Access to Functionalized Cyclohex-2-enones from a Multicomponent Cascade Reaction of Readily Available Alkynes, Ketones, and Ethyl Acetoacetate.

The synthesis of cyclohex-2-enone derivatives is a topic of current interest in organic chemistry. A novel three-component cascade reaction of alkynes with ketones and ethyl acetoacetate has been uncovered. This process provides di- and trisubstituted cyclohex-2-enones in good yields with excellent functional group tolerance. A variety of terminal alkynes and a wide range of aryl, alkyl, and cyclic ketones are viable in this transformation. Successful scale-up preparation and synthetic transformations have demonstrated the potential of this simple operating protocol.

Exploration of SERPINA family functions and prognostic value in breast cancer based on transcriptome and in vitro analysis.

Breast cancer poses a significant risk to women worldwide, yet specific role of SERPINA gene family in breast cancer remains unclarified. Data were collected from online databases. SERPINA family gene expression was presented, and prognosis value was evaluated. Multi-omics methods were employed to explore the SERPINA-related biological processes, followed by comprehensive analyses of their roles in breast cancer. Single-cell data were analyzed to characterize the SERPINA family gene expression in different cell clusters. We selected SERPINA5 as the target gene. Via pan-cancer analysis, SERPINA5 was also investigated in various cancers. The experimental validation was conducted in MDA-MB-231 cell line eventually. SERPINA family showed differential expression in breast cancer, which were mainly expressed in myeloid cells, epithelial cells, and dendritic cells. SERPINA5 expression was upregulated in breast cancer, which was associated with a better prognosis. Immune infiltration illustrated the positive correlativity between SERPINA5 intensity and eosinophilic recruitment. Pan-cancer analysis indicated the function of SERPINA5 as a potential biomarker in other cancers. Finally, experimental validation demonstrated that SERPINA5 contributes to lower invasion and metastatic potential of breast cancer cells. With bioinformatics analysis, the significant role SERPINA family genes functioned in breast cancer was comprehensively explored, with SERPINA5 emerging as a key gene in suppressing breast cancer progression.

Acupuncture exerts preventive effects in rats of chronic unpredictable mild stress: The involvement of inflammation in amygdala and brain-spleen axis.

BACKGROUND: Acupuncture has shown the preventive effects on depression in rats with chronic unpredictable mild stress (CUMS). However, the mechanisms of acupuncture for preventing depression still need to be explored. In the study, acupuncture was applied to a rat depression model of CUMS, high-mobility group box 1(HMGB1)/toll-like receptor 4 (TLR4) and brain-spleen axis were assessed. METHODS: Male Sprague Dawley (SD) rats were exposed to CUMS with two stressors per day for 28 days. In the meantime, manual acupuncture (at GV16 and GV23 acupoints, once every other day) and fluoxetine gavage (2.1 mg/kg, 0.21 mg/mL) were administered daily post CUMS stressors. Behavioral tests and biological detection methods were conducted in sequence to evaluate depression-like phenotypes in rats. RESULTS: The results showed CUMS induced depression-like behaviors, hyper-activation of HMGB1/TLR4 signaling pathway, elevated inflammation in amygdala and peripheral blood, and hyperactivation of hypothalamic-pituitary-adrenal (HPA) axis. These changes could be prevented and reversed by acupuncture to varying extents. CONCLUSION: Acupuncture prevented and ameliorated depression-like symptoms induced by CUMS, possibly via regulating inflammation through brain-spleen axis mediated by HMGB1/TLR4 signaling pathway and HPA axis regulation.

Bioinspired low-density lipoprotein co-delivery system for targeting and synergistic cancer therapy.

Epithelial-mesenchymal transition (EMT) is the culprit of tumor invasion and metastasis. As a critical transcription factor that induces EMT, snail is of great importance in tumor progression, and knocking down its expression by small interfering RNA (siRNA) may inhibit tumor metastasis. Herein, we developed a core-shelled bioinspired low-density lipoprotein (bio-LDL) in which snail siRNA-loaded calcium phosphate nanoparticles were wrapped as the core and doxorubicin was embedded in the outer phospholipids modified with a synthetic peptide of apoB100 targeting LDL receptor-abundant tumor cells. Bio-LDL exhibited pH-responsive release, lysosomal escape ability, enhanced cytotoxicity and apoptotic induction. Bio-LDL could significantly inhibit the expression of snail and regulate EMT-related proteins to reduce tumor migration and invasion in vitro. Bio-LDL also displayed favorable tumor targeting and synergistic inhibition of tumor growth and metastasis in vivo. Therefore, the multifunctional bio-LDL will be a promising co-delivery vector and holds potential value for clinical translation.

