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Abstract An increasing number of elderly individuals are experiencing postoperative cognitive dysfunction (POCD) problems after undergoing hip replacement surgery, with gut microbiota metabolites playing a role in its pathogenesis. Among these, the specific effects of trimethylamine N‐oxide (TMAO) on POCD are still unclear. This study aimed to explore the role of TMAO on cognitive dysfunction and underlying mechanisms in mice. The POCD model was created through femoral fracture surgery in elderly mice, followed by cognitive function assessments using the Morris Water Maze and Novel Object Recognition tests. The gut microbiota depletion and fecal microbiota transplantation were performed to examine the relationship between TMAO levels and cognitive outcomes. The effects of TMAO treatment on cognitive dysfunction, microglial activation, and inflammatory cytokine levels in the brain were also evaluated, with additional assessment of the role of microglial ablation in reducing TMAO‐induced cognitive impairment. Elevated TMAO levels were found to be associated with cognitive decline in mice following femoral fracture surgery, with gut microbiota depletion mitigating both TMAO elevation and cognitive dysfunction. In contrast, fecal microbiota transplantation from postoperative mice resulted in accelerated cognitive dysfunction and TMAO accumulation in germ‐free mice. Furthermore, TMAO treatment worsened cognitive deficits, neuroinflammation, and promoted microglial activation, which were reversed through the ablation of microglia. TMAO exacerbates cognitive dysfunction and neuroinflammation in POCD mice, with microglial activation playing a crucial role in this process. Our findings may provide new therapeutic strategies for managing TMAO‐related POCD and improving the quality of life for elderly patients.

An increasing number of elderly individuals are experiencing postoperative cognitive dysfunction (POCD) problems after undergoing hip replacement surgery, with gut microbiota metabolites playing a role in its pathogenesis. Among these, the specific effects of trimethylamine N‐oxide (TMAO) on POCD are still unclear. This study aimed to explore the role of TMAO on cognitive dysfunction and underlying mechanisms in mice. The POCD model was created through femoral fracture surgery in elderly mice, followed by cognitive function assessments using the Morris Water Maze and Novel Object Recognition tests. The gut microbiota depletion and fecal microbiota transplantation were performed to examine the relationship between TMAO levels and cognitive outcomes. The effects of TMAO treatment on cognitive dysfunction, microglial activation, and inflammatory cytokine levels in the brain were also evaluated, with additional assessment of the role of microglial ablation in reducing TMAO‐induced cognitive impairment. Elevated TMAO levels were found to be associated with cognitive decline in mice following femoral fracture surgery, with gut microbiota depletion mitigating both TMAO elevation and cognitive dysfunction. In contrast, fecal microbiota transplantation from postoperative mice resulted in accelerated cognitive dysfunction and TMAO accumulation in germ‐free mice. Furthermore, TMAO treatment worsened cognitive deficits, neuroinflammation, and promoted microglial activation, which were reversed through the ablation of microglia. TMAO exacerbates cognitive dysfunction and neuroinflammation in POCD mice, with microglial activation playing a crucial role in this process. Our findings may provide new therapeutic strategies for managing TMAO‐related POCD and improving the quality of life for elderly patients. [ABSTRACT FROM AUTHOR]

Emerging atomically dispersed metal catalysts (ADCs), especially carbon−based ADCs have arguably received enormous attention in diverse electrochemical energy conversion processes. Such catalysts have well−defined active centers, and their geometric and electronic structures depend greatly on their coordination microenvironments, which, in turn, govern the performances in the realm of electrocatalysis. In this review, it is focused on the state−of−the−art synthesis strategies for carbon−based ADCs, with particular emphasis on their microenvironment modulations. The advances in characterizing the microenvironment alongside understanding the synthetic pathway are outlined, and exemplified in electrochemical applications, including electrocatalytic H2 evolution, O2 evolution/reduction, CO2 reduction, and Li polysulfides conversion reactions. Rather than focusing on the catalysis metrics, this review delved deeply into the underly science and the associated reaction mechanisms of these catalysts in diverse electrochemical systems. The fundamental impacts of the microenvironments of the catalysts on electrocatalytic activities, selectivities, and stabilities are discussed. In the end, it is concluded by highlighting the current issues of the microenvironment engineering of these carbon−based ADCs and propose the prospects for future opportunities and challenges. [ABSTRACT FROM AUTHOR]

Metal-based nanomaterials (MNMs) possess exceptional properties that have led to their widespread use in various fields, including medicine, energy, electronics, and agriculture. However, this increased utilization of MNMs also raises concerns about their potential release into environmental compartments, such as soil, water bodies, and the atmosphere, which could adversely affect the environmental system and living organisms. Hence, it is crucial to investigate the environmental risks associated with MNMs. This review comprehensively discusses the adverse effects of MNMs at different levels, including organismal, tissue, metabolic, molecular, and genetic levels. Additionally, it offers a holistic perspective on their overall impact. Specifically, biological models are categorized based on the environmental medium, and the effects of MNMs on tissues, organs, growth, development, and reproduction of individual biological models are summarized. Furthermore, the mechanisms underlying the toxicity of different MNMs toward biological models are also discussed. By doing so, this review provides a comprehensive and system-level understanding of nanotoxicity. [ABSTRACT FROM AUTHOR]

The American College of Sports Medicine classifies flexibility as one out of 5 important health-related parameters that should be addressed in preventive and therapeutic training programs (Garber et al., 2011). Due to its importance in health and athletic performance development, there is an increasing number of studies to figure out flexibility training interventions as well as underlying mechanisms. While several exercise modalities are available, stretching and foam rolling (FR) are the most common training routines to improve range of motion (ROM). Interestingly, acute and chronic effects are mainly attributed to very similar mechanisms, more specifically, improved stretch tolerance and/or structural adaptations such as stiffness reductions in the muscle, the tendon, or the muscle-tendon complex (Takeuchi et al., 2023). Since stretching and FR seem to induce similar effect sizes in acute flexibility, authors suggested the replacement of static stretching to FR in movement preparation routines to avoid the stretch-induced force deficit, thus, impairments of subsequent strength related performance. Similarly, when discussing chronic flexibility routine effects, literature suggests task specificity. Therefore, increased ROM was attributed to specific stretch/foam rolling induced stiffness and passive peak torque changes. Unfortunately, statements developed from used research designs are incomprehensive. When referring to acute stretching of foam rolling effects that can be extracted from numerous systematic reviews, conclusions were drawn from comparisons to passive controls. This, however, does exclusively allow statements that stretching/FR was effective compared to doing nothing, however, does not exclude general warm-up effects, induced by muscle activity. Referring to William of Ockham (1287 – 1347), one popular philosopher from the United Kingdom, the most obvious explanatory approach would be the most likely one. In medicine diagnostics, this statement is metaphorically described as “when hearing hoof beats from behind, expect horses, not zebras”. Therefore, since both routines enhance temperature, the most likely explanation suggest acute ROM increases could rely on general warm-up effects instead of task-specific adaptations. Similarly, for chronic effects, literature suggests that ROM can be increased by several alternative interventions, e.g. full ROM resistance training, indicating shared mechanisms. Both interventions share underlying physiological mechanisms, such as inducing mechanical tension in high muscle lengths. Consequently, we extensively discussed available evidence in our published research. Key findings will be presented to challenge current paradigms (Warneke et al., 2024). References Garber, C. E., Blissmer, B., Deschenes, M. R., Franklin, B. A., Lamonte, M. J., Lee, I.-M., Nieman, D. C., & Swain, D. P. (2011). Quantity and quality of exercise for developing and maintaining cardiorespiratory, musculoskeletal, and neuromotor fitness in apparently healthy adults. Medicine & Science in Sports & Exercise, 43(7), 1334–1359. https://doi.org/10.1249/MSS.0b013e318213fefb Takeuchi, K., Nakamura, M., Fukaya, T., Konrad, A., & Mizuno, T. (2023). Acute and long-term effects of static stretching on muscle-tendon unit stiffness: A systematic review and meta-analysis. Journal of Sports Science and Medicine, 22, 465–475. https://doi.org/10.52082/jssm.2023.465 Warneke, K., Behm, D. G., Alizadeh, S., Hillebrecht, M., Konrad, A., & Wirth, K. (2024). Discussing conflicting explanatory approaches in flexibility training under consideration of physiology - A narrative review. Sports Medicine, 54, 1785-1799. https://doi.org/10.1007/s40279-024-02043-y

