A comprehensive floc model for simulating simultaneous nitrification, denitrification, and phosphorus removal.

A comprehensive floc model for simultaneous nitrification, denitrification, and phosphorus removal (SNDPR) was designed, incorporating polyphosphate-accumulating organisms (PAOs), glycogen-accumulating organisms (GAOs), intrinsic half-saturation coefficients, and explicit external mass transfer terms. The calibrated model was able to effectively describe experimental data over a range of operating conditions. The estimated intrinsic half-saturation coefficients of oxygen values for ammonia-oxidizing bacteria, nitrite-oxidizing bacteria, ordinary heterotrophic organisms (OHOs), PAOs, and GAOs were set at 0.08, 0.18, 0.03, 0.07, and 0.1 mg/L, respectively. Simulation suggested that low dissolved oxygen (DO) environments favor K-strategist nitrifying bacteria and PAOs. In SNDPR, virtually all influent and fermentation-generated volatile fatty acids were assimilated as polyhydroxyalkanoates by PAOs in the anaerobic phase. In the aerobic phase, PAOs absorbed 997 % and 171 % of the benchmark influent total phosphorus mass loading through aerobic growth and denitrification via nitrite. These high percentages were because they were calculated relative to the influent total phosphorus, rather than total phosphorus at the end of the anaerobic period. When considering simultaneous nitrification and denitrification, about 23.1 % of influent total Kjeldahl nitrogen was eliminated through denitrification by PAOs and OHOs via nitrite, which reduced the need for both oxygen and carbon in nitrogen removal. Moreover, the microbial and DO profiles within the floc indicated a distinct stratification, with decreasing DO and OHOs, and increasing PAOs towards the inner layer. This study demonstrates a successful floc model that can be used to investigate and design SNDPR for scientific and practical purposes.

Effects of social distancing provoked by COVID-19 pandemic in the functional capacity and cognitive function in nonagenarians and centenarians.

INTRODUCTION: Due to the rapid advance of coronavírus SARS-CoV-2 (COVID-19) pandemic in 2020, social distancing was the main way to reduce the transmission of the virus. Although this measure was efficient and necessary, the social distancing had severe consequences for physical function, mainly in older individuals. Thus, the aim of this study was to investigate the effects of social distancing in the functional and cognitive capacity of community-dwelling oldest-old adults. METHODS: The present study is part of a larger prospective cohort study. Fifteen participants aged 90 years old or older were assessed in the 8-foot-timed-up-and-go test (8-footTUG), sit-to-stand-up test (STS), handgrip strength test (HGS), Mini Mental State Examination (MMSE), Katz Index and Lawton Scale before and after one year of social distancing. RESULTS: A significant worsening in the 8-footTUG and MMSE score was observed, while there were no significant changes in the other variables. When analyzing the decreases in relation to previous functional capacity, it was observed that individuals categorized as dependent by STS cut-off points had the worst decreases in functional capacity. CONCLUSION: The social distancing provoked by COVID-19 pandemic negatively affected the 8-footTUG and cognition. Moreover, individuals dependents showed greater decline in their functional capacity.

Empowering Movement: Enhancing Young Adults' Physical Activity through Self-Determination Theory and Acceptance and Commitment Therapy-Based Intervention.

OBJECTIVE: This study aims to investigate the effectiveness of a combined Self-Determination Theory (SDT) and Acceptance and Commitment Therapy (ACT) intervention, the "Running Minds" program, in promoting physical activity (PA) among young adults. METHODS: The intervention, consisting of eight sessions, targeted motivational and psychological barriers to PA. It intertwined SDT's core components (autonomy, competence, relatedness) with ACT's emphasis on mindfulness and value-driven actions. This study used a qualitative approach, collecting data through semi-structured interviews with twelve participants aged 20-35, conducted post-intervention. RESULTS: Our reflexive thematic analysis of the interviews revealed five key themes: alignment with personal values, rewarding experience of the sessions, fulfillment of social connectedness, enhancement of both intrinsic and extrinsic motivation, and observable behavioral changes. These findings highlight the importance of aligning exercise with personal values and the role of supportive social environments in sustaining PA. CONCLUSIONS: The integration of SDT and ACT in the "Running Minds" program appears to be a viable approach for enhancing motivation and adherence to PA among young adults. This study offers valuable insights for future PA interventions, underscoring the need for strategies that consider psychological and social dimensions. Limitations and Future Research: Despite the promising results, limitations include potential recall bias and the short duration of the study. Further research, especially focusing on more diverse groups and employing longitudinal designs, is recommended to broaden and substantiate these findings.