Inosine Triphosphate Pyrophosphatase and NUDT15 are Good Predictors of Clinical Outcomes in Thiopurine-Treated Chinese Patients with Inflammatory Bowel Disease.

BACKGROUND: Although the relationship between NUDT15 and thiopurine-induced leukopenia has been proven in previous studies, no prominent factors explaining interindividual variations in its active metabolite, 6-thioguanine nucleotide (6-TGN), and clinical efficacy have been identified. In this study, the correlation between genotypes (thiopurine S-methyltransferase, NUDT15, and ITPA polymorphisms), 6-TGN concentrations, and clinical outcomes (efficacy and side effects) in patients with inflammatory bowel disease were investigated. METHODS: In total, 160 patients with inflammatory bowel disease were included, and the 3 genotyped genes and 6-TGN levels were measured by high-performance liquid chromatography. Statistical analyses and calculations were performed to determine their relationships. RESULTS: ITPA genotypes and 6-TGN concentration were both associated with the clinical effectiveness of azathioprine (P = 0.036 and P = 4.6 × 10-7), with a significant correlation also detected between them (P = 0.042). Patients with ITPA variant alleles exhibited higher 6-TGN levels than those with the wild-type allele. In addition, the relationship between NUDT15 and leukopenia and neutropenia was confirmed (P = 1.79 × 10-7 and 0.002). CONCLUSIONS: In summary, it is recommended that both ITPA and NUDT15 genotyping should be performed before azathioprine initiation. Moreover, the 6-TGN concentration should be routinely monitored during the later period of treatment.

The spatiotemporal patterns and network characteristics of emissions embodied in the international trade of livestock products.

Livestock production is greenhouse gas (GHG) emission intensive, and thus the increasing international trade of livestock products in recent decades has resulted in increased embodied emissions. Considering the varying emission intensity in production in different countries and the expected further increase in livestock product trade in the future, it becomes crucial to understand the spatial and temporal dynamics of such embodied GHG emissions for climate change mitigation in the livestock sector. In this study, we aimed to address such gaps and analyzed the spatiotemporal patterns and network characteristics of GHG emissions embodied in the international trade of seven major categories of livestock products among 228 world economies during 1986-2017. The results showed that the total volume of GHG emissions embodied in livestock product trade reached 92.0 MT in 2017, accounting for 2.6% of the total emissions from livestock production. Sheep meat has replaced cattle meat as the major contributor to embodied emissions. In 2017, the largest flows of embodied emissions were within Europe, followed by the flows from Oceania to Asia. The fluxes in intra-upper middle and intra-high-income economies accounted for most of the total embodied emissions. Although the global average emission intensity of livestock production declined in these four decades, the trade flows from high to low emission intensity economies increased, especially for cattle and sheep meat. This resulted in an overall increase of contribution from the global livestock trade in GHG emissions from the global livestock sector. Therefore, effective measures and policies must be designed from both consumption and production perspectives to ensure proper accounting of these embodied emissions and maximize the reduction potential for a sustainable food system transition.

Augmented Pulmonary Vasoconstrictor Reactivity after Chronic Hypoxia Requires Src Kinase and Epidermal Growth Factor Receptor Signaling.

