Enteral Route Nanomedicine for Cancer Therapy.

With the in-depth knowledge of the pathological and physiological characteristics of the intestinal barrier-portal vein/intestinal lymphatic vessels-systemic circulation axis, oral targeted drug delivery is frequently being renewed. With many advantages, such as high safety, convenient administration, and good patient compliance, many researchers have begun to explore targeted drug delivery from intravenous injections to oral administration. Over the past few decades, the fields of materials science and nanomedicine have produced various drug delivery platforms that hold great potential in overcoming the multiple barriers associated with oral drug delivery. However, the oral transport of particles into the systemic circulation is extremely difficult due to immune rejection and biochemical invasion in the intestine, which limits absorption and entry into the bloodstream. The feasibility of the oral delivery of targeted drugs to sites outside the gastrointestinal tract (GIT) is unknown. This article reviews the biological barriers to drug absorption, the in vivo fate and transport mechanisms of drug carriers, the theoretical basis for oral administration, and the impact of carrier structural evolution on oral administration to achieve this goal. Finally, this article reviews the characteristics of different nano-delivery systems that can enhance the bioavailability of oral therapeutics and highlights their applications in the efficient creation of oral anticancer nanomedicines.

Enrichment characteristics of Cd and Hg and regulation of heavy metal transporter signaling in Pleurotus ostreatus.

Currently, heavy metal pollution has emerged as a global issue. Compared with green plants, edible fungi, significant crops cultivated worldwide, present a greater capacity to accumulate heavy metals (HMs). However, the enrichment characteristics and functions of heavy metal transporters (HMATs) in the accumulation of HMs in edible fungi are still unclear. Cadmium (Cd) and mercury (Hg) are the primary HMs enriched in edible fungi. This study focused on Pleurotus ostreatus, the second largest edible mushroom worldwide, to examine the enrichment process. In this study, a series of different concentrations of CdCl2 and HgCl2 (0, 0.01, 0.05, 0.5, 2, 5, 10, and 20 mg/L) were used to mimic HMs pollution. HMs in the experimental concentration range did not affect the mycelial growth rate or fruiting body yield of P. ostreatus. However, in the 20 mg/L treatment group, the HMs were mainly concentrated in the cap, with about 4.4 mg/kg Cd and 2.7 mg/kg Hg, and were predominantly present in the most toxic ion exchange state. Thirteen HMATs were identified in the genome database of P. ostreatus. Using RT-qPCR, seven HMATs (24093, 1066001, 1106787, 1066344, 1079972, 1095088, and 1104877) whose expression levels were more than twice that of the control under most concentrations of HMs were selected for further investigation of their transport functions and their involvement in signal regulation. Among them, gene 24093 was involved in the absorption of Cd and Hg. These transporters are regulated by ROS, Ca2+, and NO signals under HM stress. This study provides target genes for reducing the risk of HM accumulation through molecular means, and serves as a reference for HM remediation using edible fungi.

Deer Blood Hydrolysate Protects against D-Galactose-Induced Premature Ovarian Failure in Mice by Inhibiting Oxidative Stress and Apoptosis.

BACKGROUND: Premature ovarian failure (POF) is a common disease among women, which can cause many complications and seriously threaten women's physical and mental health. Currently, hormone replacement therapy is the primary treatment for premature ovarian failure. However, the side effects are serious and will increase the chance of breast cancer and endometrial cancer. Deer blood hydrolysate (DBH) is the product of enzymatic hydrolysis of deer blood, has antioxidant, anti-ageing, and anti-fatigue effects, and has the potential to improve premature ovarian failure. METHODS: In our experiment, a mouse model of premature ovarian failure was established through intraperitoneal injection of 400 mg/kg/d of D-gal for 42 days. At the same time, different doses of DBH were gavaged to observe its ameliorative effect on premature ovarian failure. RESULTS: The experimental findings indicated that DBH could restore the irregular oestrus cycle of POF mice, improve the abnormal amounts in serum hormones follicle-stimulating hormone (FSH), luteinising hormone (LH), progesterone (P) and estradiol (E2), increase the number of primordial follicles and decrease the number of atretic follicles. In addition, DBH also raised the level of superoxide dismutase (SOD) and reduced the level of malondialdehyde (MDA) and reduced the apoptosis of ovarian granulosa cells in mice. The WB assay results showed that gavage of DBH restored the decrease in the indication of nuclear factor erythroid 2-related factor 2 (Nrf2), Heme Oxygenase-1 (Ho-1), and B-cell lymphoma-2 (Bcl-2) proteins and reduced the elevated expression of Kelch-like ECH-associated protein 1 (Keap1), Bcl-2 associated X protein (Bax), and Cysteinyl aspartate specific proteinase-3 (Caspase-3) proteins that were induced by D-gal. CONCLUSIONS: To sum up, the present research indicated that DBH can ameliorate D-gal-induced oxidative stress and apoptosis by regulating the Nrf2/HO-1 signalling pathway and the Bcl-2/Bax/caspase-3 apoptosis pathway, which can be used for further development as a nutraceutical product to improve premature ovarian failure.

