Heavy metal levels and human health risk implications associated with fish consumption from the lower Omo river (Lotic) and Omo delta lake (Lentic), Ethiopia.

This study is the first to determine the levels of heavy metals in commercially important fish species, namely Lates niloticus and Oreochromis niloticus and the potential human health risks associated with their consumption. A total of 120 fish samples were collected from the lower Omo river and Omo delta, with 60 samples from each water source. The fish tissue samples (liver and muscle) were analyzed using a flame atomic absorption spectrometer for nine heavy metals (Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, and Zn). The human health risk assessment tools used were the target hazard quotient (THQ), the hazard index (HI), and the target cancer risk (TCR). The mean levels of heavy metals detected in the liver and muscle of L. niloticus from the lower Omo river generally occurred in the order Fe > Zn > Pb> Cu > Mn> Cr > Co > Ni and Pb > Cu > Mn > Co > Ni, respectively. The mean levels of metals in the muscle and liver tissues of O. niloticus were in the order Fe > Pb > Zn > Mn > Cu > Cr > Co > Ni and Pb > Zn > Mn > Fe > Cu > Co > Ni, respectively. Similarly, the mean levels of heavy metals detected in the liver and muscle of L. niloticus from Omo delta occurred in the order Fe > Zn > Pb > Cu > Mn > Cr > Co > Ni and Fe > Pb > Zn > Mn > Cu > Co > Cr > Ni, respectively. The mean levels in the muscle and liver tissues of O. niloticus from the Omo delta were in the order Fe > Pb > Zn > Mn > Cu > Cr > Co > Ni and Pb > Fe > Zn > Mn > Co > Cu > Ni, respectively. The study revealed that the THQ values were below 1, indicating that consumption of L. niloticus and O. niloticus from the studied sites does not pose a potential non-carcinogenic health risk. Although the TCR values for Pb in this study were within the tolerable range, it's mean concentration in the muscle and liver tissues of both fish species from the two water bodies exceeded the permissible limit established by FAO/WHO. This is a warning sign for early intervention, and it emphasizes the need for regular monitoring of freshwater fish. Therefore, it is imperative to investigate the pollution levels and human health risks of heavy metals in fish tissues from lower Omo river and Omo delta for environmental and public health concerns.

Turn-on Coumarin Precursor: From Hydrazine Sensor to Covalent Inhibition and Fluorescence Detection of Rabbit Muscle Aldolase.

Hydrazine, a highly toxic compound, demands sensitive and selective detection methods. Building upon our previous studies with pre-coumarin OFF-ON sensors for fluoride anions, we extended our strategy to hydrazine sensing by adapting phenol protecting groups (propionate, levulinate, and γ-bromobutanoate) to our pre-coumarin scaffold. These probes reacted with hydrazine, yielding a fluorescent signal with low micromolar limits of detection. Mechanistic studies revealed that hydrazine deprotection may be outperformed by a retro-Knoevenagel reaction, where hydrazine acts as a nucleophile and a base yielding a fluorescent diimide compound (6,6'-((1E,1'E)-hydrazine-1,2diylidenebis(methaneylylidene))bis(3(diethylamino)phenol, 7). Additionally, our pre-coumarins unexpectedly reacted with primary amines, generating a fluorescent signal corresponding to phenol deprotection followed by cyclization and coumarin formation. The potential of compound 3 as a theranostic Turn-On coumarin precursor was also explored. We propose that its reaction with ALDOA produced a γ-lactam, blocking the catalytic nucleophilic amine in the enzyme's binding site. The cleavage of the ester group in compound 3 induced the formation of fluorescent coumarin 4. This fluorescent signal was proportional to ALDOA concentration, demonstrating the potential of compound 3 for future theranostic studies in vivo.

Structural Elucidation of Glycosaminoglycans in the Tissue of Flounder and Isolation of Chondroitin Sulfate C.

