Knowledge and attitudes in the prevention of vertical transmission of HIV in referral hospitals.

Background: Prevention of HIV vertical transmission programmes (VTPs) in South Africa has decreased paediatric HIV. These programmes require integration in referral hospitals. Objectives: To determine knowledge of and attitudes to the national VTP guidelines in staff from Obstetric and Paediatric disciplines at two referral hospitals. Method: Using a cross-sectional design, a questionnaire to assess knowledge of the guidelines and attitudes (awareness, ease-of-use and non-silo practice, measuring integrated practice) was developed and validated locally. Using standard statistical analyses, data from these questionnaires were used to draw comparisons and determine factors associated with knowledge and attitudes. Results: Of the 249 participants, 138 (55.4%) were in obstetrics, 125 (50.2%) were nurses, and 168 (67.5%) self-identified as junior staff. Knowledge scores were good, median score (Q1-Q3) was 91.7% (79.1-95.8), and higher in those who had discipline-specific training (P = 0.003). Junior staff (P = 0.002) had higher knowledge levels than senior staff. Most (80%) found the guidelines easy to use and had good awareness, which correlated with knowledge and training. Gaps included understanding of antenatal testing of HIV-negative women and timelines for neonatal HIV testing. Staff scored poorly on integrated practice; the median score (Q1-Q3) was 50% (33.3-58.3), which was inversely correlated with knowledge (r= -0.146, n = 249, P = 0.022). Conclusion: Staff in referral hospitals appear to be practising within silos when implementing VTPs, and this may result in failures to ensure integrated practice. Regularised interdisciplinary and interprofessional training may be important to ensure the integrated implementation of VTPs in referral hospitals.

Infectious Diarrhea Risks as a Public Health Emergency in Floods; a Systematic Review and Meta-Analysis.

Introduction: Infectious diarrhea, a significant global health challenge, is exacerbated by flooding, a consequence of climate change and environmental disruption. This comprehensive study aims to quantify the association between flooding events and the incidence of infectious diarrhea, considering diverse demographic, environmental, and pathogen-specific factors. Methods: In this systematic review and meta-analysis, adhering to PROSPERO protocol (CRD42024498899), we evaluated observational studies from January 2000 to December 2023. The analysis incorporated global data from PubMed, Scopus, Embase, Web of Science, and ProQuest, focusing on the relative risk (RR) of diarrhea post-flooding. The study encompassed diverse variables like age, sex, pathogen type, environmental context, and statistical modeling approaches. Results: The meta-analysis, involving 42 high-quality studies, revealed a substantial increase (RR = 1.40, 95% CI [1.29-1.52]) in the incidence of diarrhea following floods. Notably, bacterial and parasitic diarrheas demonstrated higher RRs (1.82 and 1.35, respectively) compared to viral etiologies (RR = 1.15). A significant sex disparity was observed, with women exhibiting a higher susceptibility (RR = 1.55) than men (RR = 1.35). Adults (over 15 years) faced a greater risk than younger individuals, highlighting age-dependent vulnerability. Conclusion: This extensive analysis confirms a significant correlation between flood events and increased infectious diarrhea risk, varying across pathogens and demographic groups. The findings highlight an urgent need for tailored public health interventions in flood-prone areas, focusing on enhanced sanitation, disease surveillance, and targeted education to mitigate this elevated risk. Our study underscores the critical importance of integrating flood-related health risks into global public health planning and climate change adaptation strategies.

Mechanical property estimation of sarcoma-relevant extracellular vesicles using transmission electron microscopy.

