Search Results (210)

Background and Objectives: The Nordic hamstring exercise (NHE) effectively strengthens the hamstrings, reduces the risk of hamstring strain, and induces fatigue in the muscles; thus, post-NHE recovery strategies should be optimized. Foam rolling (FR) is a widely used method, with the belief that it can speed up recovery. Thus, this study investigated the acute and 48-h effects of FR following the NHE on muscle stiffness, pain pressure threshold (PPT), flexibility, countermovement jump (CmJ) height, and maximal voluntary isometric contraction (MVIC). Materials and Methods: Thirty-two active males were randomly assigned to either an FR group (n = 16) or a passive recovery (PR, n = 16) group. Measurements were taken at three time points: pre-test, post-test_0h, and post-test_48h. Participants performed the NHE (3 sets × 10 reps) before the recovery interventions. Variables assessed included muscle stiffness (MyotonPro), flexibility (sit and reach), PPT (algometer), jump performance (force platform), and MVIC peak torque (dynamometer). Results: FR significantly improved acute flexibility (12.7%, p < 0.001) following the NHE and prevented flexibility loss at 48 h, compared to the PR group. However, FR showed no significant advantages over PR in terms of muscle stiffness, PPT, CmJ, or MVIC, both acutely and at 48 h (p > 0.05). Conclusions: FR is an effective acute recovery strategy for improving flexibility after the NHE but offers limited effects for muscle stiffness, PPT, and other functional muscle parameters, both acutely and at 48 h. Further research should explore the long-term effects and efficacy of FR across diverse populations and recovery scenarios. Full article

Background: Hamstring strain injuries (HSIs) are among the most common and recurrent injuries in sports involving high-speed running. While eccentric training has demonstrated efficacy in reducing HSI risk, the role of sprint training as a preventive strategy remains underexplored and often misinterpreted as solely a risk factor. Methods: This review aimed to systematically map the available evidence on the role of sprint training in hamstring injury prevention, identifying mechanisms, outcomes, and potential synergies with other strategies. This scoping review was conducted following the Joanna Briggs Institute’s methodology and reported in accordance with PRISMA-ScR guidelines. Seven databases (PubMed, Scopus, Web of Science, Cochrane CENTRAL, SPORTDiscus, CINAHL, and PEDro) were searched up to October 2024. Studies were included if they involved adult athletes and examined the effects of sprint training, ≥80–90% maximal sprint speed (MSS), on hamstring injury prevention, muscle architecture, or functional outcomes. All databases were searched from inception to 15 October 2024, and the screening and data-charting process was completed on 30 April 2025. Results: Twelve studies met the inclusion criteria. Sprint exposure, when combined with eccentric strengthening and biomechanical optimisation, led to injury reductions ranging from 56% to 94%. Eccentric interventions produced fascicle length increases of up to 20% and strength gains of 15–20%. Improvements in sprint technique and neuromuscular control were also reported. Biomechanical risk factors, including pelvic tilt and hip extension deficits, were linked to increased HSI risk. The most common eccentric protocols included Nordic Hamstring Exercises (NHE), Razor Curls, and hip-dominant exercises, typically performed 1–2 times per week for 4 to 8 weeks. Conclusions: High-speed sprint training, when properly programmed and integrated into comprehensive preventive strategies, may enhance tissue resilience and reduce HSI risk. Combining sprint exposure with eccentric strengthening and technical coaching appears to be more effective than isolated interventions alone. Practically, these results support the systematic inclusion of progressive high-intensity sprint exposure in routine hamstring-injury-prevention programmes for field-sport athletes. Full article

