstractBackgroundBecause neuronal and network deficits are the imperative immediate consequences of pathological changes of disease mechanisms, neurophysiological manifestations associated with Aβ and tau are uniquely positioned to demonstrate the abnormal homeostatic and maladaptive circuit alterations and the dynamic integrated effects of underlying genetics and neuropathological changes in Alzheimer’s disease (AD). Importantly, network dysfunction manifesting as abnormal hyper‐ as well as hypo‐active oscillatory brain rhythms is detectable even during the prodromal phase of disease. Here we leveraged the higher spatial and precise temporal resolution of Magnetoencephalography (MEG) to define frequency‐specific and region‐dependent patterns of oscillatory deficits in AD patients, and to demonstrate the earliest neurophysiological abnormalities associated with AD neuropathology and their mechanistic relationships to network hyperexcitability.MethodWe studied the resting brain oscillations in individuals with AD‐spectrum (n = 88) and age‐matched controls (n = 70) using MEG. In addition, subsets of participants were evaluated with positron emission tomography (PET) with Aβ and tau specific tracers and fluid biomarker including plasma P‐tau181 and Neuro‐Filament‐Light (NFL). We used statistical mixed models to investigate the associations between neural oscillations and pathology. We used a linear Neural‐Mass‐Model (NMM) in combination with empirical MEG spectra to derive the excitatory‐to‐inhibitory activity within neuronal subpopulations in AD patients. Based on standard neurophysiological monitoring we determined clinical evidence of hyperexcitability as AD with and without epileptiform activity (AD‐EPI+; AD‐EPI‐).ResultWhile increase and decrease of oscillatory activity are distinctly associated Aβ and tau, respectively, the characteristic frequency‐specific manifestation in AD was increased spectral signature within delta‐theta (2‐7Hz) and reduced spectral signature within alpha (8‐12Hz). Earliest spectral changes were detected in Aβ+ cognitively unimpaired and the increased spectral signature associated with Aβ was replicated in identical associations with plasma p‐tau181. The presence of APO‐E4 allele strengthened these associations. NMM demonstrated greater excitatory‐inhibitory‐activity in AD‐EPI+ vs. AD‐EPI‐ while these were specifically correlated with the reduced alpha spectrum which was more profound in AD‐EPI+ as well as uniquely associated with increased tau depositions.ConclusionOur results provide critical insights about potential mechanistic links between abnormal neural oscillations and cellular correlates of impaired excitatory and inhibitory synaptic functions associated with tau and Aβ, in patients with AD.

TMIC-67. GLIOBLASTOMA AUGMENTS SYSTEMIC IMMUNUNOSUPPRESSION UPON LOSS OF TESTOSTERONE VIA ALTERATION OF GLUCOCORTICOIDS PRODUCTION

Abstract While sex differences in incidence, genetics, and immune changes are established in glioblastoma (GBM), the specific contribution of sex hormones to these differences has not been fully explored. Testosterone has been shown to have a pro-tumorigenic effect on human and mouse GBM tumor cells. However, the systemic effect of testosterone in an immune competent model has not been tested. To test this, we performed castration or sham surgery on C57BL/6 male mice, followed by intracranial implantation of syngeneic glioma cells. Surprisingly, castrated mice exhibited more aggressive tumor growth compared to sham surgery controls, and this castration-induced aggressiveness could be reversed by administering exogenous testosterone. This finding was further confirmed by chemically blocking androgen receptor signaling using enzalutamide. We observed a significant increase in adrenocorticotropic hormone (ACTH) levels in the serum from castrated mice compared to the sham group after tumor implantation. Additionally, mass spectrometry analysis detected elevated levels of circulating glucocorticoids in castrated mice, and pharmacological blockade of glucocorticoid receptor using mifepristone reversed the shorted survival in castrated mice, but not in sham control. Flow analysis revealed decreased production of anti-tumor cytokines such as IFN-γ and TNF-α in CD4+ and CD8+ T cells from tumors and lymph nodes in castrated mice, suggesting systemic immunosuppression in these animals. Indeed, castration of immune-compromised mice, specifically NSG and RAG1KO strains, did not result in reduced survival. Moreover, when GBM cells were subcutaneously implanted into the flank, tumor growth in castrated mice was decelerated compared to sham controls. We also observed significantly lower ACTH levels in the flank tumor model compared to the brain tumor model, indicating a brain-specific effect of steroid hormones on tumor control. Taken together, these findings demonstrate that testosterone regulates T cell function through glucocorticoids, ultimately affecting GBM growth in a site-specific manner.

