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Abstract Background The mechanistic effects of gamma transcranial alternating current stimulation (tACS) on hippocampal gamma oscillation activity in Alzheimer’s Disease (AD) remains unclear. This study aimed to clarify beneficial effects of gamma tACS on cognitive functioning in AD and to elucidate effects on hippocampal gamma oscillation activity. Methods This is a double-blind, randomized controlled single-center trial. Participants with mild AD were randomized to tACS group or sham group, and underwent 30 one-hour sessions of either 40 Hz tACS or sham stimulation over consecutive 15 days. Cognitive functioning, structural magnetic resonance imaging (MRI), and simultaneous electroencephalography–functional MRI (EEG-fMRI) were evaluated at baseline, the end of the intervention and at 3-month follow-up from the randomization. Results A total of 46 patients were enrolled (23 in the tACS group, 23 in the sham group). There were no group differences in the change of the primary outcome, 11-item cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-Cog) score after intervention (group*time, p = 0.449). For secondary outcomes, compared to the control group, the intervention group showed significant improvement in MMSE (group*time, p = 0.041) and MoCA scores (non-parametric test, p = 0.025), which were not sustained at 3-month follow-up. We found an enhancement of theta-gamma coupling in the hippocampus, which was positively correlated with improvements of MMSE score and delayed recall. Additionally, fMRI revealed increase of the local neural activity in the hippocampus. Conclusion Effects on the enhancement of theta-gamma coupling and neural activity within the hippocampus suggest mechanistic models for potential therapeutic mechanisms of tACS. Trial registration ClinicalTrials.gov, NCT 03920826; Registration Date: 2019-04-19.

IntroductionFerroptosis is a crucial process contributing to neuronal damage following intracerebral hemorrhage (ICH). Didang Tang (DDT), a traditional therapeutic, has been used clinically to manage ICH for many years, yet the molecular mechanisms by which by DDT protects neurons from ferroptosis after ICH remain elusive.MethodsThis study utilized high-performance liquid chromatography-based fingerprint analysis to characterize DDT’s chemical composition. An ICH rat model and hemin and erastin-induced PC12 cell ferroptosis models were developed to investigate DDT’s neuroprotective mechanisms. Histological assessments of brain tissue morphology and iron deposition were performed using hematoxylin-eosin, Nissl, and Perl’s blue staining. Neurological function was evaluated using Longa and Berderson scores, while lipid peroxidation was measured using biochemical assays and flow cytometry. Protein expression levels of ferroptosis- and endoplasmic reticulum stress (ERS)-related markers were analyzed via Western blotting and immunofluorescence.ResultsOur results demonstrated that DDT reduced hematoma volume, decreased iron deposition, lowered malondialdehyde (MDA) levels, and upregulated glutathione peroxidase (GPX4) and SLC7A11 expression in affected brain regions. Furthermore, DDT downregulated GRP78 expression and inhibited the PERK/eIF2α/ATF4/CHOP/GPX4 pathway, exerting strong neuroprotective effects. The fluorescence staining results of MAP2/GPX4 and MAP2/CHOP suggested that DDT may regulate neuronal ferroptosis and ERs to exert the protective effect. In vitro experiments using hemin- and erastin-induced neuron-derived PC12 cells as neuronal ferroptosis models developed in our laboratory corroborated these in vivo findings, showing increased survival and reduced lipid peroxidation in DDT-treated cells, along with similar inhibitory effects on ferroptosis and ERS. Molecular docking suggested that DDT components, such as sennoside B, amygdalin, rhein, and emodin, interact favorably with PERK/eIF2α/ATF4/CHOP signaling pathway proteins, highlighting their potential role in DDT’s anti-ferroptosis effects.ConclusionDDT alleviates neuronal ferroptosis after ICH by modulating the PERK/eIF2α/ATF4/CHOP/GPX4 signaling pathway. Overall, this study provides novel insights into DDT’s protective mechanisms against ICH-induced neuronal injury by modulating ferroptosis and ERS pathways, underscoring its potential as an effective therapeutic strategy.