Glycosaminoglycans (GAGs) are valuable bioactive polysaccharides with promising biomedical and pharmaceutical applications. In this study, we analyzed GAGs using HPLC-MS/MS from the bone (B), muscle (M), skin (S), and viscera (V) of Scophthalmus maximus (SM), Paralichthysi (P), Limanda ferruginea (LF), Cleisthenes herzensteini (G), Platichthys bicoloratus (PB), Pleuronichthys cornutus (PC), and Cleisthenes herzensteini (CH). Unsaturated disaccharide products were obtained by enzymatic hydrolysis of the GAGs and subjected to compositional analysis of chondroitin sulfate (CS), heparin sulfate (HS), and hyaluronic acid (HA), including the sulfation degree of CS and HS, as well as the content of each GAG. The contents of GAGs in the tissues and the sulfation degree differed significantly among the fish. The bone of S. maximus contained more than 12 µg of CS per mg of dry tissue. Although the fish typically contained high levels of CSA (CS-4S), some fish bone tissue exhibited elevated levels of CSC (CS-6S). The HS content was found to range from 10-150 ug/g, primarily distributed in viscera, with a predominant non-sulfated structure (HS-0S). The structure of HA is well-defined without sulfation modification. These analytical results are independent of biological classification. We provide a high-throughput rapid detection method for tissue samples using HPLC-MS/MS to rapidly screen ideal sources of GAG. On this basis, four kinds of CS were prepared and purified from flounder bone, and their molecular weight was determined to be 23-28 kDa by HPGPC-MALLS, and the disaccharide component unit was dominated by CS-6S, which is a potential substitute for CSC derived from shark cartilage.

Anti-Melanogenic Effects of Takifugu flavidus Muscle Hydrolysate in B16F10 Melanoma Cells and Zebrafish.

Abnormal melanogenesis can lead to hyperpigmentation. Tyrosinase (TYR), a key rate-limiting enzyme in melanin production, is an important therapeutic target for these disorders. We investigated the TYR inhibitory activity of hydrolysates extracted from the muscle tissue of Takifugu flavidus (TFMH). We used computer-aided virtual screening to identify a novel peptide that potently inhibited melanin synthesis, simulated its binding mode to TYR, and evaluated functional efficacy in vitro and in vivo. TFMH inhibited the diphenolase activities of mTYR, reducing TYR substrate binding activity and effectively inhibiting melanin synthesis. TFMH indirectly reduced cAMP response element-binding protein phosphorylation in vitro by downregulating melanocortin 1 receptor expression, thereby inhibiting expression of the microphthalmia-associated transcription factor, further decreasing TYR, tyrosinase related protein 1, and dopachrome tautomerase expression and ultimately impeding melanin synthesis. In zebrafish, TFMH significantly reduced black spot formation. TFMH (200 µg/mL) decreased zebrafish TYR activity by 43% and melanin content by 52%. Molecular dynamics simulations over 100 ns revealed that the FGFRSP (T-6) peptide stably binds mushroom TYR via hydrogen bonds and ionic interactions. T-6 (400 µmol/L) reduced melanin content in B16F10 melanoma cells by 71% and TYR activity by 79%. In zebrafish, T-6 (200 µmol/L) inhibited melanin production by 64%. TFMH and T-6 exhibit good potential for the development of natural skin-whitening cosmetic products.

Identification of pigmentation genes in skin, muscle and tail of a Thai-flag variety of Siamese fighting fish Betta splendens.

