Brief Pup Separation in Lactation Confers Stress Resistance with Increased Prolactin and Adult Hippocampal Neurogenesis in Postpartum C57BL/6J Dams.

Prolactin (PRL) assumes a pivotal role during the postpartum phase, particularly within the hippocampus-a region densely populated with receptors for stress hormones, where stress significantly inhibits adult hippocampal neurogenesis (AHN). The reduction in neurogenesis is implicated in the pathogenesis of anxiety and depression. Mothers are at an increased risk of developing depression when exposed to chronic stress. Therefore, it is imperative to investigate the potential role of PRL in depression-like behaviors stemming from prolonged postpartum stress, and to explore any underlying mechanisms. Despite pup separation (PS) being a natural postpartum care practice, the impact of various PS methods on lactating dams remains uncertain. Lactating C57BL/6J mice, from postpartum day (PPD) 1 to PPD 21, underwent no PS (NPS), brief PS (15 min per day, PS15), or long PS (180 min per day, PS180), followed by 21 days of chronic restraint stress (CRS). Behavioral tests were conducted, and measurements included serum PRL concentration, PRL-R expression, and AHN in the hippocampus. Dams with CRS exhibited cognitive decline, depressive- and anxiety-like behaviors, and reduced PRL secretion, correlating with lower levels of AHN. PS15 dams displayed lower levels of depressive- and anxiety-like behaviors and cognitive decline compared to NPS and PS180 dams. Significantly, PS15 dams exhibited higher levels of AHN, PRL-R expression in the hippocampus, and serum PRL concentration. This study collectively reveals reduced serum PRL and AHN in dams with cognitive decline and depressive- and anxiety-like behaviors after CRS. Brief PS confers resistance to behavioral deficits after CRS, increasing serum PRL concentration and reversing AHN decrease in dams.

Serum biomarker-based risk model construction for primary Sjögren's syndrome with interstitial lung disease.

Background: Cytokine network disturbances in primary Sjögren's syndrome (pSS) have been reported in many studies. However, their functions in patients with primary Sjögren's syndrome and interstitial lung disease (pSS-ILD) is controversial. In this study, we aim to investigate the associations of immunological characteristics and cytokine profiles with pSS-ILD pathogenesis and explore their predictive values for pSS progression. Methods: A total of 256 patients initially diagnosed with pSS at Henan Provincial People's Hospital were enrolled. After excluding the patients previously diagnosed with various serious acute and chronic respiratory system diseases and cases with other connective tissue diseases or congenital heart diseases, 94 pSS patients were included for further analysis, including 40 patients with ILD (pSS-ILD) and 54 patients without ILD (pSS-N-ILD). For comparison, 41 age- and sex-matched healthy individuals were included as normal controls. Their clinical symptoms and serological data including cyclic citrullinated peptide (CCP) antibody (anti-CCP), antinuclear antibody (ANA), anti-Ro52, anti-SSA, anti-SSB, C-reactive protein, IgG, IgM, IgA, C3, C4, and 10 cytokines and chemokines were obtained. Wilcoxon test, chi-square test, Spearman correlation analysis, and logistics regression analysis were performed. Results: Higher positive rates of anti-SSB and higher incidence of dry cough, dyspnea, and arthrosis symptoms were shown in pSS-ILD patients than in the pSS-N-ILD cases. Anti-CCP antibodies and cytokines (IL-1ß, TNFα, IL-6, IL-5, IL-12p70, and IL-17) were higher, while C3 was lower in pSS-ILD patients than in pSS-N-ILD cases. Significant negative correlations of IgG with C3 and C4 and positive correlations of IL-12p70 and IL-17 with IL-6 were only shown in pSS-ILD patients. The anti-CCP antibody was positively correlated with IL-5 in pSS-ILD patients, but not in pSS-N-ILD cases. Multi-variable logistics regression analysis revealed the combination of anti-CCP, IL-17, IL-12p70, and IL-5 was effective in predicting the status of pSS-ILD in the pSS cases. Conclusion: There were significant differences in serum marker levels between pSS-ILD and pSS-N-ILD cases. The combination of anti-CCP, IL-17, IL-12p70, and IL-5 might be a potential risk predictor for pSS-ILD occurrence. The cytokines might be involved in the development and progression of pSS-ILD. These results would provide new therapeutic targets for pSS-ILD treatment.

