ABSTRACT
OBJECTIVE: Cognition impairments are considered as a fundamental characteristic of severe mental disorders (SMD). Recent studies suggest that hyperprolactinemia may exert a detrimental influence on cognitive performance in patients with SMD. The objective of this study was to investigate the correlation between serum prolactin levels and cognitive function in female individuals diagnosed with SMD. METHODS: We conducted a study on 294 patients with SMD and 195 healthy controls, aged between 14 to 55 years old. Cognitive function was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), while prolactin levels were measured in serum. Descriptive analysis and comparative analysis were performed to compare cognitive function and prolactin levels between groups, and linear regression models were used to explore the relationship between prolactin and cognitive function. RESULTS: Compared to the healthy control, individuals with SMD exhibited significantly higher levels of prolactin, while scoring lower on RBANS total and every index scores. Furthermore, a negative association between prolactin levels and cognitive function (RBANS total index score, attention, and delayed memory) was observed in SMD patients. Importantly, this inverse correlation between prolactin and cognition function (RBANS total index score, total scale score, and attention) persisted in patients who were not taking medications that could potentially influence serum prolactin levels. CONCLUSION: Our study reveals a significant correlation between elevated prolactin levels and cognitive impairment in female patients with SMD, underscoring the importance of monitoring prolactin levels in order to prevent cognitive deterioration among female SMD patients.
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Background: Schizophrenia is a devastating mental disease with high heritability. A growing number of susceptibility genes associated with schizophrenia, as well as their corresponding SNPs loci, have been revealed by genome-wide association studies. However, using SNPs as predictors of disease and diagnosis remains difficult. Here, we aimed to uncover susceptibility SNPs in a Chinese population and to construct a prediction model for schizophrenia. Methods: A total of 210 participants, including 70 patients with schizophrenia, 70 patients with bipolar disorder, and 70 healthy controls, were enrolled in this study. We estimated 14 SNPs using published risk loci of schizophrenia, and used these SNPs to build a model for predicting schizophrenia via comparison of genotype frequencies and regression. We evaluated the efficacy of the diagnostic model in schizophrenia and control patients using ROC curves and then used the 70 patients with bipolar disorder to evaluate the model's differential diagnostic efficacy. Results: 5 SNPs were selected to construct the model: rs148415900, rs71428218, rs4666990, rs112222723 and rs1716180. Correlation analysis results suggested that, compared with the risk SNP of 0, the risk SNP of 3 was associated with an increased risk of schizophrenia (OR = 13.00, 95% CI: 2.35-71.84, p = 0.003). The ROC-AUC of this prediction model for schizophrenia was 0.719 (95% CI: 0.634-0.804), with the greatest sensitivity and specificity being 60% and 80%, respectively. The ROC-AUC of the model in distinguishing between schizophrenia and bipolar disorder was 0.591 (95% CI: 0.497-0.686), with the greatest sensitivity and specificity being 60% and 55.7%, respectively. Conclusion: The SNP risk score prediction model had good performance in predicting schizophrenia. To the best of our knowledge, previous studies have not applied SNP-based models to differentiate between cases of schizophrenia and other mental illnesses. It could have several potential clinical applications, including shaping disease diagnosis, treatment, and outcomes.
ABSTRACT
Construction and functionalization of a 3D graphene architecture are crucial to harness and extend the unique features of graphene and thus essential for its numerous conventional and novel applications. Herein, a 3D honeycomb-patterned porous graphene architecture is constructed through a facile and low-cost self-assembly process and then integrated with Cu2O nanoparticles via a simple electrodeposition procedure. The 3D porous graphene structure is prepared by the breath figure method using a graphene oxide (GO)-based complex in which GO is modified by a surfactant as the casting material. Benefiting from the intercalation of the surfactant between the GO nanosheets and the fabrication of a 3D porous structure, the aggregation inhibition of GO nanosheets and increases in accessible surface area are realized at both nano- and microscales, resulting in good electrochemical performance. Moreover, the deposition of Cu2O nanoparticles can further improve the electrochemical sensing performance of the porous reduced graphene oxide (rGO) structure. Extremely low detection limit (30.72 nM) with a linear range of 0 µM to 30 µM, excellent anti-interference, repeatability, reproducibility, stability, and high accuracy for actual sample testing are shown when the 3D porous Cu2O/rGO film is applied as an electrochemical sensor for DA detection. This work provides not only a superior electrochemical biosensor but also a simple, yet effective and general strategy for the construction and functionalization of a 3D graphene structure.