Boswellic acid formulations are not suitable for treatment of pediatric high-grade glioma due to tumor promoting potential.

Background and aim: Pediatric high-grade gliomas (pedHGG) comprise a very poor prognosis. Thus, parents of affected children are increasingly resorting to complementary and alternative medicine (CAM), among those Boswellia extracts. However, nothing is known about the therapeutic effectiveness of their active substances, Boswellic acids (BA) in pedHGG. Thus, we aimed to investigate if the three main Boswellic acids (BA) present in Boswellia plants, alpha-boswellic acid (α-BA), beta-boswellic acid (ß-BA) and 3-acetyl-11-keto-beta-boswellic acid (AKBA) hold any promising potential for treatment of affected pedHGG patients. Experimental procedure: Histone 3 (H3)-wildtype and H3.3K27M-mutant pedHGG cell lines were treated with BA, either alone or in combination with radio-chemotherapy with temozolomide. Cell viability, stemness properties, apoptosis, in ovo tumor growth and the transcriptome was investigated upon BA treatment. Results and conclusion: Interestingly, α-BA and ß-BA treatment promoted certain tumor properties in both pedHGG cells. AKBA treatment reduced cell viability and colony growth accompanied by induction of slight anti-inflammatory effects especially in H3.3K27M-mutant pedHGG cells. However, no effects on apoptosis and in ovo tumor growth were found. In conclusion, besides positive anti-tumor effects of AKBA, tumor promoting effects were observed upon treatment with α-BA and ß-BA. Thus, only pure AKBA formulations may be used to exploit any potential positive effects in pedHGG patients. In conclusion, the use of commercially available supplements with a mixture of different BA cannot be recommended due to detrimental effects of certain BA whereas pure AKBA formulations might hold some potential as therapeutic supplement for treatment of pedHGG patients.

Digging into the intrinsic capacity concept: Can it be applied to Alzheimer's disease?

Historically, aging research has largely centered on disease pathology rather than promoting healthy aging. The World Health Organization's (WHO) policy framework (2015-2030) underscores the significance of fostering the contributions of older individuals to their families, communities, and economies. The WHO has introduced the concept of intrinsic capacity (IC) as a key metric for healthy aging, encompassing five primary domains: locomotion, vitality, sensory, cognitive, and psychological. Past AD research, constrained by methodological limitations, has focused on single outcome measures, sidelining the complexity of the disease. Our current scientific milieu, however, is primed to adopt the IC concept. This is due to three critical considerations: (I) the decline in IC is linked to neurocognitive disorders, including AD, (II) cognition, a key component of IC, is deeply affected in AD, and (III) the cognitive decline associated with AD involves multiple factors and pathophysiological pathways. Our study explores the application of the IC concept to AD patients, offering a comprehensive model that could revolutionize the disease's diagnosis and prognosis. There is a dearth of information on the biological characteristics of IC, which are a result of complex interactions within biological systems. Employing a systems biology approach, integrating omics technologies, could aid in unraveling these interactions and understanding IC from a holistic viewpoint. This comprehensive analysis of IC could be leveraged in clinical settings, equipping healthcare providers to assess AD patients' health status more effectively and devise personalized therapeutic interventions in accordance with the precision medicine paradigm. We aimed to determine whether the IC concept could be extended from older individuals to patients with AD, thereby presenting a model that could significantly enhance the diagnosis and prognosis of this disease.

Effect of Neuromuscular Electrostimulation With Blood Flow Restriction on Acute Muscle Swelling of the Abductor Hallucis.