Association between the duration of smoking cessation and α-Klotho levels in the US middle-aged and elderly population.

Background: α-Klotho is a molecule associated with aging and several diseases. Previous studies have reported decreased levels of serum α-Klotho (SαKl) in smokers compared to never smokers. Interestingly, we also found the SαKl level could partly recover in those who quit smoking. The objective of this study was to investigate SαKl levels in the US population who quit smoking for a certain period. Methods: A total of 9268 participants, ranging in age from 40 to 79 years were enrolled in this cross-sectional study, 37.04 % were identified as former smoker. Data from the NHANES conducted between 2007 and 2016 were utilized for analysis. The association between the period of smoking cessation and SαKl levels was evaluated through multivariate linear regression models. Additionally, a detailed analysis stratified by key clinical factors was performed. Results: The mean level of SαKl among the former smoker was 827.41 pg/mL. After full adjustment, the SαKl level increased over time after smoking cessation, with an increase of 1.20 pg/ml per year of abstinence (P = 0.005). The linear correlation persists regardless of the duration of the smoking habit before quitting. In the stratified analysis, a positive correlation was observed between duration of smoking cessation and SαKl levels in individuals aged 60-79 years, females, normal weight individuals, those involved in moderate or vigorous physical activity, and those with a history of cancer (all P<0.05). Conclusion: This study showed a positive association between the duration of smoking cessation and SαKl levels in former smokers. Prolonged abstinence may contribute to increased SαKl levels which may protect people against aging-related diseases.

Robotic Versus Laparoscopic Gastrectomy for Gastric Cancer: The Largest Systematic Reviews of 68,755 Patients and Meta-analysis.

BACKGROUND: This meta-analysis aimed to compare the efficacy of robotic gastrectomy (RG) and laparoscopic gastrectomy (LG) in treating gastric cancer (GC). PATIENTS AND METHODS: A comprehensive literature search across PubMed, MEDLINE, and Web of Science identified 86 eligible studies, including 68,755 patients (20,894 in the RG group and 47,861 in the LG group). RESULTS: The analysis revealed that RG was associated with superior outcomes in several areas: more lymph nodes were harvested, intraoperative blood loss was reduced, postoperative hospital stays were shorter, and the time to first flatus and oral intake was shortened (all p < 0.001). Additionally, RG resulted in lower incidences of conversion to open surgery (OR = 0.62, p = 0.004), reoperation (OR = 0.68, p = 0.010), overall postoperative complications (OR = 0.82, p < 0.001), severe complications (OR = 0.65, p < 0.001), and pancreatic complications (OR = 0.60, p = 0.004). However, RG had longer operative times and higher costs (both p < 0.001). No significant differences were found between RG and LG in terms of resection margin distance, mortality, anastomotic leakage, or recurrence rates. CONCLUSIONS: RG is a safe and effective surgical option for patients of GC, but further improvements in operative duration and costs are needed.

Plant-Derived as Alternatives to Animal-Derived Bioactive Peptides: A Review of the Preparation, Bioactivities, Structure-Activity Relationships, and Applications in Chronic Diseases.