Hyperinsulinemia refers to an elevated level of circulating insulin (80 and 100 µU/mL), often leading to metabolic disorders such as obesity, insulin resistance, and type 2 diabetes (T2D). There is no precise and universally accepted definition of hyperinsulinemia and insulin resistance. The literature in the field remains unclear regarding whether insulin resistance precedes the development of hyperinsulinemia. Recently, a new hypothesis has been proposed suggesting that chronic hyperinsulinemia precedes and causes insulin resistance. The causes of the initiation of hyperinsulinemia, insulin resistance, and type 2 diabetes are multifactorial. Thus, it is not easy to define in general. Recent work demonstrates that the main prediabetic factor leading to insulin resistance is chronic hyperinsulinemia. However, recent work in the literature proposes that relatively long-term hyperinsulinemia does precede insulin resistance and already promotes cardiovascular remodeling. This later may lead to the development of vascular diseases such as hypertension. Thus, defining hyperinsulinemia and insulin resistance, as well as their signaling pathways implicated in the development of type 2 diabetes (T2D), needs to be clarified. Full article

Oxidative stress is a key mediator of physiological dysfunction in aquatic organisms under environmental challenges, yet its comprehensive impacts on gill physiology require further clarification. This study investigated the molecular and cellular responses of Eriocheir sinensis gills to hydrogen peroxide (H₂O₂)-induced oxidative stress, integrating antioxidant defense, ion transport regulation, and stress-induced cell apoptosis and autophagy. Morphological alterations in the gill filaments were observed, characterized by septum degeneration, accumulation of haemolymph cells, and pronounced swelling. For antioxidant enzymes like catalase (CAT) and glutathione peroxidase (GPx), activities were enhanced, while superoxide dismutase (SOD) activity was reduced following 48 h of exposure. Overall, the total antioxidant capacity (T-AOC) showed a significant increase. The elevated concentrations of malondialdehyde (MDA) and H₂O₂ indicated oxidative stress. Ion transport genes displayed distinct transcription patterns: Na⁺-K⁺-2Cl⁻ co-transporter-1 (NKCC1), Na⁺/H⁺ exchanger 3 (NHE3), aquaporin 7 (AQP7), and chloride channel protein 2 (CLC2) were significantly upregulated; the α-subunit of Na⁺/K⁺-ATPase (NKAα) and carbonic anhydrase (CA) displayed an initial increase followed by decline; whereas vacuolar-type ATPase (VATP) consistently decreased, suggesting compensatory mechanisms to maintain osmotic balance. Concurrently, H₂O₂ triggered apoptosis (Bcl2, Caspase-3/8) and autophagy (beclin-1, ATG7), likely mediated by MAPK and AMPK signaling pathways. These findings reveal a coordinated yet adaptive response of crab gills to oxidative stress, providing new insights into the mechanistic basis of environmental stress tolerance in crustaceans. Full article

The monolithic integration of III-V semiconductors with silicon (Si) is a critical step toward advancing optoelectronic and photonic devices. In this work, we present GaAs nanoheteroepitaxy (NHE) on Si nanotips using gas-source molecular beam epitaxy (GS-MBE). We discuss the selective growth of fully relaxed GaAs nanoislands on complementary metal oxide semiconductor (CMOS)-compatible Si(001) nanotip wafers. Nanotip wafers were fabricated using a state-of-the-art 0.13 μm SiGe Bipolar CMOS pilot line on 200 mm wafers. Our investigation focuses on understanding the influence of the growth conditions on the morphology, crystalline structure, and defect formation of the GaAs islands. The morphological, structural, and optical properties of the GaAs islands were characterized using scanning electron microscopy, high-resolution X-ray diffraction, and photoluminescence spectroscopy. For samples with less deposition, the GaAs islands exhibit a monomodal size distribution, with an average effective diameter ranging between 100 and 280 nm. These islands display four distinct facet orientations corresponding to the {001} planes. As the deposition increases, larger islands with multiple crystallographic facets emerge, accompanied by a transition from a monomodal to a bimodal growth mode. Single twinning is observed in all samples. However, with increasing deposition, not only a bimodal size distribution occurs, but also the volume fraction of the twinned material increases significantly. These findings shed light on the growth dynamics of nanoheteroepitaxial GaAs and contribute to ongoing efforts toward CMOS-compatible Si-based nanophotonic technologies. Full article