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Systemic aging influences various physiological processes and contributes to structural and functional decline in cardiac tissue. These alterations include an increased incidence of left ventricular hypertrophy, a decline in left ventricular diastolic function, left atrial dilation, atrial fibrillation, myocardial fibrosis and cardiac amyloidosis, elevating susceptibility to chronic heart failure (HF) in the elderly. Age-related cardiac dysfunction stems from prolonged exposure to genomic, epigenetic, oxidative, autophagic, inflammatory and regenerative stresses, along with the accumulation of senescent cells. Concurrently, age-related structural and functional changes in the vascular system, attributed to endothelial dysfunction, arterial stiffness, impaired angiogenesis, oxidative stress and inflammation, impose additional strain on the heart. Dysregulated mechanosignalling and impaired nitric oxide signalling play critical roles in the age-related vascular dysfunction associated with HF. Metabolic aging drives intricate shifts in glucose and lipid metabolism, leading to insulin resistance, mitochondrial dysfunction and lipid accumulation within cardiomyocytes. These alterations contribute to cardiac hypertrophy, fibrosis and impaired contractility, ultimately propelling HF. Systemic low-grade chronic inflammation, in conjunction with the senescence-associated secretory phenotype, aggravates cardiac dysfunction with age by promoting immune cell infiltration into the myocardium, fostering HF. This is further exacerbated by age-related comorbidities like coronary artery disease (CAD), atherosclerosis, hypertension, obesity, diabetes and chronic kidney disease (CKD). CAD and atherosclerosis induce myocardial ischaemia and adverse remodelling, while hypertension contributes to cardiac hypertrophy and fibrosis. Obesity-associated insulin resistance, inflammation and dyslipidaemia create a profibrotic cardiac environment, whereas diabetes-related metabolic disturbances further impair cardiac function. CKD-related fluid overload, electrolyte imbalances and uraemic toxins exacerbate HF through systemic inflammation and neurohormonal renin-angiotensin-aldosterone system (RAAS) activation. Recognizing aging as a modifiable process has opened avenues to target systemic aging in HF through both lifestyle interventions and therapeutics. Exercise, known for its antioxidant effects, can partly reverse pathological cardiac remodelling in the elderly by countering processes linked to age-related chronic HF, such as mitochondrial dysfunction, inflammation, senescence and declining cardiomyocyte regeneration. Dietary interventions such as plant-based and ketogenic diets, caloric restriction and macronutrient supplementation are instrumental in maintaining energy balance, reducing adiposity and addressing micronutrient and macronutrient imbalances associated with age-related HF. Therapeutic advancements targeting systemic aging in HF are underway. Key approaches include senomorphics and senolytics to limit senescence, antioxidants targeting mitochondrial stress, anti-inflammatory drugs like interleukin (IL)-1ß inhibitors, metabolic rejuvenators such as nicotinamide riboside, resveratrol and sirtuin (SIRT) activators and autophagy enhancers like metformin and sodium-glucose cotransporter 2 (SGLT2) inhibitors, all of which offer potential for preserving cardiac function and alleviating the age-related HF burden.