CONTEXT: Plantar intrinsic foot muscle strength training is difficult to master to a degree sufficient to elicit muscle hypertrophy in most individuals. It is possible that combining neuromuscular electrostimulation (NMES) and blood flow restriction (BFR) can elicit plantar intrinsic foot muscle hypertrophy regardless of the individual's technique. This study aimed to determine the effects of NMES training with BFR on acute muscle swelling in the abductor hallucis. DESIGN: Randomized, controlled, single-blind trial design. METHODS: Forty-eight participants were randomly allocated to the NMES + BFR, NMES, or Sham NMES + BFR groups. All participants received abductor hallucis NMES for 15 minutes. Participants in the NMES + BFR and Sham NMES + BFR groups received NMES with BFR. The intensity of NMES was the sensory threshold in the Sham NMES + BFR group. The cross-sectional area of the abductor hallucis was measured pretraining and posttraining using ultrasonography by a single investigator blinded to the participants' allocations. RESULTS: After 15 minutes of training, the cross-sectional area of the abductor hallucis was significantly increased in the NMES + BFR (P < .001) and the Sham NMES + BFR (P = .004) groups. Moreover, the rate of increase was significantly higher in the NMES + BFR group than in the NMES or the Sham NMES + BFR groups (P < .001 and P = .001, respectively). CONCLUSIONS: Since it is possible that the amount of muscle swelling immediately after training correlates with muscle hypertrophy when training is continued, the results of this study suggest that NMES training with BFR is a training method that can be expected to produce plantar intrinsic foot muscle hypertrophy. Further studies are needed to confirm the long-term effects of NMES training with BFR.

Self-Healing Iron Oxide Polyelectrolyte Nanocomposites: Influence of Particle Agglomeration and Water on Mechanical Properties.

Self-healing nanocomposites can be generated by organic functionalization of inorganic nanoparticles and complementary functionalization of the polymer matrix, allowing reversible interactions between the two components. Here, we report on self-healing nanocomposites based on ionic interactions between anionic copolymers consisting of di(ethylene glycol) methyl ether methacrylate, sodium 4-(methacryloyloxy)butan-1-sulfonate, and cationically functionalized iron oxide nanoparticles. The materials exhibited hygroscopic behavior. At water contents < 6%, the shear modulus was reduced by up to 90%. The nanoparticle concentration was identified as a second factor strongly influencing the mechanical properties of the materials. Backscattered scanning electron microscopy and small-angle X-ray scattering measurements showed the formation of agglomerates in the size range of 100 nm to a few µm in diameter, independent of concentration, resulting in the disordering of the semi-crystalline ionic polymer blocks. These effects resulted in an increase in the shear modulus of the composite from 3.7 MPa to 5.6 MPa, 6.3 Mpa, and 7.5 MPa for 2, 10, and 20 wt% particles, respectively. Temperature-induced self-healing was possible for all composites investigated. However, only 36% of the maximum stress could be recovered in systems with a low nanoparticle content, whereas the original properties were largely restored (>85%) at higher particle contents.

Elucidation of the anti-colon cancer mechanism of Phellinus baumii polyphenol by an integrative approach of network pharmacology and experimental verification.