Pigmentation genes expressed in skin, body muscle and tail of Thai-flag compared with Blue, White and Red varieties of Siamese fighting fish Betta splendens were identified. In total, 22,919 new unigenes were found. Pearson correlation and PCA analysis revealed that expression profiles of genes in muscle, skin and tail across solid color variety were similar. In contrast, those in skin and red tail part of Thai-flag were closely related but they showed different expression profiles with the white tail part. Moreover, 21,347-64,965 SNPs were identified in exonic regions of identified genes. In total, 28,899 genes were differentially expressed between paired comparisons of libraries where 13,907 genes (48.12 %) were upregulated and 14,992 genes (51.88 %) were downregulated. DEGs between paired libraries were 106-5775 genes relative to the compared libraries (56-2982 and 50-2782 for upregulated and downregulated DEGs). Interestingly, 432 pigmentation genes of B. splendens were found. Of these, 297 DEGs showed differential expression between varieties. Many DEGs in melanogenesis (Bsmcr1r, Bsmcr5r, and Bsslc2a15b), tyrosine metabolism (Bstyr, Bstyrp1b and Bsdct), stripe repressor (BsAsip1 and BsAsip2b), pteridine (Bsgch2) and carotenoid (BsBco2) biosynthesis were downregulated in the Thai-flag compared with solid color varieties. Expression of Bsbco1l, Bsfrem2b, Bskcnj13, Bszic2a and Bspah in skin, muscle and tail of Thai-flag, Blue, Red and White varieties was analyzed by qRT-PCR and revealed differential expression between fish varieties and showed anatomical tissue-preferred expression patterns in the same fish variety. The information could be applied to assist genetic-based development of new B. splendens varieties in the future.

MACSPI enables tissue-selective proteomic and interactomic analyses in multicellular organisms.

Multicellular organisms are composed of many tissue types that have distinct morphologies and functions, which are largely driven by specialized proteomes and interactomes. To define the proteome and interactome of a specific type of tissue in an intact animal, we developed a localized proteomics approach called Methionine Analog-based Cell-Specific Proteomics and Interactomics (MACSPI). This method uses the tissue-specific expression of an engineered methionyl-tRNA synthetase to label proteins with a bifunctional amino acid 2-amino-5-diazirinylnonynoic acid in selected cells. We applied MACSPI in Caenorhabditis elegans, a model multicellular organism, to selectively label, capture, and profile the proteomes of the body wall muscle and the nervous system, which led to the identification of tissue-specific proteins. Using the photo-cross-linker, we successfully profiled HSP90 interactors in muscles and neurons and identified tissue-specific interactors and stress-related interactors. Our study demonstrates that MACSPI can be used to profile tissue-specific proteomes and interactomes in intact multicellular organisms.

Hedgehog signaling is required for larval muscle development and larval metamorphosis of the mussel Mytilus coruscus.

Understanding the developmental processes and signaling pathways involved in larval myogenesis and metamorphosis is crucial for comprehending the life history and adaptive strategies of marine organisms. In this study, we investigated the temporal and spatial patterns of myogenesis in the mussel Mytilus coruscus (Mc), focusing on the emergence and transformation of major muscle groups during different larval stages. We also explored the role of the Hedgehog (Hh) signaling pathway in regulating myogenesis and larval metamorphosis. The results revealed distinct developmental stages characterized by the emergence of specific muscular components, such as velum retractor muscles and anterior adductor muscles, in D-veliger and umbo larvae, which are responsible for the planktonic stage. In the pediveliger stage, posterior ventral, posterior adductor, and foot muscles appeared. After larval metamorphosis, the velum structure and its corresponding retractor muscles degenerate, indicating the transition from planktonic to benthic life. We observed a conserved pattern of larval musculature development and revealed a high degree of conservation across bivalve species, with comparable emergence times during myogenesis. Furthermore, exposure to the Hh signaling inhibitor cyclopamine impaired larval muscle development, reduced larval swimming activity, and inhibited larval metamorphosis in M. coruscus. Cyclopamine-mediated inhibition of Hh signaling led to reduced expression of four key genes within the Hh signaling pathway (McHh, McPtc, McSmo, and McGli) and the striated myosin heavy chain gene (McMHC). It is hypothesised that the abnormal larval muscle development in cyclopamine-treated groups may be an indirect effect due to disrupted McMHC expression. We provide evidence for the first time that cyclopamine treatment inhibited larval metamorphosis in bivalves, highlighting the potential involvement of Hh signaling in mediating larval muscle development and metamorphosis in M. coruscus. The present study provides insights into the dynamic nature of myogenesis and the regulatory role of the Hh signaling pathway during larval development and metamorphosis in M. coruscus. The results obtained in this study contribute to a better understanding of the evolutionary significance of Hh signaling in bivalves and shed light on the mechanisms underlying larval muscle development and metamorphosis in marine invertebrates.

