The secondary visual cortex mediated the enhancement of associative learning on methamphetamine self-administration behaviors.

RATIONALE: Methamphetamine addiction is a persistent and intractable pathological learning and memory, whereas no approved therapeutics is available. However, few attentions have been paid to how associative learning participates in the formation of intractable memory related to drug addiction OBJECTIVES AND METHODS: To investigate the role of associative learning in methamphetamine addiction and the underlying neurobiological mechanism, methamphetamine self-administration, oral sucrose self-administration, chemogenetic neuromanipulation, and fiber photometry in mice were performed in this study. RESULTS: We reported that associative learning increased methamphetamine-induced self-administration, but not oral sucrose self-administration. In addition, the enhancement of methamphetamine-induced self-administration was independent of more methamphetamine consumption, and remained with higher drug-taking and motivation in the absence of visual cues, suggesting the direct effects of the associative learning that enhanced methamphetamine-induced self-administration. Moreover, chemogenetic inactivation of the secondary visual cortex (V2) reduced the enhancement of the drug-taking induced by associative learning but did not alter sucrose-taking. Further fiber photometry of V2 neurons demonstrated that methamphetamine-associative learning elicits V2 neuron excitation, and sucrose-associative learning elicits V2 neuron inhibition. CONCLUSIONS: Therefore, this study reveals the neurobiological mechanism of V2 excitability underlying how associative learning participates in the formation of intractable memory related to drug addiction, and gives evidence to support V2 as a promising target for stimulation therapy for methamphetamine addiction.

Cannabidiol ameliorates PTSD-like symptoms by inhibiting neuroinflammation through its action on CB2 receptors in the brain of male mice.

Post-traumatic stress disorder (PTSD) is a debilitating mental health disease related to traumatic experience, and its treatment outcomes are unsatisfactory. Accumulating research has indicated that cannabidiol (CBD) exhibits anti-PTSD effects, however, the underlying mechanism of CBD remains inadequately investigated. Although many studies pertaining to PTSD have primarily focused on aberrations in neuronal functioning, the present study aimed to elucidate the involvement and functionality of microglia/macrophages in PTSD while also investigated the modulatory effects of CBD on neuroinflammation associated with this condition. We constructed a modified single-prolonged stress (SPS) mice PTSD model and verified the PTSD-related behaviors by various behavioral tests (contextual freezing test, elevated plus maze test, tail suspension test and novel object recognition test). We observed a significant upregulation of Iba-1 and alteration of microglial/macrophage morphology within the prefrontal cortex and hippocampus, but not the amygdala, two weeks after the PTSD-related stress, suggesting a persistent neuroinflammatory phenotype in the PTSD-modeled group. CBD (10 mg/kg, i.p.) inhibited all PTSD-related behaviors and reversed the alterations in both microglial/macrophage quantity and morphology when administered prior to behavioral assessments. We further found increased pro-inflammatory factors, decreased PSD95 expression, and impaired synaptic density in the hippocampus of the modeled group, all of which were also restored by CBD treatment. CBD dramatically increased the level of anandamide, one of the endocannabinoids, and cannabinoid type 2 receptors (CB2Rs) transcripts in the hippocampus compared with PTSD-modeled group. Importantly, we discovered the expression of CB2Rs mRNA in Arg-1-positive cells in vivo and found that the behavioral effects of CBD were diminished by CB2Rs antagonist AM630 (1 mg/kg, i.p.) and both the behavioral and molecular effects of CBD were abolished in CB2Rs knockout mice. These findings suggest that CBD would alleviate PTSD-like behaviors in mice by suppressing PTSD-related neuroinflammation and upregulation and activation of CB2Rs may serve as one of the underlying mechanisms for this therapeutic effect. The present study offers innovative experimental evidence supporting the utilization of CBD in PTSD treatment from the perspective of its regulation of neuroinflammation, and paves the way for leveraging the endocannabinoid system to regulate neuroinflammation as a potential therapeutic approach for psychiatric disorders.