Titanium dioxide nanoparticles (TiO2-NPs) released into the environment is becoming more prevalent due to their increased usage, marine TiO2-NPs contamination is escalating concerns in coastal areas. To understand the potential impact of TiO2-NPs on transcript changes in pearl oyster (Pinctada fucata martensii), transcriptome analysis on the gill tissues of pearl oysters was conducted after 14-day TiO2-NPs exposure and 7-day brief recovery. A total of 911 differentially expressed genes (DEGs) were identified between the control group (TC) and the experimental group (TE) exposed to 14-day TiO2-NPs. Gene ontology (GO) analyses of the DEGs demonstrated their substantial enrichments in functions related to “hydrolase activity”, “oxidoreductase activity”, and “DNA integration”. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analyses of the DEGs indicated enrichment in several pathways, including “ubiquitin-mediated protein hydrolysis”, “ECM-receptor interactions”, “NOD-like receptor signaling pathway”, “Toll-like receptor”, and “FOXO signaling pathway”. This suggests that exposure to TiO2-NPs intensifies oxidative stress and apoptosis in pearls oysters, leading to negative effects such as disrupted protein homeostasis, decreased biomineralization activity, reduced neuronal excitability, weakened immune response, and reduced cellular metabolism. Transcriptome analysis identified 844 DEGs between the TE and recovery group (TR), which underwent a 7-day brief recovery period. GO analyses of the DEGs demonstrated their substantial enrichments in functions related to “DNA integration”, “obsolete oxidation-reduction process”, and “proteolysis”. KEGG pathways analyses of the DEGs indicated enrichment in several pathways, including “lysine degradation”, “glycine, serine, and threonine metabolism”, and “NOD-like receptor signaling pathway”. The findings indicated that although pearl oysters showed only slight relief after 7 days of brief recovery, they continued to experience negative effects from TiO2-NP exposure. Our findings shed light on the complex responses of pearl oysters to TiO2-NPs stress and offer valuable theoretical insights into the toxicological impact of TiO2-NPs on pearl oysters.

The incidence of chronic wound healing is promoted by the growing trend of elderly population, obesity, and type II diabetes. Although numerous wound dressings have been studied over the years, it is still challenging for many wound dressings to perfectly adapt to the healing process due to the dynamic and complicated wound microenvironment. Aiming at an optimal reproduction of the physiological environment, multifunctional electrospinning nanofibrous membranes (ENMs) have emerged as a promising platform for the wound treatment owing to their resemblance to extracellular matrix (ECM), adjustable preparation processes, porousness, and good conformability to the wound site. Moreover, profiting from the booming development of human-machine interaction and artificial intelligence, a next generation of intelligent electrospinning nanofibrous membranes (iENMs) based wound dressing substrates that could realize the real-time monitoring of wound proceeding and individual-based wound therapy has evoked a surge of interest. In this regard, general wound-related biomarkers and process are overviewed firstly and representative iENMs stimuli-responsive materials are briefly summarized. Subsequently, the emergent applications of iENMs for the wound healing are highlighted. Finally, the opportunities and challenges for the development of next-generation iENMs as well as translating iENMs into clinical practice are evaluated.

Objective: This study aimed to estimate the effects of the volume of preperitoneal balloon (PPB) on arterial and venous hemorrhage in a swine pelvic fracture model.Methods: Twenty-four swine were randomized into 0-mL, 500-mL, 800-mL, and 1000-mL intra-hematoma PPB groups. They were subjected to open-book pelvic fracture and reproducible injuries in the external iliac artery and vein. The pelvic binder and IH-PPBs with different volumes of fluid were applied to control the active hemorrhage after arterial and venous injuries. The survival time and rate during 60-min observation and digital subtraction angiography (DSA) images were the primary endpoints in this study. Secondary endpoints included survival rate within 70 min, peritoneal pressure, hemodynamics, blood loss, infusion fluid, blood pH, and lactate concentration.Results: Our results indicated that the 800-mL and 1000-mL groups had a higher survival rate (0%, 50%, 100% and 100% for 0, 500, 800, and 1000-mL groups respectively; p < 0.0001) and longer survival time (13.83 ± 2.64, 24.50 ± 6.29, 55.00 ± 6.33, and 60.00 ± 0.00 min for 0, 500, 800, and 1,000 groups respectively; p < 0.0005) than the 0-mL or 500-mL groups during the 60 min observation. Contrastingly, survival rate and time were comparable between 800-mL and 1000-mL groups during the 60-min observation. The IH-PPB volume was associated with an increase in the pressure of the balloon and the preperitoneal pressure but had no effect on the bladder pressure. Lastly, the 1000-mL group had a higher mean arterial pressure and systemic vascular resistance than the 800-mL group.Conclusion: IH-PPB volume-dependently controls vascular bleeding after pelvic fracture in the swine model. IH-PPB with a volume of 800 mL and 1000 mL efficiently managed pelvic fracture-associated arterial and venous hemorrhage and enhanced survival time and rate in the swine model without evidences of visceral injury.