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Vestibular schwannomas are rare intracranial tumors originating from Schwann cells of the vestibular nerve. Despite their benign nature, these tumors can exert significant mass effects and debilitating symptoms, including gradual hearing loss, vertigo, facial nerve dysfunction, and headaches. Current clinical management options encompass wait-and-scan, surgery, radiation therapy, and off-label medication. However, each approach exhibits its own challenges and harbors limitations that underscore the urgent need for therapeutic treatments. Over the past 2 decades, extensive elucidation of the molecular underpinnings of vestibular schwannomas has unraveled genetic anomalies, dysregulated signaling pathways, downstream of receptor tyrosine kinases, disrupted extracellular matrix, inflammatory tumor microenvironment, and altered cerebrospinal fluid composition as integral factors in driving the development and progression of the disease. Armed with this knowledge, novel therapeutic interventions tailored to the unique molecular characteristics of those conditions are actively being pursued. This review underscores the urgency of addressing the dearth of Food and Drug Administration-approved drugs for vestibular schwannoma, highlighting the key molecular discoveries and their potential translation into therapeutics. It provides an in-depth exploration of the evolving landscape of therapeutic development, which is currently advancing from bench to bedside. These ongoing efforts hold the promise of significantly transforming the lives of vestibular schwannoma patients in the future.
ABSTRACT
The incidence of hepatocellular carcinoma (HCC) has continued to increase annually worldwide, and HCC has become a common cause of cancer-related death. Despite great progress in understanding the molecular mechanisms underlying HCC development, the treatment of HCC remains a considerable challenge. Thus, the survival and prognosis of HCC patients remain extremely poor. In recent years, the role of ion channels in the pathogenesis of diseases has become a hot topic. In normal liver tissue, ion channels and transporters maintain water and electrolyte balance and acidâbase homeostasis. However, dysfunction of these ion channels and transporters can lead to the development and progression of HCC, and thus these ion channels and transporters are expected to become new therapeutic targets. In this review, ion channels and transporters associated with HCC are reviewed, and potential targets for new and effective therapies are proposed.
ABSTRACT
Most targeted anticancer therapies fail due to drug resistance evolution. Here we show that tumor evolution can be reproducibly redirected to engineer therapeutic opportunity, regardless of the exact ensemble of pre-existing genetic heterogeneity. We develop a selection gene drive system that is stably introduced into cancer cells and is composed of two genes, or switches, that couple an inducible fitness advantage with a shared fitness cost. Using stochastic models of evolutionary dynamics, we identify the design criteria for selection gene drives. We then build prototypes that harness the selective pressure of multiple approved tyrosine kinase inhibitors and employ therapeutic mechanisms as diverse as prodrug catalysis and immune activity induction. We show that selection gene drives can eradicate diverse forms of genetic resistance in vitro. Finally, we demonstrate that model-informed switch engagement effectively targets pre-existing resistance in mouse models of solid tumors. These results establish selection gene drives as a powerful framework for evolution-guided anticancer therapy.
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Globally, Alzheimer's disease (AD) is the most widespread chronic neurodegenerative disorder, leading to cognitive impairment, such as aphasia and agnosia, as well as mental symptoms, like behavioral abnormalities, that place a heavy psychological and financial burden on the families of the afflicted. Unfortunately, no particular medications exist to treat AD, as the current treatments only impede its progression.The link between AD and type 2 diabetes (T2D) has been increasingly revealed by research; the danger of developing both AD and T2D rises exponentially with age, with T2D being especially prone to AD. This has propelled researchers to investigate the mechanism(s) underlying this connection. A critical review of the relationship between insulin resistance, Aß, oxidative stress, mitochondrial hypothesis, abnormal phosphorylation of Tau protein, inflammatory response, high blood glucose levels, neurotransmitters and signaling pathways, vascular issues in AD and diabetes, and the similarities between the two diseases, is presented in this review. Grasping the essential mechanisms behind this detrimental interaction may offer chances to devise successful therapeutic strategies.