Serum uric acid is associated with midbrain enlarged perivascular spaces: Results from Multi-modality Medical imaging sTudy bAsed on KaiLuan Study (META-KLS).

BACKGROUND: Serum uric acid (SUA) is a major cause of cardiovascular and cerebrovascular diseases. Whether and to what extent the excess risk of enlarged perivascular spaces (EPVS) conferred by SUA is unknown. The study was conducted to investigate the association between SUA and EPVS in different brain regions. METHODS: Data are from Multi-modality medical imaging study based on Kailuan study (META-KLS) in this cross-sectional study. Participants were divided into five groups based on SUA levels, and EPVS in basal ganglia (BG), centrum semiovale (CSO) and midbrain (MB) was systematically assessed and divided into Low and High group. Odds ratio (OR) and 95% confidence intervals (95% CIs) for high EPVS outcomes were estimated using multivariable logistic regression analysis. Restricted cubic spline (RCS) was used to further investigate dose-response relationship. RESULTS: A total of 1014 participants aged 25-83 years from 11 centers were enrolled in the study. In the multivariable-adjusted model, SUA, as an independent risk factor, correlated positively with high degree of MB-EPVS (OR, 1.002; 95% CI, 1.000 to 1.004; p = 0.023) in general population. In addition, RCS further demonstrated the linear association between SUA and MB-EPVS (p = 0.072). No association was found between SUA and BG-EPVS or CSO-EPVS. CONCLUSION: SUA was an independent risk factor of MB-EPVS. High SUA levels were more predictive of increased risk occurrence of high degree of MB-EPVS, supporting a linear association between SUA and MB-EPVS and further indicating that SUA may play an important role in cerebral small vessel disease. TRIAL REGISTRATION: The KaiLuan Study and META-KLS were registered online (ChiCTR2000029767 on chictr.org.cn and NCT05453877 on Clinicaltrials.gov, respectively).

Rapid ejaculator rats are more susceptible to anxiety compared with normal ejaculator rats.

By observation of Sprague-Dawley male rats with different ejaculatory behaviors, we have identified distinct behavioral characteristics in rapid ejaculator rats. To validate these differential behaviors, we conducted multifaceted behavioral experiments on rapid ejaculator rats and normal rats. Through mating experiments, 42 male rats were categorized into 5 rapid ejaculator rats, 29 normal ejaculator rats, and 8 sluggish ejaculator rats according to their ejaculation frequency. We selected 5 rats exhibiting rapid ejaculation and 5 rats with normal ejaculation for participation in the Morris water maze, open-field test, and balance beam experiments. The open-field tests revealed that rapid ejaculator rats spent shorter time in the center region (1.23 ± 1.21 vs. 6.56 ± 2.40 s, P = 0.0041), less entered the center region (0.80 ± 0.75 vs. 3.40 ± 1.50, time, P = 0.0145), traveled shorter distances (17,003.77 ± 3339.42 vs. 25,037.90 ± 5499.94 mm, P = 0.0371), and had a lower average speed compared with normal rats (66.09 ± 62.36 vs. 195.56 ± 83.41 mm/s, P = 0.0377). However, no significant differences were observed in the Morris water maze and balance beam experiments (0.25 ± 0.05 vs. 0.26 ± 0.07, P = 0.7506;16.40 ± 3.77 vs. 16.25 ± 2.05, P = 0.9515). These behavioral results indicated that the rapid ejaculator rats were more prone to anxiety. To further substantiate this claim, we examined Brain-derived neurotrophic factor expression levels in the hippocampus of rat brains using immunohistochemistry and western blotting. The results demonstrate lower Brain-derived neurotrophic factor expression in the hippocampus of rapid ejaculator rats compared with that in normal rats (P = 0.0093). Thus, our experiments indicate that rapid ejaculator rats exhibit a higher propensity for anxiety, potentially linked to their abnormal neurophysiologic state. It is concluded that rapid ejaculator rats may be more susceptible to anxiety on a pathophysiological basis.

Enhancement Effect Induced by the Second Metal to Promote Ozone Catalytic Oxidation of VOCs.

