Irradiated engineered tumor cell-derived microparticles remodel the tumor immune microenvironment and enhance antitumor immunity.

Radiotherapy (RT), administered to roughly half of all cancer patients, occupies a crucial role in the landscape of cancer treatment. However, expanding the clinical indications of RT remains challenging. Inspired by the radiation-induced bystander effect (RIBE), we used the mediators of RIBE to mimic RT. Specifically, we discovered that irradiated tumor cell-released microparticles (RT-MPs) mediated the RIBE and had immune activation effects. To further boost the immune activation effect of RT-MPs to achieve cancer remission, even in advanced stages, we engineered RT-MPs with different cytokine and chemokine combinations by modifying their production method. After comparing the therapeutic effect of the engineered RT-MPs in vitro and in vivo, we demonstrated that tIL-15/tCCL19-RT-MPs effectively activated antitumor immune responses, significantly prolonged the survival of mice with malignant pleural effusion (MPE), and even achieved complete cancer remission. When tIL-15/tCCL19-RT-MPs were combined with PD-1 monoclonal antibody (mAb), a cure rate of up to 60% was achieved. This combination therapy relied on the activation of CD8+ T cells and macrophages, resulting in the inhibition of tumor growth and the establishment of immunological memory against tumor cells. Hence, our research may provide an alternative and promising strategy for cancers that are not amenable to conventional RT.

Novel CAR-T cells targeting TRKB for the treatment of solid cancer.

Chimeric antigen receptor (CAR) T-cell therapy is highly effective for treating blood cancers such as B-cell malignancies, however, its effectiveness as an approach to treat solid tumors remains to be further explored. Here, we focused on the development of CAR-T cell therapies targeting tropomyosin-related kinase receptor B (TRKB), a highly expressed protein that is significantly associated with tumor progression, malignancy, and drug resistance in multiple forms of aggressive solid tumors. To achieve this, we screened brain-derived neurotrophic factor (BDNF) and neurotrophin 4 (NTF4) ligand-based CAR-T cells for their efficiency in targeting the TRKB receptor in the context of solid tumors, particularly hepatocellular carcinoma and pancreatic cancer. We demonstrated that TRKB is overexpressed not only in hepatocellular carcinoma and pancreatic carcinoma cell lines but also in cancer stem-like cells (CSCs). Notably, BDNF-CAR T and NTF4-CAR T cells could not only effectively target and kill TRKB-expressing pan-cancer cell lines in a dose-dependent manner but also effectively kill CSCs. We also performed in vivo studies to show that NTF4-CAR T cells have a better potential to inhibit the tumor growth of hepatocellular carcinoma xenografts in mice, compared with BDNF-CAR T cells. Taken together, our findings suggest that CAR-T targeting TRKB may be a promising approach for developing novel therapies to treat solid cancers.

The degree of risk factor and accumulation effect for large niche in individuals after cesarean section.

BACKGROUND: The risk factors associated with niche on the cesarean scar have been reported, however, the degree of these factors associated with large niche and the accumulation effects of these risk factors on the development of large niche are unclear. METHODS: Large niche was evaluated by transvaginal sonography during mid-follicular phase. Logistic regression model was used to assess 32 risk factors by univariate analysis. Then, a scoring model based on the screened risk factors was generated. The performance of this model was evaluated by area under curve (AUC). Finally, the scoring model was applied in 123 women to assess the external validation. RESULT(S): In the training cohort study, 163 women were diagnosed with large niche. The final scoring model involves eight risk factors with the rating scores including age at delivery (30-34 years: 1 point; ≥ 35 years: 4.5 points), retroflexed uterus (8.5 points), meconium-stained amniotic fluid (4.5 points), twice CSs (4.0 points), postpartum endometritis (4.5 points), premature rupture of membranes (2.5 points), intrahepatic cholestasis of pregnancy (mild to moderate: 3 points; severe: 6.5 points), and cervical dilatation (1-3 cm: 2.0 points; 4-10 cm: 4.5 points). The accumulation effect with a cut-off value of 8.0 in the scoring was associated with the large niche after CS. CONCLUSION(S): This is the first scoring model to objectively quantify the risk of a large niche after CS. Optimal risk factors control by avoiding high score factors and multiple factors accumulation may eliminate the risk of large niche development.