Background/Objectives: At present, a large number of bioactive peptides have been found from plant sources with potential applications for the prevention of chronic diseases. By promoting plant-derived bioactive peptides (PDBPs), we can reduce dependence on animals, reduce greenhouse gas emissions, and protect the ecological environment. Methods: In this review, we summarize recent advances in sustainably sourced PDBPs in terms of preparation methods, biological activity, structure-activity relationships, and their use in chronic diseases. Results: Firstly, the current preparation methods of PDBPs were summarized, and the advantages and disadvantages of enzymatic method and microbial fermentation method were introduced. Secondly, the biological activities of PDBPs that have been explored are summarized, including antioxidant, antibacterial, anticancer and antihypertensive activities. Finally, based on the biological activity, the structure-activity relationship of PDBPs and its application in chronic diseases were discussed. All these provide the foundation for the development of PDBPs. However, the study of PDBPs still has some limitations. Conclusions: Overall, PDBPs is a good candidate for the prevention and treatment of chronic diseases in humans. This work provides important information for exploring the source of PDBPs, optimizing its biological activity, and accurately designing functional foods or drugs.

Incommensurate charge super-modulation and hidden dipole order in layered kitaev material α-RuCl3.

The magnetism of Kitaev materials has been widely studied, but their charge properties and the coupling to other degrees of freedom are less known. Here we investigate the charge states of α-RuCl3, a promising Kitaev quantum spin liquid candidate, in proximity to graphite. We discover that few-layered α-RuCl3 experiences a clear modulation of charge states, where a Mott-insulator to weak charge-transfer-insulator transition in the 2D limit occurs by means of heterointerfacial polarization. More notably, distinct signals of incommensurate charge and lattice super-modulations, regarded as an unconventional charge order, accompanied in the insulator. Our theoretical calculations have reproduced the incommensurate charge order by taking into account the antiferroelectricity of α-RuCl3 that is driven by dipole order in the internal electric fields. The findings imply that there is strong coupling between the charge, spin, and lattice degrees of freedom in layered α-RuCl3 in the heterostructure, which offers an opportunity to electrically access and tune its magnetic interactions inside the Kitaev compounds.

Modulation of empathic abilities by the interplay between estrogen receptors and arginine vasopressin.

This review examines the complex interactions between estrogen receptors α and ß (ERα and ERß) and arginine vasopressin (AVP), delving into their significant roles in modulating empathy, a critical psychological component in human social dynamics. Empathy, integrating affective and cognitive elements, is anchored in neural regions like the amygdala and prefrontal cortex. ERα and ERß, pivotal in estrogen regulation, influence neurotransmitter dynamics and neural network activities, crucial for empathic development. AVP, key in regulating water balance, blood pressure, and social behaviors, interplays with these receptors, profoundly impacting empathic responses. The study highlights that ERα predominantly enhances empathy, especially affective empathy, by stimulating AVP synthesis and release. In contrast, ERß may diminish empathy in certain contexts by suppressing AVP expression and activity. The intricate interplay, homeostatic balance, and mutual conversion between ERα and ERß in AVP regulation are identified as challenging yet crucial areas for future research. These findings provide essential insights into the neurobiological underpinnings of empathy, offering new avenues for therapeutic interventions in social cognitive disorders and emotional dysregulation.

Potential functions and mechanisms of lysine crotonylation modification (Kcr) in tumorigenesis and lymphatic metastasis of papillary thyroid cancer (PTC).

OBJECTIVES: To examine the putative functions and mechanisms of lysine crotonylation (Kcr) during the development and progression of papillary thyroid cancer (PTC). METHODS: Samples of thyroid cancer tissues were collected and subjected to liquid chromatography-tandem mass spectrometry. Crotonylated differentially expressed proteins (DEPs) and differentially expressed Kcr sites (DEKSs) were analyzed by Motif, dynamic expression model analysis (Mfuzz), subcellular localization, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation, Go Ontology (GO) annotation, and protein-protein interaction analysis (PPI). Validation was performed by immunohistochemistry (IHC). RESULTS: A total of 262 crotonylated DEPs and 702 DEKSs were quantitated. First, for the tumor/normal comparison, a dynamic expression model analysis (Mfuzz) of the DEKSs revealed that clusters 1, 3, and 4 increased with the progression of thyroid cancer; however, cluster 6 showed a dramatic increase during the transition from N0-tumor to N1-tumor. Furthermore, based on GO annotation, KEGG, and PPI, the crotonylated DEPs were primarily enriched in the PI3K-Akt signaling pathway, Cell cycle, and Hippo signaling pathway. Of note, crosstalk between the proteome and Kcr proteome suggested a differential changing trend, which was enriched in Thyroid hormone synthesis, Pyruvate metabolism, TCA cycle, Cell cycle, and Apoptosis pathways. Similarly, for the LNM comparison group, the DEKSs and related DEPs were primarily enriched in Hydrogen peroxide catabolic process and Tight junction pathway. Finally, according to The Cancer Genome Atlas Program (TCGA) database, the differential expression of Kcr DEPs were associated with the prognosis of thyroid cancer, indicating the prognostic significance of these proteins. Moreover, based on the clinical validation of 47 additional samples, Kcr was highly expressed in thyroid tumor tissues compared with normal tissue (t = 9.792, P < 0.001). In addition, a positive correlation was observed between Kcr and N-cadherin (r = 0.5710, P = 0.0015). Moreover, N-cadherin expression was higher in the relatively high Kcr expression group (χ2 = 18.966, P < 0.001). CONCLUSIONS: Higher Kcr expression was correlated with thyroid tumorigenesis and lymphatic metastasis, which may regulate thyroid cancer progression by Pyruvate metabolism, TCA cycle, Cell cycle, and other pathways.