Analysis of single extracellular vesicles (EVs) has the potential to yield valuable label-free information on their morphological structure, biomarkers and therapeutic targets, though such analysis is hindered by the lack of reliable and quantitative measurements of the mechanical properties of these compliant nanoscale particles. The technical challenge in mechanical property measurements arises from the existing tools and methods that offer limited throughput, and the reported elastic moduli range over several orders of magnitude. Here, we report on a flow-based method complemented by transmission electron microscopy (TEM) imaging to provide a high throughput, whole EV deformation analysis for estimating the mechanical properties of liposarcoma-derived EVs as a function of their size. Our study includes extracting morphological data of EVs from a large dataset of 432 TEM images, with images containing single to multiple EVs, and implementing the thin-shell deformation theory. We estimated the elastic modulus, E = 0.16 ± 0.02 MPa (mean±SE) for small EVs (sEVs; 30-150 nm) and E = 0.17 ± 0.03 MPa (mean±SE) for large EVs (lEVs; >150 nm). To our knowledge, this is the first report on the mechanical property estimation of LPS-derived EVs and has the potential to establish a relationship between EV size and EV mechanical properties.

Characterising HIV-1 transmission in Victoria, Australia: a molecular epidemiological study.

Background: In Australia the incidence of HIV has declined steadily, yet sustained reduction of HIV transmission in this setting requires improved public health responses. As enhanced public health responses and prioritisation of resources may be guided by molecular epidemiological data, here we aimed to assess the applicability of these approaches in Victoria, Australia. Methods: A comprehensive collection of HIV-1 pol sequences from individuals diagnosed with HIV in Victoria, Australia, between January 1st 2000 and December 31st 2020 were deidentified and used as the basis of our assessment. These sequences were subtyped and surveillance drug resistance mutations (SDRMs) identified, before definition of transmission groups was performed using HIV-TRACE (0.4.4). Phylodynamic methods were applied using BEAST (2.6.6), assessing effective reproductive numbers for large groups, and additional demographic data were integrated to provide a high resolution view of HIV transmission in Victoria on a decadal time scale. Findings: Based on standard settings for HIV-TRACE, 70% (2438/3507) of analysed HIV-1 pol sequences were readily assigned to a transmission group. Individuals in transmission groups were more commonly males (aOR 1.50), those born in Australia (aOR 2.13), those with probable place of acquisition as Victoria (aOR 6.73), and/or those reporting injectable drug use (aOR 2.13). SDRMs were identified in 375 patients (10.7%), with sustained transmission of these limited to a subset of smaller groups. Informative patterns of epidemic growth, stabilisation, and decline were observed; many transmission groups showed effective reproductive numbers (R e ) values reaching greater than 4.0, representing considerable epidemic growth, while others maintained low R e values. Interpretation: This study provides a high resolution view of HIV transmission in Victoria, Australia, and highlights the potential of molecular epidemiology to guide and enhance public health responses in this setting. This informs ongoing discussions with community groups on the acceptability and place of molecular epidemiological approaches in Australia. Funding: National Health and Medical Research Council, Australian Research Council.

Effects on cerebral blood flow after single doses of the ß2 agonist, clenbuterol, in healthy volunteers and patients with mild cognitive impairment or Parkinson's disease.

AIMS: Cerebral hypometabolism occurs years prior to a diagnosis of neurodegenerative diseases and coincides with reduced cerebral perfusion and declining noradrenergic transmission from the locus coeruleus. In pre-clinical models, ß-adrenoceptor (ß-AR) agonists increase cerebrocortical glucose metabolism, and may have therapeutic potential for neurodegenerative diseases. This study investigated the safety and effects on regional cerebral blood flow (rCBF) of the oral, brain-penetrant ß2-AR agonist, clenbuterol, in healthy volunteers (HV) and patients with mild cognitive impairment (MCI) or Parkinson's disease (PD). METHODS: This study evaluated the safety and effects on cerebral activity of the oral, brain-penetrant, ß2-AR agonist clenbuterol (20-160 µg) in healthy volunteers and patients with MCI or PD. Regional CBF, which is tightly coupled to glucose metabolism, was measured by arterial spin labelling MRI in 32 subjects (25 HV and 8 MCI or PD) across five cohorts. In some cohorts, low doses of nadolol (1-5 mg), a ß-AR antagonist with minimal brain penetration, were administered with clenbuterol to control peripheral ß2-AR responses. RESULTS: Significant, dose-dependent increases in rCBF were seen in multiple brain regions, including hippocampus, amygdala and thalamus, following the administration of clenbuterol to HVs (mean changes from baseline in hippocampal rCBF of -1.7%, 7.3%, 22.9%, 28.4% 3 h after 20, 40, 80 and 160 µg clenbuterol, respectively). In patients with MCI or PD, increases in rCBF following 80 µg clenbuterol were observed both without and with 5 mg nadolol (in hippocampus, 18.6%/13.7% without/with nadolol). Clenbuterol was safe and well-tolerated in all subjects; known side effects of ß2-agonists, including increased heart rate and tremor, were mild in intensity and were blocked by low-dose nadolol. CONCLUSIONS: The effects of clenbuterol on rCBF were evident both in the absence and presence of low-dose nadolol, suggesting central nervous system (CNS) involvement. Concomitant inhibition of the peripheral effects of clenbuterol by nadolol confirms that meaningful ß2-AR antagonism in the periphery was achieved without interrupting the central effects of clenbuterol on rCBF.