Colon cancer, a prevalent malignant tumor affecting the digestive system, presents a substantial risk to human health due to its high occurrence and mortality rates. Phellinus baumii polyphenol (PBP), a natural product derived from traditional Chinese medicine, has gained widespread popularity due to its low toxicity and minimal side effects, compared to radiation and chemotherapy. This study used an integrated approach of network pharmacology and experimental verification to elucidate the anti-colon cancer effects of PBP and its potential mechanisms. In network pharmacology, the identification of relevant targets involved a comprehensive search across multiple databases using keywords such as "active components of PBP" and "colon cancer". Venn diagram analysis was subsequently performed to ascertain the shared targets. To identify the key active components and core targets, we constructed a network of "Disease-Drug-Pathways-Targets" and a protein-protein interaction (PPI) network among the targets using Cytoscape 3.9.1. Furthermore, molecular docking was carried out to predict the binding affinity and conformation between the main active compounds (davallialactone and citrinin) of PBP and the core targets (TP53, STAT3, CASP3, CTNNB1, PARP1, MYC). To validate our findings, in vitro experiments were conducted. We verified that PBP exerted an anti-colon cancer effect on human colon cancer HCT116 cells by significantly inhibiting cell proliferation, promoting apoptosis and arresting the cell cycle in S phase by using Cell Counting Kit-8 (CCK-8) and flow cytometry. Finally, we determined the key regulatory proteins related to apoptosis and the cell cycle by western blot analysis, and proposed the potential mechanism by which PBP exerts an anti-colon cancer effect by inducing the caspase-dependent mitochondrial-mediated intrinsic apoptotic pathway and arresting the cell cycle in S phase in HCT116 cells. These results suggest that PBP possesses substantial potential for the treatment of colon cancer and may serve as a viable alternative therapeutic strategy in colon cancer treatment.

[Relationship between acupoint sensitization and changes in dorsal root ganglion neuron excitability in myocardial ischemia mice].

OBJECTIVE: To investigate the relationship between the sensitization state of acupoints on the surface of the myocardial ischemia (MI) model mice and the changes in the electrophysiological properties of the dorsal root ganglion (DRG) neurons in the corresponding spinal cord segment, and its underlying mechanism. METHODS: Sixty-eight male C57BL/6J mice were randomly divided into control and model groups (34 mice in each group). The model group received an intraperitoneal injection of 160 mg/kg isoproterenol (ISO) to establish the MI model, and the control group received an injection of the same dose of normal saline as the model group. After modeling for about 6 days, MI proportion was measured by HE staining to verify the pathological changes in the heart tissue. Evans blue (EB) dye was injected into the tail vein of mice to reflect the size, location, distribution, and number of exudates on the body surface. Then, whole-cell membrane currents, intrinsic excitability and membrane properties of different types of DRG neurons were evaluated by electrophysiological experiment in vitro. RESULTS: Compared with the control group, the heart size was larger, with pathological outcomes showing enlarged myocardial hypertrophy, destroyed structure of cardiomyocytes, with mononuclear cell infiltration among the cardiomyocytes in the model group. Compared with the control group, the number of EB exudation points was significantly increased (P<0.01), which were mainly concentrated in the epidermis near the T1-T5 segment of the spinal cord, "Feishu" (BL13), "Jueyinshu" (BL14) and "Xinshu" (BL15) in the model group. Compared with the control group, the rheobase and action potential amplitude (APA) of DRG medium-sized neurons were obviously decreased (P<0.01, P<0.05), while the whole-cell membrane currents, the spike numbers, the average instantaneous frequency, and the average discharge frequency were markedly increased (P<0.01). There were no significant alterations in the membrane properties and intrinsic excitability induced by depolarized currents of small-sized neurons between groups. Compared with the control group, the whole-cell membrane currents, spike numbers, and the average instantaneous frequency were significantly increased in the model group(P<0.05, P<0.01) while rheobase was significantly decreased (P<0.05) in DRG medium-sized neurons labeled with biotin and CGRP. CONCLUSION: After the mice were modeled by ISO, the DRG medium-size neurons in the T1-T5 segment of the spinal cord may mediate the sensitization of acupoints on the body surface through their different neuronal membrane properties and intrinsic excitabilities.

Physiotherapeutic Interventions for Individuals Suffering From Plantar Fasciitis: A Systematic Review.