Chronic hypoxia augments pressure- and agonist-induced pulmonary vasoconstriction through myofilament calcium sensitization. NADPH oxidases contribute to the development of pulmonary hypertension, and both epidermal growth factor receptor and Src kinases can regulate NADPH oxidase. We tested the hypothesis that Src-epidermal growth factor receptor (EGFR) signaling mediates enhanced vasoconstrictor sensitivity after chronic hypoxia through NADPH oxidase-derived superoxide generation. Protocols employed pharmacological inhibitors in isolated, pressurized rat pulmonary arteries to examine the contribution of a variety of signaling moieties to enhanced vascular tone after chronic hypoxia. Superoxide generation in pulmonary arterial smooth muscle cells was assessed using the fluorescent indicator dihydroethidium. Indices of pulmonary hypertension were measured in rats treated with the EGFR inhibitor gefitinib. Inhibition of NADPH oxidase, Rac1 (Ras-related C3 botulinum toxin substrate 1), and EGFR abolished pressure-induced pulmonary arterial tone and endothelin-1 (ET-1)-dependent calcium sensitization and vasoconstriction after chronic hypoxia. Consistently, chronic hypoxia augmented ET-1-induced superoxide production through EGFR signaling, and rats treated chronically with gefitinib displayed reduced right ventricular pressure and diminished arterial remodeling. Src kinases were also activated by ET-1 after chronic hypoxia and contributed to enhanced basal arterial tone and vasoconstriction in response to ET-1. A role for matrix metalloproteinase 2 to mediate Src-dependent EGFR activation is further supported by our findings. Our studies support a novel role for an Src kinase-EGFR-NADPH oxidase signaling axis to mediate enhanced pulmonary vascular smooth muscle Ca2+ sensitization, vasoconstriction, and pulmonary hypertension after chronic hypoxia.

Altered Lipid Domains Facilitate Enhanced Pulmonary Vasoconstriction after Chronic Hypoxia.

Chronic hypoxia (CH) augments depolarization-induced pulmonary vasoconstriction through superoxide-dependent, Rho kinase-mediated Ca2+ sensitization. Nicotinamide adenine dinucleotide phosphate oxidase and EGFR (epidermal growth factor receptor) signaling contributes to this response. Caveolin-1 regulates the activity of a variety of proteins, including EGFR and nicotinamide adenine dinucleotide phosphate oxidase, and membrane cholesterol is an important regulator of caveolin-1 protein interactions. We hypothesized that derangement of these membrane lipid domain components augments depolarization-induced Ca2+ sensitization and resultant vasoconstriction after CH. Although exposure of rats to CH (4 wk, ∼380 mm Hg) did not alter caveolin-1 expression in intrapulmonary arteries or the incidence of caveolae in arterial smooth muscle, CH markedly reduced smooth muscle membrane cholesterol content as assessed by filipin fluorescence. Effects of CH on vasoreactivity and superoxide generation were examined using pressurized, Ca2+-permeabilized, endothelium-disrupted pulmonary arteries (∼150 µm inner diameter) from CH and control rats. Depolarizing concentrations of KCl evoked greater constriction in arteries from CH rats than in those obtained from control rats, and increased superoxide production as assessed by dihydroethidium fluorescence only in arteries from CH rats. Both cholesterol supplementation and the caveolin-1 scaffolding domain peptide antennapedia-Cav prevented these effects of CH, with each treatment restoring membrane cholesterol in CH arteries to control levels. Enhanced EGF-dependent vasoconstriction after CH similarly required reduced membrane cholesterol. However, these responses to CH were not associated with changes in EGFR expression or activity, suggesting that cholesterol regulates this signaling pathway downstream of EGFR. We conclude that alterations in membrane lipid domain signaling resulting from reduced cholesterol content facilitate enhanced depolarization- and EGF-induced pulmonary vasoconstriction after CH.

Intermittent Hypoxia Augments Pulmonary Vasoconstrictor Reactivity through PKCß/Mitochondrial Oxidant Signaling.