It is a promising research direction to develop catalysts with high stability and ozone utilization for low-temperature ozone catalytic oxidation of VOCs. While bimetallic catalysts exhibit excellent catalytic activity compared with conventional single noble metal catalysts, limited success has been achieved in the influence of the bimetallic effect on the stability and ozone utilization of metal catalysts. Herein, it is necessary to systematically study the enhancement effect in the ozone catalytic reaction induced by the second metal. With a simple continuous impregnation method, a platinum-cerium bimetallic catalyst is prepared. Also highlighted are studies from several aspects of the contribution of the second metal (Ce) to the stability and ozone utilization of the catalysts, including the "electronic effect" and "geometric effect". The synergistic removal rate of toluene and ozone is nearly 100% at 30 °C, and it still shows positive stability after high humidity and a long reaction time. More importantly, the instructive significance, which is the in-depth knowledge of enhanced catalytic mechanism of bimetallic catalysts resulting from a second metal, is provided by this work.

Single-Nucleus Transcriptome Profiling from the Hippocampus of a PTSD Mouse Model and CBD-Treated Cohorts.

Post-traumatic stress disorder (PTSD) is the most common psychiatric disorder after a catastrophic event; however, the efficacious treatment options remain insufficient. Increasing evidence suggests that cannabidiol (CBD) exhibits optimal therapeutic effects for treating PTSD. To elucidate the cell-type-specific transcriptomic pathology of PTSD and the mechanisms of CBD against this disease, we conducted single-nucleus RNA sequencing (snRNA-seq) in the hippocampus of PTSD-modeled mice and CBD-treated cohorts. We constructed a mouse model by adding electric foot shocks following exposure to single prolonged stress (SPS+S) and tested the freezing time, anxiety-like behavior, and cognitive behavior. CBD was administrated before every behavioral test. The PTSD-modeled mice displayed behaviors resembling those of PTSD in all behavioral tests, and CBD treatment alleviated all of these PTSD-like behaviors (n = 8/group). Three mice with representative behavioral phenotypes were selected from each group for snRNA-seq 15 days after the SPS+S. We primarily focused on the excitatory neurons (ExNs) and inhibitory neurons (InNs), which accounted for 68.4% of the total cell annotations. A total of 88 differentially upregulated genes and 305 differentially downregulated genes were found in the PTSD mice, which were found to exhibit significant alterations in pathways and biological processes associated with fear response, synaptic communication, protein synthesis, oxidative phosphorylation, and oxidative stress response. A total of 63 overlapping genes in InNs were identified as key genes for CBD in the treatment of PTSD. Subsequent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that the anti-PTSD effect of CBD was related to the regulation of protein synthesis, oxidative phosphorylation, oxidative stress response, and fear response. Furthermore, gene set enrichment analysis (GSEA) revealed that CBD also enhanced retrograde endocannabinoid signaling in ExNs, which was found to be suppressed in the PTSD group. Our research may provide a potential explanation for the pathogenesis of PTSD and facilitate the discovery of novel therapeutic targets for drug development. Moreover, it may shed light on the therapeutic mechanisms of CBD.

Anthropogenic and biological activities elevate microplastics pollution in headwater ecosystem of Yangtze tributaries in Hindu Kush-Himalayan region.

Microplastic (MP) pollution is widely spread in oceans, freshwater, and terrestrial environments but MPs in mountainous headwater ecosystem are rarely reported. This study focuses on the headwater of Yangtze tributaries of the Hindu Kush-Himalayan (HKH) region. Five streams at elevations of 900 to 3300 m were selected to investigate the distribution of MPs in water and sediments across altitudes. MPs were found in all water and sediment samples from top stream zone nearly in absence of anthropogenic activity, low anthropogenic zone, and high anthropogenic zone, increased from 12-54, 81-185 to 334-847 items/L, and 2-35, 26-84 to 124-428 items/kg, respectively. This elevation-dependent MP distribution indicated that as elevation decreased, anthropogenic activities intensified and increased MPs input and their abundance, size, and diversity. Notably, hydraulic projects, such as damming, were identified as potential barriers to the migration of MPs downstream. Microbiome analyses revealed the presence of bacterial genes associated with plastic biodegradation in all sediment samples. The study indicates that Shangri-la mountainous streams have been polluted with MPs for years with potential risk of generation of nano-sized particles via natural fragmentation and biodegradation, and thus raises concern on MPs pollution in headwaters streams in mountainous regions.