Formation of High-Photoresponsivity BaSi2 Films by Radio-Frequency Sputtering and Evaluation of a BaSi2/TiN/Glass Heterojunction by Transmission Electron Microscopy.

Barium disilicide (BaSi2) is a thin-film solar cell material composed of abundant elements, and its application potential is further enhanced by its formation on inexpensive substrates, such as glass. The effect of the substrate temperature on the co-sputtering of BaSi2 and Ba targets to form BaSi2 films on Si(111) and TiN/glass substrates was investigated. Contrary to expectations, the photoresponsivity reached maximum values exceeding 5 and 2 A W-1, respectively, the highest value ever reported for as-deposited samples formed at 750 °C, more than 100 °C higher than those reported previously. Because the photoresponsivity is proportional to carrier lifetime, this result indicates that high-temperature growth can bring out the high performance of BaSi2 as a light-absorbing layer. Because amorphous SiC (a-SiC) has a larger forbidden band gap and electron affinity than BaSi2, it is considered suitable as an electron transport layer (ETL) material for BaSi2 solar cells. On the basis of this, the formation of BaSi2 (absorption layer)/a-SiC (ETL)/TiN (electrode)/glass heterojunctions was also attempted, and the layered structure was examined by cross-sectional transmission electron microscopy (TEM). Polycrystalline BaSi2 films were found to be even on the amorphous layer by TEM. A high photoresponsivity of over 2 A W-1 was obtained. Therefore, the BaSi2/a-SiC/TiN structure provides a guideline for the structural design of BaSi2-based thin-film solar cells on glass.

Enhancing collaboration of anammox with heterotrophic microbes mediated selectively by iron of different valences: Activities balance, metabolic mechanism, and functional genes regulation.

The partial denitrification/anammox (PD/A) process is receiving increasing attention due to its cost-effectiveness advantages. However, effective strategies to alleviate organic matter inhibition and promote anammox activity have been proven to be a big challenge. This study investigated the effects of three types of iron (nano zero-valent iron (nZVI), Fe(II), and Fe(III)) on the PD/A process. It is worth noting that nZVI of 5-50 mg/L and Fe(III) of 5-120 mg/L promoted both PD and anammox activity. Long-term intermittent addition of nZVI (50 mg/L) resulted in a nitrogen removal efficiency of 98.2% in the mixotrophic PD/A system driven by iron and organic matter. The contribution of anammox for nitrogen removal reached as high as 93.8%. The organic carbon demand decreased due to the external electron donor provided by nZVI for PD. Multiple Fe-N metabolic pathways, primarily involving ammonia oxidation by Fe(III) and nitrate reduction by nZVI, play a crucial role in facilitating nitrogen transformation. Conversely, the direct addition of 30-120 mg/L Fe (II) resulted in a significant decrease in pH to below 5.0 and severe inhibition of PD and anammox activity. Following prolonged operation in the presence of nZVI, it was demonstrated that there is an enhancing effect on robust nitrite production for anammox. This was accompanied by a remarkable up-regulation of genes encoding nitrate reductase and iron-transporting proteins dominated by Thauera. Overall, this study has provided an efficient approach for advanced nitrogen removal through organic- and iron-driven anammox processes.

Correlation of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio with serum α-klotho levels in US middle-aged and older individuals: Results from NHANES 2007-2016.