Investigation of the Alternations in the Muscle Quality of Swimming Crab (Ovalipes punctatus) during Cold-Chain Transportation Using Physicochemical and TMT-Based Quantitative Proteomic Analysis.

Physicochemical properties and protein alterations in Ovalipes punctatus during cold-chain transportation were examined via sensory scores, water-holding capacity (WHC), glucose (GLU) content, catalase (CAT) activity, urea nitrogen (UN) content, and tandem mass tag (TMT)-based proteomic analysis. The results revealed that sensory characteristics and texture of crab muscle deteriorated during transportation. Proteomic analysis revealed 442 and 470 different expressed proteins (DEPs) in crabs after 18 h (FC) and 36 h (DC) of transportation compared with live crabs (LC). Proteins related to muscle structure and amino acid metabolism significantly changed, as evidenced by the decreased WHC and sensory scores of crab muscle. Glycolysis, calcium signaling, and peroxisome pathways were upregulated in the FC/LC comparison, aligning with the changes in GLU content and CAT activity, revealing the stress response of energy metabolism and immune response in crabs during 0-18 h of transportation. The downregulated tricarboxylic acid (TCA) cycle and carcinogenesis-reactive oxygen species pathways were correlated with the decreasing trend in CAT activity, suggesting a gradual retardation in both energy and antioxidant metabolism in crabs during 18-36 h of transportation. Furthermore, the regulated purine nucleoside metabolic and nucleoside diphosphate-related processes, with the increasing changes in UN content, revealed the accumulation of metabolites in crabs.

A fluorescently-tagged tick kinin neuropeptide triggers peristalsis and labels tick midgut muscles.

Ticks are blood-feeding arthropods that require heme for their successful reproduction. During feeding they also acquire pathogens that are subsequently transmitted to humans, wildlife and/or livestock. Understanding the regulation of tick midgut is important for blood meal digestion, heme and nutrient absorption processes and for aspects of pathogen biology in the host. We previously demonstrated the activity of tick kinins on the cognate G protein-coupled receptor. Herein we uncovered the physiological role of the kinin receptor in the tick midgut. A fluorescently-labeled kinin peptide with the endogenous kinin 8 sequence (TMR-RK8), identical in the ticks Rhipicephalus microplus and R. sanguineus, activated and labeled the recombinant R. microplus receptor expressed in CHO-K1 cells. When applied to the live midgut the TMR-RK8 labeled the kinin receptor in muscles while the labeled peptide with the scrambled-sequence of kinin 8 (TMR-Scrambled) did not. The unlabeled kinin 8 peptide competed TMR-RK8, decreasing confocal microscopy signal intensity, indicating TMR-RK8 specificity to muscles. TMR-RK8 was active, inducing significant midgut peristalsis that was video-recorded and evaluated with video tracking software. The TMR-Scrambled peptide used as a negative control did not elicit peristalsis. The myotropic function of kinins in eliciting tick midgut peristalsis was established.

Gluconeogenesis in frogs during cooling and dehydration exposure: new insights into tissue plasticity of the gluconeogenic pathway dependent on abiotic factors.

Anurans undergo significant physiological changes when exposed to environmental stressors such as low temperatures and humidity. Energy metabolism and substrate management play a crucial role in their survival success. Therefore, understanding the role of the gluconeogenic pathway and demonstrating its existence in amphibians is essential. In this study, we exposed the subtropical frog Boana pulchella to cooling (-2.5°C for 24 h) and dehydration conditions (40% of body water loss), followed by recovery (24 h), and assessed gluconeogenesis activity from alanine, lactate, glycerol and glutamine in the liver, muscle and kidney. We report for the first time that gluconeogenesis activity by 14C-alanine and 14C-lactate conversion to glucose occurs in the muscle tissue of frogs, and this tissue activity is influenced by environmental conditions. Against the control group, liver gluconeogenesis from 14C-lactate and 14C-glycerol was lower during cooling and recovery (P<0.01), and gluconeogenesis from 14C-glutamine in the kidneys was also lower during cooling (P<0.05). In dehydration exposure, gluconeogenesis from 14C-lactate in the liver was lower during recovery, and that from 14C-alanine in the muscle was lower during dehydration (P<0.05). Moreover, we observed that gluconeogenesis activity and substrate preference respond differently to cold and dehydration. These findings highlight tissue-specific plasticity dependent on the nature of the encountered stressor, offering valuable insights for future studies exploring this plasticity, elucidating the importance of the gluconeogenic pathway and characterizing it in anuran physiology.