Nanomaterial-induced Changes in Plant Physiology and Genetics: Implications for Crop Improvement Strategies

The utilization of nanomaterials in agriculture has gained significant attention due to their potential to induce changes in plant physiology and genetics, thereby offering new avenues for enhancing crop improvement strategies. This paper delves into the intricate interplay between nanomaterials and plants, shedding light on their molecular mechanisms of uptake and interaction. It explores the physiological responses that ensue following nanomaterial exposure, unraveling the intricate network of signaling pathways and stress responses. Moreover, the paper delves into the alterations in genetic expression triggered by nanomaterials, providing insights into the underlying regulatory mechanisms. The influence of epigenetic factors and potential transgenerational effects further accentuates the complexity of these interactions. Underpinning this understanding, the paper discusses the prospects of harnessing nanomaterial-induced changes to enhance crop traits. It investigates how these changes can be employed to boost crop resilience, nutrient uptake, and stress tolerance. The integration of nanomaterial-induced alterations into breeding and genetic modification strategies offers a promising approach for developing improved crop varieties. Ultimately, this comprehensive exploration of nanomaterial-induced changes in plant physiology and genetics highlights their far-reaching implications for revolutionizing crop improvement strategies in the face of evolving agricultural challenges.

Impacts of Micro(nano)plastics on Terrestrial Plants: Germination, Growth, and Litter.

Micro(nano)plastics (MNP) are pervasive in various environmental media and pose a global environmental pollution issue, particularly in terrestrial ecosystems, where they exert a significant impact on plant growth and development. This paper builds upon prior research to analyze and consolidate the effects of MNP on soil properties, seed germination, plant growth, and litter decomposition. The objective is to elucidate the environmental behavior of MNP and their mechanisms of influence on the plant life cycle. The unique physicochemical and electrical properties of MNP enable them to modify soil structure, water retention capacity, and pH. They can potentially act as "electron shuttles" or disrupt natural "electron shuttles" in litter decomposition, thereby interfering with nutrient transport and availability in the soil. Furthermore, MNP can physically obstruct nutrient and water channels within plants, impacting nutrient and water absorption. Once infiltrating plant tissues, MNP can form eco-coronas with plant proteins. Together with MNP adsorbed on the plant's surface and within its tissues, they disrupt normal physiological processes, leading to changes in photosynthesis, biomass, cellular toxicity, genetics, nutrient uptake, and gene expression. These changes, in turn, influence seed germination and plant growth and development. As a burgeoning research field, future studies should delve deeper into various aspects of these changes, such as elucidating the pathways and mechanisms through which MNP enter plant tissues, assessing their intensity and mechanisms of toxicity on different plant species, and exploring the relationship between micro(nano)plastics and "electron shuttles". These endeavors will contribute to establishing a more comprehensive theoretical framework for understanding the environmental behavior of MNP and their impact on plants.

Integrative analysis reveals that SLC38A1 promotes hepatocellular carcinoma development via PI3K/AKT/mTOR signaling via glutamine mediated energy metabolism.

Although hepatocellular carcinoma (HCC) is rather frequent, little is known about the molecular pathways underlying its development, progression, and prognosis. In the current study, we comprehensively analyzed the deferentially expressed metabolism-related genes (MRGs) in HCC based on TCGA datasets attempting to discover the potentially prognostic genes in HCC. The up-regulated MRGs were further subjected to analyze their prognostic values and protein expressions. Twenty-seven genes were identified because their high expressions were significant in OS, PFS, DFS, DSS, and HCC tumor samples. They were then used for GO, KEGG, methylation, genetics changes, immune infiltration analyses. Moreover, we established a prognostic model in HCC using univariate assays and LASSO regression based on these MRGs. Additionally, we also found that SLC38A1, an amino acid metabolism closely related transporter, was a potential prognostic gene in HCC, and its function in HCC was further studied using experiments. We found that the knockdown of SLC38A1 notably suppressed the growth and migration of HCC cells. Further studies revealed that SLC38A1 modulated the development of HCC cells by regulating PI3K/AKT/mTOR signaling via glutamine mediated energy metabolism. In conclusion, this study identified the potentially prognostic MRGs in HCC and uncovered that SLC38A1 regulated HCC development and progression by regulating PI3K/AKT/mTOR signaling via glutamine mediated energy metabolism, which might provide a novel marker and potential therapeutic target in HCC.