Suppression of excitatory synaptic transmission in the centrolateral amygdala via presynaptic histamine H3 heteroreceptors.

The central histaminergic system has a pivotal role in emotional regulation and psychiatric disorders, including anxiety, depression and schizophrenia. However, the effect of histamine on neuronal activity of the centrolateral amygdala (CeL), an essential node for fear and anxiety processing, remains unknown. Here, using immunostaining and whole-cell patch clamp recording combined with optogenetic manipulation of histaminergic terminals in CeL slices prepared from histidine decarboxylase (HDC)-Cre rats, we show that histamine selectively suppresses excitatory synaptic transmissions, including glutamatergic transmission from the basolateral amygdala, on both PKC-δ- and SOM-positive CeL neurons. The histamine-induced effect is mediated by H3 receptors expressed on VGLUT1-/VGLUT2-positive presynaptic terminals in CeL. Furthermore, optoactivation of histaminergic afferent terminals from the hypothalamic tuberomammillary nucleus (TMN) also significantly suppresses glutamatergic transmissions in CeL via H3 receptors. Histamine neither modulates inhibitory synaptic transmission by presynaptic H3 receptors nor directly excites CeL neurons by postsynaptic H1, H2 or H4 receptors. These results suggest that histaminergic afferent inputs and presynaptic H3 heteroreceptors may hold a critical position in balancing excitatory and inhibitory synaptic transmissions in CeL by selective modulation of glutamatergic drive, which may not only account for the pathophysiology of psychiatric disorders but also provide potential psychotherapeutic targets. KEY POINTS: Histamine selectively suppresses the excitatory, rather than inhibitory, synaptic transmissions on both PKC-δ- and SOM-positive neurons in the centrolateral amygdala (CeL). H3 receptors expressed on VGLUT1- or VGLUT2-positive afferent terminals mediate the suppression of histamine on glutamatergic synaptic transmission in CeL. Optogenetic activation of hypothalamic tuberomammillary nucleus (TMN)-CeL histaminergic projections inhibits glutamatergic transmission in CeL via H3 receptors.

The Chemokine CCL2 Promotes Excitatory Synaptic Transmission in Hippocampal Neurons via GluA1 Subunit Trafficking.

The CC chemokine ligand 2 (CCL2, also known as MCP-1) and its cognate receptor CCR2 have well-characterized roles in chemotaxis. CCL2 has been previously shown to promote excitatory synaptic transmission and neuronal excitability. However, the detailed molecular mechanism underlying this process remains largely unclear. In cultured hippocampal neurons, CCL2 application rapidly upregulated surface expression of GluA1, in a CCR2-dependent manner, assayed using SEP-GluA1 live imaging, surface GluA1 antibody staining, and electrophysiology. Using pharmacology and reporter assays, we further showed that CCL2 upregulated surface GluA1 expression primarily via Gαq- and CaMKII-dependent signaling. Consistently, using i.p. injection of lipopolysaccharide to induce neuroinflammation, we found upregulated phosphorylation of S831 and S845 sites on AMPA receptor subunit GluA1 in the hippocampus, an effect blocked in Ccr2-/- mice. Together, these results provide a mechanism through which CCL2, and other secreted molecules that signal through G-protein coupled receptors, can directly regulate synaptic transmission.