Intensification of rice flour gel structure by fermenting corresponding rice with Lactobacillus plantarum.

In starch gel foods processing, lactic acid fermentation is an effective strategy to improve the quality of the gel. This study revealed the effects of Lactobacillus plantarum fermentation for rice on the textural and rheological properties of the corresponding gels. The hardness, adhesiveness and chewiness of the gel showed ascending trends with the forwarding of fermentation. The role of Lactobacillus plantarum on rheological properties of gel depended on fermentation time. As the time was within 3 days, the process reduced the viscoelastic of the gel, while as the time was for 5 days, the process enhanced the viscoelastic of the gel. During fermentation, amylose content increased from 21.56 ± 1.17% to 27.39 ± 0.63%, and crude protein content descended from 12.60 ± 0.44 g/100 g DW to 4.8 ± 0.49 g/100 g DW. Total organic acids were ascending in the whole process, and lactic acid (LA), acetic acid (AA) and citric acid (CA) made the dominant contribution. The enthalpy change (ΔH) of the rice flour fermented for 5 days was significantly (p < 0.05) increased to 9.90 ± 0.24 J/g, indicating the formation of more double helix structures. These organic acids may contribute to the formation of the pores on the surface of granules by hydrolyzing the components, which provides a channel for enzymes to enter the interior of granules. These results provide the basis for the development of fermented rice-based foods.

High-mobility group box 1 and its related receptors: potential therapeutic targets for contrast-induced acute kidney injury.

Percutaneous coronary intervention (PCI) is a crucial diagnostic and therapeutic approach for coronary heart disease. Contrast agents' exposure during PCI is associated with a risk of contrast-induced acute kidney injury (CI-AKI). CI-AKI is characterized by a sudden decline in renal function occurring as a result of exposure to intravascular contrast agents, which is associated with an increased risk of poor prognosis. The pathophysiological mechanisms underlying CI-AKI involve renal medullary hypoxia, direct cytotoxic effects, endoplasmic reticulum stress, inflammation, oxidative stress, and apoptosis. To date, there is no effective therapy for CI-AKI. High-mobility group box 1 (HMGB1), as a damage-associated molecular pattern molecule, is released extracellularly by damaged cells or activated immune cells and binds to related receptors, including toll-like receptors and receptor for advanced glycation end product. In renal injury, HMGB1 is expressed in renal tubular epithelial cells, macrophages, endothelial cells, and glomerular cells, involved in the pathogenesis of various kidney diseases by activating its receptors. Therefore, this review provides a theoretical basis for HMGB1 as a therapeutic intervention target for CI-AKI.

Association between Body Mass Index and Brain Health in Adults: A 16-Year Population-Based Cohort and Mendelian Randomization Study.