Arsenic bioaccumulation and biotransformation in different tissues of Nile tilapia (Oreochromis niloticus): A comparative study between As(III) and As(V) exposure and evaluation of antagonistic effects of selenium.

The speciation of arsenic in fish has been widely investigated, but bioaccumulation and biotransformation of inorganic As in different tissues of Nile tilapia (Oreochromis niloticus) are not fully understood. The present study aimed to investigate the bioaccumulation of As in Nile tilapia, as well as to evaluate the distribution of the main arsenic species (As(III), As(V), MMA, DMA, and AsB) in liver, stomach, gill, and muscle, after controlled exposures to As(III) and As(V) at concentrations of 5.0 and 10.0 mg L-1 during periods of 1 and 7 days. Total As was determined by inductively coupled plasma mass spectroscopy (ICP-MS). For both exposures (As(III) and As(V)), the total As levels after 7-day exposure were highest in the liver and lowest in the muscle. Overall, the Nile tilapia exposed to As(III) showed higher tissue levels of As after the treatments, compared to As(V) exposure. Speciation of arsenic present in the tissues employed liquid chromatography coupled to ICP-MS (LC-ICP-MS), revealing that the biotransformation of As included As(V) reduction to As(III), methylation to monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA), and subsequent conversion to nontoxic arsenobetaine (AsB), which was the predominant arsenic form. Finally, the interactions and antagonistic effects of selenium in the bioaccumulation processes were tested by the combined exposure to As(III), the most toxic species of As, together with tetravalent selenium (Se(IV)). The results indicated a 4-6 times reduction of arsenic toxicity in the tilapia.

Morphology of the pterothoracic musculature in Paraneoptera and its phylogenetic implication (Insecta: Neoptera).

Although the monophyly of Paraneoptera (=hemipteroid orders or Acercaria, composed of Psocodea, Thysanoptera and Hemiptera) has been widely accepted morphologically, the results from molecular phylogenetic and phylogenomic analyses contradict this hypothesis. In particular, phylogenomic analyses provide strong bootstrap support for the sister group relationship between Psocodea and Holometabola, that is, paraphyly of Paraneoptera. Here, we examined the pterothoracic musculature of Paraneoptera, as well as a wide range of other neopterous insect orders, and analysed its phylogenetic implication. By using the synchrotron microcomputed tomography (µCT) and parsimony-based ancestral state reconstruction, several apomorphic conditions suggesting the monophyly of Paraneoptera, such as the absence of the II/IIItpm7, IIscm3, IIIspm2 and IIIscm3 muscles, were identified. In contrast, no characters supporting Psocodea + Holometabola were recovered from the thoracic muscles. These results provide additional support for the monophyly of Paraneoptera, together with the previously detected morphological apomorphies of the head, wing base, and abdomen.

Association Between Frequency of Muscle-Strengthening Exercise and Depression Symptoms Among Middle and High School Students: Cross-Sectional Survey Study.