Subject(s)
Alzheimer Disease , Humans , Alzheimer Disease/therapy , Alzheimer Disease/metabolism , Alzheimer Disease/diagnosis , Diabetes Mellitus, Type 2/therapy , Diabetes Mellitus, Type 2/complications , Animals , Oxidative Stress/physiologyABSTRACT
Despite the high mortality rate associated with sepsis, no specific drugs are available. Decoy receptor 3 (DcR3) is now considered a valuable biomarker and therapeutic target for managing inflammatory conditions. DcR3-SUMO, an analog of DcR3, has a simple production process and high yield. However, its precise underlying mechanisms in sepsis remain unclear. This study investigated the protective effects of DcR3-SUMO on lipopolysaccharide (LPS)-induced inflammatory cells and septic mice. We evaluated the effects of DcR3 intervention and overexpression on intracellular inflammatory cytokine levels in vitro. DcR3-SUMO significantly reduced cytokine levels within inflammatory cells, and notably increased DcR3 protein and mRNA levels in LPS-induced septic mice, confirming its anti-inflammatory efficacy. Our in vitro and in vivo results demonstrated comparable anti-inflammatory effects between DcR3-SUMO and native DcR3. DcR3-SUMO protein administration in septic mice notably enhanced tissue morphology, decreased sepsis scores, and elevated survival rates. Furthermore, DcR3-SUMO treatment effectively lowered inflammatory cytokine levels in the serum, liver, and lung tissues, and mitigated the extent of tissue damage. AlphaFold3 structural predictions indicated that DcR3-SUMO, similar to DcR3, effectively interacts with the three pro-apoptotic ligands, namely TL1A, LIGHT, and FasL. Collectively, DcR3-SUMO and DcR3 exhibit comparable anti-inflammatory effects, making DcR3-SUMO a promising therapeutic agent for sepsis.
Subject(s)
Cytokines , Lipopolysaccharides , Receptors, Tumor Necrosis Factor, Member 6b , Sepsis , Animals , Sepsis/metabolism , Sepsis/drug therapy , Receptors, Tumor Necrosis Factor, Member 6b/metabolism , Receptors, Tumor Necrosis Factor, Member 6b/genetics , Mice , Cytokines/metabolism , Inflammation/metabolism , Male , Humans , Recombinant Fusion Proteins/pharmacology , Anti-Inflammatory Agents/pharmacology , Tumor Necrosis Factor Ligand Superfamily Member 15/metabolism , Mice, Inbred C57BLABSTRACT
The design and development of a bio-adhesive hydrogel with on-demand removability and excellent antibacterial activities are meaningful to achieve high wound closure effectiveness and post-wound-closure care, which is desirable in clinical applications. In this work, a series of adhesive antioxidant antibacterial hydrogels containing peptides from Periplaneta americana (PAP) were prepared through multi-dynamic-bond cross-linking among 3,4-dihydroxybenzaldehyde (DBA) containing catechol and aldehyde groups and chitosan grafted with 3-carboxy-4-fluorophenylboronic acid (CS-FPBA) to enable the effective adhesion of skin tissues and prevention of bacterial infection of wound. PAP was derived from alcohol-extracted residues generated during the pharmaceutical process, aiming to minimize resource wastage and achieve the high-value development of such a medicinal insect. The hydrogel was prepared by freezing-thawing with no toxic crosslinkers. The multi-dynamic-bond cross-linking of dynamic borate ester bonds and dynamic Schiff base bonds can achieve reversible breakage and re-formation and the adhesive strength of CS-FPBA-DBA-P-gel treated with a 20 % glucose solution dramatically decreased from 3.79 kPa to 0.35 kPa within 10 s. Additionally, the newly developed hydrogel presents ideal biocompatibility, hemostasis and antibacterial activity against Staphylococcus aureus and Escherichia coli compared to commercial chitosan gel (approximately 50 % higher inhibition rate), demonstrating its great potential in dealing with infected full-thickness skin wounds.