Induction of therapeutic immunity and cancer eradication through biofunctionalized liposome-like nanovesicles derived from irradiated-cancer cells.

Immunotherapy has revolutionized the treatment of cancer. However, its efficacy remains to be optimized. There are at least two major challenges in effectively eradicating cancer cells by immunotherapy. Firstly, cancer cells evade immune cell killing by down-regulating cell surface immune sensors. Secondly, immune cell dysfunction impairs their ability to execute anti-cancer functions. Radiotherapy, one of the cornerstones of cancer treatment, has the potential to enhance the immunogenicity of cancer cells and trigger an anti-tumor immune response. Inspired by this, we fabricate biofunctionalized liposome-like nanovesicles (BLNs) by exposing irradiated-cancer cells to ethanol, of which ethanol serves as a surfactant, inducing cancer cells pyroptosis-like cell death and facilitating nanovesicles shedding from cancer cell membrane. These BLNs are meticulously designed to disrupt both of the aforementioned mechanisms. On one hand, BLNs up-regulate the expression of calreticulin, an "eat me" signal on the surface of cancer cells, thus promoting macrophage phagocytosis of cancer cells. Additionally, BLNs are able to reprogram M2-like macrophages into an anti-cancer M1-like phenotype. Using a mouse model of malignant pleural effusion (MPE), an advanced-stage and immunotherapy-resistant cancer model, we demonstrate that BLNs significantly increase T cell infiltration and exhibit an ablative effect against MPE. When combined with PD-1 inhibitor (α-PD-1), we achieve a remarkable 63.6% cure rate (7 out of 11) among mice with MPE, while also inducing immunological memory effects. This work therefore introduces a unique strategy for overcoming immunotherapy resistance.

Cell-Surface GRP78-Targeted Chimeric Antigen Receptor T Cells Eliminate Lung Cancer Tumor Xenografts.

Lung cancer is one of the most common and intractable malignancies. It is associated with low survival rates despite existing treatments, indicating that new and more effective therapies are urgently needed such as the chimeric antigen receptor-T (CAR-T) cell immunotherapy. The cell-surface glucose-regulated protein 78 (csGRP78) is expressed in various hematological malignancies and solid tumor cells including lung cancer in response to cancer-related endoplasmic reticulum stress, while GRP78 is restricted to inside the normal cells. Here, we detected the prominent expression of csGRP78 in both lung cancer cell lines, A549 and H1299, as well as cancer stemlike cells derived from A549 by immunofluorescence. Next, a csGRP78-targeted CAR was constructed, and the transduced CAR-T cells were tested for their potency to kill the two lung cancer cell lines and derived stemlike cells, which was correlated with specific interferon γ release in vitro. Finally, we found that csGRP78 CAR-T cells also efficiently killed both lung cancer cells and cancer stemlike cells, resulting into the elimination of tumor xenografts in vivo, neither with any evidence of relapse after 63 days of tumor clearance nor any detrimental impact on other body organs we examined. Our study reveals the capacity of csGRP78 as a therapeutic target and offers valuable insight into the development of csGRP78 CAR-T cells as potential therapy for lung cancer.

Glutamate dehydrogenase 1: A novel metabolic target in inhibiting acute myeloid leukaemia progression.