A Cyclometalated Iridium(III) Complex Exerts High Anticancer Efficacy via Fatty Acid Beta-Oxidation Inhibition and Sphingolipid Metabolism Reprogramming.

Given the extensive role of lipids in cancer development, there is substantial clinical interest in developing therapies that target lipid metabolism. In this study, we identified one cyclometalated iridium complex (Ir2) that exhibits potent antiproliferation activity in MIA PaCa-2 cells by regulating fatty acid metabolism and sphingolipid metabolism simultaneously. Ir2 also efficiently overcomes cisplatin resistance in vitro. Satisfyingly, the generated Ir2@F127 carriers, as a temperature-sensitive in situ gelling system of Ir2, showed effective cancer treatment with minimal side effects in an in vivo xenograft study. To the best of our knowledge, Ir2 is the first reported cyclometalated iridium complex that exerts anticancer activity in MIA PaCa-2 cells by intervening in lipid metabolism, which provides an alternative pathway for the anticancer mechanism of cyclometalated iridium complexes.

Comparative Analysis of Chemical Profiles and Biological Activities of Essential Oils Derived from Torreya grandis Arils and Leaves: In Vitro and In Silico Studies.

Torreya grandis (T. grandis, Taxaceae) is a well-known nut tree species. Its fruit aril and leaves possess a unique aroma, making it an ideal natural raw material for extracting essential oils (EOs). This study aims to comprehensively compare the composition, biological activities, and pharmacological mechanism of EOs extracted from the arils (AEO) and leaves (LEO) of T. grandis. The results revealed that the chemical composition of the two EOs was highly consistent, with α-pinene and D-limonene as the main components. Both EOs significantly reduced cellular melanin production and inhibited tyrosinase activity in α-MSH-stimulated B16 cells (p < 0.05). AEO and LEO suppressed inflammatory responses in LPS-stimulated RAW 264.7 macrophages, significantly inhibiting cellular NO production and proinflammatory cytokines such as TNF-α and IL-6 (p < 0.05). A network pharmacology analysis reveals that AEO and LEO share similar molecular mechanisms and pharmacological pathways for treating skin pigmentation and inflammation. Regulating inflammatory cytokines may be a critical pathway for AEO and LEO in treating skin pigmentation. These findings suggest that AEO and LEO have potential for cosmetic applications. The leaves of T. grandis could be a valuable source of supplementary materials for producing T. grandis aril EO.

Effects of two-person synchronized cycling exercise on interpersonal cooperation: A near-infrared spectroscopy hyperscanning study.

Objective: Although psychological research indicating the synchronous activities can promote interpersonal cooperation, thus far there is no direct evidence that two-person synchronous exercise effectively enhances interpersonal cooperative behaviors in Physical exercise field. This suggests that, although synchronization phenomenon is widespread in sports and is considered a potential tool for enhancing teamwork, its specific effects and functioning mechanisms still need to be clarified by further scientific research. This study intends to use two-person synchronized cycling exercise to investigate the synchronized exercise effect on interpersonal cooperative behavior and its underlying neural mechanisms. Methods: Eighty college students without regular exercise habits will be randomly assigned to the experimental group (10 male dyads and 10 female dyads) and the control group (10 male dyads and 10 female dyads). During the experiment, dyads in the experimental group performed a 30-minute synchronized cycling exercise with synchronized pedaling movements; dyads in the control group rested sedentary in the same environment for 30 minutes. Interpersonal cooperative behavior was assessed with the Prisoner's Dilemma task, and the interpersonal neural synchronization(INS) data were collected in the prefrontal cortex using near-infrared hyperscanning. Results: This study compared behavior and brain activity before and after synchronous exercise. Behavioral results revealed that, compared to pre-exercise, dyads in the post-exercise had higher average cooperation rates, higher cooperation efficiency and shorter cooperation response times. Compared to post-sedentary, dyads in the post-exercise had shorter cooperation response times and higher cooperation efficiency. Furthermore, brain data showed that,compared to pre-exercise, dyads in the post-exercise had stronger INS in the dorsolateral prefrontal cortex(DLPFC), whereas the dyads in the post-exercise had stronge INS in the DLPFC compared to post-sedentary. After controlling for dyads' anxiety and mood states, this study also found a marginally significant negative correlation between INS differences in the left DLPFC and cooperation response time differences. Conclusions: This research confirms, from both behavioral and neuroscience perspectives, that one synchronization cycle can significantly enhance interpersonal cooperative behavior, and this positive effect is closely associated with increased INS in the left DLPFC. This study provides new insights into understanding how positive interactive exercises promote interpersonal cooperation through specific neural mechanisms.