BACKGROUND: Existing literature on the association between the frequency of muscle-strengthening exercise (MSE) and depression among adolescents is limited and contradictory. OBJECTIVE: This study aimed to elucidate the association of MSE frequency with depression symptoms among middle and high school students in China. METHODS: A total of 27,070 students in grades 7-12 from 376 middle and high schools were surveyed using an anonymous self-administered questionnaire between April and June 2022. Information on engaging in MSE was self-reported, and depression symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9). Poisson regression was used to examine the association between MSE frequency and depression symptoms. RESULTS: Among the 27,006 eligible students, 51.6% (n=13,933) were boys, and the mean age was 15.6 (SD 1.7) years. The overall prevalence of meeting MSE recommendations (ie, engaging in MSE ≥3 days/week) was 34.6% (95% CI 32.6%-36.6%; n=9145); the prevalence was higher in boys (43.8%, 95% CI 41.8%-45.8%; 6067/13,933) than in girls (24.3%, 95% CI 22%-26.6%; 3078/13,073; P<.001). A total of 5882 (21.8%) students reported having depression symptoms. After adjustment for sociodemographic status, lifestyle factors, academic performance, and experience of physical fighting, compared to students who did not engage in MSE, the prevalence ratios (PRs) for depression symptoms were 0.98 (95% CI 0.97-0.99) for those engaging in MSE once a week, 0.95 (95% CI 0.93-0.97) for 2 days/week, 0.93 (95% CI 0.90-0.96) for 3 days/week, 0.90 (95% CI 0.87-0.94) for 4 days/week, 0.88 (95% CI 0.84-0.93) for 5 days/week, 0.86 (95% CI 0.81-0.92) for 6 days/week, and 0.84 (95% CI 0.78-0.90) for 7 days/week, respectively. CONCLUSIONS: The overall prevalence of meeting MSE recommendations among Chinese adolescents is low. The frequency of MSE was inversely associated with depression symptoms.

Machine learning reveals the control mechanics of an insect wing hinge.

Insects constitute the most species-rich radiation of metazoa, a success that is due to the evolution of active flight. Unlike pterosaurs, birds and bats, the wings of insects did not evolve from legs1, but are novel structures that are attached to the body via a biomechanically complex hinge that transforms tiny, high-frequency oscillations of specialized power muscles into the sweeping back-and-forth motion of the wings2. The hinge consists of a system of tiny, hardened structures called sclerites that are interconnected to one another via flexible joints and regulated by the activity of specialized control muscles. Here we imaged the activity of these muscles in a fly using a genetically encoded calcium indicator, while simultaneously tracking the three-dimensional motion of the wings with high-speed cameras. Using machine learning, we created a convolutional neural network3 that accurately predicts wing motion from the activity of the steering muscles, and an encoder-decoder4 that predicts the role of the individual sclerites on wing motion. By replaying patterns of wing motion on a dynamically scaled robotic fly, we quantified the effects of steering muscle activity on aerodynamic forces. A physics-based simulation incorporating our hinge model generates flight manoeuvres that are remarkably similar to those of free-flying flies. This integrative, multi-disciplinary approach reveals the mechanical control logic of the insect wing hinge, arguably among the most sophisticated and evolutionarily important skeletal structures in the natural world.

MIR145 Core Promoter Methylation in Pretreatment Cell-Free DNA: A Liquid Biopsy Tool for Muscle-Invasive Bladder Cancer Treatment Outcome.

PURPOSE: The lack of personalized management of bladder cancer (BlCa) results in patients' lifelong post-treatment monitoring with invasive interventions, underlying the urgent need for tailored and minimally invasive health care services. On the basis of our previous findings on miR-143/145 cluster methylation in bladder tumors, we evaluated its clinical significance in pretreatment cell-free DNA (cfDNA) of patients with BlCa. MATERIALS AND METHODS: Methylation analysis was performed in our screening cohort (120 patients with BlCa; 20 age-matched healthy donors) by bisulfite-based pyrosequencing. Tumor recurrence/progression for patients with non-muscle-invasive bladder cancer, and progression and mortality for patients with muscle-invasive bladder cancer (MIBC) were used as clinical end point events in survival analysis. Bootstrap analysis was applied for internal validation of Cox regression models and decision curve analysis for assessment of clinical benefit on disease prognosis. RESULTS: Decreased methylation of MIR145 core promoter in pretreatment cfDNA was associated with short-term disease progression (multivariate Cox: hazard ratio [HR], 2.027 [95% CI, 1.157 to 3.551]; P = .010) and poor overall survival (multivariate Cox: HR, 2.098 [95% CI, 1.154 to 3.817]; P = .009) of patients with MIBC after radical cystectomy (RC). Multivariate models incorporating MIR145 promoter methylation in cfDNA with tumor stage clearly ameliorated patients' risk stratification, highlighting superior clinical benefit in MIBC prognostication. CONCLUSION: Reduced pretreatment cfDNA methylation of MIR145 core promoter was markedly correlated with increased risk for short-term progression and worse survival of patients with MIBC after RC and adjuvant therapy, supporting modern personalized and minimally invasive prognosis. Methylation profiling of MIR145 core promoter in pretreatment cfDNA could serve as a minimally invasive and independent predictor of MIBC treatment outcome and emerge as a promising marker for blood-based test in BlCa.