Pulmonary vasoconstriction resulting from intermittent hypoxia (IH) contributes to pulmonary hypertension (pHTN) in patients with sleep apnea (SA), although the mechanisms involved remain poorly understood. Based on prior studies in patients with SA and animal models of SA, the objective of this study was to evaluate the role of PKCß and mitochondrial reactive oxygen species (mitoROS) in mediating enhanced pulmonary vasoconstrictor reactivity after IH. We hypothesized that PKCß mediates vasoconstriction through interaction with the scaffolding protein PICK1 (protein interacting with C kinase 1), activation of mitochondrial ATP-sensitive potassium channels (mitoKATP), and stimulated production of mitoROS. We further hypothesized that this signaling axis mediates enhanced vasoconstriction and pHTN after IH. Rats were exposed to IH or sham conditions (7 h/d, 4 wk). Chronic oral administration of the antioxidant Tempol or the PKCß inhibitor LY-333531 abolished IH-induced increases in right ventricular systolic pressure and right ventricular hypertrophy. Furthermore, scavengers of O2- or mitoROS prevented enhanced PKCß-dependent vasoconstrictor reactivity to endothelin-1 in pulmonary arteries from IH rats. In addition, this PKCß/mitoROS signaling pathway could be stimulated by the PKC activator PMA in pulmonary arteries from control rats, and in both rat and human pulmonary arterial smooth muscle cells. These responses to PMA were attenuated by inhibition of mitoKATP or PICK1. Subcellular fractionation and proximity ligation assays further demonstrated that PKCß acutely translocates to mitochondria upon stimulation and associates with PICK1. We conclude that a PKCß/mitoROS signaling axis contributes to enhanced vasoconstriction and pHTN after IH. Furthermore, PKCß mediates pulmonary vasoconstriction through interaction with PICK1, activation of mitoKATP, and subsequent mitoROS generation.

PKCß and reactive oxygen species mediate enhanced pulmonary vasoconstrictor reactivity following chronic hypoxia in neonatal rats.

Reactive oxygen species (ROS), mitochondrial dysfunction, and excessive vasoconstriction are important contributors to chronic hypoxia (CH)-induced neonatal pulmonary hypertension. On the basis of evidence that PKCß and mitochondrial oxidative stress are involved in several cardiovascular and metabolic disorders, we hypothesized that PKCß and mitochondrial ROS (mitoROS) signaling contribute to enhanced pulmonary vasoconstriction in neonatal rats exposed to CH. To test this hypothesis, we examined effects of the PKCß inhibitor LY-333,531, the ROS scavenger 1-oxyl-2,2,6,6-tetramethyl-4-hydroxypiperidine (TEMPOL), and the mitochondrial antioxidants mitoquinone mesylate (MitoQ) and (2-(2,2,6,6-tetramethylpiperidin-1-oxyl-4-ylamino)-2-oxoethyl)triphenylphosphonium chloride (MitoTEMPO) on vasoconstrictor responses in saline-perfused lungs (in situ) or pressurized pulmonary arteries from 2-wk-old control and CH (12-day exposure, 0.5 atm) rats. Lungs from CH rats exhibited greater basal tone and vasoconstrictor sensitivity to 9,11-dideoxy-9α,11α-methanoepoxy prostaglandin F2α (U-46619). LY-333,531 and TEMPOL attenuated these effects of CH, while having no effect in lungs from control animals. Basal tone was similarly elevated in isolated pulmonary arteries from neonatal CH rats compared with control rats, which was inhibited by both LY-333,531 and mitochondria-targeted antioxidants. Additional experiments assessing mitoROS generation with the mitochondria-targeted ROS indicator MitoSOX revealed that a PKCß-mitochondrial oxidant signaling pathway can be pharmacologically stimulated by the PKC activator phorbol 12-myristate 13-acetate in primary cultures of pulmonary artery smooth muscle cells (PASMCs) from control neonates. Finally, we found that neonatal CH increased mitochondrially localized PKCß in pulmonary arteries as assessed by Western blotting of subcellular fractions. We conclude that PKCß activation leads to mitoROS production in PASMCs from neonatal rats. Furthermore, this signaling axis may account for enhanced pulmonary vasoconstrictor sensitivity following CH exposure.NEW & NOTEWORTHY This research demonstrates a novel contribution of PKCß and mitochondrial reactive oxygen species signaling to increased pulmonary vasoconstrictor reactivity in chronically hypoxic neonates. The results provide a potential mechanism by which chronic hypoxia increases both basal and agonist-induced pulmonary arterial smooth muscle tone, which may contribute to neonatal pulmonary hypertension.

LncRNA SNHG1 exerts a protective role in cardiomyocytes hypertrophy via targeting miR-15a-5p/HMGA1 axis.