Endoplasmic reticulum-targeting fluorescence turn-on probe for nitric oxide detection in living cells and serum samples.

Nitric oxide (NO) is an important gas signaling molecule, and endoplasmic reticulum (ER) stress induced by NO may be related to the pathogenesis of many diseases. Therefore, the development of ER-targeted fluorescent probes for NO is of great significance to investigate the relationship between ER stress and NO concentration changes in related diseases. Herein, an ER-targeted fluorescent probe (ER-Np) for sensing NO was constructed. ER-Np was served as an excellent tool for detection NO with high selectivity, sensitivity and ER-targetable ability. Moreover, fluorescence imaging experiments indicated that ER-Np is capable of imaging NO in living cells. Impressively, visualization of endogenous NO production during dithiothreitol (DTT)-induced ER stress in living cells was successfully observed. In addition, we found that serum NO levels were upregulated in epilepsy children, which opens up a new avenue for further understanding the relationship between the diagnostic of epilepsy.

Strategically Engineered Ru(II) Complexes with Enhanced ROS Activity Enabling Potent Sonodynamic Effect against Multidrug-Resistant Biofilms.

Sonodynamic therapy (SDT) can generate reactive oxygen species (ROS) to combat multidrug-resistant biofilms, which pose significant challenges to human health. As the key to producing ROS in SDT, the design of sonosensitizers with optimal molecular structures for sufficient ROS generation and activity in complex biofilm matrix is essential. In this study, we propose a π-expansion strategy and synthesize a series of small-molecule metal Ru(II) complexes (Ru1-Ru4) as sonosensitizers (Ru1-Ru4) to enhance the efficacy of SDT. Among these complexes, Ru4 demonstrates remarkable ROS generation capability (∼65.5-fold) that surpasses most commercial sonosensitizers (1.3- to 6.7-fold). Through catalyzing endogenous H2O2 decomposition, Ru4 facilitates the production of abundant O2 as a resource for 1O2 and the generation of new ROS (i.e., •OH) for improving SDT. Furthermore, Ru4 maintains the sustained ROS activity via consuming the interferences (e.g., glutathione) that react with ROS. Due to these unique advantages, Ru4 exhibits potent biofilm eradication ability against methicillin-resistant Staphylococcus aureus (MRSA) both in vitro and in vivo, underscoring its potential use in clinical settings. This work introduces a new approach for designing effective sonosensitizers to eliminate biofilm infections, addressing a critical need in healthcare management.

Basal forebrain-lateral habenula inputs and control of impulsive behavior.

Deficits in impulse control are observed in several neurocognitive disorders, including attention deficit hyperactivity (ADHD), substance use disorders (SUDs), and those following traumatic brain injury (TBI). Understanding brain circuits and mechanisms contributing to impulsive behavior may aid in identifying therapeutic interventions. We previously reported that intact lateral habenula (LHb) function is necessary to limit impulsivity defined by impaired response inhibition in rats. Here, we examine the involvement of a synaptic input to the LHb on response inhibition using cellular, circuit, and behavioral approaches. Retrograde fluorogold tracing identified basal forebrain (BF) inputs to LHb, primarily arising from ventral pallidum and nucleus accumbens shell (VP/NAcs). Glutamic acid decarboxylase and cannabinoid CB1 receptor (CB1R) mRNAs colocalized with fluorogold, suggesting a cannabinoid modulated GABAergic pathway. Optogenetic activation of these axons strongly inhibited LHb neuron action potentials and GABA release was tonically suppressed by an endogenous cannabinoid in vitro. Behavioral experiments showed that response inhibition during signaled reward omission was impaired when VP/NAcs inputs to LHb were optogenetically stimulated, whereas inhibition of this pathway did not alter LHb control of impulsivity. Systemic injection with the psychotropic phytocannabinoid, Δ9-tetrahydrocannabinol (Δ9-THC), also increased impulsivity in male, and not female rats, and this was blocked by LHb CB1R antagonism. However, as optogenetic VP/NAcs pathway inhibition did not alter impulse control, we conclude that the pro-impulsive effects of Δ9-THC likely do not occur via inhibition of this afferent. These results identify an inhibitory LHb afferent that is controlled by CB1Rs that can regulate impulsive behavior.