Glutamine metabolic reprogramming in acute myeloid leukaemia (AML) cells contributes to the decreased sensitivity to antileukemic drugs. Leukaemic cells, but not their myeloid counterparts, largely depend on glutamine. Glutamate dehydrogenase 1 (GDH1) is a regulation enzyme in glutaminolysis. However, its role in AML remains unknown. Here, we reported that GDH1 was highly expressed in AML: high GDH1 was one of the independent negative prognostic factors in AML cohort. The dependence of leukaemic cells on GDH1 was proved both in vitro and in vivo. High GDH1 promoted cell proliferation and reduced survival time of leukaemic mice. Targeting GDH1 eliminated the blast cells and delayed AML progression. Mechanistically, GDH1 knockdown inhibited glutamine uptake by downregulating SLC1A5. Moreover, GDH1 invalidation also inhibited SLC3A2 and abrogated the cystine-glutamate antiporter system Xc- . The reduced cystine and glutamine disrupted the synthesis of glutathione (GSH) and led to the dysfunction of glutathione peroxidase-4 (GPX4), which maintains the lipid peroxidation homeostasis by using GSH as a co-factor. Collectively, triggering ferroptosis in AML cells in a GSH depletion manner, GDH1 inhibition was synthetically lethal with the chemotherapy drug cytarabine. Ferroptosis induced by inhibiting GDH1 provides an actionable therapeutic opportunity and a unique target for synthetic lethality to facilitate the elimination of malignant AML cells.

circSLC25A13 acts as a ceRNA to regulate AML progression via miR-616-3p/ADCY2 axis.

Circular RNAs (circRNAs), a type of endogenous noncoding RNA (ncRNA), exert vital roles in leukemia progression and are promising prognostic factors. Here, we report a novel circRNA, circSLC25A13 (hsa_circ_0081188), which was increased in acute myeloid leukemia (AML) patients with poor overall survival (OS) comparing to patients with good prognosis. Knockdown of circSLC25A13 in AML cells inhibited proliferation and increased cell apoptosis in vitro and in vivo. Enhanced circSLC25A13 expression promoted the survival of AML cells. Mechanistically, circSLC25A13 played as a microRNA sponge of miR-616-3p, which inhibited the expression of adenylate cyclase 2 (ADCY2). Downregulation of miR-616-3p and overexpression of ADCY2 partially rescued circSLC25A13 deficient induced cell growth arrest. In summary, through competitive absorption of miR-616-3p and thereby upregulating ADCY2 expression, circSLC25A13 promoted AML progression. Moreover, circSLC25A13 may represent a potential novel biomarker for the prognosis of AML and offer a potential therapeutic target for AML treatment.

Chimeric antigen receptor T cells targeting cell surface GRP78 efficiently kill glioblastoma and cancer stem cells.

BACKGROUND: Glioblastoma (GBM) is recognized as among the most aggressive forms of brain tumor. Patients typically present with a five-year survival rate of less than 6% with traditional surgery and chemoradiotherapy, which calls for novel immunotherapies like chimeric antigen receptor T (CAR-T) cells therapy. In response to endoplasmic reticulum (ER) stress in multiple tumor cells including GBM, the glucose-regulated protein 78 (GRP78) expression increases and the protein is partially translocated to the cell surface, while it is restricted to the cytoplasm and the nucleus in normal cells. METHODS: In this study, to target the cell surface GRP78 (csGRP78), CAR-T cells based on its binding peptide were generated. In vitro two GBM cell lines and glioma stem cells (GSCs) were used to confirm the localization of csGRP78 and the cytotoxicity of the CAR-T cells. In vivo a GBM xenograft model was used to assess the killing activity and the safety of the CAR-T cells. RESULTS: We confirmed the localization of csGRP78 at the cell surface of two GBM cell lines (U-251MG and U-87MG) and in GSCs. Co-culture experiments revealed that the CAR-T cells could specifically kill the GBM tumor cells and GSCs with specific IFN-γ release. Furthermore, in the tumor xenograft model, the CAR-T cells could decrease the number of GSCs and significantly suppress tumor cell growth. Importantly, we found no obvious off-target effects or T cell infiltration in major organs following systemic administration of these cells. CONCLUSIONS: The csGRP78 targeted CAR-T cells efficiently kill GBM tumor cells and GSCs both in vitro and in vivo, and ultimately suppress the xenograft tumors growth without obvious tissue injuries. Therefore, our study demonstrates that csGRP78 represents a valuable target and the csGRP78-targeted CAR-T cells strategy is an effective immunotherapy against GBM.