Ion transport in muscle acetylcholine receptor maintained by conserved salt bridges between the pore and lipid membrane.

Pores through ion channels rapidly transport small inorganic ions along their electrochemical gradients. Here, applying single-channel electrophysiology and mutagenesis to the archetypal muscle nicotinic acetylcholine receptor (AChR) channel, we show that a conserved pore-peripheral salt bridge partners with those in the other subunits to regulate ion transport. Disrupting the salt bridges in all five receptor subunits greatly decreases the amplitude of the unitary current and increases its fluctuations. However, disrupting individual salt bridges has unequal effects that depend on the structural status of the other salt bridges. The AChR ε- and δ-subunits are structurally unique in harboring a putative palmitoylation site near each salt bridge and bordering the lipid membrane. The effects of disrupting the palmitoylation sites mirror those of disrupting the salt bridges, but the effect of disrupting either of these structures depends on the structural status of the other. Thus, rapid ion transport through the AChR channel is maintained by functionally interdependent salt bridges linking the pore to the lipid membrane.

Estimation of lower back muscle force in a lifting task using wearable IMUs.

Low back pain is commonly reported in occupational settings due to factors such as heavy lifting and poor ergonomic practices, often resulting in significant healthcare expenses and lowered productivity. Assessment tools for human motion and ergonomic risk at the workplace are still limited. Therefore, this study aimed to assess lower back muscle and joint reaction forces in laboratory conditions using wearable inertial measurement units (IMUs) during weight lifting, a frequently high-risk workplace task. Ten able-bodied participants were instructed to lift a 28 lbs. box while surface electromyography sensors, IMUs, and a camera-based motion capture system recorded their muscle activity and body motion. The data recorded by IMUs and motion capture system were used to estimate lower back muscle and joint reaction forces via musculoskeletal modeling. Lower back muscle patterns matched well with electromyography recordings. The normalized mean absolute differences between muscle forces estimated based on measurements of IMUs and cameras were less than 25 %, and the statistical parametric mapping results indicated no significant difference between the forces estimated by both systems. However, abrupt changes in motion, such as lifting initiation, led to significant differences (p < 0.05) between the muscle forces. Furthermore, the maximum L5-S1 joint reaction force estimated using IMU data was significantly lower (p < 0.05) than those estimated by cameras during weight lifting and lowering. The study showed how kinematic errors from IMUs propagated through the musculoskeletal model and affected the estimations of muscle forces and joint reaction forces. Our findings showed the potential of IMUs for in-field ergonomic risk evaluations.

Severe fibromyalgia alleviated by the unique muscle relaxation method of applying low force: A case report.

RATIONALE: Fibromyalgia (FM) is characterized by idiopathic persistent chronic pain in the ligaments or musculoskeletal system, and more than half of the patients with FM might have migraine headaches. Direct musculoskeletal intervention could be a non-pharmacological management to relieve symptoms. However, patients with severe FM often have intense pain from only a soft touch, thereby rendering musculoskeletal intervention challenging. PATIENT CONCERNS: A 47-year-old man had progressing intense pain, and this affected his everyday life. There were no abnormal physical findings on laboratory examination such as levels of complement, antinuclear antibodies, and C-reactive protein, which were within normal limits. Magnetic resonance imaging did not indicate abnormalities. DIAGNOSES, INTERVENTIONS, AND OUTCOMES: The patient satisfied the American College of Rheumatology criteria. Finally, we made a final diagnosis of fibromyalgia. The therapeutic intervention of Kanshoho, the unique muscle relaxation technique with low force, relieved his pain. LESSONS: If Kanshoho is carefully applied in a state of hospitalization under surveillance by an experienced physician, it could be a promising muscle relaxation method. Relaxing the trapezius muscle and reducing its intramuscular pressure might be key in treating patients with severe FM. However, it needs elucidation of its mechanism.