New Daily Persistent Headache (NDPH): Unraveling the Complexities of Diagnosis, Pathophysiology, and Treatment.

The current article aims to provide an overview of new daily persistent headache (NDPH), with a particular emphasis on its pathophysiology, evaluation, and current treatment options. NDPH is an uncommon and heterogeneous condition associated with various comorbidities and is of great significance due to its prolonged duration and high severity. Variable causes and clinical aspects of NDPH may reflect differences in its underlying pathophysiological mechanisms, including genetics, environmental triggers, neuroinflammation, and brain changes. When assessing a patient with NDPH, potential triggers, past medical history, and differential diagnosis should be carefully considered. Non-pharmacological interventions aimed to improve diet, sleep patterns, and reduce consumption of caffeine and alcohol are recommended for all patients. Nerve blockade and nerve stimulation seem to be more efficacious in children than adults. Antiviral medications and neuroinflammation-targeting treatments may be helpful, particularly, when an infectious disease or severe inflammation is suspected. NDPH patients with concurrent affective disorders may benefit from treatment with serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, or benzodiazepines. Cerebrospinal-fluid-lowering medications may be useful for headaches started with a thunderclap or a Valsalva maneuver. Possible treatments for refractory NDPH include intravenous ketamine or lidocaine, onabotulinumtoxinA, and calcitonin gene-related peptide antibodies. Considering the variety of NDPH, it is critical to properly screen patients for correct diagnosis. Proper identification of potential mimics may enable precise therapy opportunities, yet there is no gold standard treatment for NDPH. Further well-designed studies are needed to elucidate the underlying mechanisms and develop effective treatment strategies for NDPH.

Fibrocartilaginous lipoma: a clinicopathological analysis of six cases

Objective: To investigate the clinicopathological characteristics, immunophenotype, molecular genetics and differential diagnoses of fibrocartilaginous lipomas which consist of adipose tissue, fibrocartilage and fibrous elements. Methods: The clinicopathological features, immunohistochemical profiles and molecular profiles in six cases of fibrocartilaginous lipomas diagnosed at Foshan Traditional Chinese Medicine Hospital, Fudan University Shanghai Cancer Center, the Fifth Affiliated Hospital of Zhengzhou University and the Fourth Affiliated Hospital of Harbin Medical University from January 2017 to February 2022 were included. The follow-up information, diagnosis and differential diagnoses were evaluated. Results: There were three males and three females with a median age of 53 years (range 36-69 years) at presentation. Tumors were located in the extremities, the head and neck region and trunk; and presented as painless masses that were located in the subcutaneous tissue or deep soft tissue. Grossly, three cases were well defined with thin capsule, one case was well circumscribed without capsule, two cases were surrounded by some skeletal muscle. The tumors were composed of fatty tissue with intermingled gray-white area. The tumors ranged from 1.50-5.50 cm (mean 2.92 cm). Microscopically, the hallmark of these lesions was the complex admixture of mature adipocytes, fibrocartilage and fibrous element in varying proportions; the fibrocartilage arranged in a nodular, sheet pattern with some adipocytes inside. Tumor cells had a bland appearance without mitotic activity. Immunohistochemical analysis using antibodies to SMA, desmin, S-100, SOX9, HMGA2, RB1, CD34, adipopholin was performed in six cases; the fibrocartilage was positive for S-100 and SOX9, adipocytes were positive for S-100, adipopholin and HMGA2; CD34 was expressed in the fibroblastic cells, while desmin and SMA were negative. Loss of nuclear RB1 expression was not observed. Other genetic abnormalities had not been found yet in four cases. Follow-up information was available in six cases; there was no recurrence in five, and one patient only underwent biopsy of the mass. Conclusions: Fibrocartilaginous lipoma is a benign lipomatous tumor with mature adipocytes, fibrocartilage and fibrous elements. By immunohistochemistry, they show the expression of fat and cartilage markers. No specific molecular genetics changes have been identified so far. Familiarity with its clinicopathological features helps the distinction from its morphologic mimics.