Cancer and diabetes are significant diseases that pose a threat to human health. Their interconnection is complex, particularly when they coexist, often necessitating multiple therapeutic approaches to attain remission. Sodium-glucose cotransporter protein two inhibitors (SGLT-2i) emerged as a treatment for hyperglycemia, but subsequently exhibited noteworthy extra-glycemic properties, such as being registered for the treatment of heart failure and chronic kidney disease, especially with co-existing albuminuria, prompting its assessment as a potential treatment for various non-metabolic diseases. Considering its overall tolerability and established use in diabetes management, SGLT-2i may be a promising candidate for cancer therapy and as a supplementary component to conventional treatments. This narrative review aimed to examine the potential roles and mechanisms of SGLT-2i in the management of diverse types of cancer. Future investigations should focus on elucidating the antitumor efficacy of individual SGLT-2i in different cancer types and exploring the underlying mechanisms. Additionally, clinical trials to evaluate the safety and feasibility of incorporating SGLT-2i into the treatment regimen of specific cancer patients and determining appropriate dosage combinations with established antitumor agents would be of significant interest.

BackgroundPatients with age-related hearing loss (ARHL) often struggle with tracking and locating sound sources, but the neural signature associated with these impairments remains unclear.Materials and methodsUsing a passive listening task with stimuli from five different horizontal directions in functional magnetic resonance imaging, we defined functional regions of interest (ROIs) of the auditory “where” pathway based on the data of previous literatures and young normal hearing listeners (n = 20). Then, we investigated associations of the demographic, cognitive, and behavioral features of sound localization with task-based activation and connectivity of the ROIs in ARHL patients (n = 22).ResultsWe found that the increased high-level region activation, such as the premotor cortex and inferior parietal lobule, was associated with increased localization accuracy and cognitive function. Moreover, increased connectivity between the left planum temporale and left superior frontal gyrus was associated with increased localization accuracy in ARHL. Increased connectivity between right primary auditory cortex and right middle temporal gyrus, right premotor cortex and left anterior cingulate cortex, and right planum temporale and left lingual gyrus in ARHL was associated with decreased localization accuracy. Among the ARHL patients, the task-dependent brain activation and connectivity of certain ROIs were associated with education, hearing loss duration, and cognitive function.ConclusionConsistent with the sensory deprivation hypothesis, in ARHL, sound source identification, which requires advanced processing in the high-level cortex, is impaired, whereas the right–left discrimination, which relies on the primary sensory cortex, is compensated with a tendency to recruit more resources concerning cognition and attention to the auditory sensory cortex. Overall, this study expanded our understanding of the neural mechanisms contributing to sound localization deficits associated with ARHL and may serve as a potential imaging biomarker for investigating and predicting anomalous sound localization.

Owing to the presence of drugs targeting adrenergic receptors in aquatic ecosystems, considerable attention has been directed towards their environmental distribution and fate in recent decades. However, their potential impacts on non-target aquatic organisms, particularly fish, have received relatively limited investigation. In this study, moxisylyte (MOX) and propranolol (PRO) were selected as representatives of α- or β-adrenergic receptor antagonist, respectively, and we assessed their effects on the early life stages of zebrafish, especially on the nervous and cardiovascular systems. Although both compounds exhibited marginal effects on zebrafish survival, hatching and gross abnormality following exposure to concentrations ranging from 1 to 625 μg/L, they adversely affected the development of cardiovascular and nervous systems, but through different mechanisms of action, as evidenced by variations in gene transcriptional responses and enzyme activities. Notably, cardiovascular responses appear promising for use as potential biomarkers for exposure to drugs targeting adrenergic receptors. This study enhances our understanding of the ecotoxicological risks posed by α- and β-blockers in fish. Nonetheless, further investigation is needed to elucidate the precise mechanisms underlying the impacts of drugs targeting adrenergic receptors due to our limited knowledge of the physiological functions of the adrenergic system in fish.