Premature ovarian insufficiency (POI) or premature ovarian failure (POF) is a multifactorial disorder occurring in reproductive-age women, characterized by elevated levels of follicle-stimulating hormone (FSH) and irregular or absent menstrual cycles, often accompanied by perimenopausal symptoms and infertility. While assisted reproductive technology can address the reproductive aspirations of some POI-affected women, it is hindered by issues such as exorbitant expenses, substantial risks, and poor rates of conception. Encouragingly, extensive research is exploring novel approaches to enhance fertility, particularly in the realm of stem cell therapy, showcasing both feasibility and significant potential. Human amniotic epithelial cells (hAECs) from discarded placental tissues are crucial in regenerative medicine for their pluripotency, low immunogenicity, non-tumorigenicity, accessibility, and minimal ethical concerns. Preclinical studies highlight the underlying mechanisms and therapeutic effects of hAECs in POI treatment, and current research is focusing on innovative interventions to augment hAECs’ efficacy. However, despite these strides, overcoming application challenges is essential for successful clinical translation. This paper conducted a comprehensive analysis of the aforementioned issues, examining the prospects and challenges of hAECs in POI, with the aim of providing some insights for future research and clinical practice.

Rongqian Wu,1– 3 Junping Zhang,1– 3 Guilin Zou,1– 3 Shanshan Li,1 Jinying Wang,1 Xiaoxinlei Li,1 Jixiong Xu1– 3 1Department of Endocrinology and Metabolism, The 1st Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, People’s Republic of China; 2Jiangxi Clinical Research Center for Endocrine and Metabolic Disease, Nanchang, People’s Republic of China; 3Jiangxi Branch of National Clinical Research Center for Metabolic Disease, Nanchang, People’s Republic of ChinaCorrespondence: Jixiong Xu, Email Jixiong.Xu@ncu.edu.cnAbstract: The incidences of thyroid cancer and diabetes are rapidly increasing worldwide. The relationship between thyroid cancer and diabetes is a popular topic in medicine. Increasing evidence has shown that diabetes increases the risk of thyroid cancer to a certain extent. This mechanism may be related to genetic factors, abnormal thyroid-stimulating hormone secretion, oxidative stress injury, hyperinsulinemia, elevated insulin-like growth factor-1 levels, abnormal secretion of adipocytokines, and increased secretion of inflammatory factors and chemokines. This article reviews the latest research progress on the relationship between thyroid cancer and diabetes, including the association between diabetes and the risk of developing thyroid cancer, its underlying mechanisms, and potential anti-thyroid cancer effects of hypoglycemic drugs. It providing novel strategies for the prevention, treatment, and improving the prognosis of thyroid cancer.Keywords: diabetes, thyroid cancer, underlying mechanisms, hypoglycemic drugs

People with acquired apraxia of speech (AOS) and aphasia commonly experience long-term communication disability without support for their ongoing recovery or self-management. Little is known about their lived experience of metalinguistic abilities and capacity to harness them for self-management of speech production. The author, a speech and language therapist (SLT), revisited her previous qualitative study after her own more recent lived experience of recovering from mild aphasia. Participant perspectives were explored from a longitudinal case series (eleven people with confirmed AOS and aphasia discharged from SLT), with full ethical approval. The anonymized data comprised detailed transcripts from videoed semi-structured interviews, participant assessments, field notes and reflections, member checking, and reflexivity. The original systematic thematic analysis of these data in NVivo software was re-interrogated by the author, deriving three overarching themes: Metalinguistic awareness of spoken communication breakdown, Self-management, and Therapeutic assessment. The participants conveyed the nature, occurrence, context, mechanism, and purpose underlying errors in spoken communication (themes of What, When, Where, How and Why). They generated compensatory strategies, elucidated via subthemes with quotations, verified contemporaneously by an original participant volunteer. The findings support the value of metalinguistic co-construction during in-depth assessments of communication disability, offering fresh avenues for long-term self-management in aphasia and AOS. [ABSTRACT FROM AUTHOR]

Background: Emerging research suggests that attention-deficit/hyperactivity disorder (ADHD) increases the risk for cardiovascular (CVDs) and metabolic disorders (i.e., cardiometabolic disorders) in adulthood. Yet, available studies are scarce and have mainly been focused on individuals receiving clinical ADHD diagnoses. We aimed to investigate the prospective associations of ADHD symptoms in young and mid-adulthood with subsequent cardiometabolic disorders and the underlying mechanisms. Methods: We studied 10,394 twins from the Swedish Twin Registry (STR), born between 1958 and 1985 without previous medical history of cardiometabolic disorders. They provided self-assessment of ADHD symptoms (score range 0–36) via a validated, DSM-IV-based scale in a web-based questionnaire/telephone interview within the Study of Twin Adults: Genes and Environment (STAGE), in 2005–2006 (aged 19–47 years), and were followed until the end of 2018 (33–59 years) to identify incident clinical diagnoses/medication prescriptions for cardiometabolic disorders acquired from Swedish national registers. We used Cox regression models to investigate the associations between ADHD symptoms score and cardiometabolic outcomes, with and without adjustment for relevant covariates, and a co-twin control design to study familial confounding. Results: A one-unit increase in the level of ADHD symptoms was associated with a 2% increase in the rate of CVDs (hazard ratio [HR] = 1.02, 95% confidence interval 1.01–1.04) and a 3% increase in the rate of metabolic disorders (HR = 1.03, 1.02–1.05), after adjusting for birth year and sex. The associations were no longer significant after adjusting for educational attainment, lifestyle factors, and comorbid psychiatric disorders. The associations remained significant after adjusting for familial factors shared by dizygotic twin pairs but became nonsignificant after adjusting for factors shared by monozygotic twin pairs. However, the strength of the associations attenuated significantly in monozygotic twins compared to dizygotic twins for CVDs only, suggesting genetic confounding. Conclusions: ADHD symptom score is associated with a higher risk for cardiometabolic disorders, which may be explained by lower educational attainment, adverse lifestyle factors, and psychiatric comorbidities. Moreover, the associations appear to be partly confounded by shared genetic factors, especially for CVDs. Further research is needed to investigate the identified associations at the level of individual cardiometabolic disorders and to follow-up participants until a more advanced older age. [ABSTRACT FROM AUTHOR]