Background: The α-klotho (αKl) is widely accepted as an anti-aging and anti-inflammatory protein. However, it is rarely reported on the function and mechanism of αKl in the overall population (including healthy people and those with history of chronic disease). The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are established as predictors of systemic inflammation. This study aims to investigate the relationship between NLR, PLR, and αKl levels in the overall population. Methods: Data from 10,124 adults aged 40 years old and above, collected from NHANES 2007-2016, were analyzed. Associations between NLR, PLR, and αKl levels were assessed by weighted multivariate linear regression analyses, adjusting for potential confounders. Subgroup analysis was conducted by gender, age, diabetes, cardiovascular disease, and chronic kidney disease. Results: Weighted linear regression models showed that a significant negative correlation was observed between both NLR and PLR with αKl levels. Subgroup analysis revealed that the negative correlation between NLR and serum αKl levels was not significant in individuals aged 40-59 years and males, while this relationship remained stable across most other subgroups. The negative correlation between PLR and serum αKl levels was consistent across most subgroups but not significant in individuals with cardiovascular disease. Conclusion: Our study revealed a significant negative relationship between inflammatory markers (NLR and PLR) and serum αKl levels, suggesting systemic inflammation may be linked to reduced αKl expression. Subgroup analyses showed that the relationship varies across different demographic and health-related factors. We provided insight into the significance of managing inflammation and preserving αKl levels.

Cynomorium songaricum Rupr. flavonoids improve cyclophosphamide-induced reproductive function damage by regulating the testosterone synthesis pathway.

Introduction: The prevalence of male infertility has been increasing globally, necessitating the search for safe and nontoxic active compounds to alleviate reproductive dysfunction. Although the precise mechanism remains unknown, Cynomorium songaricum Rupr. (CS) extract has protective effects on the reproductive system. The effect of C. songaricum Rupr. flavonoids (CSF) on reproductive injury and testicular mesenchymal stem cell viability in male mice and TM3 cells was investigated. Methods: We explored the possible association between these effects and the testosterone (T) synthesis pathway. Mice were administered cyclophosphamide to induce reproductive damage, followed by CSF administration. Body mass and organ index were recorded. Pathological changes in T and the epididymis were observed using hematoxylin-eosin staining. ELISA measured the serum levels of T, luteinizing hormone (LH), gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH), and estradiol (E2) in mice. Fructose and zinc ion levels in the seminal plasma were measured. TM3 cells were treated with Bisphenol A (BPA) and different concentrations of CSF, followed by proliferative evaluations using the CCK-8 assay and T and LH level assessments using ELISA. Furthermore, the expression of steroidogenic enzyme genes and proteins was investigated using western blotting and RT-PCR. Results: CSF exhibited a notable reduction in reproductive damage and improved pathological changes in testicular and epididymal tissues. CSF group demonstrated substantially higher levels of seminal plasma fructose and zinc ions; markedly elevated serum levels of T, LH, GnRH, and FSH; and lower levels of E2 than those of the model group. Intracellular T content and secretion of T and LH increase with CSF while effectively mitigating BPA-induced damage to TM3 cells. CSF group exhibited substantially higher gene and protein expression of steroidogenic enzymes than those of the model group, both in vivo and in vitro. CSF ameliorates reproductive impairment by enhancing the expression of pivotal enzymes involved in synthesizing T. Discussion: CSF ameliorates cyclophosphamide-induced reproductive impairment and bisphenol A-induced TM3 cell damage in mice by regulating sex hormone levels in the Hypothalamic-Pituitary-Gonadal Axis (HPG axis) and upregulating the expression of steroidogenic enzymes. Therefore, CS is a potential treatment for male reproductive impairment.

Pilose Antler Protein Relieves UVB-Induced HaCaT Cells and Skin Damage.

Extended exposure to UVB (280-315 nm) radiation results in oxidative damage and inflammation of the skin. Previous research has demonstrated that pilose antler extracts have strong anti-inflammatory properties and possess antioxidant effects. This study aimed to elucidate the mechanism of pilose antler protein in repairing photodamage caused by UVB radiation in HaCaT cells and ICR mice. Pilose antler protein (PAP) was found to increase the expression of type I collagen and hyaluronic acid in HaCaT cells under UVB irradiation while also inhibiting reactive oxygen species (ROS) production and oxidative stress in vitro. In vivo, the topical application of pilose antler protein effectively attenuated UVB-induced skin damage in ICR mice by reducing interleukin-1ß (IL-ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) and inhibiting skin inflammation while alleviating UVB-induced oxidative stress. It was shown that pilose antler protein repaired UVB-induced photodamage through the MAPK and TGF-ß/Smad pathways.