Spermatogenesis associated serine rich 2 like plays a prognostic factor and therapeutic target in acute myeloid leukemia by regulating the JAK2/STAT3/STAT5 axis.

BACKGROUND: Spermatogenesis associated serine rich 2 like (SPATS2L) was highly expressed in homoharringtonine (HHT) resistant acute myeloid leukemia (AML) cell lines. However, its role is little known in AML. The present study aimed to investigate the function of SPATS2L in AML pathogenesis and elucidate the underlying molecular mechanisms. METHODS: Overall survival (OS), event-free survival (EFS), relapse-free survival (RFS) were used to evaluate the prognostic impact of SPATS2L for AML from TCGA database and ourcohort. ShRNA was used to knockdown the expression of SPATS2L. Apoptosis was assessed by flow cytometry. The changes of proteins were assessed by Western blot(WB). A xenotransplantation mice model was used to evaluate in vivo growth and survival. RNA sequencing was performed to elucidate the molecular mechanisms underlying the role of SPATS2L in AML. RESULTS: SPATS2L expression increased with increasing resistance indexes(RI) in HHT-resistant cell lines we had constructed. Higher SPATS2L expression was observed in intermediate/high-risk patients than in favorable patients. Meanwhile, decreased SPATS2L expression was observed in AML patients achieving complete remission (CR). Multivariate analysis showed high SPATS2L expression was an independent poor predictor of OS, EFS, RFS in AML. SPATS2L knock down (KD) suppressed cell growth, induced apoptosis, and suppressed key proteins of JAK/STAT pathway, such as JAK2, STAT3, STAT5 in AML cells. Inhibiting SPATS2L expression markedly enhanced the pro-apoptotic effects of traditional chemotherapeutics (Ara-c, IDA, and HHT). CONCLUSIONS: High expression of SPATS2L is a poor prognostic factor in AML, and targeting SPATS2L may be a promising therapeutic strategy for AML patients.

The genetic risk factors for pregnancy-induced hypertension: Evidence from genetic polymorphisms.

Pregnancy-induced hypertension (PIH) is a multifactorial and severe pregnancy complication including preeclampsia/eclampsia, gestational hypertension, chronic (pre-existing) hypertension, and preeclampsia/eclampsia variants superimposed on chronic hypertension. PIH-induced maternal mortality accounts for approximately 9% of all maternal deaths over the world. A large number of case-control studies have established the importance of various genetic factors in the occurrence and development of PIH. In this narrative review, we summarized the genetic risk factors involved in the renin-angiotensin system, endothelin system, inflammatory factors, oxidative stress, and other functional networks, with the aim of sorting out the genetic factors that may play a potential role in PIH and providing new ideas to elucidate the pathogenesis of PIH.

FLOT1 knockdown inhibits growth of AML cells through triggering apoptosis and pyroptosis.

Acute myeloid leukemia (AML) is a group of hematological malignancies characterized by clonal proliferation of immature myeloid cells. Lipid rafts are highly organized membrane subdomains enriched in cholesterol, sphingolipids, and gangliosides and play roles in regulating apoptosis through subcellular redistribution. Flotillin1 (FLOT1) is a component and also a marker of lipid rafts and had been reported to be involved in the progression of cancers and played important roles in cell death. However, the role of FLOT1 in AML remains to be explored. In this study, we found that increased expression of FLOT1 was correlated with poor clinical outcome in AML patients. Knockdown of FLOT1 in AML cells not only promoted cell death in vitro but also inhibited malignant cells engraftment in vivo. Mechanically, FLOT1 knockdown triggered apoptosis and pyroptosis. FLOT1 overexpression promoted AML cell growth and apoptosis resistance. Our findings indicate that FLOT1 is a prognostic factor of AML and may be a potential target for AML treatment.

HGF-Based CAR-T Cells Target Hepatocellular Carcinoma Cells That Express High Levels of c-Met.