Heart failure preceded by pathological cardiac hypertrophy is a leading cause of death. Long noncoding RNA small nucleolar RNA host gene 1 (SNHG1) was reported to inhibit cardiomyocytes apoptosis, but the role and underlying mechanism of SNHG1 in pathological cardiac hypertrophy have not yet been understood. This study was designed to investigate the role and molecular mechanism of SNHG1 in regulating cardiac hypertrophy. We found that SNHG1 was upregulated during cardiac hypertrophy both in vivo (transverse aortic constriction treatment) and in vitro (phenylephrine [PE] treatment). SNHG1 overexpression attenuated the cardiomyocytes hypertrophy induced by PE, while SNHG1 inhibition promoted hypertrophic response of cardiomyocytes. Furthermore, SNHG1 and high-mobility group AT-hook 1 (HMGA1) were confirmed to be targets of miR-15a-5p. SNHG1 promoted HMGA1 expression by sponging miR-15a-5p, eventually attenuating cardiomyocytes hypertrophy. There data revealed a novel protective mechanism of SNHG1 in cardiomyocytes hypertrophy. Thus, targeting of SNHG1-related pathway may be therapeutically harnessed to treat cardiac hypertrophy.

[Expression of nucleolin in pressure overload-induced cardiac hypertrophy rats].

OBJECTIVE: To detect the expression of nucleolin in cardiac hypertrophy rats induced by pressure overload. METHODS: A total of 40 SD rats with body weight 180 g and 220 g were recruited and randomly divided into 2 groups: a transverse aortic constriction (TAC) group and a sham surgery group. Cardiac hypertrophy model was employed by transverse aortic constriction surgery. Then 2 weeks and 4 weeks after the experiment, the heart mass index (HMI), left ventricle mass index (LVMI) were measured. ß-MHC mRNA in the heart tissue was detected with RT-PCR. Nucleolin in the heart, brain and kidney was respectively detected with Western blot. RESULTS: Compared with the sham surgery group, HMI, LVMI in the TAC group increased significantly (P<0.01) 4 weeks after the surgery; the expression of ß-MHC mRNA in the heart tissue increased (P<0.05) in the TAC group 4 weeks after the surgery; and the expression of nucleolin protein in the heart tissue of the TAC group was remarkably upregulated (P<0.05) 2 weeks after the surgery, with no change in the brain and kidney tissue between the 2 groups. CONCLUSION: Expression of nucleolin protein has been upregulated in response to pressure overload, which may suggest that nucleolin plays a role in cardiac hypertrophy induced by pressure overload.

A positive FOXP3/lncRNA SNHG1 feedback axis ameliorates cardiomyocytes hypertrophy by negatively regulating Parkin-mediated mitophagy.

In this study, we identified FOXP3 as a transcription factor for lncRNA SNHG1, which exerts a significant protective role against cardiomyocyte hypertrophy. Through DNA-pull down experiments and ChIP analysis, we confirmed that FOXP3 could bind to the promoter of SNHG1. Luciferase reporter and RT-qPCR experiments validated that FOXP3 overexpression promoted SNHG1 expression in cardiomyocytes. Furthermore, in a model of cardiomyocyte hypertrophy, FOXP3 expression was upregulated, particularly in cardiomyocytes. Functional assays demonstrated that FOXP3 overexpression inhibited cardiomyocyte hypertrophy, while FOXP3 knockdown held the opposite effect. Additionally, we revealed that lncRNA SNHG1 acted as a sponge for miR-182, miR-326, and miR-3918, thereby stabilizing FOXP3 mRNA in cardiomyocytes. The protective role of SNHG1 against cardiomyocyte hypertrophy was found to depend on the presence of FOXP3, forming a positive FOXP3/SNHG1 feedback axis. Moreover, we unveiled this positive FOXP3/SNHG1 feedback axis suppressed cardiomyocyte hypertrophy by negatively regulating Parkin-mediated mitophagy. These findings provide novel insights into the molecular mechanisms underlying cardiomyocyte hypertrophy and offer potential therapeutic targets for related interventions.

Acupuncture alleviates CUMS-induced depression-like behaviors of rats by regulating oxidative stress, neuroinflammation and ferroptosis.