Subject(s)
Anti-Bacterial Agents , Chitosan , Hydrogels , Peptides , Periplaneta , Staphylococcus aureus , Chitosan/chemistry , Chitosan/pharmacology , Hydrogels/chemistry , Hydrogels/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Animals , Periplaneta/chemistry , Peptides/chemistry , Peptides/pharmacology , Staphylococcus aureus/drug effects , Escherichia coli/drug effects , Adhesives/chemistry , Adhesives/pharmacology , Cross-Linking Reagents/chemistry , Microbial Sensitivity TestsABSTRACT
A new composite sponge assisted by magnetic field-mediated guidance was developed for effective hemostasis. It was based on polydopamine capillary-channel agarose (PDA-CAGA) sponge as matrix; meanwhile, the combination of deep eutectic solvent (DES, choline chloride:glycerol = 1:1, M/M)-dispersed Fe3O4 nanoparticles after fabrication by tannic acid (DES-Fe3O4@TA) was applied as hemostatic magnetic fluid. This sponge had oriented and aligned capillary channels realized by a 3D printed pattern, which endowed them with obvious shape memory and liquid absorption performance. Computational simulation was performed to describe the fluid status in channels; DES-Fe3O4@TA exhibited good magnetic properties, fluidity, and stability. In addition, the sponge driven to react rapidly with the bleeding site under the effect of a magnetic field presented a shorter hemostasis time (reduced by 85.02% in the tail and 81.07% in the liver of rats) and less blood loss (reduced by 97.08% in the tail and 91.50% in the liver) than those of medical gelatin sponge (GS). Meanwhile, the multifunctional material also exhibited better biocompatibility, procoagulant performance, and significant inhibition on S. aureus and E. coli than GS. As a whole, this work proposed a new strategy for rapid hemostasis by designing a magnetic field assisted composite bacteriostatic material, which also expanded the applications of green solvents in the clinical management field.
Subject(s)
Escherichia coli , Sepharose , Staphylococcus aureus , Animals , Rats , Sepharose/chemistry , Staphylococcus aureus/drug effects , Escherichia coli/drug effects , Solvents/chemistry , Hemostasis/drug effects , Polymers/chemistry , Polymers/pharmacology , Indoles/chemistry , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Hemostatics/chemistry , Hemostatics/pharmacology , Magnetic Fields , Male , Rats, Sprague-DawleyABSTRACT
The utilization of atypical antipsychotics (AAPs) often leads to metabolic syndrome (MetS) in schizophrenia (SZ) patients. Macrophage migration inhibitory factor (MIF) is an important MetS-related cytokine. To investigate the potential association between the MIF-794 CATT5-8 polymorphism and AAP-induced MetS in SZ patients, data from 375 chronic SZ patients who received AAP treatment for a minimum of one year were included. MIF-794 CATT polymorphism genotyping and plasma MIF quantification was performed. The metabolism status of all patients was assessed according to the NCEP-ATP III criteria. Individuals who displayed at least three of the five risk factors (waist circumference, high-density lipoprotein cholesterol, triglycerides, fasting glucose levels, and blood pressure) were diagnosed with MetS. The prevalence of MetS in SZ patients with MIF CATT >5/6 was significantly higher than in those with CATT 5/5-5/6. In female patients, MIF CATT >5/6 was associated with an elevated risk of AAP-induced MetS after adjusting for covariates, particularly regarding abdominal obesity, and the mediating effect of plasma MIF levels was significant. In conclusion, MIF CATT >5/6 increased the risk of AAP-induced MetS among females with chronic SZ. The MIF-794 CATT5-8 microsatellite polymorphism may be a unique indicator for AAP-induced metabolic adverse effects in female SZ patients.