BACKGROUND: CAR-T is emerging as an effective treatment strategy for hematologic malignancies, however its effectiveness for treating solid tumors, such as Hepatocellular Carcinoma (HCC) is limited. Here, we screened a variety of CAR-T cells that target c-Met to investigate their potential to induce HCC cell death in vitro. METHODS: Human T cells were transduced to express CARs by lentiviral vector transfection. c-Met expression in human HCC cell lines and CARs expression were monitored by flow cytometry. Tumor cell killing was evaluated by Luciferase Assay System Kit. The concentrations of cytokine were tested by Enzyme-linked immunosorbent assays. Knock down and overexpression studies targeting c-Met were conducted to assess the targeting specificity of CARs. RESULTS: We found that CAR T cells expressing a minimal amino-terminal polypeptide sequence comprising the first kringle (kringle 1) domain (denoted as NK1 CAR-T cells), efficiently killed HCC cell lines that expressed high levels of the HGF receptor c-Met. Furthermore, we report that while NK1 CAR-T cells were efficient at targeting SMMC7221 cells for destruction, and its potency was significantly attenuated in parallel experiments with cells stably expressing short hairpin RNAs (shRNAs) that suppressed c-Met expression. Correspondingly, overexpression of c-Met in the embryonic kidney cell line HEK293T led to their enhanced killing by NK1 CAR-T cells. CONCLUSION: Our studies demonstrate that a minimal amino-terminal polypeptide sequence comprising the kirngle1 domain of HGF is highly relevant to the design of effective CAR-T cell therapies that kill HCC cells expressing high levels of c-Met.

How loneliness linked to anxiety and depression: a network analysis based on Chinese university students.

BACKGROUND: There is conclusive evidence of a multifaceted and bidirectional relationship between loneliness and depression and anxiety. Nonetheless, more extensive research is needed to examine their relationships at a more granular level. This study employed a network analysis approach to identify the pathological mechanisms underpinning those relationships and to identify important bridge nodes as potential targets for intervention. METHODS: 941 University students were included in this study. The ULS-6 (the short-form UCLA Loneliness Scale) was used to assess loneliness, the PHQ-9 (Patient Health questionnaire-9) and GAD-7 (Generalized anxiety disorder 7-item) scales were used to assess the symptoms of depression and anxiety. We constructed two network structures of loneliness-anxiety and loneliness-depression and computed bridge expected influence for each symptom. In addition, we showed a flow network of "Suicide" containing symptoms of depression and loneliness. RESULTS: All edges were positive in both networks constructed and the strongest edges were present within disorder communities. The overall connection between loneliness and depression was stronger compared to anxiety. The results demonstrated that the loneliness item "People are around me but not with me" was identified as bridge symptom in both networks. Furthermore, "Suicide" was directly connected to five symptoms of depression and four items of loneliness, with the strongest connections being between it and "Feeling of worthlessness" and "Psychomotor agitation/retardation". CONCLUSIONS: Our findings provide a more nuanced explanation of the link between loneliness and depression and anxiety. The results identified the bridge symptom "People are around me but not with me", which had the strongest effect on enhancing symptoms of depression and anxiety. Clinical improvements based on the findings of this study and the impact of the intervention are discussed.

Ulinastatin inhibits the metastasis of nasopharyngeal carcinoma by involving uPA/uPAR signaling.

Distant metastasis is the primary reason for treatment failure in patients with nasopharyngeal carcinoma (NPC). In this study, we investigated the effect of ulinastatin (UTI) on NPC metastasis and its underlying mechanism. Highly-metastatic NPC cell lines S18 and 58F were treated with UTI and the effect on cell proliferation, migration, and invasion were determined by MTS and Transwell assays. S18 cells with luciferase-expressing (S18-1C3) were injected into the left hind footpad of nude mice to establish a model of spontaneous metastasis from the footpad to popliteal lymph node (LN). The luciferase messenger RNA (mRNA) was measured by quantitative polymerase chain reaction (qPCR), and the metastasis inhibition rate was calculated. Key molecular members of the UTI-related uPA, uPAR, and JAT/STAT3 signaling pathways were detected by qPCR and immunoblotting. UTI suppressed the migration and infiltration of S18 and 5-8F cells and suppressed the metastasis of S18 cells in vivo without affecting cell proliferation. uPAR expression decreased from 24 to 48 h after UTI treatment. The antimetastatic effect of UTI is partly due to the suppression of uPA and uPAR. UTI partially suppresses NPC metastasis by downregulating the expression of uPA and uPAR.