Impact of infectious diseases on wild bovidae populations in Thailand: insights from population modelling and disease dynamics.

The wildlife and livestock interface is vital for wildlife conservation and habitat management. Infectious diseases maintained by domestic species may impact threatened species such as Asian bovids, as they share natural resources and habitats. To predict the population impact of infectious diseases with different traits, we used stochastic mathematical models to simulate the population dynamics over 100 years for 100 times in a model gaur (Bos gaurus) population with and without disease. We simulated repeated introductions from a reservoir, such as domestic cattle. We selected six bovine infectious diseases; anthrax, bovine tuberculosis, haemorrhagic septicaemia, lumpy skin disease, foot and mouth disease and brucellosis, all of which have caused outbreaks in wildlife populations. From a starting population of 300, the disease-free population increased by an average of 228% over 100 years. Brucellosis with frequency-dependent transmission showed the highest average population declines (-97%), with population extinction occurring 16% of the time. Foot and mouth disease with frequency-dependent transmission showed the lowest impact, with an average population increase of 200%. Overall, acute infections with very high or low fatality had the lowest impact, whereas chronic infections produced the greatest population decline. These results may help disease management and surveillance strategies support wildlife conservation.

Evolution of Life Cycles of Nematodes Parasitizing Woody Plants As a Result of Ecological and Phylogenetic Co-Adaptations with Hosts and Vectors.

Fundamental aspects in the evolution of nematodes parasitizing woody plants are reviewed. (1) Nematode faunal lists of natural refugia are useful to predict the risks of opportunistic pathogens becoming true pathogens in the forest and park communities. (2) Nematode composition in natural refugia gives a chance to identify nematode antagonists of insect vectors of dangerous fungal and nematode infections, which can be potentially used as the biological agents for woody plants' protection. (3) Dauers in the ancestors of wood-inhabiting nematodes played a role as a survival stage in the detritus decomposition succession, and they later acquired the functions of dispersal and adaptations for transmission using insect vectors. (4) When inspecting wilted trees, it is necessary to use dauers for diagnostics, as sexually mature nematodes may be absent in tree tissues. (5) Plant parasitic nematodes originated from members of the detritus food web and retained a detritivorous phase in the life cycle as a part of the propagative generation. (6) Vectors in the life cycles of plant parasitic nematodes are inherited from the ancestral detritivorous nematode associations, rather than inserted in the dixenic life cycle of the 'nematode-fungus-plant' association. (7) Despite the significant difference in the duration of the nematode-tree and nematode-vector phases of the life cycle, the actual parasitic nematode specificity is dual: firstly to the vector and secondly to the natural host plant (as demonstrated in phytotests excluding a vector).

Household Transmission of Tinea Infections: Analysis of a Large Commercial Health Insurance Claims Database, United States, 2021.

Among 207 914 multimember households with a tinea case, a secondary case was diagnosed in another household member in 8.5%. Excluding same-day diagnoses (20%), the median time from index case to first secondary case was 138 days. To prevent household tinea transmission, appropriate treatment and strategies to reduce environmental contamination are needed.

Evaluation of clopidogrel response in healthy cats using a novel viscoelastic test and thromboelastography.