MUSCLE: multi-view and multi-scale attentional feature fusion for microRNA-disease associations prediction.

MicroRNAs (miRNAs) synergize with various biomolecules in human cells resulting in diverse functions in regulating a wide range of biological processes. Predicting potential disease-associated miRNAs as valuable biomarkers contributes to the treatment of human diseases. However, few previous methods take a holistic perspective and only concentrate on isolated miRNA and disease objects, thereby ignoring that human cells are responsible for multiple relationships. In this work, we first constructed a multi-view graph based on the relationships between miRNAs and various biomolecules, and then utilized graph attention neural network to learn the graph topology features of miRNAs and diseases for each view. Next, we added an attention mechanism again, and developed a multi-scale feature fusion module, aiming to determine the optimal fusion results for the multi-view topology features of miRNAs and diseases. In addition, the prior attribute knowledge of miRNAs and diseases was simultaneously added to achieve better prediction results and solve the cold start problem. Finally, the learned miRNA and disease representations were then concatenated and fed into a multi-layer perceptron for end-to-end training and predicting potential miRNA-disease associations. To assess the efficacy of our model (called MUSCLE), we performed 5- and 10-fold cross-validation (CV), which got average the Area under ROC curves of 0.966${\pm }$0.0102 and 0.973${\pm }$0.0135, respectively, outperforming most current state-of-the-art models. We then examined the impact of crucial parameters on prediction performance and performed ablation experiments on the feature combination and model architecture. Furthermore, the case studies about colon cancer, lung cancer and breast cancer also fully demonstrate the good inductive capability of MUSCLE. Our data and code are free available at a public GitHub repository: https://github.com/zht-code/MUSCLE.git.

Total muscle-to-fat ratio influences urinary incontinence in United States adult women: a population-based study.

Purpose: This study aims to investigate the relationship between the total muscle-to-fat ratio (tMFR) and female urinary incontinence (UI), determine whether tMFR can serve as a useful index for predicting UI, and identify factors that may influence this relationship. Methods: We retrospectively analyzed data from 4391 adult women participating in the National Health and Nutrition Examination Survey (NHANES) conducted between 2011 and 2018. The correlation between tMFR and UI was examined using a dose-response curve generated through a restricted cubic spline (RCS) function, LASSO and multivariate logistic regression. Furthermore, predictive models were constructed incorporating factors such as age, race, hypertension, diabetes, cotinine levels, and tMFR. The performance of these predictive models was evaluated using training and test datasets, employing calibration curves, receiver operating characteristic curves, and clinical decision curves. Mediation effects were also analyzed to explore potential relationships between tMFR and female UI. Results: In a sample of 4391 adult women, 1073 (24.4%) self-reported experiencing UI, while 3318 (75.6%) reported not having UI. Based on the analyses involving LASSO regression and multivariate logistic regression, it was found that tMFR exhibited a negative association with UI (OR = 0.599, 95% CI: 0.497-0.719, P < 0.001). The results from the restricted cubic spline chart indicated a decreasing risk of UI in women as tMFR increased. Furthermore, the model constructed based on logistic regression analysis demonstrated a certain level of accuracy (in the training dataset: area under the curve (AUC) = 0.663; in the test dataset: AUC = 0.662) and clinical applicability. The mediation analysis revealed that the influence of tMFR on the occurrence of UI in women might potentially occur through the blood index lymphocyte count (P = 0.040). Conclusion: A high tMFR serves as a protective factor against UI in women. Furthermore, lymphocyte might be involved in the relationship between tMFR and female UI.