Homoharringtonine is synergistically lethal with BCL-2 inhibitor APG-2575 in acute myeloid leukemia.

BACKGROUND: Despite advances in targeted agent development, effective treatment of acute myeloid leukemia (AML) remains a major clinical challenge. The B-cell lymphoma-2 (BCL-2) inhibitor exhibited promising clinical activity in AML, acute lymphoblastic leukemia (ALL) and diffuse large B-cell lymphoma (DLBCL) treatment. APG-2575 is a novel BCL-2 selective inhibitor, which has demonstrated anti-tumor activity in hematologic malignancies. Homoharringtonine (HHT), an alkaloid, exhibited anti-AML activity. METHODS: The synergistic effects of APG-2575 and HHT were studied in AML cell lines and primary samples. MTS was used to measure the cell viability. Annexin V/propidium iodide staining was used to measure the apoptosis rate by flow cytometry. AML cell xenografted mouse models were established to evaluate the anti-leukemic effect of BCL-2 inhibitor, HHT and their combination in vivo. Western blot was used to determine the expression of related proteins. RESULTS: APG-2575 showed comparable anti-leukemic effect to the FDA-approved BCL-2 inhibitor ABT-199 in vitro and in vivo. Combined treatment of HHT with APG-2575 synergistically inhibited AML cell growth and engraftment. Mechanistically, HHT promoted degradation of myeloid cell leukemia-1 (MCL-1), which was reported to induce BCL-2 inhibitor resistant, through the PI3K/AKT/GSK3ß signaling pathway. CONCLUSION: Our results provide an effective AML treatment strategy through combination of APG-2575 and HHT, which is worthy of further clinical research.

Inhibition of CPT1a as a prognostic marker can synergistically enhance the antileukemic activity of ABT199.

BACKGROUND: Fatty acid oxidation (FAO) provides an important source of energy to promote the growth of leukemia cells. Carnitine palmitoyltransferase 1a(CPT1a), a rate-limiting enzyme of the essential step of FAO, can facilitate cancer metabolic adaptation. Previous reports demonstrated that CPT1a acts as a potential molecular target in solid tumors and hematologic disease. However, no systematic study was conducted to explore the prognostic value of CPT1a expression and possible treatment strategies with CPT1a inhibitor on acute myeloid leukemia (AML). METHODS: The expression of CPT1a in 325 cytogenetically normal AML (CN-AML) patients was evaluated using RT-PCR. The combination effects of ST1326 and ABT199 were studied in AML cells and primary patients. MTS was used to measure the cell proliferation rate. Annexin V/propidium iodide staining and flow cytometry analysis was used to measure the apoptosis rate. Western blot was used to measure the expression of Mcl-1. RNAseq and GC-TOFMS were used for genomic and metabolic analysis. RESULTS: In this study, we found AML patients with high CPT1a expression (n = 245) had a relatively short overall survival (P = 0.01) compared to patients in low expression group (n = 80). In parallel, downregulation of CPT1a inhibits proliferation of AML cells. We also conducted genomic and metabolic interactive analysis in AML patients, and found several essential genes and pathways related to aberrant expression of CPT1a. Moreover, we found downregulation of CPT1a sentitized BCL-2 inhibitor ABT199 and CPT1a-selective inhibitor ST1326 combined with ABT199 had a strong synergistic effect to induce apoptosis in AML cells and primary patient blasts for the first time. The underlying synergistic mechanism might be that ST1326 inhibits pGSK3ß and pERK expression, leading to downregulation of Mcl-1. CONCLUSION: Our study indicates that overexpression of CPT1a predicts poor clinical outcome in AML. CPT1a-selective inhibitor ST1326 combined with Bcl-2 inhibitor ABT199 showed strong synergistic inhibitory effects on AML.