Introduction: Cats with cardiomyopathy face an increased risk of arterial thromboembolism (ATE). Although clopidogrel is frequently utilized to mitigate this risk, feline responses to this therapy exhibit variability. This study evaluated 2 viscoelastic devices, thromboelastography (TEG) and Viscoelastic Coagulation Monitor (VCM), for monitoring clopidogrel in cats in comparison to light transmission aggregometry (LTA). Methods: Twenty-eight healthy cats received clopidogrel for 7 days. Blood was collected at baseline and after treatment for analysis by TEG, VCM, and LTA. Results: On LTA, maximum amplitude, slope, and area under the curve (AUC) significantly decreased after treatment (p < 0.0001). On VCM, maximum clot firmness (MCF) significantly increased after treatment (p = 0.002). On TEG, R-time significantly prolonged (p = 0.024), while K and alpha angle significantly changed (p = 0.0002 and p = 0.0014, respectively). There was a moderate negative correlation between TEG R-time and LTA AUC (r = -0.39, p = 0.042). Eight cats were identified as non-responders to clopidogrel. Of the 8 non-responders, 6 (75%) had shortened R time after treatment. VCM appeared to be less discriminatory in identifying non-responders. Discussion: LTA remained the gold standard of monitoring clopidogrel treatment in cats. Unexpected changes on VCM and TEG were likely related to high interindividual and assay variability and increased sensitivity of feline platelets. R-time on TEG may have potential utility for point-of-care monitoring of clopidogrel response in cats.

Test-treat-track-test-treat (5T) approach for Schistosoma haematobium elimination on Pemba Island, Tanzania.

BACKGROUND: After decades of praziquantel mass drug administration (MDA), several countries approach schistosomiasis elimination. Continuing MDA in largely uninfected populations no longer seems justified. Alternative interventions to maintain the gains or accelerate interruption of transmission are needed. We report results, strengths, and shortcomings of novel test-treat-track-test-treat (5T) interventions in low Schistosoma haematobium prevalence areas on Pemba, Tanzania. METHODS: School- and household-based surveys were conducted in 2021 and 2022 to monitor the S. haematobium and microhematuria prevalence and assess the impact of interventions. In 2021, 5T interventions were implemented in 15 low-prevalence areas and included: (i) testing schoolchildren in primary and Islamic schools for microhematuria as a proxy for S. haematobium, (ii) treating positive children, (iii) tracking them to their households and to water bodies they frequented, (iv) testing individuals at households and water bodies, and (v) treating positive individuals. Additionally, test-and-treat interventions were implemented in the 22 health facilities of the study area. RESULTS: The S. haematobium prevalence in the school-based survey in 15 low-prevalence implementation units was 0.5% (7/1560) in 2021 and 0.4% (6/1645) in 2022. In the household-based survey, 0.5% (14/2975) and 0.7% (19/2920) of participants were infected with S. haematobium in 2021 and 2022, respectively. The microhematuria prevalence, excluding trace results, in the school-based survey was 1.4% (21/1560) in 2021 and 1.5% (24/1645) in 2022. In the household-based survey, it was 3.3% (98/2975) in 2021 and 5.4% (159/2920) in 2022. During the 5T interventions, the microhaematuria prevalence was 3.8% (140/3700) and 5.8% (34/594) in children in primary and Islamic schools, respectively, 17.1% (44/258) in household members, and 16.7% (10/60) in people at water bodies. In health facilities, 19.8% (70/354) of patients tested microhematuria-positive. CONCLUSIONS: The targeted 5T interventions maintained the very low S. haematobium prevalence and proved straightforward and feasible to identify and treat many of the few S. haematobium-infected individuals. Future research will show whether 5T interventions can maintain gains in the longer-term and expedite elimination. TRIAL REGISTRATION: ISRCTN, ISCRCTN91431493. Registered 11 February 2020, https://www.isrctn.com/ISRCTN91431493 .

Prevention of sexual transmission of mpox: a systematic review and qualitative evidence synthesis of approaches.