Subject(s)
Antipsychotic Agents , Intramolecular Oxidoreductases , Macrophage Migration-Inhibitory Factors , Metabolic Syndrome , Schizophrenia , Humans , Schizophrenia/drug therapy , Schizophrenia/blood , Female , Macrophage Migration-Inhibitory Factors/blood , Macrophage Migration-Inhibitory Factors/genetics , Metabolic Syndrome/chemically induced , Metabolic Syndrome/epidemiology , Metabolic Syndrome/blood , Antipsychotic Agents/adverse effects , Adult , Male , Intramolecular Oxidoreductases/blood , Intramolecular Oxidoreductases/genetics , Middle Aged , Chronic DiseaseABSTRACT
Chemotherapy is one of the most commonly used methods for treating cancer, but its side effects severely limit its application and impair treatment effectiveness. Removing off-target chemotherapy drugs from the serum promptly through adsorption is the most direct approach to minimize their side effects. In this study, we synthesized a series of adsorption materials to remove the chemotherapy drug doxorubicin by modifying MOF nanosheets with sulfonated azocalix[4]arenes. The strong affinity of sulfonated azocalix[4]arenes for doxorubicin results in high adsorption strength (Langmuir adsorption constant = 2.45-5.73 L mg-1) and more complete removal of the drug. The extensive external surface area of the 2D nanosheets facilitates the exposure of a large number of accessible adsorption sites, which capture DOX molecules without internal diffusion, leading to a high adsorption rate (pseudo-second-order rate constant = 0.0058-0.0065 g mg-1 min-1). These adsorbents perform effectively in physiological environments and exhibit low cytotoxicity and good hemocompatibility. These features make them suitable for removing doxorubicin from serum during "drug capture" procedures. The optimal adsorbent can remove 91% of the clinical concentration of doxorubicin within 5 min.
ABSTRACT
Hepatocellular carcinoma (HCC) is one of the deadliest cancers. The prevention and therapy for this deadly disease remain a global medical challenge. In this study, we investigated the effect of pantoprazole (PPZ) on the carcinogenesis and growth of HCC. Both diethylnitrosamine (DEN) plus CCl4-induced and DEN plus high fat diet (HFD)-induced HCC models in mice were established. Cytokines and cell proliferation-associated gene in the liver tissues of mice and HCC cells were analyzed. Cellular glycolysis and Na+/H+ exchange activity were measured. The preventive administration of pantoprazole (PPZ) at a clinically relevant low dose markedly suppressed HCC carcinogenesis in both DEN plus CCl4-induced and HFD-induced murine HCC models, whereas the therapeutic administration of PPZ at the dose suppressed the growth of HCC. In the liver tissues of PPZ-treated mice, inflammatory cytokines, IL1, CXCL1, CXCL5, CXCL9, CXCL10, CCL2, CCL5, CCL6, CCL7, CCL20, and CCL22, were reduced. The administration of CXCL1, CXCL5, CCL2, or CCL20 all reversed PPZ-suppressed DEN plus CCL4-induced HCC carcinogenesis in mice. PPZ inhibited the expressions of CCNA2, CCNB2, CCNE2, CDC25C, CDCA5, CDK1, CDK2, TOP2A, TTK, AURKA, and BIRC5 in HCC cells. Further results showed that PPZ reduced the production of these inflammatory cytokines and the expression of these cell proliferation-associated genes through the inhibition of glycolysis and Na+/H+ exchange. In conclusion, PPZ suppresses the carcinogenesis and growth of HCC, which is related to inhibiting the production of inflammatory cytokines and the expression of cell proliferation-associated genes in the liver through the inhibition of glycolysis and Na+/H+ exchange.
Subject(s)
Carcinoma, Hepatocellular , Cell Proliferation , Glycolysis , Liver Neoplasms , Pantoprazole , Animals , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/chemically induced , Carcinoma, Hepatocellular/metabolism , Glycolysis/drug effects , Liver Neoplasms/drug therapy , Liver Neoplasms/chemically induced , Liver Neoplasms/metabolism , Mice , Pantoprazole/pharmacology , Male , Cell Proliferation/drug effects , Humans , Mice, Inbred C57BL , Carcinogenesis/drug effects , Diethylnitrosamine/toxicity , Cytokines/metabolism , Cell Line, Tumor , Diet, High-Fat/adverse effectsABSTRACT
Nanomedicines often rely on noncovalent self-assembly and encapsulation for drug loading and delivery. However, challenges such as reproducibility issues due to the multicomponent nature, off-target activation caused by premature drug release, and complex pharmacokinetics arising from assembly dissociation have hindered their clinical translation. In this study, we introduce an innovative design concept termed single molecular nanomedicine (SMNM) based on macrocyclic carrier-drug conjugates. Through the covalent linkage of two chemotherapy drugs to a hypoxia-cleavable macrocyclic carrier, azocalix[4]arene, we obtained two self-included complexes to serve as SMNMs. The intramolecular inclusion feature of the SMNMs has not only demonstrated comprehensive shielding and protection for the drugs but also effectively prevented off-target drug leakage, thereby significantly reducing their side effects and enhancing their antitumor therapeutic efficacy. Additionally, the attributes of being a single component and molecularly dispersed confer advantages such as ease of preparation and good reproducibility for SMNMs, which is desirable for clinical applications.