Valproic acid (VPA) is a widely prescribed antiepileptic agent whose teratogenic potential has been recognized. In recent years, VPA has been shown to promote neuronal regeneration; however, the exact molecular mechanisms are not fully understood. This study elucidates the pH-dependent pathway through which VPA promotes the differentiation of satellite glial cells (SGCs) into neurons. We observed sustained intracellular pH elevation during the VPA-induced neural differentiation of SGCs, and the modulation of intracellular pH was shown to influence this differentiation process. Then, we found that VPA regulates intracellular pH through NHE1 (sodium–hydrogen exchanger 1), and that the pharmacological inhibition of NHE1 not only attenuated intracellular pH elevation but also substantially impaired VPA-induced neuronal differentiation. Finally, our results showed that the elevated intracellular pH promoted the neuronal differentiation of SGCs by activating β-catenin signaling. These findings provide novel insights into the mechanisms of VPA-induced neurogenesis, advancing our understanding of its pharmacological profile and informing its potential therapeutic application in neuronal regeneration strategies. Full article

Background/Objectives: A healthy diet helps prevent noncommunicable diseases, and dairy is an essential part of this diet. Multiple meta-analyses have shown an inverse association between yogurt intake and type 2 diabetes (T2D). This study aimed to develop a simulation model and evaluate the medical and economic effects of increased yogurt intake on T2D. Methods: It predicted the T2D incidence rate, T2D mortality rate, and national healthcare expenditures (NHE) over 10 years using a Markov model for the Japanese population aged 40–79 years. Results: By increasing yogurt intake to 160 g/day or 80 g/day, the incidence rate of T2D decreased by 16.1% or 5.9%, the T2D-related mortality rate decreased by 1.6% or 0.6%, and the NHE was predicted to decrease by 2.4% and 0.9%, respectively. Conclusions: Increasing yogurt intake may be an effective strategy to prevent T2D and reduce NHE. Full article

Avian leukosis virus subgroup J (ALV-J), an α-retrovirus, mediates infection by binding to the host-specific receptor chNHE1 (chicken sodium–hydrogen exchanger type 1), leading to immunosuppression and tumorigenesis, which severely threatens the sustainable development of the poultry industry. Studies have shown that the tryptophan residue at position 38 (W38) of the chNHE1 protein is the critical site for ALV-J infection. In this study, we employed the CRISPR/Cas9 system to construct a lentiviral vector targeting the W38 site of chNHE1, transfected it into chicken primordial germ cells (PGCs), and validated its antiviral efficacy through ALV-J infection assays, successfully establishing an in vitro gene-editing system for chicken PGCs. The constructed dual lentiviral vector efficiently targeted the W38 site. PGCs isolated from 5.5- to 7-day-old chicken embryos were suitable for in vitro gene editing. Stable fluorescence expression was observed within 24–72 h post-transfection, confirming high transfection efficiency. ALV-J challenge tests demonstrated that no viral env gene expression was detected in transfected PGCs at 48 h or 72 h post-infection, while high env expression was observed in control groups. After 7 days of infection, p27 antigen ELISA tests were negative in transfected groups but positive in controls, indicating that W38-deleted PGCs exhibited strong resistance to ALV-J. This study successfully generated ALV-J-resistant gene-edited PGCs using CRISPR/Cas9 technology, providing a novel strategy for disease-resistant poultry breeding and advancing avian gene-editing applications. Full article

Topmouth Gudgeon (Pseudorasbora parva), a typical invasive fish worldwide, has successfully invaded various aquatic ecosystems and colonized saline–alkali waters from freshwater due to its broad environmental tolerances. However, the molecular mechanisms of adaptation to saline–alkali stress for P. parva remain poorly characterized. To explore the potential genetic mechanisms, we conducted differential gene expression analysis using gill transcriptome of wild P. parva populations collected from four waters with different salinity–alkalinity levels. Comparative transcriptomics analysis showed that DEGs involved in osmoregulation, ano6, cftr, aqp1, and aqp3, were down-regulated; DEGs related to ammonia excretion, Rhcg and Rhbg, were up-regulated; DEGs for acid–base accommodation, nhe2, slc4a1, and ca2, were down-regulated while ca4 was up-regulated; and immune-system-related DEGs, il8 and il17, were down- and up-regulated, respectively, in a high saline–alkaline water environment. The DEGs were enriched in multiple KEGG pathways, such as the ribosome, thermogenesis, oxidative phosphorylation, necroptosis, and HIF-1 signaling pathways. In addition, more DEGs were significantly enriched in immune-disease-related pathways in high saline–alkaline water populations. This suggests that P. parva exposed to chronic saline–alkali stress, despite survival, still needed immune system regulation to defend against potential diseases. These results revealed the gill molecular mechanisms underlying P. parva saline–alkaline adaptation and offered valuable insights into the development of saline–alkaline water aquaculture fisheries Full article