BACKGROUND: The ongoing multi-country mpox outbreak in previously unaffected countries is primarily affecting sexual networks of men who have sex with men. Evidence is needed on the effectiveness of recommended preventive interventions. To inform WHO guidelines, a systematic review and qualitative evidence synthesis were conducted on mpox preventive behavioural interventions to reduce: (i) sexual acquisition; (ii) onward sexual transmission from confirmed/probable cases; and (iii) utility of asymptomatic testing. METHODS: Medline, EMBASE, PubMed, Cochrane and WHO trial databases, grey literature and conferences were searched for English-language primary research published since 1 January 2022. A reviewer team performed screening, data extraction and bias assessment. A qualitative thematic synthesis explored views and experiences of engagement in prevention in individuals at increased risk. RESULTS: There were 16 studies: 1 on contact-tracing, 2 on sexual behaviour, and 13 on asymptomatic testing. Although MPXV was detected in varying proportions of samples (0.17%-6.5%), the testing studies provide insufficient evidence to fully evaluate this strategy. For the qualitative evidence synthesis, four studies evaluated the experiences of most affected communities. Preferences about preventive interventions were shaped by: mpox information; the diversity of sexual practices; accessibility and quality of mpox testing and care; and perceived cost to wellbeing. CONCLUSIONS: Evidence on the effectiveness of interventions to prevent the sexual transmission of mpox remains scarce. Limited qualitative evidence on values and preferences provides insight into factors influencing intervention acceptability. Given global and local inequities in access to vaccines and treatment, further research is needed to establish the effectiveness of additional interventions.

Junctionless Structure Indium-Tin Oxide Thin-Film Transistors Enabling Enhanced Mechanical and Contact Stability.

In recent years, considerable attention has focused on high-performance and flexible crystalline metal oxide thin-film transistors (TFTs). However, achieving both high performance and flexibility in semiconductor devices is challenging due to the inherently conductive and brittle nature of crystalline metal oxide. In this study, we propose a facile way to overcome this limitation by employing a junctionless (JL) TFT structure via oxygen plasma treatment of the crystalline indium-tin oxide (ITO) films. The oxygen plasma treatment significantly reduced oxygen vacancies in the ITO films, contributing to the significant reduction in the carrier concentration from 4.67 × 1020 to 1.39 × 1016. Importantly, this reduction was achieved without inducing any noticeable structural changes in the ITO, enabling the successful realization of ITO JL TFTs with an adjustable threshold voltage. Furthermore, the ITO JL TFTs demonstrate good stability and reliability under various bias stress conditions, aging in the air atmosphere, and high-temperature processes. In addition, the ITO JL TFTs exhibit low light sensitivity due to the wide bandgap of ITO and further suppression of Vo defects, making them suitable for applications requiring stable performance under light exposure. To compare and analyze the flexibility of the JL structure and conventional structure with additional source/drain (S/D) junction in ITO TFTs with nonencapsulation, we utilized mechanical simulations and transmission line method (TLM). By employing the JL structure in ITO TFT through carefully optimized oxygen plasma treatment, we successfully mitigated stress concentration at the S/D-channel interface. This resulted in a JL ITO TFT that exhibited a change in contact resistance of less than 20% even after 20,000 bending cycles. Consequently, a stable and flexible ITO TFT with field-effect mobility (µFE) of 12.74 cm2/(V s) was realized, outperforming conventionally structured ITO TFTs with additional S/D junction, where the contact resistance nearly tripled.

Countering Zoonotic Diseases: Current Scenario and Advances in Diagnostics, Monitoring, Prophylaxis and Therapeutic Strategies.

Human life and health have interacted reciprocally with the surrounding environment and animal fauna for ages. This relationship is evident in developing nations, where human life depends more on the animal population for food, transportation, clothing, draft power, and fuel sources, among others. This inseparable link is a potent source of public health issues, especially in outbreaks of zoonotic diseases transmitted from animals to humans. Zoonotic diseases are referred to as diseases that are naturally transmitted between vertebrate animals and humans. Among the globally emerging diseases in the last decade, 75% are of animal origin, most of which are life-threatening. Since most of them are caused by potent new pathogens capable of long-distance transmission, the impact is widespread and has serious public health and economic consequences. Various other factors also contribute to the transmission, spread, and outbreak of zoonotic diseases, among which industrialization-led globalization followed by ecological disruption and climate change play a critical role. In this regard, all the possible strategies, including advances in rapid and confirmatory disease diagnosis and surveillance/monitoring, immunization/vaccination, therapeutic approaches, appropriate prevention and control measures to be adapted, and awareness programs, need to be adopted collaboratively among different health sectors in medical, veterinary, and concerned departments to implement the necessary interventions for the effective restriction, minimization, and timely control of zoonotic threats. The present review focuses on the current scenario of zoonotic diseases and their counteracting approaches to safeguard their health impact on humans.