Efficient Charge Carriers Separation and Transfer Driven by Interface Electric Field in FeS2@ZnIn2S4 Heterojunction Boost Hydrogen Evolution.

Photocatalytic H2 evolution technology is regarded as a promising and green route for the urgent requirement of efficient H2 production. At present, low efficiency is a major bottleneck that limits the practical application of photocatalytic H2 evolution. The construction of high-activity photocatalysts is highly crucial for achieving advanced hydrogen generation. Herein, a new S-scheme FeS2@ZnIn2S4 (FeS2@ZIS) heterostructure as the photocatalyst was developed for enhanced photocatalytic H2 evolution. Density function theory (DFT) calculation results strongly demonstrated that FeS2@ZIS generates a giant interface electric field (IEF), thus promoting the separation efficiency of photogenerated charge carriers for efficient visible-light-driven hydrogen evolution. At optimal conditions, the H2 production rate of the 8%FeS2@ZIS is 5.3 and 3.6 times higher than that of the pure FeS2 and ZIS, respectively. The experimental results further indicate that the close contact between FeS2 and ZIS promotes the formation of the S-scheme heterojunction, where the interfacial charge transfer achieves spatial separation of charge carriers. This further broadens the light absorption range of the FeS2@ZIS and improves the utilization rate of photogenerated charge carriers. This work thus offers new insights that the FeS2-based co-catalyst can enrich the research on S-scheme heterojunction photocatalysts and improve the transfer and separation efficiency of photogenerated carriers for photocatalytic hydrogen production.

Saturated dissolved oxygen-driven high-rate and ultrastable partial nitrification in municipal wastewater.

Achieving stable and high-rate partial nitrification (PN) remains a worldwide technical conundrum in low-strength mainstream conditions. This study successfully achieved ultrarapid mainstream PN within 8 days under a saturated dissolved oxygen (DO) supply strategy, reaching a record-breaking PN rate of over 1.0 kg N m-3 d-1 treating municipal wastewater. Stable PN was maintained for over 200 days with an ultrahigh nitrite accumulation ratio of 98.5 ± 0.9 %, resilient to seasonal fluctuations in temperature (16.0-25.6 °C) and load (NH4+-N, 40-80 mg N/L). Kinetics revealed a remarkable 159.1-fold increase in the maximum activity ratio of ammonia-oxidizing bacteria (AOB) to nitrite-oxidizing bacteria (NOB). The faster response of AOB to saturated DO stimulated its highest activity difference with NOB, contributing to the AOB (Nitrosomonas oligotropha) boom and the elimination of NOB groups (-99.9 %). Our results highlight the importance of promoting AOB rather than solely focusing on NOB suppression for initiating and stabilizing high-rate mainstream PN.

Dyadic social interaction paradigm reveals selective role of ovarian estrogen in the caring behavior and socially transferred pain in female mice.

When a naïve observer meets with a familiar conspecific in pain, mice may have a myriad of social (sniffing, allolicking, allogrooming, huddling) and non-social (self-grooming) behaviors under dyadic social interaction (DSI) paradigm. Unlike male, female observers express more allolicking behavior toward injury site of a familiar female in pain, but with less body allogrooming. In current study, we investigated roles of natural estrus cycle phases and ovarian estrogen in these behaviors and results showed that: (1) there was no changes in above behaviors in terms of latency, time and bouts across different natural estrus cycle phases in intact female. (2) however, ovariectomy (OVX) changed estrus cycle phases, lowered circulating level of ovarian estrogen, reduced time and bouts of allolicking behavior and increased time of self-grooming without affecting other behaviors. Moreover, OVX in observers decreased social buffering effect of DSI on spontaneous pain-related behavior in demonstrator relative to naïve and sham controls. (3) treatment of OVX-female with ß-estradiol (E2) or progesterone (PROG) as replacement therapies, only E2 reversed impairment of allolicking behavior. (4) Additionally, socially transferred pain could be identified in intact female across all estrus cycle phases post-DSI, but disappeared in OVX-female, which could be reversed completely by E2 but not by PROG. (5) Finally, serum levels of estrogen, PROG, oxytocin, arginine vasopressin (AVP), prolactin, norepinephrine and 5-HT were examined by ELISA after E2, results showed only AVP level was significantly increased. These results suggest both injury site-targeted caring behavior and socially transferred pain are selectively dependent on ovarian estrogen. This article is part of the Special Issue on "Empathic Pain".