Aims: The aim of this review is to outline recent advancements in the application and mechanistic studies of aromatic plant extracts in Alzhermer's disease (AD) to demonstrate their value in the management of this disease. Background: AD is a neurodegenerative disease with a complex pathogenesis characterized by severe cognitive impairment. Currently, there are very few drugs available for the treatment of AD, and treatments are primarily focused on symptom relief. Aromatherapy is a traditional complementary alternative therapy that focuses on the prevention and treatment of the disease through the inhalation or transdermal administration of aromatic plant extracts. Over the past few years, studies on the use of aromatic plant extracts for the treatment of AD have been increasing and have demonstrated a definitive therapeutic effect. Methods: We systematically summarized in vitro, in vivo, and clinical studies focusing on the potential use of aromatic plant extracts in the treatment of AD in PubMed, ScienceDirect, Google Scholar, and the Chinese National Knowledge Infrastructure from 2000 to 2022. Results: Our literature survey indicates that aromatic plant extracts exert anti‐AD effects by modulating pathological changes through anti‐amyloid, anti‐tau phosphorylation, anti‐cholinesterase, anti‐inflammation, and anti‐oxidative stress mechanisms (Figure 1). Conclusion: This review provides a future strategy for the research of novel anti‐AD drugs from aromatic plant extracts. [ABSTRACT FROM AUTHOR]

Transcranial magnetic stimulation (TMS) is a non-invasive brain neurostimulation technique that can be used as one of the adjunctive treatment techniques for neurological recovery after stroke. Animal studies have shown that TMS treatment of rats with middle cerebral artery occlusion (MCAO) model reduced cerebral infarct volume and improved neurological dysfunction in model rats. In addition, clinical case reports have also shown that TMS treatment has positive neuroprotective effects in stroke patients, improving a variety of post-stroke neurological deficits such as motor function, swallowing, cognitive function, speech function, central post-stroke pain, spasticity, and other post-stroke sequelae. However, even though numerous studies have shown a neuroprotective effect of TMS in stroke patients, its possible neuroprotective mechanism is not clear. Therefore, in this review, we describe the potential mechanisms of TMS to improve neurological function in terms of neurogenesis, angiogenesis, anti-inflammation, antioxidant, and anti-apoptosis, and provide insight into the current clinical application of TMS in multiple neurological dysfunctions in stroke. Finally, some of the current challenges faced by TMS are summarized and some suggestions for its future research directions are made. [ABSTRACT FROM AUTHOR]

Water color, often quantified using the Forel-Ule Index (FUI), is a crucial parameter for assessing the water quality and ecological health of coastal waters. However, there is limited research on the spatiotemporal variations of FUI and the associated influencing factors in the Bohai and Yellow Seas. In this study, we utilized multi-sensor satellite datasets to retrieve monthly FUI products for the Bohai and Yellow Seas spanning the period from September 1997 to December 2019. Subsequently, we examined significant spatial disparities and variations across multiple timescales in the remotely sensed FUI time series. The climatological annual mean FUI map reveals a decreasing trend from nearshore to offshore regions, with similar spatial patterns observed in terms of overall and interannual FUI variability. The annual variations in wind field, sea surface temperature (SST), and ocean stratification play a key role in the seasonal dynamics of FUI by modulating the sediment resuspension process, resulting in low FUI values in summer and high FUI values in winter. Linear regression analysis of FUI anomaly indicates a long-term decreasing trend in FUI for the three bays of the Bohai Sea, while upward trends in FUI predominantly prevail in the central Yellow Sea. Factors related to interannual FUI variations, such as surface winds, SST, river outflow, rainfall, and anthropogenic activities, are qualitatively discussed. The findings of this study provide the first comprehensive evaluation of water color variations and their underlying mechanisms in the Bohai and Yellow Seas. [ABSTRACT FROM AUTHOR]

A growing body of evidence suggests the positive impact of arts on health and wellbeing. The mechanisms underlying the impact however, remain overlooked. 38 Semi-structured interviews were held with 30 older adults and 10 artists, involved in five participatory art projects in the Netherlands. Case-based framework and cross-over analyses were done on the basis of Cousins et al.'s taxonomy. Participatory art initiatives contributed to the wellbeing of older adults in a complex interplay with the artist, art form, group of participants, material aspects and continuity of activities. A welcoming environment appeared a consistent underlying mechanism for participants to grow on a personal and artistic level, connect with others and feel supported in their psychosocial wellbeing. This article demonstrates the important social function participatory art can have for older adults, and argues for the importance of a thorough consideration of the context wherein underlying mechanisms and outcomes emerge. [ABSTRACT FROM AUTHOR]

TP53 mutation is a frequent tumor suppressor mutation and a critical prognostic indicator across studies in many malignant tumors including hematologic malignancies. However, the role of TP53 and its correlative pathway in acute myeloid leukemia (AML) is enigmatic, which may provide possible emerging strategies with the potential to improve outcomes in AML. Accordingly, we focus not only on the TP53 mutation but also on the underlying mechanisms of the mutated TP53 signal pathway. While it is now generally accepted that TP53 mutations are widely associated with a dismal prognosis, resistance to chemotherapy, and high incidence of relapse and refractory AML. Hereby, the current therapeutics targeting TP53 mutant AML are summarized in this review. This will address emerging TP53‐based therapeutic approaches, facilizing the TP53‐targeted treatment options. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is the most malignant form of glioma and is difficult to diagnose, leading to high mortality rates. Circular RNAs (circRNAs) are noncoding RNAs with a covalently closed loop structure. CircRNAs are involved in various pathological processes and have been revealed to be important regulators of GBM pathogenesis. CircRNAs exert their biological effects by 4 different mechanisms: serving as sponges of microRNAs (miRNAs), serving as sponges of RNA binding proteins (RBPs), modulating parental gene transcription, and encoding functional proteins. Among the 4 mechanisms, sponging miRNAs is predominant. Their good stability, broad distribution and high specificity make circRNAs promising biomarkers for GBM diagnosis. In this paper, we summarized the current understanding of the characteristics and action mechanisms of circRNAs, illustrated the underlying regulatory mechanisms of circRNAs in GBM progression and explored the possible diagnostic role of circRNAs in GBM. [ABSTRACT FROM AUTHOR]

Music and arts for healing purposes look back over a multifaceted evolution and a myriad of phenomena in various cultures. Interdisciplinary considerations suggest to distinguish five different, but partly overlapping stages. The first refers to historical roots and ethnological sources, which have also influenced modern meta-theoretical perspectives and practices. The next stage marks the heterogeneous origins of modern music therapy in the 20th century that mirror psychological positions and novel clinical ideas about the healing power of music and the arts. The following heyday of music therapeutic models and schools of thought yielded an enormous variety of concepts and methods such as Nordoff-Robbins MT, Orff MT, Analytic MT, Regulatory MT, GIM or Sound Work. As music and arts therapies gained in international importance, clinical applications required research about their therapeutic efficacy. According to standards of evidence based medicine and with regard to clearly defined diagnoses research on music therapeutic practice became the core of stage four. The present stage is characterised by an emerging epistemological dissatisfaction with the paradigmatic reductionism of evidence based medicine and the strong will to discover the ‘true healing nature’ of music. This trend has given birth to interdisciplinary hermeneutics for novel foundations of music and arts therapies. Epigenetics, neuroplasticity, regulatory and chronobiological sciences, quantum physical philosophies, universal harmonies, spiritual and religious views, and the cultural anthropological phenomenon of aesthetics and creativity have become guiding principles. The present paper relates to the author’s EASA-speech on the 2nd of December 2022 about landmarks in the evolution of modern music therapy and its interdisciplinary perspectives. [ABSTRACT FROM AUTHOR]