Curcumin Nanocapsules based on carbon dots for photodynamic sterilization towards Listeria monocytogenes and Staphylococcus aureus.

Curcumin (Cur) as a natural food additive and photosensitizer has been widely applied on photodynamic sterilization and preservation for food, but the poor aqueous solubility and light stability restrict its extensive application. In this study, we report a Cur nanocapsules (Cur-CDs) made by carbon dots (CDs). Attributing to the hydrogen bonds formed between Cur and CDs, Cur-CDs exhibits excellent Cur aqueous solubility each to 9286.98 ng/mL (enhanced by 246.27 times) and light stability (enhanced by 1.51 times). The photogenerated electron transmission from Cur to CDs in addition resulted in >1.23 and 1.60 times generation of •O2- and •OH, compared to that of bare Cur. Accordingly, 5.73 × 103 CFU L. monocytogenes, and 5.43 × 103 CFU S. aureus were killed by 0.06 mg/mL Cur-CDs within 20 mins of blue light, showing the promising potential in the development and application of safe and environmentally friendly non-thermal sterilization technology based on Cur-CDs.

ErbB4 deficiency exacerbates olfactory dysfunction in an early-stage Alzheimer's disease mouse model.

Olfactory dysfunction is increasingly recognized as an early indicator of Alzheimer's disease (AD). Aberrations in GABAergic function and the excitatory/inhibitory (E/I) balance within the olfactory bulb (OB) have been implicated in olfactory impairment during the initial stages of AD. While the neuregulin 1 (NRG1)/ErbB4 signaling pathway is known to regulate GABAergic transmission in the brain and is associated with various neuropsychiatric disorders, its specific role in early AD-related olfactory impairment remains incompletely understood. This study demonstrated that olfactory dysfunction preceded cognitive decline in young adult APP/PS1 mice and was characterized by reduced levels of NRG1 and ErbB4 in the OB. Further investigation revealed that deletion of ErbB4 in parvalbumin interneurons reduced GABAergic transmission and increased hyperexcitability in mitral and tufted cells (M/Ts) in the OB, thereby accelerating olfactory dysfunction in young adult APP/PS1 mice. Additionally, ErbB4 deficiency was associated with increased accumulation of Aß and BACE1-mediated cleavage of APP, along with enhanced CDK5 signaling in the OB. NRG1 infusion into the OB was found to enhance GABAergic transmission in M/Ts and alleviate olfactory dysfunction in young adult APP/PS1 mice. These findings underscore the critical role of NRG1/ErbB4 signaling in regulating GABAergic transmission and E/I balance within the OB, contributing to olfactory impairment in young adult APP/PS1 mice, and provide novel insights for early intervention strategies in AD. This work has shown that ErbB4 deficiency increased the burden of Aß, impaired GABAergic transmission, and disrupted the E/I balance of mitral and tufted cells (M/Ts) in the OB, ultimately resulting in olfactory dysfunction in young adult APP/PS1 mice. NRG1 could enhance GABAergic transmission, rescue E/I imbalance in M/Ts, and alleviate olfactory dysfunction in young adult APP/PS1 mice. OB: olfactory bulb, E/I: excitation/inhibition, Pr: probability of release, PV: parvalbumin interneurons, Aß: ß-amyloid, GABA: gamma-aminobutyric acid.

In Situ Lattice-Resolution Revelation of the Origins of Unexplored Anisotropic Sodiation Kinetics and Phase Transition in the Niobium Sulfide Anode.