The foot and the lower leg comprise the ankle joint complex. The foot is crucial for the maintenance of posture. Frequently, overuse or repeated microtrauma to the fascia causes plantar fasciitis. This review aims to suggest the efficacy of various plantar fasciitis (PF) interventions based on modifications in clinical results. This review included studies from 2019 to March 2023 identified through a systematic literature search. The measures used to predict improvement in pain, discomfort, and foot function symptoms included the Visual Analog scale, Numerical Pain Rating Scale, Pressure Point Threshold by algometer, Weight-Bearing Lunge Test by inch tape, and range of motion. The review included 20 studies that fulfilled the inclusion criteria. Therapeutic interventions included insoles, foot orthosis, foam roller stretching, manual stretching, muscle strengthening, intrinsic muscle activities, extracorporeal shock wave lithotripsy, dry needling, laser, ultrasound, and others, which resulted in pain reduction, improved foot function, and ease of everyday routine. All therapeutic strategies used impacts resulting from minimal to maximal recovery. Various advanced approaches are more effective than conventional physical therapy. In conclusion, conservative therapeutic strategies with manual techniques, orthoses, and alternative intervention strategies can be combined to effectively relieve pain and improve function and overall results. Further high-quality studies are essential to learn more about the ideal dose, treatment approaches, and long-term impacts of these therapies.

Antimicrobial Resistance: Is There a 'Light' at the End of the Tunnel?

In recent years, with the increases in microorganisms that express a multitude of antimicrobial resistance (AMR) mechanisms, the threat of antimicrobial resistance in the global population has reached critical levels. The introduction of the COVID-19 pandemic has further contributed to the influx of infections caused by multidrug-resistant organisms (MDROs), which has placed significant pressure on healthcare systems. For over a century, the potential for light-based approaches targeted at combatting both cancer and infectious diseases has been proposed. They offer effective killing of microbial pathogens, regardless of AMR status, and have not typically been associated with high propensities of resistance development. To that end, the goal of this review is to describe the different mechanisms that drive AMR, including intrinsic, phenotypic, and acquired resistance mechanisms. Additionally, the different light-based approaches, including antimicrobial photodynamic therapy (aPDT), antimicrobial blue light (aBL), and ultraviolet (UV) light, will be discussed as potential alternatives or adjunct therapies with conventional antimicrobials. Lastly, we will evaluate the feasibility and requirements associated with integration of light-based approaches into the clinical pipeline.

Carbon Dots Derived from Traditional Chinese Medicines with Bioactivities: A Rising Star in Clinical Treatment.

In the field of carbon nanomaterials, carbon dots (CDs) have become a preferable choice in biomedical applications. Based on the concept of green chemistry, CDs derived from traditional Chinese medicines (TCMs) have attracted extensive attention, including TCM charcoal drugs, TCM extracts, and TCM small molecules. The design and preparation of CDs from TCMs (TCMs-CDs) can improve the inherent characteristics of TCMs, such as solubility, particle size distribution, and so on. Compared with other precursor materials, TCMs-CDs have outstanding intrinsic bioactivities and potential pharmacological effects. However, the research of TCMs-CDs in biomedicine is not comprehensive, and their mechanisms have not been understood deeply either. In this review, we will provide concise insights into the recent development of TCMs-CDs, with a major focus on their preparation, formation, precursors, and bioactivities. Then we will discuss the perfect transformation from TCMs to TCMs-CDs. Finally, we discuss the opportunities and challenges for the application of TCMs-CDs in clinical treatment.

Diagnostic performance analysis of the Integrated Care for Older People (ICOPE) screening tool for identifying decline in intrinsic capacity.

BACKGROUND: Intrinsic capacity (IC) is a comprehensive indicator of an individual's positive attributes. The World Health Organization (WHO) recommends a two-step approach to assess IC decline among older people. The first step involves the used of the integrated care for older people (ICOPE) screening tool to identify potential issues, and the second step involves using detailed assessments for confirmation. This study aimed to assess the diagnostic performance of the ICOPE screening tool as a simple preliminary screening to identify IC decline among community-dwelling older people, which has been rarely reported in China. METHODS: This cross-sectional study included 228 community-dwelling older individuals aged ≥ 75 (mean age, 84.0 ± 4.4 years; 131 [57.5%] females) who completed the IC evaluation according to the WHO IC assessment pathway. The diagnostic performance of the ICOPE screening tool was calculated using a 2 × 2 table and a receiver operating characteristic curve. RESULTS: The proportion of possible IC decline identified by the ICOPE screening tool was 79.4%, whereas the actual IC decline assessed by the detailed assessment was 73.2%, mainly in locomotion. The ICOPE screening tool showed sensitivity and specificity of 94.6% and 62.3%, respectively, with an overall diagnostic accuracy of 86.0%. The diagnostic effectiveness of the ICOPE screening tool was 0.91 (95% confidence interval: 0.87-0.95, p = 0.020). Except for the sensory dimension, the sensitivity of the ICOPE screening tool for diagnosing impairments in each dimension of the IC was the highest in the cognition domain (100%) and the lowest in the vitality domain (51.3%), whereas the specificity was the highest in vitality (94.7%) and the lowest in cognition (55.6%). CONCLUSIONS: The ICOPE screening tool exhibits high sensitivity and can be used as an IC screening tool in community-dwelling older people. However, further improvements are needed in the vitality dimension of the ICOPE screening tool to enhance its sensitivity in identifying individuals at risk of malnutrition.