Mechanism understanding of PIKfyve inhibitor YM201636 with human serum albumin: Insights from molecular modeling and multiple spectroscopic techniques.

YM201636 is the potent PIKfyve inhibitor that is being actively investigated for liver cancer efficacy. In this study, computer simulations and experiments were conducted to investigate the interaction mechanism between YM201636 and the transport protein HSA. Results indicated that YM201636 is stably bound between the subdomains IIA and IIIA of HSA, supported by site marker displacement experiments. YM201636 quenched the endogenous fluorescence of HSA by static quenching since a decrease in quenching constants was observed from 7.74 to 2.39 × 104 M-1. UV-vis and time-resolved fluorescence spectroscopy confirmed the YM201636-HSA complex formation and this binding followed a static mechanism. Thermodynamic parameters ΔG, ΔH, and ΔS obtained negative values suggesting the binding was a spontaneous process driven by Van der Waals interactions and hydrogen binding. Binding constants ranged between 5.71 and 0.33 × 104 M-1, which demonstrated a moderately strong affinity of YM201636 to HSA. CD, synchronous, and 3D fluorescence spectroscopy revealed that YM201636 showed a slight change in secondary structure. The increase of Kapp and a decrease of PSH with YM201636 addition showed that YM201636 changed the surface hydrophobicity of HSA. The research provides reasonable models helping us further understand the transportation and distribution of YM201636 when it absorbs into the blood circulatory system.

The double-layer emulsions loaded with bitter melon (Momordica charantia L.) seed oil protect against dextran sulfate sodium-induced ulcerative colitis in mice.

In this study, a whey protein isolate (WPI)-chitooligosaccharide (COS) stabilized bitter melon (Momordica charantia L.) seed oil emulsions (WC-BSOE) were prepared using the electrostatic layer-by-layer self-assembly technique, and their modulating effects on ulcerative colitis (UC) were investigated in dextran sulfate sodium (DSS)-induced UC mice model. The stability and releasing ability of WC-BSOE under simulated gastrointestinal digestion condition and their acute toxicity were also investigated. The results showed that WC-BSOE was stable to droplet aggregation in the simulated gastric and intestinal fluids and exhibited sustained release profile during gastrointestinal transit, evidenced by the measurement of particle size, polydispersity index, zeta-potential and released free fatty acids contents. Moreover, WC-BSOE had no toxic effects on BALB/c mice within the dose range of 40,000 mg/kg body weight (BW), and treatment with WC-BSOE at a dosage of 15 mg/kg BW effectively relieved DSS-induced UC symptoms in mice. Furthermore, WC-BSOE could improve the IL-4 and IgA contents in serum, as well as up-regulate the occludin and ZO-1 expressions and down-regulate MPO, MDA and ROS levels in colon tissues of colitis mice, and it also elevated the diversity and relative abundances of Firmicutes, Bacteroides, and Lactobacillus in the intestinal microbiota. These findings indicated that WC-BSOE exerted protective effects in UC through decreasing proinflammatory cytokines, increasing tight junction proteins, suppressing oxidative stress, and regulating intestinal microbiota. Collectively, this study suggested WC-BSOE might be developed as a promising dietary supplement for UC protection.

Acyl chloride-mediated synthesis of rhodanine-modified UiO-66 for high-efficiency silver recovery.