Layered transition metal dichalcogenides (TMDs) have exhibited huge potential as anode materials for sodium-ion batteries. Most of them usually store sodium via an intercalation-conversion mechanism, but niobium sulfide (NbS2) may be an exception. Herein, through in situ transmission electron microscopy, we carefully investigated the insertion behaviors of Na ions in NbS2 and directly visualized anisotropic sodiation kinetics. Lattice-resolution imaging coupled with density functional theory calculations reveals the preferential diffusion of Na ions within layers of NbS2, accompanied by observable interlayer lattice expansion. Impressively, the Na-inserted layers can still withstand in situ mechanical testing. Further in situ observation vertical to the a/b plane of NbS2 tracked the illusive conversion reaction, which could result from interlayer gliding or wrinkling associated with stress accumulation. In situ electron diffraction measurements ruled out the possibility of such a conversion mechanism and identified a phase transition from pristine 3R-NbS2 to 2H-NaNbS2. Therefore, the NbS2 anode stores Na ions via only the intercalation mechanism, which conceptually differs from the well-known intercalation-conversion mechanism of typical TMDs. These findings not only decipher the whole sodiation process of the NbS2 anode but also provide valuable reference for unraveling the precise sodium storage mechanism in other TMDs.

Crystallographic Pathways to Tailoring Metal-Insulator Transition through Oxygen Transport in VO2.

The metal-insulator (MI) transition of vanadium dioxide (VO2) is effectively modulated by oxygen vacancies, which decrease the transition temperature and insulating resistance. Oxygen vacancies in thin films can be driven by oxygen transport using electrochemical potential. This study delves into the role of crystallographic channels in VO2 in facilitating oxygen transport and the subsequent tuning of electrical properties. A model system is designed with two types of VO2 thin films: (100)- and (001)-oriented, where channels align parallel and perpendicular to the surface, respectively. Growing an oxygen-deficient TiO2 layer on these VO2 films prompted oxygen transport from VO2 to TiO2. Notably, in (001)-VO2 film, where oxygen ions move along the open channels, the oxygen migration deepens the depleted region beyond that in (100)-VO2, leading to more pronounced changes in metal-insulator transition behaviors. The findings emphasize the importance of understanding the intrinsic crystal structure, such as channel pathways, in controlling ionic defects and customizing electrical properties for applications.

Understanding electrical and chemical transmission in the brain.

The histochemical Falck-Hillarp method for the localization of dopamine (DA), noradrenaline (NA) and serotonin in the central nervous system (CNS) of rodents was introduced in the 1960s. It supported the existence of chemical neurotransmission in the CNS. The monoamine neurons in the lower brain stem formed monosynaptic ascending systems to the telencephalon and diencephalon and monoamine descending systems to the entire spinal cord. The monoamines were early on suggested to operate via synaptic chemical transmission in the CNS. This chemical transmission reduced the impact of electrical transmission. In 1969 and the 1970s indications were obtained that important modes of chemical monoamine communication in the CNS also took place through the extra-synaptic fluid, the extracellular fluid, and long-distance communication in the cerebrospinal fluid involving diffusion and flow of transmitters like DA, NA and serotonin. In 1986, this type of transmission was named volume transmission (VT) by Agnati and Fuxe and their colleagues, also characterized by transmitter varicosity and receptor mismatches. The short and long-distance VT pathways were characterized by volume fraction, tortuosity and clearance. Electrical transmission also exists in the mammalian CNS, but chemical transmission is in dominance. One electrical mode is represented by electrical synapses formed by gap junctions which represent low resistant passages between nerve cells. It allows for a more rapid passage of action potentials between nerve cells compared to chemical transmission. The second mode is based on the ability of synaptic currents to generate electrical fields to modulate chemical transmission. One aim is to understand how chemical transmission can be integrated with electrical transmission and how putative (aquaporin water channel, dopamine D2R and adenosine A2AR) complexes in astrocytes can significancy participate in the clearance of waste products from the glymphatic system. VT may also help accomplish the operation of the acupuncture meridians essential for Chinese medicine in view of the indicated existence of extracellular VT pathways.