A meta-analysis of the association between mindfulness and motivation.

Introduction: Mindfulness reflects attention to the present moment in a non-judgmental way and has been linked to individual autonomy and motivation, but conclusions are inconsistent. The purpose of this review was to summarize previous studies to explore the relationship between mindfulness and motivation and its intervention effects. Methods: Literature searches were conducted in five electronic databases. Both correlational studies assessing the association between motivation and mindfulness and experimental studies to verify the effect of intervention were included. Results: Six papers with seven intervention studies and twenty-three papers with twenty-seven correlational studies met the inclusion criteria. Meta-analysis showed that mindfulness was positively correlated with intrinsic motivation (r = 0.28, p < 0.0001) and total motivation (r = 0.37, p < 0.0001) but had no significant correlation with extrinsic motivation (r = 0.01, p = 0.93) or amotivation (r = -0.17, p = 0.14). Effect-size estimates suggested that mindfulness intervention was beneficial to motivation promotion, but the effect was at a low level (g = 0.12). Conclusion: We found consistent support for mindfulness practice relating to motivation promotion, especially on intrinsic motivation development. However, there was still a portion of heterogeneity that could not be explained and needed to be identified in future studies.

Recent Advances in the Biological Responses to Nano-black Phosphorus: Understanding the Importance of Intrinsic Properties and Cell Types.

The production scalability and increasing demand for nano-black phosphorus materials (nano-BPs) inevitably lead to their environmental leakage, thereby raising the risk of human exposure through inhalation, ingestion, dermal, and even intravenous pathways. Consequently, a systematic evaluation of their potential impacts on human health is necessary. This Review outlines recent progress in the understanding of various biological responses to nano-BPs. Attention is particularly given to the inconsistent toxicological findings caused by a wide variation of nano-BPs' physicochemical properties, toxicological testing methods, and cell types examined in each study. Additionally, cellular uptake and intracellular trafficking, cell death modes, immunological effects, and other biologically relevant processes are discussed in detail, providing evidence for the potential health implications of nano-BPs. Finally, we address the remaining challenges related to the health risk evaluation of nano-BPs and propose a broader range of applications for these promising nanomaterials.

How Green Mindfulness and Green Shared Vision Interact to Influence Green Creative Behavior.

Aim: The study is based on the self-determination theory and aims to investigate the mediating role of green intrinsic motivation and the moderating role of green shared vision in the association between frontline managers' green mindfulness and green creative behavior to leverage their capacity to think creatively and act sustainably. Methods: The study employs a time-lagged, multi-source research methodology to collect data from frontline managers of service businesses in the tourism and hospitality industry. Data are analyzed using SmartPLS Structural Equation Model to evaluate the structural and measurement models. The authors evaluated the measurement model by employing the criteria of internal consistency: reliability and Cronbach's alpha, validity: convergent and discriminant validity; and the structural model using the path coefficient, coefficient of determination, predictive relevance, and goodness-of-fit metrics. Results: Our findings indicate that green mindfulness significantly improves frontline managers' green creative behavior. Additionally, green intrinsic motivation mediates the connection between green mindfulness and green creative behavior. In addition, the direct effect of green mindfulness on green intrinsic motivation as well as the indirect effect of green mindfulness on green creative behavior through green intrinsic motivation, are both significantly moderated by green shared vision. Discussion: To the best of the authors' knowledge, this is one of the few efforts that outstretch the boundary conditions of green mindfulness and green creative behavior through the mediating role of green intrinsic motivation and the moderating role of green shared vision.