Decomposition is vital for nutrient cycling and is sensitive to atmospheric nutrient depositions. However, the influences and underlying mechanisms of nutrient deposition on the long-term decomposition of leaves and absorptive roots remain unclear. Here, we explored the responses of leaves and absorptive roots to nutrient deposition (control, +N, +P, and +NP) in Pinus massoniana and Schima superba forests in subtropical China based on two stages (early-stage (1-year) and late-stage (3-year)) of a decomposition experiment. The chemical factions (acid-unhydrolysable residue (AUR), cellulose, and hemicellulose concentrations) and microbial enzymatic activities (hydrolase and oxidase) were also determined. The +N treatment had persistent negative effects on absorptive root decomposition, except for P. massoniana during the late stage. The +P treatment had a positive effect on leaf decomposition in all stages. The +NP treatment had a positive effect on leaf decomposition during the late stage. The increasing decomposition rates of foliar under +P treatment were more correlated with the increasing acid phosphatase activity than chemical factions, indicating a microbial mechanism. The decreasing decomposition rates of roots under +N treatment were weakly correlated with increasing AUR concentrations and strongly correlated with decreasing oxidase activity during the late stage, indicating both chemical and microbial mechanisms. Overall, our findings highlight that, despite contrasting responses to nutrient deposition, the mechanisms underlying aboveground and belowground decomposition tend to converge as decomposition progresses. [ABSTRACT FROM AUTHOR]

This article proposes a more individualized approach to organizational and food safety culture development through the creation of culture change agents. The study used action research with individual therapeutic training of sensory and emotional skills as the action intervention to reveal underlying mechanisms of the culture and create long-term culture change. The study was conducted with a group of voluntary employees over a 3-year period at a department under Food Safety and Veterinary Issues in Danish Agriculture and Food Council. Data was collected using individual in-depth qualitative interviews with a novel questionnaire technique that facilitated participants to bring otherwise unconscious underlying assumptions to awareness. The study found that working intensely and therapeutically on an individual and group level, had a significant impact on the surrounding culture and social capital. Five underlying mechanisms were revealed linking individual culture change to changes in the social capital and culture of the department. Going through the five underlying mechanisms may enable individuals to get to the root causes of issues, facilitate more sharing and collaboration to learn from near-misses and failures, and take action despite facing uncomfortable situations, all important abilities to develop FSC. Based on the underlying mechanisms a ‘Change Agent Model’ was developed. The model illustrates the important underlying mechanisms that any individual or group can work through to become culture change agents and drivers for organizational culture and FSC development. This is the first of two articles.

Shear-wave elastography is a method that is increasingly used to assess muscle stiffness in clinical practice and human health research. Recently, shear-wave elastography has been suggested and used to assess exercise-induced muscle damage. This review aimed to summarize the current knowledge of the utility of shear-wave elastography for assessment of muscle damage. In general, the literature supports the shear-wave elastography as a promising method for assessment of muscle damage. Increases in shear modulus are reported immediately and up to several days after eccentric exercise, while studies using shear-wave elastography during and after endurance events are showing mixed results. Moreover, it seems that shear modulus increases are related to the decline in voluntary strength loss. We recommend that shear modulus is measured at multiple muscles within a muscle group and preferably at longer muscle lengths. While further studies are needed to confirm this, the disruption of calcium homeostasis seems to be the primary candidate for the underlying mechanism explaining the increases in shear modulus observed after eccentric exercise. It remains to be investigated how well the changes in shear modulus correlate with directly assessed amount of muscle damage (biopsy). [ABSTRACT FROM AUTHOR]

Ultra-high performance cementitious composite (UHPCC) is an advanced composite material with superior compressive strength. UHPCC with low steel fiber content typically fails in a single-crack mode under tension, resulting in a high risk of catastrophic structural collapse and limiting its wide application. However, high steel fiber content adversely affects the electrochemical corrosion resistance and long-term performance of UHPCC. Therefore, enhancing the tensile performance of UHPCC with low fiber content has attracted great attention. Polyvinyl alcohol (PVA) fiber is characterized by outstanding crack control ability in cementitious materials. In this study, the macroscale flowability, tensile and flexural properties, ductility and failure mode of UHPCC containing steel and PVA fibers at low fiber content level were explored and analyzed. Results indicate that the post-crack energy absorption of UHPCC improved by more than 40% following fibers hybridization. The failure mode of UHPCC with low fiber content shifted from single crack mode to ductile multiple cracks mode. Microscale observations show that PVA fibers can bridge crack and transfer load at the interface after first cracking, and impede slippage between steel fiber and matrix, thus endows UHPCC with desirable ductile multiple cracks failure mode. The findings of this study provide a foundation for designing UHPCC with ductile tensile performance and give an in-depth understanding of underlying mechanisms of hybrid fibers, promoting the application of ductile UHPCC in innovative structures.

Water color, often quantified using the Forel-Ule Index (FUI), is a crucial parameter for assessing the water quality and ecological health of coastal waters. However, there is limited research on the spatiotemporal variations of FUI and the associated influencing factors in the Bohai and Yellow Seas. In this study, we utilized multi-sensor satellite datasets to retrieve monthly FUI products for the Bohai and Yellow Seas spanning the period from September 1997 to December 2019. Subsequently, we examined significant spatial disparities and variations across multiple timescales in the remotely sensed FUI time series. The climatological annual mean FUI map reveals a decreasing trend from nearshore to offshore regions, with similar spatial patterns observed in terms of overall and interannual FUI variability. The annual variations in wind field, sea surface temperature (SST), and ocean stratification play a key role in the seasonal dynamics of FUI by modulating the sediment resuspension process, resulting in low FUI values in summer and high FUI values in winter. Linear regression analysis of FUI anomaly indicates a long-term decreasing trend in FUI for the three bays of the Bohai Sea, while upward trends in FUI predominantly prevail in the central Yellow Sea. Factors related to interannual FUI variations, such as surface winds, SST, river outflow, rainfall, and anthropogenic activities, are qualitatively discussed. The findings of this study provide the first comprehensive evaluation of water color variations and their underlying mechanisms in the Bohai and Yellow Seas.