Gestational Diabetes Mellitus: The Genetic Susceptibility Behind the Disease.

Gestational diabetes mellitus (GDM), a type of pregnancy-specific glucose intolerance or hyperglycemia, is one of the most common metabolic disorders in pregnant women with 16.9% of the global prevalence of gestational hyperglycemia. Not only are women with GDM likely to develop T2DM, but their children are also at risk for birth complications or metabolic disease in adulthood. Therefore, identifying the potential risk factors for GDM is very important in the prevention and treatment of GDM. Previous studies have shown that genetic predisposition is an essential component in the occurrence of GDM. In this narrative review, we describe the role of polymorphisms in different functional genes associated with increased risk for GDM, and available evidence on genetic factors in the risk of GDM is summarized and discussed.

Dihydrochalcones from the leaves of Lithocarpus litseifolius.

Three new phlorizin derivatives, 6"-O-vanilloylphlorizin (1), 6"-O-(4-hydroxybenzoyl)phlorizin (2), 6"-O-feruloylphlorizin (3), along with four known dihydrochalcones, phlorizin (4), 3-hydroxyphlorizin, trilobatin, and 6"-O-acetylphlorizin were isolated from the leaves of Lithocarpus litseifolius. Their structures were established by analysis of extensive spectroscopic data. The new compounds were shown to be non-cytotoxic when tested against A549, HeLa, HepG2, and MCF-7 cell lines.

Changes in cardiovascular function and related psychophysiological pathways in a rat model of post-traumatic stress disorder.

This study was aimed to investigate the cardiovascular function in rats with post-traumatic stress disorder (PTSD) and the potential association with the activities of the rostral ventrolateral medulla (RVLM) and the medial habenular nucleus (MHb). Multi-channel in vivo recordings were used to simultaneously acquire spontaneous neuronal firing and peripheral physiological indices, and FluoroGold (FG) retrograde tracing technique was used to observe the projections of labeled neurons in the MHb. The results showed that the discharge frequency of RVLM and MHb neurons, the systolic blood pressure (SBP), and the mean arterial pressure (MAP) in the PTSD group were all increased significantly compared with those in control group (P < 0.05). MHb neurons were retrogradely labeled by FG through microinjection (4% FG, 0.5 µL) into the RVLM. In the control group, electrical stimulation in the MHb increased heart rate (HR) at 100-300 µA (P < 0.05), elevated SBP and MAP at 200-300 µA (P < 0.05), and remarkably increased the RVLM neuronal discharge frequency at 100-500 µA (P < 0.05 or P < 0.01). In the PTSD group, however, only the discharge frequency of RVLM neurons was increased by the electrical stimulation at 100-300 µA (P < 0.05). These results suggest that cardiovascular activities of the PTSD model rat are enhanced, and this change may be related to the activity changes of RVLM and MHb and the potential connection between the two nuclei.

Rapid and Non-Destructive Detection of Compression Damage of Yellow Peach Using an Electronic Nose and Chemometrics.

The rapid and non-destructive detection of mechanical damage to fruit during postharvest supply chains is important for monitoring fruit deterioration in time and optimizing freshness preservation and packaging strategies. As fruit is usually packed during supply chain operations, it is difficult to detect whether it has suffered mechanical damage by visual observation and spectral imaging technologies. In this study, based on the volatile substances (VOCs) in yellow peaches, the electronic nose (e-nose) technology was applied to non-destructively predict the levels of compression damage in yellow peaches, discriminate the damaged fruit and predict the time after the damage. A comparison of the models, established based on the samples at different times after damage, was also carried out. The results show that, at 24 h after damage, the correct answer rate for identifying the damaged fruit was 93.33%, and the residual predictive deviation in predicting the levels of compression damage and the time after the damage, was 2.139 and 2.114, respectively. The results of e-nose and gas chromatography-mass spectrophotometry (GC-MS) showed that the VOCs changed after being compressed-this was the basis of the e-nose detection. Therefore, the e-nose is a promising candidate for the detection of compression damage in yellow peach.