Whole-brain network transitions within the framework of ignition and transfer entropy following VIM-MRgFUS in essential tremor patients.

Magnetic resonance-guided focused ultrasound (MRgFUS) lesioning of the ventralis intermedius nucleus (VIM) has shown promise in treating drug-refractory essential tremor (ET). It remains unknown whether focal VIM lesions by MRgFUS have broader restorative effects on information flow within the whole-brain network of ET patients. We applied an information-theoretical approach based on intrinsic ignition and the concept of transfer entropy (TE) to assess the spatiotemporal dynamics after VIM-MRgFUS. Eighteen ET patients (mean age 71.44 years) underwent repeated 3T resting-state functional magnetic resonance imaging combined with Clinical Rating Scale for Tremor (CRST) assessments one day before (T0) and one month (T1) and six months (T2) post-MRgFUS, respectively. We observed increased whole brain ignition-driven mean integration (IDMI) at T1 (p < 0.05), along with trend increases at T2. Further, constraining to motor network nodes, we identified significant increases in information-broadcasting (bilateral supplementary motor area (SMA) and left cerebellar lobule III) and information-receiving (right precentral gyrus) at T1. Remarkably, increased information-broadcasting in bilateral SMA was correlated with relative improvement of the CRST in the treated hand. In addition, causal TE-based effective connectivity (EC) at T1 showed an increase from right SMA to left cerebellar lobule crus II and from left cerebellar lobule III to right thalamus. In conclusion, results suggest a change in information transmission capacity in ET after MRgFUS and a shift towards a more integrated functional state with increased levels of global and directional information flow.

The development of intrinsic timescales: A comparison between the neonate and adult brain.

In human adults and other mammals, different brain regions have distinct intrinsic timescales over which they integrate information, from shorter in unimodal sensory-motor regions to longer in transmodal higher-order regions. These have been related to cognitive performance and clinical symptoms, but it remains unclear how they develop. We asked if there are regional differences in timescales at birth that could shape learning by acting as an inductive bias, or if they develop later as the temporal statistics of the environment are learned. We used resting-state fMRI to characterise timescales in human neonates and adults. They were highly consistent across two independent neonatal groups, but in both sensory-motor and higher order areas, timescales were longer in infants compared to adults, as might be expected from their less developed myelination, and recent evidence of longer neural segments in infants watching naturalistic stimuli. In adults, we replicated the finding that transmodal areas have longer timescales than sensory-motor areas, but in infants the opposite pattern was found, driven by long infant timescales in the somotomotor network. Across regions within single brain networks, both positive (limbic) and negative (visual) correlations were found between neonates and adults. In conclusion, neonatal timescales were found to be highly structured, but distinct from adults, suggesting they act as an inductive bias that favours learning on longer timescales, particularly in unimodal regions and then develop with experience or maturation. This "take it slow" initial approach might help human infants to create more regularised, holistic representations of the input less bound to fleeting details, which would favour the development of abstract and contextual representations.

Co-Delivery of Ylang Ylang Oil of Cananga odorata and Oxaliplatin Using Intelligent pH-Sensitive Lipid-Based Nanovesicles for the Effective Treatment of Triple-Negative Breast Cancer.