Subject(s)
Antineoplastic Agents , Calixarenes , Drug Carriers , Nanomedicine , Humans , Drug Carriers/chemistry , Nanomedicine/methods , Calixarenes/chemistry , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/administration & dosage , Animals , Macrocyclic Compounds/chemistry , Mice , Cell Line, Tumor , Drug LiberationABSTRACT
It is well known that hyperthermia greatly impairs neuromuscular function and dynamic balance. However, whether a greater level of hyperthermia could potentially alter the lower limb simulated muscle activation when crossing an obstacle in female participants remains unknown. Therefore we examined the effect of a systematic increase in oral temperature on lower limb simulated muscle activation when crossing an obstacle in female participants. Eighteen female participants were recruited where they underwent a control trial (Con) and two progressive passive heating trials with Δ 1°C and Δ 2°C increase of oral temperature (Toral) using a 45°C water bath. In each trial, we assessed lower limb simulated muscle activation when crossing an obstacle height of 10%, 20%, and 30% of the participant's leg length and toe-off, toe-above-obstacle and heel-strike events were identified and analyzed. In all events, the lower limb simulated muscle activation were greater in Δ2°C than Δ1°C and Con when both leading and trailing limbs crossed the obstacle height of 20% and 30% leg length (all p < 0.001). However, the lower limb simulated muscle activation were not different between Δ1°C and Con across all obstacle heights (p > 0.05). This study concluded that a greater level of hyperthermia resulted in a greater lower limb simulated muscle activation to ensure safety and stability when females cross an obstacle height of 20% leg length or higher.
Subject(s)
Muscle, Skeletal , Humans , Female , Muscle, Skeletal/physiology , Muscle, Skeletal/physiopathology , Adult , Young Adult , Hyperthermia/physiopathology , Lower Extremity/physiologyABSTRACT
Lactate is a byproduct of glycolysis, and before the Warburg effect was revealed (in which glucose can be fermented in the presence of oxygen to produce lactate) it was considered a metabolic waste product. At present, lactate is not only recognized as a metabolic substrate that provides energy, but also as a signaling molecule that regulates cellular functions under pathophysiological conditions. Lactylation, a posttranslational modification, is involved in the development of various diseases, including inflammation and tumors. Liver disease is a major health challenge worldwide. In normal liver, there is a net lactate uptake caused by gluconeogenesis, exhibiting a higher net lactate clearance rate compared with any other organ. Therefore, abnormalities of lactate and lactate metabolism lead to the development of liver disease, and lactate and lactate metabolismrelated genes can be used for predicting the prognosis of liver disease. Targeting lactate production, regulating lactate transport and modulating lactylation may be potential treatment approaches for liver disease. However, currently there is not a systematic review that summarizes the role of lactate and lactate metabolism in liver diseases. In the present review, the role of lactate and lactate metabolism in liver diseases including liver fibrosis, nonalcoholic fatty liver disease, acute liver failure and hepatocellular carcinoma was summarized with the aim to provide insights for future research.