Background: The cumulative effect of body mass index (BMI) on brain health remains ill-defined. The effects of overweight on brain health across different age groups need clarification. We analyzed the effect of cumulative BMI on neuroimaging features of brain health in adults of different ages. Methods: This study was based on a multicenter, community-based cohort study. We modeled the trajectories of BMI over 16 years to evaluate cumulative exposure. Multimodality neuroimaging data were collected once for volumetric measurements of the brain macrostructure, white matter hyperintensity (WMH), and brain microstructure. We used a generalized linear model to evaluate the association between cumulative BMI and neuroimaging features. Two-sample Mendelian randomization analysis was performed using summary level of BMI genetic data from 681,275 individuals and neuroimaging genetic data from 33,224 individuals to analyze the causal relationships. Results: Clinical and neuroimaging data were obtained from 1,074 adults (25 to 83 years). For adults aged under 45 years, brain volume differences in participants with a cumulative BMI of >26.2 kg/m2 corresponded to 12.0 years [95% confidence interval (CI), 3.0 to 20.0] of brain aging. Differences in WMH were statistically substantial for participants aged over 60 years, with a 6.0-ml (95% CI, 1.5 to 10.5) larger volume. Genetic analysis indicated causal relationships between high BMI and smaller gray matter and higher fractional anisotropy in projection fibers. Conclusion: High cumulative BMI is associated with smaller brain volume, larger volume of white matter lesions, and abnormal microstructural integrity. Adults younger than 45 years are suggested to maintain their BMI below 26.2 kg/m2 for better brain health. Trial Registration: This study was registered on clinicaltrials.gov (Clinical Indicators and Brain Image Data: A Cohort Study Based on Kailuan Cohort; No. NCT05453877; https://clinicaltrials.gov/ct2/show/NCT05453877).

The interplay between autophagy and ferroptosis presents a novel conceptual therapeutic framework for neuroendocrine prostate cancer.

In American men, the incidence of prostate cancer (PC) is the highest among all types of cancer, making it the second leading cause of mortality associated with cancer. For advanced or metastatic PC, antiandrogen therapies are standard treatment options. The administration of these treatments unfortunately carries the potential risk of inducing neuroendocrine prostate cancer (NEPC). Neuroendocrine differentiation (NED) serves as a crucial indicator of prostate cancer development, encompassing various factors such as phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR), Yes-associated protein 1 (YAP1), AMP-activated protein kinase (AMPK), miRNA. The processes of autophagy and ferroptosis (an iron-dependent form of programmed cell death) play pivotal roles in the regulation of various types of cancers. Clinical trials and preclinical investigations have been conducted on many signaling pathways during the development of NEPC, with the deepening of research, autophagy and ferroptosis appear to be the potential target for regulating NEPC. Due to the dual nature of autophagy and ferroptosis in cancer, gaining a deeper understanding of the developmental programs associated with achieving autophagy and ferroptosis may enhance risk stratification and treatment efficacy for patients with NEPC.

YAP1 Regulates the YAP1/AR/PSA Axis through Autophagy in Castration-Resistant Prostate Cancer and Mediates T-Cell Immune and Inflammatory Cytokine Infiltration.

The emergence of castration-resistant prostate cancer (CRPC) following androgen deprivation therapy (ADT) is associated with increased malignancy and limited treatment options. This study aims to investigate potential connections between immune cell infiltration and inflammatory cytokines with the YAP1/AR/PSA axis by exploring their interactions with autophagy. Our research reveals heightened levels of Yes-associated protein 1 (YAP1) expression in CRPC tissues compared with tissues from androgen-dependent prostate cancer (ADPC) and benign prostate hyperplasia (BPH). Additionally, a correlation was observed between YAP1 and PSA expressions in CRPC tissues, suggesting that YAP1 may exert a regulatory influence on PSA expression within CRPC. Enhanced YAP1 expression in C4-2 cells resulted in the upregulation of androgen receptor (AR) nuclear translocation and intracellular prostate-specific antigen (PSA) levels. Conversely, the suppression of YAP1 led to a decrease in PSA expression, suggesting that YAP1 may positively regulate the PSA in castration-resistant prostate cancer (CRPC) by facilitating AR nuclear import. The modulation of the autophagy activity exerts a significant impact on the expression levels of YAP1, the AR, and the PSA. Moreover, recent advancements in immunity and inflammation studies present promising avenues for potential therapies targeting prostate cancer (PC).

A convenient and reproducible protocol for acquisition of the hepatocyte phase for liver function-impaired patients in gadoxetic acid disodium-enhanced magnetic resonance imaging.