This paper focuses on the selection and application of scale inhibitor by studying the problem of pipeline scaling in geothermal well development. Adding scale inhibitor can effectively reduce the treatment cost and achieve a good scale resistance effect, but the commonly used polyaspartic acid scale inhibitor has problems such as poor scale inhibition effect and large use limitations. Therefore, a new modified polyaspartic acid scale inhibitor (His-Tyr-SA-PASP) was prepared using polysuccinimide (PSI) as the raw material and histidine (His), tyrosine (Tyr), and sulfonic acid (SA) as the modification reagent. When the dosage of His-Tyr-SA-PASP was 8 mg/L, the scale inhibition rate of CaCO3 was 94.40%. In addition, the scale inhibition effect of His-Tyr-SA-PASP on CaCO3 was better than that of PASP. At the same time, under the condition of a static experiment at 75 °C, according to the ion concentration of water samples in different scale zones, this paper also identified the ratio of four composite scale inhibitors. When the dosage of compound scale inhibitor was 100 mg/L, Sodium of Polyaspartic Acid–Diethylene Triamine Penta (Methylene Phosphonic Acid)–2-Phosphonobutane-1,2,4-Tricarboxylic Acid–Amino Trimethylene Phosphonic Acid–Copolymer of Maleic and Acrylic Acid = (10:10:5:1:9), (15:10:5:2.5:2.5), (12.5:5:10:1:6.5), and (15:5:10:4:1) and the scale inhibition rate was more than 95%. Under the condition of a dynamic experiment, the optimized composite scale inhibitor still showed a scale inhibition rate of more than 90%. It provides a useful reference for the practical application of water treatment in geothermal wells and has the prospect of industrial application.

Enhanced denitrification has been reported under weak electric fields. However, it is difficult to investigate the mechanism of enhanced denitrification due to the complex interspecific interactions of mixed-culture systems. In this study, Pseudomonas stutzeri, capable of denitrification under anaerobic conditions, was selected for treating low COD/N (2.0, ratio between concentration of chemical oxygen demand and NO3−-N) artificial wastewater under constant external voltages of 0.2, 0.4, and 0.6 V. The results revealed that P. stutzeri exhibited the highest efficiency in nitrate reduction at 0.2 V. Moreover, the maximum nitrate removal rate was 15.96 mg/(L·h) among the closed-circuit groups, 19.39% higher than that under the open-circuit group. Additionally, a notable reduction in nitrite accumulation was observed under weak electric fields. Enzyme activity analysis showed that the nitrate reductase activities were significantly increased among the closed-circuit groups, while nitrite reductase activities were inhibited. Transcriptomic analysis indicated that amino acid metabolism, carbohydrate metabolism, and energy metabolism were increased, enhancing the resistance of P. stutzeri to environmental stress and the efficiency of carbon source utilization for denitrification. The current study examined the impacts of weak electric fields on enzyme activities and microbial metabolic pathways and offers valuable insights into the mechanism by which denitrification is enhanced by weak electric fields.

The world is rich in coalbed methane (CBM) resources and has broad exploration and development prospects. In this paper, first, the technical difficulties of drilling and completion in deep shale formations in the Sichuan and Chongqing region is systematically summarized. Second, a systematic evaluation was conducted on the optimization of temperature resistance performance and trajectory control technology of the rotary guidance system. Third, evaluation and economic analysis were conducted on the experimental effects of different technologies. Results show that: (a) the optimization technology for temperature resistance performance of integrated high-temperature resistant guide head and surface cooling equipment has been formed, which can effectively reduce the circulation cooling time and improve drilling efficiency. (b) Real time measurement of underground engineering parameters and monitoring and evaluation of wellbore cleanliness can reduce drilling risks, while achieving quantitative evaluation of drilling fluid gas content. (c) Assisted by real-time optimization technology of mechanical drilling speed based on underground surface engineering parameters, the acceleration effect has been significantly improved.