Silver (Ag) recovery is essential for ecological protection, human health and economic benefits. Effective capture of Ag(I) from wastewater is still challenging due to insufficient accessible sites of adsorbents. Herein, an acyl chloride-mediated strategy is developed to synthesize rhodanine (Rd) modified UiO-66 derivatives for Ag(I) adsorption. Benefitting from the high grafting density of Rd, the optimal Rd-modified UiO-66-NH2 (UiO-66-NH2@20Rd) features an ultra-high uptake capacity (maximum capacity of 923.9 mg·g-1) and selectivity (maximum selectivity coefficient of 1665.52) for Ag(I). Almost 90 % of Ag(I) could be captured in one minute over UiO-66-NH2@20Rd and maintained a removal rate of 98.9 % even after six cycles. Moreover, a fixed-bed column test demonstrates that approximately 21,780 bed volumes of Ag(I) simulated wastewater can be effectively treated, indicating great promise for practical application. Mechanism investigation illustrates that outstanding performance can be attributed to the synergistic effect of Ag(I) adsorption and reduction on dense rhodanine sites. This study highlights that such a general strategy can provide a valuable avenue toward various functional adsorption materials.

VTA glutamatergic projections to the nucleus accumbens suppress psychostimulant-seeking behavior.

Converging evidence indicates that both dopamine and glutamate neurotransmission within the nucleus accumbens (NAc) play a role in psychostimulant self-administration and relapse in rodent models. Increased NAc dopamine release from ventral tegmental area (VTA) inputs is critical to psychostimulant self-administration and NAc glutamate release from prelimbic prefrontal cortex (PFC) inputs synapsing on medium spiny neurons (MSNs) is critical to reinstatement of psychostimulant-seeking after extinction. The regulation of the activity of MSNs by VTA dopamine inputs has been extensively studied, and recent findings have demonstrated that VTA glutamate neurons target the NAc medial shell. Here, we determined whether the mesoaccumbal glutamatergic pathway plays a role in psychostimulant conditioned place preference and self-administration in mice. We used optogenetics to induce NAc release of glutamate from VTA inputs during the acquisition, expression, and reinstatement phases of cocaine- or methamphetamine-induced conditioned place preference (CPP), and during priming-induced reinstatement of cocaine-seeking behavior. We found that NAc medial shell release of glutamate resulting from the activation of VTA glutamatergic fibers did not affect the acquisition of cocaine-induced CPP, but it blocked the expression, stress- and priming-induced reinstatement of cocaine- and methamphetamine CPP, as well as it blocked the priming-induced reinstatement of cocaine-seeking behavior after extinction. These findings indicate that in contrast to the well-recognized mesoaccumbal dopamine system that is critical to psychostimulant reward and relapse, there is a parallel mesoaccumbal glutamatergic system that suppresses reward and psychostimulant-seeking behavior.

Mapping Brain Synergy Dysfunction in Schizophrenia: Understanding Individual Differences and Underlying Molecular Mechanisms.

To elucidate the brain-wide information interactions that vary and contribute to individual differences in schizophrenia (SCZ), an information-resolved method is employed to construct individual synergistic and redundant interaction matrices based on regional pairwise BOLD time-series from 538 SCZ and 540 normal controls (NC). This analysis reveals a stable pattern of regionally-specific synergy dysfunction in SCZ. Furthermore, a hierarchical Bayesian model is applied to deconstruct the patterns of whole-brain synergy dysfunction into three latent factors that explain symptom heterogeneity in SCZ. Factor 1 exhibits a significant positive correlation with Positive and Negative Syndrome Scale (PANSS) positive scores, while factor 3 demonstrates significant negative correlations with PANSS negative and general scores. By integrating the neuroimaging data with normative gene expression information, this study identifies that each of these three factors corresponded to a subset of the SCZ risk gene set. Finally, by combining data from NeuroSynth and open molecular imaging sources, along with a spatially heterogeneous mean-field model, this study delineates three SCZ synergy factors corresponding to distinct symptom profiles and implicating unique cognitive, neurodynamic, and neurobiological mechanisms.

Wheel Running During Pregnancy Alleviates Anxiety-and Depression-Like Behaviors During the Postpartum Period in Mice: The Roles of NLRP3 Neuroinflammasome Activation, Prolactin, and the Prolactin Receptor in the Hippocampus.