BACKGROUND: The treatment of depression with acupuncture has been documented. The mechanism behind acupuncture's curative and preventative effects is still unknown. METHODS: The current study examined the effects of acupuncture on depression-like behaviors in a rat model of chronic unpredictable mild stress (CUMS), while also exploring its potential mechanisms. A total of six groups of rats were randomly assigned: control, CUMS, acupuncture, fluoxetine, acupoint catgut embedding and sham acupoint catgut embedding. Fluoxetine (2.1 mg/kg) and acupoint catgut embedding were used for comparative research to acupuncture. The modelling evaluation is measured by body weight and behavior tests. Western blotting and reverse transcription-polymerase chain reaction were used to detect the proteins and mRNA expression of Silent information regulator 1 (Sirt1)/ nuclear factor-erythroid 2-related factor 2 (Nrf2)/ heme oxygenase-1 (HO-1)/ Glutathione peroxidase 4 (GPX4) pathway in the hippocampus. The expression of oxidative stress (OS)-related proteins and inflammatory cytokines in the serum was detected with ELISA. Immunofluorescence showed microglia and astrocytes activity in the hippocampus. RESULTS: Acupuncture and fluoxetine could alleviate CUMS-induced depression-like behaviors. Acupuncture was also found to effectively reverse the levels of MDA, SOD, GSH, GSH-PX and T-AOC, IL-1ß, IL-6 and TNF-α in the serum of CUMS-induced rats. Rats with CUMS showed decreased levels of Sirt1, Nrf2, HO-1 and GPX4 in the hippocampus, while acupuncture treatment could partly reverse the diminished effects. In addition, acupuncture treatment significantly reduced the activation of hippocampal microglia and astrocytes in CUMS-induced rats. CONCLUSION: The study's findings indicate that acupuncture has the potential to mitigate depression-like behaviors in rats induced with CUMS by mitigating OS and reducing neuroinflammation.

Electroacupuncture ameliorates chronic unpredictable mild stress-induced depression-like behavior and cognitive impairment through suppressing oxidative stress and neuroinflammation in rats.

BACKGROUND: Depression is associated with lowered mood, anxiety, anhedonia, cognitive impairments, and even suicidal tendencies in severe cases. Yet few studies have directed acupuncture's mechanism toward enhancing axonal repair correlated with synaptic plasticity and anti-inflammatory effects related to oxidative stress in the hippocampus. METHODS: Male Sprague-Dawley (SD) rats were randomly divided into control group (CON), chronic unpredictable mild stress (CUMS) group, CUMS + electroacupuncture group (EA), and CUMS + fluoxetine group (FLX) (n = 10/group). Rats were given a 28-day treatment at the Shangxing (GV23) and Fengfu (GV16) acupoints with electroacupuncture or fluoxetine (2.1 mg/kg). RESULTS: Rats exposed to CUMS induced depression-like behaviors and spatial learning-memory impairment, changed the ionized calcium binding adaptor molecule 1 (IBA-1), Vglut1, myelin basic protein (MBP), and postsynaptic density protein 95 (PSD95) level of hippocampal, increased the Nod-like receptor protein 3 (NLRP3), atypical squamous cell (ASC), Caspase level and hippocampal reactive oxygen species (ROS), and prompted the activation of Epha4-mediated signaling and an inflammatory response. Conversely, electroacupuncture administration reduced these changes and prevented depression-like behaviors and cognitive impairment. Electroacupuncture also promoted hippocampal expression of Sirtuin1(SIRT1), Nuclear factor erythroid 2-like (Nrf2), Heme oxygenase-1 (HO-1); reduced the expression of interleukin-1ß (IL-1ß), interleukin-18 (IL-18), and tumor necrosis factor-alpha (TNF-α); and prevented neural damage, particularly the synaptic myelin sheath, and neuroinflammation by regulating Eph receptor A4 (EphA4) in the hippocampal. CONCLUSION: These results indicate that electroacupuncture prevents depression-like behaviors with cognitive impairment and synaptic and neuronal damage, probably by reducing EphA4, which mediates ROS hyperfunction and the inflammatory response.

Trade for Food Security: The Stability of Global Agricultural Trade Networks.