Subject(s)
Lactic Acid , Liver Diseases , Humans , Lactic Acid/metabolism , Liver Diseases/metabolism , Animals , Liver/metabolism , Liver/pathologyABSTRACT
A single tunable filter simplifies complexity, reduces insertion loss, and minimizes size compared to frequency switchable filter banks commonly used for radio frequency (RF) band selection. Magnetostatic wave (MSW) filters stand out for their wide, continuous frequency tuning and high-quality factor. However, MSW filters employing electromagnets for tuning consume excessive power and space, unsuitable for consumer wireless applications. Here, we demonstrate miniature and high selectivity MSW tunable filters with zero static power consumption, occupying less than 2 cc. The center frequency is continuously tunable from 3.4 GHz to 11.1 GHz via current pulses of sub-millisecond duration applied to a small and nonvolatile magnetic bias assembly. This assembly is limited in the area over which it can achieve a large and uniform magnetic field, necessitating filters realized from small resonant cavities micromachined in thin films of Yttrium Iron Garnet. Filter insertion loss of 3.2 dB to 5.1 dB and out-of-band third order input intercept point greater than 41 dBm are achieved. The filter's broad frequency range, compact size, low insertion loss, high out-of-band linearity, and zero static power consumption are essential for protecting RF transceivers from interference, thus facilitating their use in mobile applications like IoT and 6 G networks.
ABSTRACT
Liver diseases include all types of viral hepatitis, alcoholic liver disease (ALD), nonalcoholic fatty liver disease (NAFLD), cirrhosis, liver failure (LF) and hepatocellular carcinoma (HCC). Liver disease is now one of the leading causes of disease and death worldwide, which compels us to better understand the mechanisms involved in the development of liver diseases. Anoctamin 1 (ANO1), a calcium-activated chloride channel (CaCC), plays an important role in epithelial cell secretion, proliferation and migration. ANO1 plays a key role in transcriptional regulation as well as in many signalling pathways. It is involved in the genesis, development, progression and/or metastasis of several tumours and other diseases including liver diseases. This paper reviews the role and molecular mechanisms of ANO1 in the development of various liver diseases, aiming to provide a reference for further research on the role of ANO1 in liver diseases and to contribute to the improvement of therapeutic strategies for liver diseases by regulating ANO1.
Subject(s)
Anoctamin-1 , Liver Diseases , Humans , Anoctamin-1/metabolism , Anoctamin-1/genetics , Liver Diseases/metabolism , Liver Diseases/pathology , Liver Diseases/genetics , Animals , Signal Transduction , Neoplasm Proteins/metabolism , Neoplasm Proteins/genetics , Liver Neoplasms/metabolism , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/pathology , Gene Expression RegulationABSTRACT
OBJECTIVE: CT and MRI are synergistic in the information provided for neurosurgical planning. While obtaining both types of images lends unique data from each, doing so adds to cost and exposes patients to additional ionizing radiation after MRI has been performed. Cross-modal synthesis of high-resolution CT images from MRI sequences offers an appealing solution. The authors therefore sought to develop a deep learning conditional generative adversarial network (cGAN) which performs this synthesis. METHODS: Preoperative paired CT and contrast-enhanced MR images were collected for patients with meningioma, pituitary tumor, vestibular schwannoma, and cerebrovascular disease. CT and MR images were denoised, field corrected, and coregistered. MR images were fed to a cGAN that exported a "synthetic" CT scan. The accuracy of synthetic CT images was assessed objectively using the quantitative similarity metrics as well as by clinical features such as sella and internal auditory canal (IAC) dimensions and mastoid/clinoid/sphenoid aeration. RESULTS: A total of 92,981 paired CT/MR images obtained in 80 patients were used for training/testing, and 10,068 paired images from 10 patients were used for external validation. Synthetic CT images reconstructed the bony skull base and convexity with relatively high accuracy. Measurements of the sella and IAC showed a median relative error between synthetic CT scans and ground truth images of 6%, with greater variability in IAC reconstruction compared with the sella. Aerations in the mastoid, clinoid, and sphenoid regions were generally captured, although there was heterogeneity in finer air cell septations. Performance varied based on pathology studied, with the highest limitation observed in evaluating meningiomas with intratumoral calcifications or calvarial invasion. CONCLUSIONS: The generation of high-resolution CT scans from MR images through cGAN offers promise for a wide range of applications in cranial and spinal neurosurgery, especially as an adjunct for preoperative evaluation. Optimizing cGAN performance on specific anatomical regions may increase its clinical viability.