The deployment of new 5G NR technology has significantly raised public concerns in possible negative effects on human health by radiofrequency electromagnetic fields (RF EMF). The current review is aimed to clarify the differences between possible health effects caused by the various generations of telecommunication technology, especially discussing and projecting possible health effects by 5G. The review of experimental studies on the human brain over the last fifteen years and the discussion on physical mechanisms and factors determining the dependence of the RF EMF effects on frequency and signal structure have been performed to discover and explain the possible distinctions between health effects by different telecommunication generations. The human experimental studies on RF EMF effects on the human brain by 2G, 3G and 4G at frequencies from 450 to 2500 MHz were available for analyses. The search for publications indicated no human experimental studies by 5G nor at the RF EMF frequencies higher than 2500 MHz. The results of the current review demonstrate no consistent relationship between the character of RF EMF effects and parameters of exposure by different generations (2G, 3G, and 4G) of telecommunication technology. At the RF EMF frequencies lower than 10 GHz, the impact of 5G NR FR1 should have no principal differences compared to the previous generations. The radio frequencies used in 5G are even higher and the penetration depths of the fields are smaller; therefore, the effect is rather lower than at previous generations. At the RF EMF frequencies higher than 10 GHz, the mechanism of the effects might differ and the impact of 5G NR FR2 becomes unpredictable. Existing knowledge about the mechanism of RF EMF effects at millimeter waves lacks sufficient experimental data and theoretical models for reliable conclusions. The insufficient knowledge about the possible health effects at millimeter waves and the lack of in vivo experimental studies on 5G NR underline an urgent need for the theoretical and experimental investigations of health effects by 5G NR, especially by 5G NR FR2. [ABSTRACT FROM AUTHOR]

Mushroom polysaccharides are recognized as "biological response modifiers". Besides several bioactivities, a growing interest in their prebiotic potential has been raised due to the gut microbiota modulation potential. This review comprehensively summarizes mushroom polysaccharides' biological properties, structure-function relationship, and underlying mechanisms. It provides a recent overview of the key findings in the field (2018–2024). Key findings and limitations on structure-function correlation are discussed. Although most studies focus on β-glucans or extracts, α-glucans and chitin have gained interest. Prebiotic capacity has been associated with α-glucans and chitin, while antimicrobial and wound healing potential is attributed to chitin. However, further research is of utmost importance. Human fecal fermentation is the most reported approach to assess prebiotic potential, indicating impacts on intestinal biological, mechanical, chemical and immunological barriers. Gut microbiota dysbiosis has been directly connected with intestinal, cardiovascular, metabolic, and neurological diseases. Concerning gut microbiota modulation, animal experiments have suggested proinflammatory cytokines reduction and redox balance re-establishment. Most literature focused on the anticancer and immunomodulatory potential. However, anti-inflammatory, antimicrobial, antiviral, antidiabetic, hypocholesterolemic, antilipidemic, antioxidant, and neuroprotective properties are discussed. A significant overview of the gaps and research directions in synergistic effects, underlying mechanisms, structure-function correlation, clinical trials and scientific data is also given. [Display omitted] • Direct and gut microbiota-related effects of mushroom polysaccharides (MP)- chitin, α- and β-glucans. • Further structural research is mandatory to robust structure-function correlations. • MP promote gut metabolite production, impacting the heart, liver, and brain axis. • MP impact intestinal biological, mechanical, chemical and immunological barriers. • β-glucans exhibit a strong immunomodulating, antioxidant and metabolic regulation effect. [ABSTRACT FROM AUTHOR]

The current study aimed to assess the anti-diabetic effects and potential mechanisms of two Sargassum fusiform polysaccharide fractions (SFPs, named SFP-1 and SFP-2). The carbohydrate-loading experiment revealed that SFP-2 could control postprandial hyperglycemia by inhibiting the activity of digestive enzymes in rats. The analysis of diabetic symptoms and serum profiles indicated that SFPs could mitigate diabetes accompanied by dyslipidemia, and SFP-2 showed better regulatory effects on body weight, food intake and the levels of total cholesterol (TC), triglycerides (TG), low density lipoprotein-cholesterol (LDL-C) and free fatty acid (FFA) in diabetic rats. Intestinal bacterial analysis showed that SFP treatment could reshape the gut flora of diabetic rats, and SFP-2 possessed a greater regulatory effect on the growth of Lactobacillus and Blautia than SFP-1. RT-qPCR analysis revealed that SFPs could regulate the genes involved in the absorption and utilization of blood glucose, hepatic glucose production and lipid metabolism, and the effects of SFP-2 on the relative expressions of Protein kinase B (Akt), Glucose-6-phosphatase (G-6-Pase), Glucose transporter 2 (GLUT2), AMP-activated protein kinase-α (AMPKα), Peroxisome proliferator-activated receptor γ (PPARγ) and Cholesterol 7-alpha hydroxylase (CYP7A1) were greater than SFP-1. All above results indicated that SFPs could be exploited as functional foods or pharmaceutical supplements for the treatment of diabetes and its complications. [ABSTRACT FROM AUTHOR]

Premature ovarian insufficiency (POI) or premature ovarian failure (POF) is a multifactorial disorder occurring in reproductive-age women, characterized by elevated levels of follicle-stimulating hormone (FSH) and irregular or absent menstrual cycles, often accompanied by perimenopausal symptoms and infertility. While assisted reproductive technology can address the reproductive aspirations of some POI-affected women, it is hindered by issues such as exorbitant expenses, substantial risks, and poor rates of conception. Encouragingly, extensive research is exploring novel approaches to enhance fertility, particularly in the realm of stem cell therapy, showcasing both feasibility and significant potential. Human amniotic epithelial cells (hAECs) from discarded placental tissues are crucial in regenerative medicine for their pluripotency, low immunogenicity, non-tumorigenicity, accessibility, and minimal ethical concerns. Preclinical studies highlight the underlying mechanisms and therapeutic effects of hAECs in POI treatment, and current research is focusing on innovative interventions to augment hAECs' efficacy. However, despite these strides, overcoming application challenges is essential for successful clinical translation. This paper conducted a comprehensive analysis of the aforementioned issues, examining the prospects and challenges of hAECs in POI, with the aim of providing some insights for future research and clinical practice.

Magnesium and its alloys, as a promising class of materials, is popular in lightweight application and biomedical implants due to their low density and good biocompatibility. Additive manufacturing (AM) of Mg and its alloys is of growing interest in academia and industry. The domain-by-domain localized forming characteristics of AM leads to unique microstructures and performances of AM-process Mg and its alloys, which are different from those of traditionally manufactured counterparts. However, the intrinsic mechanisms still remain unclear and need to be in-depth explored. Therefore, this work aims to discuss and analyze the possible underlying mechanisms regarding defect appearance and elimination, microstructure formation and evolution, and performance improvement, based on presenting a comprehensive and systematic review on the relationship between process parameters, forming quality, microstructure characteristics and resultant performances. Lastly, some key perspectives requiring focus for further progression are highlighted to promote development of AM-processed Mg and its alloys and accelerate their industrialization.