Toxicity studies of compound spermatogenic pill:Acute toxicity and subacute toxicity.

ETHNOPHARMACOLOGICAL RELEVANCE: Spermatogenic Pill (SP) is a commonly used clinical preparation in the Third Clinical Hospital of Changchun University of Traditional Chinese Medicine. Has accumulated a good reputation for more than a decade. However, because SP is a hospital clinical agent, it has received little extensive attention from researchers, which has led to a systematic lack of basic research on it. Therefore, it is impossible to determine whether there are safety hazards that may limit its widespread clinical application, and an in-depth toxicological evaluation of SP is essential and urgent. AIM OF THE STUDY: The aim of this study was to assess the safety of SP by conducting acute and subacute toxicity examinations. MATERIALS AND METHODS: Identify active compounds contained in SP by LC-MS, and determination of inorganic elements in SP using ICP-MS. The in vivo acute toxicity of SP was assessed over a duration of 14 days following administration at doses of 7.5, 15, or 30 g/kg. To evaluate subacute toxicity, mice were administered daily doses of SP (7.5, 15, or 30 g/kg) for a period of 28 days. After the treatment period, the animals were euthanized, and standard blood tests, liver and kidney function tests, as well as tests related to glycolipid metabolism, were performed. The principal organs of the mice were collected to calculate organ coefficients and undergo hematoxylin-eosin (HE) staining. RESULTS: LC-MS analysis showed that the active components of SP include Quercetin, Kaempferol, Beta-sitosterol, Stigmasterol, Diosbulbin B, Schizandrin, Naringenin, 2,3-hydroxycinnamic acid, L-proline, Histidine and Pluviatolide. The total amount of detected inorganic elements accounted for 3.0919% of SP. During the SP acute toxicity experiment, the groups that received the drug exhibited no signs of adverse reactions or poisoning symptoms. In subacute toxicity experiments, drug-treated mice showed overall favorable status, but the effects of continuous administration of the 30 g/kg group on body weight and food intake were reduced. An increase in the white marrow of spleen tissue after long-term administration of the drug treatment was also observed, suggesting that the drug can increase the maturation process and the number of mature lymphocytes in the spleen, and improve the lymphocyte immunity and humoral immunity function of the organism. Suggests that possibly this should be taken into account in clinical application. The routine blood examinations, as well as the assessments of liver and kidney functions, and the tests for glucose and lipid metabolism, did not reveal any notable toxic effects. CONCLUSION: SP contains more flavonoids, and terpenoid active ingredients, and is non-toxic in the body. This discovery not only strengthens the safety foundation of its clinical application, provides a solid scientific basis for the establishment of reasonable clinical dosage and the implementation of effective clinical toxicity monitoring, but also further lays a solid theoretical cornerstone for the subsequent clinical drug trials.

Deer Skin Collagen Peptides Bound to Calcium: In Vitro Gastrointestinal Simulation of Digestion, Cellular Uptake and Analysis of Antioxidant Activity.

The by-product of deer skin, which has mostly been used as a decorative material, is rich in collagen and amino acids that could bind to Ca2+. Therefore, the preparation process, stability, antioxidant activity and calcium transport capacity of deer skin collagen peptide calcium chelate (Ca-DSCP) were investigated. In addition, the structure of the new chelate was characterized. The preparation process of Ca-DSCP was optimized using one-way experiments and response surface methodology. The ideal conditions were pH 9, 48 °C, and a peptide-to-calcium mass ratio of 5:1. The chelation rate was (60.73 ± 1.54)%. Zeta potential, XRD, UV-vis and FTIR analyses yielded that deer skin collagen peptides (DSCP) underwent a chelating reaction with calcium ions to form new structures. The stability of Ca-DSCP and the fraction of bioavailability of calcium ions were determined using in vitro gastrointestinal digestion and a Caco-2 cell monolayer model. The results showed that fraction of bioavailability and stability of DSCP were improved by influencing the structural characterization. The antioxidant activities of DSCP and Ca-DSCP were evaluated by measuring relevant oxidative stress indicators, DPPH radical scavenging capacity and hydroxyl radical scavenging capacity. Finally, bioinformatics and molecular docking techniques were utilized to screen and study the antioxidant mechanism of DSCP.