Ferroptosis is a type of controlled cell death caused by lipid peroxidation, which results in the rupture of the cell membrane. ferroptosis has been repeatedly demonstrated over the past ten years to be a significant factor in a number of diseases. The liver is a significant iron storage organ, thus ferroptosis will have great potential in the treatment of liver diseases. Ferroptosis is particularly prevalent in HCC. In the opening section of this article, we give a general summary of the pertinent molecular mechanisms, signaling pathways, and associated characteristics of ferroptosis. The primary regulating mechanisms during ferroptosis are then briefly discussed, and we conclude by summarizing the development of a number of novel therapeutic strategies used to treat HCC in recent years. Ferroptosis is a crucial strategy for the treatment of HCC and offers new perspectives on the treatment of liver cancer.

Background: Ischemic stroke (IS) is a leading cause of long-term disability and even mortality, threatening people's lives. Yinao Fujian (YNFJ) formula is a Traditional Chinese Medicine formula that has been widely used to treat patients with IS. However, the molecular mechanism of YNFJ for the treatment of IS is still elusive. Our study aimed to explore the potential protective effect and the underlying mechanisms of YNFJ on IS using a network pharmacology approach coupled with experimental validation. Materials and methods: Effective compounds of YNFJ were collected from BATMAN-TCM and TCMSP databases, while IS targets were obtained from GeneCards, OMIM, TTD and DrugBank databases. The protein-protein interaction (PPI) network was constructed to further screen the hub targets of YNFJ in IS treatment. GO and KEGG enrichment analyses were used to identify the critical biological processes and signaling pathways of YNFJ for IS. Moreover, Nissl staining, HE, TTC staining and Tunel staining were used in the MCAO model to prove the neuroprotective effect of YNFJ. Oxidative damage, inflammatory factor release and related pathways were tested in MCAO rat model and hypoxia-induced BV2 cell model, respectively. Results: We found that YNFJ treatment significantly alleviated MCAO-induced nerve damage and apoptosis. Then, network pharmacology screening combined with literature research revealed IL6, TNF, PTGS2, NFKBIA and NFE2L2 as the critical targets in a PPI network. Moreover, the top 20 signaling pathways and biological processes associated with the protective effects of YNFJ on IS were enriched through GO and KEGG analyses. Further analysis indicated that NF-κB and Nrf2/HO-1 signaling pathways might be highly involved in the protective effects of YNFJ on IS. Finally, in vitro and in vivo experiments confirmed that YNFJ inhibited the release of inflammatory factors (IL-6 and TNF-α) and MDA content, and increased the activity of SOD. In terms of the mechanism, YNFJ inhibited the release of inflammatory factors by suppressing the NF-κB pathway and decreased the expression of iNOS and COX-2 to protect microglia from inflammation damage. In addition, YNFJ initiated the dissociation of Keap-1 and Nrf2, and activated the downstream protein HO-1, NQO1, thus decreasing oxidative stress. Conclusion: Taken together, the findings in our research showed that the protective effects of YNFJ on IS were mainly achieved by regulating the NF-κB and Nrf2/HO-1 signaling pathways to inhibit oxidative stress damage and inflammatory damage of microglia.

The risk of developing chronic illnesses and disabilities is increasing with age. To predict and prevent aging, biomarkers relevant to the aging process must be identified. This paper reviews the known molecular, cellular, and physiological biomarkers of aging. Moreover, we discuss the currently available technologies for identifying these biomarkers, and their applications and potential in aging research. We hope that this review will stimulate further research and innovation in this emerging and fast-growing field. [ABSTRACT FROM AUTHOR]

To address the nonlinearity and dynamics of industrial processes, an incremental isometric mapping (IISOMAP) in combination with double local density (DLD) is proposed as a fault detection method (IISOMAP-DLD) based on stream shape learning. First, IISOMAP is used to map the raw data into a low-dimensional manifold feature subspace and a residual subspace. Then, the double local density method is introduced in the two subspaces respectively to construct statistics to monitor the process. Finally, the IISOMAP-DLD method is applied to the Tennessee-Eastman (TE) process, and the experimental results show that IISOMAP-DLD has a higher fault detection rate than the other methods. IISOMAP preserves the intrinsic characteristics of the data and solves the nonlinear problems of the process, while the double local density method can eliminate the dynamic of the process.