Survivors of severe hypothermia frequently exhibit cognitive impairments. However, the underlying mechanisms remain inadequately understood. In order to reveal the scientific problem of cognitive dysfunction caused by severe hypothermia, providing an experimental basis for clinical treatment, this study utilized animal models and combined cognitive behavioral, morphological, and molecular biological experiments. The results showed that severe hypothermia leads to an accumulation of iron ions in the cerebral cortex tissue exceeding 70%, while increased Acyl-coenzyme A synthetase long-chain family member 4 (ACSL4) expression enhances sensitivity to ferroptosis. This process results in a nearly 50% decrease in glutathione (GSH) expression and over 50% degradation of glutathione peroxidase 4 (GPX4), leading to GPX4 deactivation and increased lipid peroxidation, which in turn nearly doubles the levels of oxidative products such as MDA and 4NHE. Notably, ferroptosis inhibition using Ferrostatin-1 (Fer-1) effectively mitigates the degenerative death of cerebral cortical neurons induced by severe hypothermia, significantly improving the associated cognitive deficits. These findings suggest that severe hypothermia may induce ferroptosis in cortical neurons through the Nrf2/SLC7A11/GSH/GPX4 signaling axis. Targeted inhibition of ferroptosis has the potential to be a promising therapeutic direction for the prevention and treatment of cognitive impairment caused by severe hypothermia. Full article

Nordic exercises are widely used to improve physical performance and prevent injuries; however, their applicability across different sports remains unclear. Objective: This study examined the effects of Nordic exercises on the lower limbs and their relationship with absolute strength and vertical jump performance across various sports disciplines (soccer, athletics, basketball, sport climbing, cycling, and taekwondo). Methods: We conducted a quasi-experimental study involving 122 athletes (mean age 18.2 ± 3.2 years), who were not in pre-competitive or competitive periods, distributed across the following disciplines: soccer (n = 24), sprinting/athletics (n = 20), sport climbing (n= 20), basketball (n = 24), taekwondo (n = 14), and cycling (n = 20). Participants were randomly assigned to a control group (CG), n = 57, with regular training and an experimental group (EG), n = 65, that performed Nordic hamstring exercises (NHEs). The effects of a 7-week NHE program were assessed on absolute strength (measured with a dynamometer) and vertical jump performance (Vert). A mixed-design repeated measures ANOVA was used, considering the factors time, group, and sport discipline, with a significance level set at p < 0.05. Results: Both groups (CG and EG) presented homogeneous baseline values for absolute strength (dominant and non-dominant sides) and vertical jump (p > 0.05). The EG exhibited significant gains in dominant-leg strength (from 12.4 kg to 14.5 kg), non-dominant side strength (from 11.1 kg to 13.8 kg), and vertical jump (from 42.4 cm to 45.8 cm), with statistically significant differences between pre- and post-tests (p < 0.01). No relevant changes were observed in the CG. The repeated measures ANOVA confirmed a significant time × group effect in all three variables (p < 0.01), although no significant time × sport × group interaction was found. The largest strength gains occurred in strength were observed in sport climbing, basketball, and athletics and in vertical jump in soccer. Conclusions: Absolute strength improvements were most notable in sport climbing, basketball, football, and sprinting. Vertical jump performance improved notably in soccer, sprinting/athletics, climbing, and basketball. These results justify incorporating NHEs into youth athletes’ training, tailored to the specific demands of each sport. Full article