Despite the increase in the prevalence of postpartum depression among maternal disorder, its treatment outcomes remain suboptimal. Studies have shown that exercise can reduce postpartum depressive episodes in the mother, but the effects of exercise during pregnancy on maternal behavior and the potential mechanisms involved remain poorly understood. From the second day of pregnancy to the day of birth, dams exercised for 1 h a day by running on a controlled wheel. The maternal behaviors of the dams were assessed on postpartum day 2 to postpartum day 8. Chronic restraint stress was applied from postpartum day 2 to day 12. Blood was collected on postpartum days 3 and 8, then subjected to ELISA to determine the serum concentration of prolactin. The weight of each dam and the food intake were recorded. Anxiety- and depression-like behavioral tests were conducted, and hippocampal neuroinflammation and prolactin receptor levels were measured. The dams exhibited elevated levels of anxiety and depression, decreased serum prolactin levels, decreased prolactin receptor expression, and activation of NLRP3-mediated neuroinflammation in the hippocampus following the induction of postpartum chronic restraint stress, which were reversed with controlled wheel running during pregnancy. Overall, the findings of this study revealed that the preventive effects of exercise during pregnancy on postpartum anxiety-and depression-like behaviors were accompanied by increased serum prolactin levels, hippocampal prolactin receptor expression and hippocampal NLRP3-mediated neuroinflammation.

Potentially functional variants of CHMP4A and PANX1 in the pyroptosis-related pathway predict survival of patients with non-oropharyngeal head and neck squamous cell carcinoma.

BACKGROUND: Pyroptosis has been implicated in the advancement of various cancers. Triggering pyroptosis within tumors amplifies the immune response, thereby fostering an antitumor immune environment. Nonetheless, few published studies have evaluated associations between functional variants in the pyroptosis-related genes and clinical outcomes of patients with non-oropharyngeal head and neck squamous cell carcinoma (NON-ORO HNSCC). METHODS: We conducted an association study of 985 NON-ORO HNSCC patients who were randomly divided into two groups: the discovery group of 492 patients and the replication group of 493 patients. We used Cox proportional hazards regression analysis to examine associations between genetic variants of the pyroptosis-related genes and survival of patients with NON-ORO HNSCC. Bayesian false discovery probability (BFDP) was used for multiple testing correction. Functional annotation was applied to the identified survival-associated genetic variants. RESULTS: There are 8254 single-nucleotide polymorphisms (SNPs) located in 82 pyroptosis-related genes, of which 202 SNPs passed multiple testing correction with BFDP < 0.8 in the discovery and six SNPs retained statistically significant in the replication. In subsequent stepwise multivariable Cox regression analysis, two independent SNPs (CHMP4A rs1997996 G > A and PANX1 rs56175344 C > G) remained significant with an adjusted hazard ratios (HR) of 1.31 (95% confidence interval [CI] = 1.09-1.57, p = 0.004) and 0.65 (95% CI = 0.51-0.83, p = 0.0005) for overall survival (OS), respectively. Further analysis of the combined genotypes revealed progressively worse OS associated with the number of unfavorable genotypes (ptrend < 0.0001 and 0.021 for OS and disease-specific survival, respectively). Moreover, both PANX1 rs56175344G and CHMP4A rs1997996A alleles were correlated with reduced mRNA expression levels. CONCLUSIONS: Genetic variants in the pyroptosis pathway genes may predict the survival of NON-ORO HNSCC patients, likely by reducing the gene expression, but our findings need to be replicated by larger studies.

Involvement of the TRPV1 receptor and the endocannabinoid system in schizophrenia.

BACKGROUND: Schizophrenia (SCZ) is a severe mental disorder, but its pathogenesis is still unknown, and its clinical treatment effect is very limited. Transient receptor potential vanilloid 1 (TRPV1) channel and the Endocannabinoid System (ECS)have been confirmed to be involved in the pathogenesis of SCZ, although their actions have not been fully clarified yet. The objective is to examine TRPV1 and ECS expression in the blood of schizophrenia patients and investigate their correlation with disease severity. METHODS: This is a cross-sectional investigation. Peripheral blood samples were gathered from normal controls (NC, n=37), as well as individuals with schizophrenia, including first episode (n=30) and recurrent (n=30) cases. We employed western blot and ELISA techniques to quantify TRPV1, cannabinoid receptors 1(CB1), anandamide (AEA), and 2-arachidonoylglycerol (2-AG), and assess the severity of the patient's symptoms by means of the PANSS scale. RESULTS: Compared to NC, TRPV1 levels showed a noticeable decrease in both first episode schizophrenia (f-SCZ group) and recurrent schizophrenia (r-SCZ group) subjects. Additionally, CB1 levels appeared increased in f-SCZ group. Furthermore, 2-AG levels were found to be elevated in both f-SCZ group and r-SCZ group compared to NC, whereas AEA levels were decreased in f-SCZ group but increased in r-SCZ group. Moreover, among schizophrenia patients, TRPV1 demonstrated a negative correlation with negative symptoms. Within r-SCZ subjects, CB1 displayed a negative correlation with relapse number, while 2-AG showed a correlation in the opposite direction. CONCLUSIONS: This study provides initial clinical evidence of changed TRPV1 expression in schizophrenia, potentially linked to negative symptoms. These results suggest a possible dysfunction of TRPV1 and the endocannabinoid system (ECS), which might offer new avenues for medical interventions.