Decomposition is vital for nutrient cycling and is sensitive to atmospheric nutrient depositions. However, the influences and underlying mechanisms of nutrient deposition on the long-term decomposition of leaves and absorptive roots remain unclear. Here, we explored the responses of leaves and absorptive roots to nutrient deposition (control, +N, +P, and +NP) in Pinus massoniana and Schima superba forests in subtropical China based on two stages (early-stage (1-year) and late-stage (3-year)) of a decomposition experiment. The chemical factions (acid-unhydrolysable residue (AUR), cellulose, and hemicellulose concentrations) and microbial enzymatic activities (hydrolase and oxidase) were also determined. The +N treatment had persistent negative effects on absorptive root decomposition, except for P. massoniana during the late stage. The +P treatment had a positive effect on leaf decomposition in all stages. The +NP treatment had a positive effect on leaf decomposition during the late stage. The increasing decomposition rates of foliar under +P treatment were more correlated with the increasing acid phosphatase activity than chemical factions, indicating a microbial mechanism. The decreasing decomposition rates of roots under +N treatment were weakly correlated with increasing AUR concentrations and strongly correlated with decreasing oxidase activity during the late stage, indicating both chemical and microbial mechanisms. Overall, our findings highlight that, despite contrasting responses to nutrient deposition, the mechanisms underlying aboveground and belowground decomposition tend to converge as decomposition progresses.

Gastric diseases have emerged as one of the main chronic diseases in humans, leading to considerable health, social, and economic burdens. As a result, using food or "food and medicinal homologous substances" has become an effective strategy to prevent gastric diseases. Diet may play a crucial role in the prevention and mitigation of gastric diseases, particularly long-term and regular intake of specific dietary components that have a protective effect on the stomach. These key components, extracted from food, include polysaccharides, alkaloids, terpenoids, polyphenols, peptides, probiotics, etc. The related mechanisms involve regulating gastric acid secretion, protecting gastric mucosa, increasing the release of gastric defense factors, decreasing the level of inflammatory factors, inhibiting Helicobacter pylori infection, producing antioxidant effects or reducing oxidative damage, preventing gastric oxidative stress by inhibiting lipid peroxides, activating Nrf2 signaling pathway, and inhibiting NF-κB, TLR4, and NOS/NO signaling pathways.

Circular RNAs (circRNAs) are covalently closed RNAs that function in various physiological and pathological processes. CircRNAs are widely involved in the development of cardiovascular disease (CVD), one of the leading causes of morbidity and mortality worldwide. CircHIPK3 is generated from the second exon of the HIPK3 gene, a corepressor of homeodomain transcription factors. As an exonic circRNA (ecRNA), circHIPK3 is produced through intron-pairing driven circularization facilitated by Alu elements. In the past 5 years, a growing number of studies have revealed the multifunctional roles of circHIPK3 in different diseases, such as cancer and CVD. CircHIPK3 mainly participates in CVD pathogenesis through interacting with miRNAs. This paper summarizes the current literature on the biogenesis and functions of circHIPK3, elucidates the role of circHIPK3 in different CVD patterns, and explores future perspectives.

Shear-wave elastography is a method that is increasingly used to assess muscle stiffness in clinical practice and human health research. Recently, shear-wave elastography has been suggested and used to assess exercise-induced muscle damage. This review aimed to summarize the current knowledge of the utility of shear-wave elastography for assessment of muscle damage. In general, the literature supports the shear-wave elastography as a promising method for assessment of muscle damage. Increases in shear modulus are reported immediately and up to several days after eccentric exercise, while studies using shear-wave elastography during and after endurance events are showing mixed results. Moreover, it seems that shear modulus increases are related to the decline in voluntary strength loss. We recommend that shear modulus is measured at multiple muscles within a muscle group and preferably at longer muscle lengths. While further studies are needed to confirm this, the disruption of calcium homeostasis seems to be the primary candidate for the underlying mechanism explaining the increases in shear modulus observed after eccentric exercise. It remains to be investigated how well the changes in shear modulus correlate with directly assessed amount of muscle damage (biopsy).

Traditional Chinese medicine (TCM) is a valuable form of medicine with a long history in China. It has played a significant role in the control and prevention of infectious diseases including SARS and H7N9 flu. After the outbreak of COVID-19, China's National Health Commission included TCM in the Diagnosis and Treatment Protocol for COVID-19. During the COVID-19 pandemic, three traditional Chinese medicines (Jinhua Qinggan granules, Lianhua Qingwen medicine, and a Xuebijing Injection) and three TCM preparations (a Qingfei Paidu decoction, a Huashi Baidu decoction, and a Xuanfei Baidu decoction) have been screened for their efficacy against COVID-19. More than 150 trials involving TCMs are registered in the Chinese Clinical Trial Registry (ChiCTR), and those trials cover prevention, treatment, recovery, and illnesses diagnosed in accordance with TCM principles. TCM can effectively alleviate the symptoms of patients with COVID-19, delay the disease's progression from mild to severe or critical, and reduce severe and critical all-cause mortality. The underlying mechanisms of TCM mainly involve action against SARS-CoV-2, anti-inflammatory and immunomodulatory action, and organ protection. The current work provides a brief description of the current status of and issues with TCM to treat this novel infectious disease. The hope is that TCM can help considerably to control this global epidemic. [ABSTRACT FROM AUTHOR]

[Display omitted] • Two ACE inhibitory peptides were obtained from garlic proteins by in silico screening. • They interacted with ACE mainly through hydrogen bonding as competitive inhibitors. • They showed good stability against temperature, pH and gastrointestinal digestion. • Two peptides effectively lowered blood pressure in spontaneously hypertensive rats. • They rebalanced the RAS and improved renal, cardiac and endothelial impairments. This study aimed to screen novel angiotensin I-converting enzyme (ACE) inhibitory peptides from garlic proteins and to explore their underlying antihypertensive mechanisms in vivo. After simulated hydrolysis and in silico screening, two novel peptides (MGR and HDCF) were obtained with the highest ACE inhibitory activity (IC 50 of 4.50 μM and 26.38 μM) and acted as competitive inhibitors. They interacted with key residues in the ACE receptor mainly through hydrogen bonding and exhibited excellent stability against high temperature, extreme pH, and gastrointestinal digestion. In spontaneously hypertensive rats, MGR and HDCF effectively lowered blood pressure after single or continuous treatments. This was mainly achieved by balancing the renin-angiotensin system, improving renal and cardiac impairment, and regulating endothelial dysfunction. These findings suggested that garlic proteins were potentially suitable materials to prepare ACE inhibitory peptides and provided two promising candidates for ACE inhibition as functional food ingredients. [ABSTRACT FROM AUTHOR]

Hawthorn, a well‐known traditional Chinese medicine is used for the treatment of dyspepsia syndrome, cardiovascular disease, and hyperlipidemia. Hawthorn has complex composition. However, the effective fraction and mechanisms of action in alleviating hyperlipidemia are unknown. Therefore, the aim of this study was to evaluate the effects of four different polar components of hawthorn on hyperlipidemia rats, and to explore underlying mechanisms of action through liquid chromatography‐mass spectrometry based plasma metabolomics. Hyperlipidemia rat model was established by feeding rats using a high‐fat diet. High‐fat model rats were then treated with four polar components of hawthorn for 14 consecutive days. Plasma samples were collected and subjected to biochemical and metabolomics analysis. Biochemical analysis showed that hawthorn n‐butanol and ethyl acetate extracts had the highest efficacy on hyperlipidemia rats. Water fraction showed a partial effect, whereas petroleum ether extract was not effective against hyperlipidemia rats. Furthermore, liquid chromatography‐mass spectrometry metabolomics analysis showed that the most effective fraction of hawthorn reversed the metabolic disorder in plasma of hyperlipidemia rats. Metabolomics analysis showed that hawthorn exerts its activity by modulating lipid metabolism, energy metabolism, oxidative stress, and amino acid metabolism. [ABSTRACT FROM AUTHOR]