Global food production is facing increasing uncertainties under climate change and the coronavirus pandemic, provoking challenges and severe concerns to national food security. The role of global agricultural trade in bridging the imbalance between food supply and demand has come to the fore. However, the impact of multifaceted and dynamic factors, such as trade policies, national relations, and epidemics, on the stability of the agricultural trade network (ATN) needs to be better addressed. Quantitatively, this study estimated grouping characteristics and network stability by analyzing the changing global ATN from 1986 to 2018. We found that the evolution of global agricultural trade communities has gone through four stages: the dominance of the US-Asian community, the rise of the European-African community, the formation of tri-pillar communities, and the development of a multipolar community with a more complex structure. Despite witnessing a progressive increase in the nodal stability of the global ATN during the decades, particular gaps can still be found in stability across countries. Specifically, the European community achieved stability of 0.49 and its trade relations were effectively secured. Meanwhile, the remaining leading communities' stability shows a stable and upward trend, albeit with more significant challenges in trade relations among some of them. Therefore, how to guarantee the stability of trade relations and strengthen the global ATN to resist external shocks has become an essential question to safeguard global food security.

Pharmacist-led iodinated contrast media infusion risk assessment service.

Background: With the increasing development of medical imaging, the use of iodinated contrast media has become more widespread. Adverse reactions caused by iodinated contrast media have drawn much attention. Despite this, there is still a lack of unified standards for the safe infusion process of iodinated contrast media in clinical practice both domestically and internationally. Objectives: Establishing a risk management service system to better predict the risks associated with iodinated contrast media infusion, reduce the incidence of adverse reactions and minimize patient harm. Method: A prospective interventional study was carried out from April 2021 to December 2021 at Nanjing Drum Tower Hospital in China. During this study, a service system was established to manage the risks associated with the infusion of iodinated contrast media. Personalized risk identification and assessment were performed by a pharmacist-led multidisciplinary team before iodinated contrast media infusion. Early warning, prevention, and adverse reaction management were performed according to different risk levels during and after infusion. Results: A multidisciplinary team led by pharmacists was established to evaluate the risks associated with infusion of iodinated contrast media. A total of 157 patients with risk factors related to the iodinated contrast media were screened out, which prevented 22 serious adverse events and enhanced the quality of medical care. All participants expressed high satisfaction with the service. Conclusion: Through practical exploration, the pharmacist-led multidisciplinary team can provide advance warning and effectively limit the risks of adverse reactions caused by iodinated contrast media to a preventable and controllable level. This approach serves as a valuable reference for developing strategies and schemes to reduce the incidence of such reactions. Therefore, we encourage the implementation of this intervention in other areas of China.

Contribution of Mitochondrial Reactive Oxygen Species to Chronic Hypoxia-Induced Pulmonary Hypertension.

Pulmonary hypertension (PH) resulting from chronic hypoxia (CH) occurs in patients with chronic obstructive pulmonary diseases, sleep apnea, and restrictive lung diseases, as well as in residents at high altitude. Previous studies from our group and others demonstrate a detrimental role of reactive oxygen species (ROS) in the pathogenesis of CH-induced PH, although the subcellular sources of ROS are not fully understood. We hypothesized that mitochondria-derived ROS (mtROS) contribute to enhanced vasoconstrictor reactivity and PH following CH. To test the hypothesis, we exposed rats to 4 weeks of hypobaric hypoxia (PB ≈ 380 mmHg), with control rats housed in ambient air (PB ≈ 630 mmHg). Chronic oral administration of the mitochondria-targeted antioxidant MitoQ attenuated CH-induced decreases in pulmonary artery (PA) acceleration time, increases in right ventricular systolic pressure, right ventricular hypertrophy, and pulmonary arterial remodeling. In addition, endothelium-intact PAs from CH rats exhibited a significantly greater basal tone compared to those from control animals, as was eliminated via MitoQ. CH also augmented the basal tone in endothelium-disrupted PAs, a response associated with increased mtROS production in primary PA smooth muscle cells (PASMCs) from CH rats. However, we further uncovered an effect of NO synthase inhibition with Nω-nitro-L-arginine (L-NNA) to unmask a potent endothelial vasoconstrictor influence that accentuates mtROS-dependent vasoconstriction following CH. This basal tone augmentation in the presence of L-NNA disappeared following combined endothelin A and B receptor blockade with BQ123 and BQ788. The effects of using CH to augment vasoconstriction and PASMC mtROS production in exogenous endothelin 1 (ET-1) were similarly prevented by MitoQ. We conclude that mtROS participate in the development of CH-induced PH. Furthermore, mtROS signaling in PASMCs is centrally involved in enhanced pulmonary arterial constriction following CH, a response potentiated by endogenous ET-1.