Phosphorus is one of the most abundant minerals in the body and plays a critical role in numerous cellular and metabolic processes. Most of the phosphate is deposited in bones, 14% is present in soft tissues as various organic phosphates, and only 1% is found in extracellular space, mainly as inorganic phosphate. The plasma inorganic phosphate concentration is closely maintained between 2.5 and 4.5 mg/dL by intertwined interactions between fibroblast growth factor 23 (FGF-23), parathyroid hormone (PTH), and vitamin D, which tightly regulate the phosphate trafficking across the gastrointestinal tract, kidneys, and bones. Disruption of the strict hemostatic control of phosphate balance can lead to altered cellular and organ functions that are associated with high morbidity and mortality. In the past three decades, there has been a steady increase in the prevalence of kidney failure (KF) among populations. Individuals with KF have unacceptably high mortality, and well over half of deaths are related to cardiovascular disease. Abnormal phosphate metabolism is one of the major factors that is independently associated with vascular calcification and cardiovascular mortality in KF. In early stages of CKD, adaptive processes involving FGF-23, PTH, and vitamin D occur in response to dietary phosphate load to maintain plasma phosphate level in the normal range. However, as the CKD progresses, these adaptive events are unable to overcome phosphate retention from continued dietary phosphate intake and overt hyperphosphatemia ensues. As these hormonal imbalances and the associated adverse consequences are driven by the underlying hyperphosphatemic state in KF, it appears logical to strictly control serum phosphate. Conventional dialysis is inadequate in removing phosphate and most patients require dietary restrictions and pharmacologic interventions to manage hyperphosphatemia. However, diet control comes with many challenges with adherence and may place patients at risk for inadequate protein intake and malnutrition. Phosphate binders help to reduce phosphate levels but come with a sizable pill burden and high financial costs and are associated with poor adherence and psychosocial issues. Additionally, long-term use of binders may increase the risk of calcium, lanthanum, or iron overload or promote gastrointestinal side effects that exacerbate malnutrition and affect quality of life. Given the aforesaid challenges with phosphorus binders, novel therapies targeting small intestinal phosphate absorption pathways have been investigated. Recently, tenapanor, an agent that blocks paracellular absorption of phosphate via inhibition of enteric sodium–hydrogen exchanger-3 (NHE3) was approved for the treatment of hyperphosphatemia in KF. While various clinical tools are now available to manage hyperphosphatemia, there is a lack of convincing clinical data to demonstrate improvement in outcomes in KF with the lowering of phosphorus level. Conceivably, deleterious effects associated with hyperphosphatemia could be attributable to disruptions in phosphorus-sensing mechanisms and hormonal imbalance thereof. Further exploration of mechanisms that precisely control phosphorus sensing and regulation may facilitate development of strategies to diminish the deleterious effects of phosphorus load and improve overall outcomes in KF. Full article