The current study aimed to assess the anti-diabetic effects and potential mechanisms of two Sargassum fusiform polysaccharide fractions (SFPs, named SFP-1 and SFP-2). The carbohydrate-loading experiment revealed that SFP-2 could control postprandial hyperglycemia by inhibiting the activity of digestive enzymes in rats. The analysis of diabetic symptoms and serum profiles indicated that SFPs could mitigate diabetes accompanied by dyslipidemia, and SFP-2 showed better regulatory effects on body weight, food intake and the levels of total cholesterol (TC), triglycerides (TG), low density lipoprotein-cholesterol (LDL-C) and free fatty acid (FFA) in diabetic rats. Intestinal bacterial analysis showed that SFP treatment could reshape the gut flora of diabetic rats, and SFP-2 possessed a greater regulatory effect on the growth of Lactobacillus and Blautia than SFP-1. RT-qPCR analysis revealed that SFPs could regulate the genes involved in the absorption and utilization of blood glucose, hepatic glucose production and lipid metabolism, and the effects of SFP-2 on the relative expressions of Protein kinase B (Akt), Glucose-6-phosphatase (G-6-Pase), Glucose transporter 2 (GLUT2), AMP-activated protein kinase-α (AMPKα), Peroxisome proliferator-activated receptor γ (PPARγ) and Cholesterol 7-alpha hydroxylase (CYP7A1) were greater than SFP-1. All above results indicated that SFPs could be exploited as functional foods or pharmaceutical supplements for the treatment of diabetes and its complications.

Rheumatoid arthritis (RA) is a chronic autoimmune disease primarily affecting joints but often also associated with lung involvement such as bronchiectasis (BE). The aim of the present systematic review and meta-analysis is to provide an update on the current evidence regarding the prevalence and association between RA and BE. This systematic review and meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines with literature search using the terms 'Bronchiectasis AND Rheumatoid Arthritis' without a date limitation on PubMed during May 2020. A total of 28 studies fulfilled the predefined criteria and were included in the present review, with 19 being cross-sectional studies. Twenty-three studies were included in the meta-analysis. The pooled prevalence estimate was 2.69% (95% CI 1.63–4.42) in clinically defined BE, and 24.9% (95% CI 19.21–31.67) in radiologic disease. Many inconsistencies exist regarding potential risk factors for BE in RA patients such as gender, RA duration and severity, as both negative and positive associations have been reported. Although very little is known about possible causative mechanisms between RA and BE, potential pathways might be antigenic stimulation from pulmonary mucus and/or systemic inflammation from joint disease affecting the lungs. At present, the available evidence of bronchiectasis in patients with RA is insufficient to identify RA-associated risk factors for the development of BE, possibly apart from duration of RA, and, consequently, also to fully explore a possible causal relationship between the two disease. However, the increased prevalence of BE in RA patients warrants further studies to explore the association between RA and BE. [ABSTRACT FROM AUTHOR]

Air pollution is a major global environment and health concern. Recent studies have suggested an association between air pollution and COVID-19 mortality and morbidity. In this context, a close association between increased levels of air pollutants such as particulate matter ≤2.5 to 10 µM, ozone and nitrogen dioxide and SARS-CoV-2 infection, hospital admissions and mortality due to COVID 19 has been reported. Air pollutants can make individuals more susceptible to SARS-CoV-2 infection by inducing the expression of proteins such as angiotensin converting enzyme (ACE)2 and transmembrane protease, serine 2 (TMPRSS2) that are required for viral entry into the host cell, while causing impairment in the host defence system by damaging the epithelial barrier, muco-ciliary clearance, inhibiting the antiviral response and causing immune dysregulation. The aim of this review is to report the epidemiological evidence on impact of air pollutants on COVID 19 in an up-to-date manner, as well as to provide insights on in vivo and in vitro mechanisms., Competing Interests: Conflicts of interest None., (Copyright © 2024 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.)

The objective of current work was to explore the potential anti-diabetic mechanisms of Hizikia fusifarme polysaccharide (HFP) in type 2 diabetic rats. The carbohydrate loading experiment illustrated that HFP supplement could reduce blood sugar fluctuations caused by eating through inhibiting the hydrolysis of starch in mice. The analysis of typically diabetic symptoms and serum profiles showed that oral administration of HFP could mitigate hyperglycemia, insulin resistance, dyslipidemia, chronic inflammation and oxidative stress in rats. The 16s rRNA gene sequencing analysis indicated that HFP treatment could restore beneficial composition of gut flora in diabetic rats, and the correlation analysis revealed that the improvement of diabetes is closely related to the modification of gut flora by HFP intervention. Furthermore, the RT-qPCR and western blotting analysis clarified that HFP administration could increase glycogen storage in liver and skeletal muscle of diabetic rats through activating IRS/PI3K/AKT/GLUT signaling pathway and restrain gluconeogenesis via affecting the relative expression of Egr-1 and PEPCK genes. [ABSTRACT FROM AUTHOR]

BackgroundThe coronavirus disease 2019 (COVID-19) has become a worldwide public health crisis. At present, there are no effective antiviral drugs to treat COVID-19. Although some vaccines have been developed, late-stage clinical trials that allow licensure by regulatory agencies are still needed. Previous reports have indicated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and SARS-CoV are highly homologous and both use angiotensin-converting enzyme 2 (ACE2) as the receptor to enter cells, and SARS-CoV infection reduces the ACE2 expression in the lung. Therefore, the analysis of genes co-expressed with ACE2 in the lung may uncover the underlying mechanism of COVID-19. Finally, we used the Connectivity map (Cmap) database to search for candidate drugs using transcriptome profiles of patients with COVID-19.MethodBased on the differentially expressed genes (DEGs), indicated by the expression of RNAs isolated from bronchoalveolar lavage fluid (BALF) cells of patients with COVID-19, we performed functional enrichment analysis and hub gene cluster analysis. Furthermore, we identified genes co-expressed with ACE2 in healthy lung samples and analyzed the significant genes. Additionally, to identify several candidate drugs for the treatment of COVID-19, we queried Cmap using DEGs and genes co-expressed with ACE2.Results and ConclusionThe up-regulated genes in the BALF cells of patients with COVID-19 are related to viral mRNA translation. The down-regulated genes are related to immune response functions. Genes positively correlated with ACE2 are related to immune defense and those negatively correlated are enriched in synaptic transmission functions. The results reflected prosperous viral proliferation and immune dysfunction in patients. Furthermore, ACE2 may not only mediate viral entrance, but also play an important role in immune defense. By using Cmap with transcriptome profiles of patients with COVID-19, we identified candidate drugs for the treatment of COVID-19, such as amantadine and acyclovir.