Background: The hepatocyte phase (HCP) in gadoxetic acid disodium (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) plays an important role in the detection and characterization of liver lesions, treatment planning, and liver function evaluation. However, the imaging protocol is complicated and time-consuming. This cross-sectional study aimed to develop a convenient and reproducible protocol for the HCP acquisition in Gd-EOB-DTPA-enhanced MRI. Methods: A total of 107 patients were prospectively included and assigned to three groups based on Child-Pugh (CP) classification, with 37, 40, and 30 in the non-cirrhosis, CP A, and CP B groups, respectively. Dynamic HCPs were acquired every 5 min after the Gd-EOB-DTPA administration and ended in 25 min in non-cirrhosis patients and 40 min in cirrhotic patients. The HCP acquired 5 min after the initial visualization of the intrahepatic bile duct (IBD) was selected from the dynamic HCPs as the adequate HCP (HCPproposed) and the corresponding acquisition time was recorded as Timeproposed. In addition, according to the 2016 Expert Consensus (EC) on the definition of the adequate HCP from the European Society of Gastrointestinal and Abdominal Radiology (ESGAR), the adequate HCPEC and the corresponding TimeEC were also determined from the dynamic HCPs. The hepatic relative enhancement ratio (RER), the contrast-to-noise ratio (CNR), and signal-to-noise ratio (SNR) of hepatic focal lesions in the HCPEC and HCPproposed images, as well as the TimeEC and Timeproposed were compared by the paired t-test for the three groups, respectively. Inter-observer agreement of the determination of the HCPEC and HCPproposed was compared by the χ2 test. Results: The RER, CNR, and SNR showed no significant difference between the HCPEC and HCPproposed in all three groups (all P>0.05). The paired differences between TimeEC and Timeproposed were 1.08±3.56 min (P=0.07), 2.88±4.22 min (P<0.001), and 5.83±5.27 min (P<0.001) in the three groups, respectively. Inter-observer agreement of the determination of the HCPEC and HCPproposed were 0.804 (86/107) and 0.962 (103/107), respectively (χ²=13.09, P=0.001). Conclusions: The adequate HCP could be acquired 5 min after the initial visualization of the IBD, which could serve as a convenient and reproducible protocol for the HCP imaging.

Decoding the transcriptional heterogeneity, differentiation lineage, clinical significance in tissue-resident memory CD8 T cell of the small intestine by single-cell analysis.

Resident memory T (Trm) cells which are specifically located in non-lymphoid tissues showed distinct phenotypes and functions compared to circulating memory T cells and were vital for the initiation of robust immune response within tissues. However, the heterogeneity in the transcriptional features, development pathways, and cancer response of Trm cells in the small intestine was not demonstrated. Here, we integrated scRNA-seq and scTCR-seq data pan-tissue T cells to explore the heterogeneity of Trm cells and their development pathways. Trm were enriched in tissue-specific immune response and those in the DUO specially interacted with B cells via TNF and MHC-I signatures. T cell lineage analyses demonstrated that Trm might be derived from the T_CD4/CD8 subset within the same organ or migrated from spleen and mesenteric lymph nodes. We compared the immune repertoire of Trm among organs and implied that clonotypes in both DUO and ILE were less expanded and hydrophilic TRB CDR3s were enriched in the DUO. We further demonstrated that Trm in the intestine infiltrated the colorectal cancer and several effector molecules were highly expressed. Finally, the TCGA dataset of colorectal cancer implied that the infiltration of Trm from the DUO and the ILE was beneficial for overall survival and the response to immune checkpoint blockade.

Regulation of I1-imidazoline receptors on the sedation effect of dexmedetomidine in mice.