Smart pH-responsive niosomes loaded with either Oxaliplatin (Ox), Ylang ylang essential oil (Y-oil), or co-loaded with both compounds (Ox-Y) (Ox@NSs, Y@NSs, and Ox-Y@NSs, respectively) were formulated utilizing the thin film method. The developed nanocontainers had a spherical morphology with mean particle sizes lower than 170 nm and showed negative surface charges, high entrapment efficiencies, and a pH-dependent release over 24 h. The prepared pH-responsive niosomes' cytotoxicity was tested against the invasive triple-negative breast cancer (MDA-MB-231) cells, compared to free OX and Y-oil. All niosomal formulations loaded with Ox and/or Y-oil significantly improved cytotoxic activity relative to their free counterparts. The Ox-Y@NSs demonstrated the lowest IC50 (0.0002 µg/mL) when compared to Ox@NSs (0.006 µg/mL) and Y@NSs (18.39 µg/mL) or unloaded Ox (0.05 µg/mL) and Y-oil (29.01 µg/mL). In addition, the percentages of the MDA-MB-231 cell population in the late apoptotic and necrotic quartiles were profoundly higher in cells treated with the smart Ox-Y@NSs (8.38% and 5.06%) than those exposed to free Ox (7.33% and 1.93%) or Y-oil (2.3% and 2.13%) treatments. Gene expression analysis and protein assays were performed to provide extra elucidation regarding the molecular mechanism by which the prepared pH-sensitive niosomes induce apoptosis. Ox-Y@NSs significantly induced the gene expression of the apoptotic markers Tp53, Bax, and Caspase-7, while downregulating the antiapoptotic Bcl2. As such, Ox-Y@NSs are shown to activate the intrinsic pathway of apoptosis. Moreover, the protein assay ascertained the apoptotic effects of Ox-Y@NSs, generating a 4-fold increase in the relative protein quantity of the late apoptotic marker Caspase-7. Our findings suggest that combining natural essential oil with synthetic platinum-based drugs in pH-responsive nanovesicles is a promising approach to breast cancer therapy.

[Research on mechanisms of acupoint sensitization in gastric ulcer mice from perspective of dorsal root ganglion neuronal excitability].

OBJECTIVE: To investigate the relationship between acupoint sensitization on the body surface and neuronal intrinsic excitability of the medium- and small-size dorsal root ganglion (DRG) neurons from the perspective of ion channel kinetics in mice with gastric ulcer. METHODS: Male C57BL/6J mice were randomly divided into control (n=32) and model groups (n=34). The gastric ulcer model was established by injection of 60% glacial acetic acid (0.2 mL/100 g) into the gastric wall muscle layer and submucosa near the pylorus in the minor curvature of the stomach. In contrast, the same dose of normal saline was injected in the same way in the control group. Six days after modeling, Evans blue (EB) solution was injected into the mouse's tail vein for observing the number and distribution of the exudation blue spots on the body surface. Histopathological changes of the gastric tissue were observed by H.E. staining. Then, whole-cell membrane currents and intrinsic excitability of medium- and small-size neurons in the spinal T9-T11 DRGs were measured by in vitro electrophysiology combining with biocytin-ABC method. RESULTS: In the control group, EB exudation blue spots were not obvious, while in the model group, the blue spots on the body surface were densely distributed in the area of spinal T9-T11 segments, the epigastric region, and the skin around "Zhongwan" (CV12) and "Huaroumen" (ST24) regions, and near the surgical incision region. Compared with the control group, the model group had a high level of eosinophilic infiltrates in the submucosa of gastric tissues, severe gastric fossa structure damage, gastric fundus gland dilation and other pathological manifestations. The number of exudation blue spots was proportional to the degree of inflammatory reaction in the stomach. In comparison with the control group, the spike discharges of type II of medium-size DRG neurons in T9-T11 segments were decreased, and the current of whole-cell membrane was increased, basic intensity was decreased (P<0.05), discharge frequency and discharge number were increased (P<0.01,P<0.000 1); while the discharges of type I small-size DRG neurons were decreased, those of type II neurons increased, the whole-cell membrane current was decreased, and discharge frequency and discharge number were decreased (P<0.01, P<0.000 1). CONCLUSION: Both the medium- and small-size DRG neurons from the spinal T9-T11 segments involve in gastric ulcer-induced acupoint sensitization via their different spike discharge activities. And intrinsic excitability of these DRG neurons can not only dynamically encode the plasticity of acupoint sensitization, but also can help us understand the neural mechanism of acupoint sensitization induced by visceral injury.