The effects of acupuncture on depression by regulating BDNF-related balance via lateral habenular nucleus BDNF/TrkB/CREB signaling pathway in rats.

Depression is a major mental disease worldwide, causing dysfunction of Lateral Habenular (LHb). As a non-invasive alternative, acupuncture (AP) has been widely used to treat depression in clinic, yet few basic studies have been focused on the effects and mechanism of acupuncture on synaptic plasticity in LHb. Therefore, this study aimed to explore the potential mechanism of the antidepressant effect of acupuncture. Male Sprague-Dawley (SD) rats were randomly divided into control, chronic unpredictable mild stress (CUMS), AP, fluoxetine (FLX), acupoint catgut embedding (ACE), sham-ACE groups (n = 9/group). Rats were given a 28-day treatment at the Shangxing (GV23) and Fengfu (GV16) acupoints with acupuncture, ACE, sham-ACE or fluoxetine (2.1 mg/kg). The results showed that AP, FLX and ACE suppressed the behavioral deficits, increased the level of the 5-hydroxytryptamine and FNDC5/IRISIN in serum, also reduced the expression of pro-BDNF impacted by CUMS. Both AP and FLX ameliorated the %area of IBA-1, GFAP, BrdU and DCX in the LHb and increased the expression of BDNF/TrkB/CREB, with non-significant difference between the two groups These findings suggest that AP therapy relieves depression-related manifestations in depressed rats, suggesting a potential mechanism via the BDNF/TrkB/CREB pathway in LHb.

The effect of acupuncture on lateral habenular nucleus and intestinal microflora in depression model rats.

BACKGROUND: Depression is a severe emotional condition that significantly affects the quality of life. Acupuncture exerts preventive effects on depression in rats with post-chronic unpredictable mild stress (CUMS). Methods The study involved chronic unpredictable mild stress (CUMS) depression model mice to administer acupuncture as a preventative measure to investigate the mechanism of acupuncture's antidepressant and observe the effect of acupuncture on impact via the Lateral Habenula (LHb) and Gut-Liver-Brain Axis. The researcher investigated molecules correlating with a nitric oxide/cyclic guanosine monophosphate (NO/cGMP) pathway and assessed inflammation in the LHb and liver. In addition, 16 S rDNA bioinformatics study revealed the quantity and variety of gut microbiota. Rats were randomly divided into five groups: control (CON), CUMS, CUMS + acupuncture (AP), CUMS + fluoxetine (FX) and CUMS + N(G) -nitro -L- arginine methyl ester (LNAME) group. Except for the CON group, other rats were exposed to CUMS condition for 28 days. Simultaneously, manual acupuncture (at Fengfu and Shangxing acupoints, once every other day) and fluoxetine gavage (2.1 mg/kg, 0.21 mg/mL, daily) were conducted to the groups of AP and FX, respectively, after stressors. Rats in LNAME group were treated with LNAME normal saline (10 mg/kg, 1 mg/mL, i.p.) solution. Behavioural tests and biological detection methods were conducted sequentially to evaluate depressionlike phenotype in rats. RESULTS: The results showed CUMS induced depression-like behaviours, hyper-activation of NO/cGMP signaling pathway, inflammation in serum, LHb and liver, and dysbiosis of the gut microbiota. These changes could be prevented and ameliorated by acupuncture to varying extents. CONCLUSION: Acupuncture prevented and attenuated depression-like phenotype induced by CUMS, possibly via regulating the NO/cGMP signaling pathway and thus improving inflammation in serum, LHb and liver, and gut microbiota dysbiosis. In addition, these can be evidence of the existence of the gut-liver-brain axis.