Dexmedetomidine has been used as a sedative drug in the clinic for a long time. Many studies demonstrated that the sedative mechanism of dexmedetomidine might be related to the activation of α2-adrenoceptor (α2AR). In addition, it was reported that dexmedetomidine had some affinity for the I1-imidazoline receptor (I1R); however, the role of I1R in dexmedetomidine-induced sedative effects and its possible mechanism are poorly studied. In the present study, we found that agmatine, an I1R agonist, was able to enhance the sedative effect of dexmedetomidine in mice. Efaroxan, an α2AR and I1R antagonist, could prevent and rescue the sedative action of dexmedetomidine in mice, and its preventive effect was better than atipamezole, the specific α2AR antagonist. Knockout of imidazoline receptor antisera-selected (IRAS), the functional I1R candidate protein, suppressed the dexmedetomidine-induced sedation. Moreover, IRAS knockout led to the inhibition of agmatine and efaroxan in regulating dexmedetomidine-induced sedative effects in mice, but not of atipamezole. We then used CHO cell lines that stably expressed α2AR and IRAS to investigate the possible molecular mechanism of IRAS in regulating the dexmedetomidine-induced sedative effect. The results showed that IRAS expression significantly up-regulated dexmedetomidine-induced ERK phosphorylation, which was enhanced by agmatine and inhibited by efaroxan at low concentrations. Therefore, by taking advantage of pharmacological and genetic approaches, our finding revealed the evidence that IRAS plays an important role in the sedative effects of dexmedetomidine, and the ERK signal pathway may be involved in the mechanism of IRAS in regulating dexmedetomidine-induced sedation. This study may offer valuable insights for the advancement of novel anesthetic adjuvants.

Thermal Rectification across an Asymmetric Layer Carbon Nanotube van der Waals Heterostructure.

The exceptional thermal conductivity and strength of carbon nanotubes (CNTs) position them as outstanding materials for thermal conduction. The intriguing properties introduced by van der Waals (vdW) heterojunctions have also captured the interest of researchers. However, further refinement of the research concerning the integration of these two elements is required. In our study, a vdW heterostructure with asymmetric layer nesting of multiwalled CNTs (ALCNTs) is devised, with a specific focus on the model's heat flux and thermal rectification (TR) properties, which are analyzed using nonequilibrium molecular dynamics (NEMD). Notably, the greatest TR ratio is observed in the connection of three-layer and single-layer ALCNTs. Moreover, multilayer variable-length nested models exhibit a sluggish TR ratio. An examination of the interface thermal resistance (ITR) reveals that the maximum ITR in the multilayer nested model resides at the rightmost interface. However, it is essential to highlight that the determinant of the TR ratio and heat flux in the multilayer nested model is not the maximum ITR of the rightmost interface but rather the ITR of the outermost layer on the left. Additionally, the impacts of the defect density, length, temperature difference, and hydrogenation on the model's heat flux and TR are explored, yielding noteworthy conclusions. For instance, defects in the outer CNT have a minimal influence on the heat flux and TR compared with those in the inner CNT. As the length increases, the heat flux initially decreases and then increases. Hydrogenation significantly enhances the model's heat flux but does not favor the TR. Our study contributes to advancing the understanding of CNT vdW heterojunctions and offers valuable insights for their practical applications.

Targeting Estrogen Receptor Beta Ameliorates Diminished Ovarian Reserve via Suppression of the FOXO3a/Autophagy Pathway.

Diminished ovarian reserve (DOR) refers to a decrease in the number and/or quality of oocytes, leading to infertility, poor ovarian response and adverse pregnancy outcomes. Currently, the pathogenesis of DOR is largely unknown, and the efficacy of existing therapeutic methods is limited. Therefore, in-depth exploration of the mechanism underlying DOR is highly important for identifying molecular therapeutic targets for DOR. Our study showed that estrogen receptor beta (ERß) mRNA and protein expression was upregulated in granulosa cells (GCs) from patients with DOR and in the ovaries of DOR model mice. Mechanistically, elevated ERß promotes forkhead transcription factor family 3a (FOXO3a) expression, which contributes to autophagic activation in GCs. Activation of FOXO3a/autophagy signalling leads to decreased cell proliferation and increased cell apoptosis and ultimately leads to DOR. In a cyclophosphamide (Cy)-induced DOR mouse model, treatment with PHTPP, a selective ERß antagonist, rescued fertility by restoring normal sex hormone secretion, estrus cycle duration, follicle development, oocyte quality and litter size. Taken together, these findings reveal a pathological mechanism of DOR based on ERß overexpression and identify PHTPP as a potential therapeutic agent for DOR.