Background: The coronavirus disease 2019 (COVID-19) has become a worldwide public health crisis. At present, there are no effective antiviral drugs to treat COVID-19. Although some vaccines have been developed, late-stage clinical trials that allow licensure by regulatory agencies are still needed. Previous reports have indicated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and SARS-CoV are highly homologous and both use angiotensin-converting enzyme 2 (ACE2) as the receptor to enter cells, and SARS-CoV infection reduces the ACE2 expression in the lung. Therefore, the analysis of genes co-expressed with ACE2 in the lung may uncover the underlying mechanism of COVID-19. Finally, we used the Connectivity map (Cmap) database to search for candidate drugs using transcriptome profiles of patients with COVID-19. Method: Based on the differentially expressed genes (DEGs), indicated by the expression of RNAs isolated from bronchoalveolar lavage fluid (BALF) cells of patients with COVID-19, we performed functional enrichment analysis and hub gene cluster analysis. Furthermore, we identified genes co-expressed with ACE2 in healthy lung samples and analyzed the significant genes. Additionally, to identify several candidate drugs for the treatment of COVID-19, we queried Cmap using DEGs and genes co-expressed with ACE2. Results and Conclusion: The up-regulated genes in the BALF cells of patients with COVID-19 are related to viral mRNA translation. The down-regulated genes are related to immune response functions. Genes positively correlated with ACE2 are related to immune defense and those negatively correlated are enriched in synaptic transmission functions. The results reflected prosperous viral proliferation and immune dysfunction in patients. Furthermore, ACE2 may not only mediate viral entrance, but also play an important role in immune defense. By using Cmap with transcriptome profiles of patients with COVID-19, we identified candidate drugs for the treatment of COVID-19, such as amantadine and acyclovir. [ABSTRACT FROM AUTHOR]

Cervical squamous cell carcinoma (CESC) is a human papillomavirus-driven tumor that the underlying molecular mechanisms are unclear. This study aimed to elucidate the key candidate genes and potential mechanism in CESC by bioinformatics analysis. A total of 132 common differentially expressed genes (DEGs) were identified based on three expression profile data sets. A multivariate Cox proportional regression model was used to develop a four-gene prognostic signature. Mechanistically, the correlationship between MMP1 and tumor-infiltrating lymphocytes was further analyzed. Furthermore, annotations were investigated by Gene Ontology (GO) and The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Finally, potential drugs for CESC treatment were predicted by Connectivity Map. We profiled four genes (EFNA1, ANLN, MMP1, and ZWINT) with significant prognostic values for CESC. Multiple public available data sets were used for mRNA expression and prognostic characterization. Subsequently, GO and KEGG pathway analyses showed DEGs were mainly enriched in cell cycle, immunity, and metabolic-related pathway. We then conducted an integrated analysis of MMP1, and the expression of MMP1 showed significantly inverse association with the amount of CD8+ T cells, CD4+ T cells, and macrophages infiltration. Our findings suggest the four-gene signature may be associated with prognosis. We further revealed that MMP1 may be a novel biomarker for immunotherapy, and prognostic judgment of patients with cervical cancer. [ABSTRACT FROM AUTHOR]

This study examines the slow modulation of El Niño–Southern Oscillation (ENSO) intensity and its underlying mechanism. A 10–15-yr ENSO intensity modulation cycle is identified from historical and paleoclimate data by calculating the envelope function of boreal winter Niño-3.4 and Niño-3 sea surface temperature (SST) indices. Composite analyses reveal interesting spatial asymmetries between El Niño and La Niña events within the modulation cycle. In the enhanced intensity periods of the cycle, El Niño is located in the eastern tropical Pacific and La Niña in the central tropical Pacific. The asymmetry is reversed in the weakened intensity periods: El Niño centers in the central Pacific and La Niña in the eastern Pacific. El Niño and La Niña centered in the eastern Pacific are accompanied with basin-scale surface wind and thermocline anomalies, whereas those centered in the central Pacific are accompanied with local wind and thermocline anomalies. The El Niño–La Niña asymmetries provide a possible mechanism for ENSO to exert a nonzero residual effect that could lead to slow changes in the Pacific mean state. The mean state changes are characterized by an SST dipole pattern between the eastern and central tropical Pacific, which appears as one leading EOF mode of tropical Pacific decadal variability. The Pacific Walker circulation migrates zonally in association with this decadal mode and also changes the mean surface wind and thermocline patterns along the equator. Although the causality has not been established, it is speculated that the mean state changes in turn favor the alternative spatial patterns of El Niño and La Niña that manifest as the reversed ENSO asymmetries. Using these findings, an ENSO–Pacific climate interaction mechanism is hypothesized to explain the decadal ENSO intensity modulation cycle.

Biosensors play a very important role in pollutant monitoring, but there are still some problems such as stability, repeatability and low detection limits. Therefore, it is necessary to explore ways to increase the performance of biosensors. In this study, biochar-MFC sensors were constructed for heavy metals monitoring in constructed wetlands (CWs), and the correlation, repeatability and anti-interference were studied. At 1.0 M/L concentrations of heavy metals (Ni, Cu, Zn and Cr), CW with biochar as filler (B-CW) had an output voltage of 0.69 V, extending the detection limit of the sensor. B-CW had advantages in anti-interference and reproducibility. The results showed that B-CW had higher abundance of electrogenic bacteria than CW. Shewanella and Proteobacteria , main electricity-producing bacteria, increased 3-fold. The electrochemically active microorganism Shewanellaceae made up 6.2% of the B-CW microbial population, but was not detected in CW. The abundance of key genes AarC increased by 1295.8% in B-CW. More importantly, the abundance of extracellular electron transport chain related genes (MtrA , OmcA) increased significantly (p < 0.01). Biochar can promote oxidative phosphorylation, thus increasing the sensor's output voltage and detection range. This study is expected to provide support for the engineering application of MFC sensor in CWs. [Display omitted] • MFC-sensors can effectively detect heavy metals in constructed wetlands. • Extracellular electron transfer significantly increased in biochar system. • Biochar increased genes associated with oxidative phosphorylation by about 27%. • Biochar significantly enhanced the repeatability and anti-interference of the sensor. [ABSTRACT FROM AUTHOR]

Post-surgical adhesions are common in almost all surgical areas and are associated with significant rates of morbidity, mortality, and increased healthcare costs, especially when a patient requires repeat operative interventions. Many groups have studied the mechanisms driving post-surgical adhesion formation. Despite continued advancements, we are yet to identify a prevailing mechanism. It is highly likely that post-operative adhesions have a multifactorial etiology. This complex pathophysiology, coupled with our incomplete understanding of the underlying pathways, has resulted in therapeutic options that have failed to demonstrate safety and efficacy on a consistent basis. The translation of findings from basic and preclinical research into robust clinical trials has also remained elusive. Herein, we present and contextualize the latest findings surrounding mechanisms that have been implicated in post-surgical adhesion formation.

Dyslipidemia is a key risk factor for cardiovascular diseases, which are a major cause of morbidity and mortality worldwide. However, despite the advancement of the treatment and prevention of dyslipidemia, medications used to treat dyslipidemia are limited to chemical drugs. Herbal medicine, as an alternative treatment, has a long history of usage and provides more treatment options, and related studies have revealed intervention targets for dyslipidemia. Four lipid-lowering mechanisms of herbal medicines have been proposed and are discussed in this paper. These mechanisms are the inhibition of cholesterol absorption in enterocytes, reduction of cholesterol synthesis, elevation of reverse cholesterol transport, and promotion of cholesterol excretion in the liver. This review elaborates on the underlying molecular pathways involved in plasma lipid balance via bioactive compounds from herbal medicines.