Toxicological evaluation and preliminary exposure assessment on glycerol monocaprylate.

As a commonly used food preservative, glycerol monocaprylate (GMC) has limited information and lacked a comprehensive risk assessment. In this study, we conducted in vitro genotoxicity tests, a 90-day subchronic toxicity study, and dietary exposure assessment in China. Rats (n = 10/sex/group) were orally administered GMC at doses of 1.02, 2.04, and 4.08 g/kg BW/day along with a water and corn oil for 90 days, including satellite groups (n = 5/sex/group) in the control groups and 4.08 g/kg BW dose group for observation after 90 days. Body weight, food consumption, hematology, serum biochemistry, urinalysis, endocrine hormone level and other metrics were examined. GMC did not exhibit genotoxicity based on the genotoxicity tests results, and an acceptable daily intake (ADI) of 40.8 mg/kg BW/day was established based on the 90-day subchronic toxicity study. Estimated daily intake of GMC for general population and consumer population in China were 0.99 mg/kg BW/day and 3.19 mg/kg BW/day respectively, which were significantly lower than the ADI. Our findings suggest that GMC does not pose a known health risk to Chinese consumers at the current usage level.

M-F noncoding region sequences of H1 genotype measles virus provide higher resolution for virus transmission tracing.

As countries and regions move toward measles elimination, extended sequence window including noncoding region located between the matrix and fusion protein genes (M - F NCR) was considered to be used in molecular surveillance. The molecular resolution of M - F NCR was evaluated with 192 genotype H1 strains circulating during 2011-2018 in China. Phylogenetic analyses of the N450 and M - F NCR targets indicated that both two targets could confirm epi-linked outbreak, while M - F NCR target could further improve resolution of the molecular characterization: (1) it could differentiate the strains with identical N450 circulated in one county within one month of disease onset; (2) different transmission chains could be distinguished for strains with identical N450; (3) better spatial-temporal consistency with topology could be provided among sporadic cases with inconsistent N450. Accordingly, M - F NCR could be used to complement the information from N450 to address the specific questions in tracking the virus transmission chains.

The gelation characteristics of Torreya grandis wax in diacylglycerol and its preparation of oleogel substitution for shortening.

Torreya grandis wax (TGW), a new nut wax and by-product of refined Torreya grandis oil, lacks sufficient research and application. In this study, the gelling behavior in diacylglycerol (DAG) and chemical compositions of TGW were investigated. Compared with four typical natural waxes, TGW exhibited the lowest critical gelling concentration (Cg, 1 %wt) in DAG. The results performed that TGW-DAG oleogels at Cg possessed the highest G'LVR and G″, highest critical stress, good thermal stability, moderate viscosity recovery, and osc. yields stress, indicating strong gel. The microstructure and correlation analysis revealed that excellent gelling behaviors of TGW-DAG oleogels were due to the solid three-dimensional network formed by rod-like TGW crystal, and the higher hydrocarbon compound (HC) content and HC/wax ester in TGW. Formulation optimization suggested that oleogel containing 3.2 % TGW and 1.0 % diosgenin (DSG) better mimicked the characteristics of shortening in terms of hardness, adhesiveness, spreadability. The bread prepared with TGW/DSG-DAG oleogel owned uniform and dense pores, the best moisture retention capability, and soft and firm taste, demonstrating that TGW/DSG-DAG oleogel was a good shortening substitute. Therefore, this study provides the systematically fundamental knowledge of TGW and develops DSG-TGW-DAG oleogels as promising shortening substitutions.