Nitrite and carbon dioxide (CO₂) are common environmental substances in intensive aquaculture ponds. However, the effects and mechanisms of their combined exposure on aquatic animals remain unclear. In this study, we investigated the toxic effects of 2.5, 5, and 10 mg/L CO₂ in the presence of 2 mg/L nitrite on hematological, blood gas parameters, and liver physiological and pathological changes in zebrafish (Danio rerio) over 14 days and 28 days. Our results demonstrated a reduced nitrite uptake and accumulation in the gills and liver of zebrafish exposed to nitrite and varying levels of CO₂. Increased CO₂ levels also led to a decrease in the expression of gill ae1, whereas the transcriptional levels of nhe1 and nhe3b, nkcc and nbc1 were notably upregulated. Moreover, there was a decrease in Cl⁻ and Na⁺ concentrations, along with an increase in K⁺ concentrations. These changes suggested that zebrafish responded to increased CO₂ stress by reducing their absorption of chloride-dependent nitrite, excreting H⁺ and maintaining their internal pH. Exposure to higher CO₂ levels in the presence of nitrite resulted in lower blood MetHb levels and liver oxidative stress compared to the nitrite single-exposure treatment. Furthermore, co-treatment with CO₂ and nitrite attenuated the nitrite-induced damage to genes related to mitochondrial respiratory chain function (ndufs1, mtnd5, mtycb, atp5f1b, mtatp8), leading to elevated ATP levels. Exposure to nitrite alone increased the expression of lipolytic genes (hsla, cpt1aa, atgl) and decreased the expression of lipid synthesis genes (fasn, acaca), resulting in a decrease in TG and TC content in zebrafish liver. However, co-treatment with CO₂ and nitrite prevented the nitrite-induced disruption of lipid metabolism, as evidenced by the improvement in TG and TC levels, as well as transcriptional levels of lipid metabolism-related genes. In conclusion, our study suggests that in the presence of 2 mg/L nitrite, increased CO₂ (2.5–10 mg/L) may modulate ion transporter genes to reduce the chloride-dependent nitrite uptake and maintain pH homeostasis, concurrently alleviating oxidative stress, restoring mitochondrial respiratory function, and improving lipid metabolism in a dose-dependent manner. These changes may be related to the increase in the concentration of bicarbonate ions in the water as the CO₂ level rises. These findings shed light on the potential protective effects of CO₂ in mitigating the harmful effects of nitrite exposure in aquatic animals. Full article

The sodium/proton exchanger NHA2, also known as SLC9B2, is important for insulin secretion, renal blood pressure regulation, and electrolyte retention. Recent structures of bison NHA2 has revealed its unique 14-transmembrane helix architecture, which is different from SLC9A/NHE members made up from 13-TM helices. Sodium/proton exchangers are functional homodimers, and the additional N-terminal helix in NHA2 was found to alter homodimer assembly. Here, we present the cryo-electron microscopy structures of apo human NHA2 in complex with a Fab fragment and also with the inhibitor phloretin bound at 2.8 and 2.9 Å resolution, respectively. We show how phosphatidic acid (PA) lipids bind to the homodimer interface of NHA2 on the extracellular side, which we propose has a regulatory role linked to cell volume regulation. The ion binding site of human NHA2 has a salt bridge interaction between the ion binding aspartate D278 and R432, an interaction previously broken in the bison NHA2 structure, and these differences suggest a possible ion coupling mechanism. Lastly, the human NHA2 structure in complex with phloretin offers a template for structure-guided drug design, potentially leading to the development of more selective and potent NHA2 inhibitors. Full article

Background/Objectives: Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by excessive extracellular matrix (ECM) production and tissue stiffening, resulting in impaired lung function. Sodium hydrogen exchanger isoform 1 (NHE1) is a key mediator of intracellular and extracellular pH regulation, influencing fibroblast activation, motility, and proliferative pathways. This study investigates the role of NHE1 in actin stress fiber formation, fibroblast-to-myofibroblast differentiation, and cytokine secretion in IPF progression. Methods: Fibroblasts were treated with profibrotic agonists, including transforming growth factor-beta (TGFβ), lysophosphatidic acid (LPA), and serotonin (THT), in the presence or absence of the NHE1-specific inhibitor, EIPA. Actin stress fibers were visualized using phalloidin staining, while α-smooth muscle actin (α-SMA) expression and cytokine secretion (TGFβ, IL-6, and IL-8) were quantified using immunostaining and ELISA. Intracellular pH changes were measured using BCECF-AM fluorescence. Results: Profibrotic agonists induced significant actin stress fiber formation and α-SMA expression in fibroblasts, both of which were abolished by EIPA. NHE1 activity was shown to mediate intracellular alkalization, a critical factor for fibroblast activation. Cytokine secretion, including TGFβ, IL-6, and IL-8, was enhanced by agonist treatments but reduced with NHE1 inhibition. Chronic TGFβ exposure increased intracellular pH and sustained myofibroblast differentiation, which was partially reversed by EIPA. Conclusions: NHE1 is indicated to play a novel and potential role in processes supporting profibrotic agonists driving fibroblast activation and IPF progression. Targeting NHE1 could present a potential therapeutic approach to disrupt profibrotic pathways and mitigate IPF severity. Full article