Mechanism of V-Shaped Pits on Promoting Hole Injection in the InGaN MQWs: First-Principles Investigation.

In the InGaN multiple quantum wells (MQWs), V-shaped pits play a crucial role in carrier transport, which directly affects emitting efficiency. First-principles calculations are applied to investigate the formation of the V-shaped pits, and the results indicate that they are inclined to form in the N-rich environment. Meanwhile, we calculate the interfacial electronic properties of the sidewalls of the V-shaped pits with varying indium (In) and magnesium (Mg) compositions. The calculated valence band offset (VBO) of the In0.3Ga0.7N/Ga0.94Mg0.06N (0001) is 0.498 eV, while that of the In0.07Ga0.93N/Ga0.94Mg0.06N (101̅1) is 0.340 eV. The band alignment results show that the valence band edges in the Ga1-yMgyN layer are in higher energy than in the InxGa1-xN layer. These are in good agreement with the values reported in the previous numerical simulation. Moreover, the calculation of the projected density of states (PDOS) of interfaces discloses that the strong hybridization between the N 2p orbital and the Mg 2p orbital exerts a vital influence on the upward shifts of the valence band edges in the superlattices (SLs). All these results reveal that holes are easier to inject into the quantum wells (QWs) via the sidewall of V-shaped pits rather than the c-plane QWs, providing a theoretical basis for the growth of InGaN MQWs samples containing V-shaped pits.

Fluorescent sensor based on bismuth metal-organic frameworks (Bi-MOFs) mimic enzyme for H2O2 detection in real samples and distinction of phenylenediamine isomers.

Although peroxidase-like nano-enzymes have been widely utilized in biosensors, nano-enzyme based biosensors are seldom used for both quantitative analysis of H2O2 and differentiation of isomers of organic compounds simultaneously. In this study, a dual-functional mimetic enzyme-based fluorescent sensor was constructed using metal-organic frameworks (Bi-MOFs) with exceptional oxidase activity and fluorescence properties. This mimetic enzyme sensor facilitated quantitative analysis of H2O2 and accurate discrimination of phenylenediamine isomers. The sensor exhibited a wide linear range (0.5-400 µM) and low detection limit (0.16 µM) for the detection of H2O2. Moreover, the sensor can also be used for the discrimination of phenylenediamine isomers, in which the presence of o-phenylenediamine (OPD) leads to the appearance of a new fluorescence emission peak at 555 nm, while the presence of p-phenylenediamine (PPD) significantly quenched its fluorescence due to the internal filtration effect. The proposed strategy exhibited a commendable capability in distinguishing phenylenediamine isomers, thereby paving the way for novel applications of MOFs in the field of environmental science.

Low molecular weight fucoidan LF2 improves the immunosuppressive tumor microenvironment and enhances the anti-pancreatic cancer activity of oxaliplatin.

Chemotherapy remains the cornerstone of pancreatic cancer treatment. However, the dense interstitial and immunosuppressive microenvironment frequently render the ineffective anti-tumor activity of chemotherapeutic agents. Macrophages play a key role in the tumor immunomodulation. In this study, we found that low molecular weight of fucoidan (LF2) directly regulated the differentiation of mononuclear macrophages into the CD86+ M1 phenotype. LF2 significantly upregulated the expressions of M1 macrophage-specific cytokines, including iNOS, IL-6, TNFα and IL-12. LF2 modulated macrophage phenotypic transformation through activation of TLR4-NFκB pathway. Furthermore, we observed that LF2 enhanced the pro-apoptotic activity of oxaliplatin (OXA) in vitro by converting macrophages to a tumoricidal M1 phenotype. Meanwhile, LF2 increased intratumoral M1 macrophage infiltration and ameliorated the immunosuppressed tumor microenvironment, which in turn enhanced the anti-pancreatic ductal adenocarcinoma (PDAC) activity of OXA in vivo. Taken together, our results suggested that LF2 could act as a TLR4 agonist targeting macrophages and has a synergistic effect against PDAC when combined with OXA.