Skeletal Transformations of Terpenoid Forskolin Employing an Oxidative Rearrangement Strategy.

The skeletal transformations of diterpenoid forskolin were achieved by employing an oxidative rearrangement strategy. A library of 36 forskolin analogues with structural diversity was effectively generated. Computational analysis shows that 12 CTD compounds with unique scaffolds and ring systems were produced during the course of this work.

Electroacupuncture attenuates nociceptive behaviors in a mouse model of cancer pain.

Pain is a major symptom in cancer patients, and cancer-induced bone pain (CIBP) is the most common type of moderate and severe cancer-related pain. The current available analgesic treatments for CIBP have adverse effects as well as limited therapeutic effects. Acupuncture is proved effective in pain management as a safe alternative therapy. We evaluated the analgesic effect of acupuncture in treatment of cancer pain and try to explore the underlying analgesic mechanisms. Nude mice were inoculated with cancer cells into the left distal femur to establish cancer pain model. Electroacupuncture (EA) treatment was applied for the xenograft animals. Pain behaviors of mice were evaluated, followed by the detections of neuropeptide-related and inflammation-related indicators in peripheral and central levels. EA treatment alleviated cancer-induced pain behaviors covering mechanical allodynia, thermal hyperalgesia and spontaneous pain, and also down-regulated immunofluorescence expressions of neuropeptide CGRP and p75 in the skin of affected plantar area in xenograft mice, and inhibited expressions of overexpressed neuropeptide-related and inflammation-related protein in the lumbar spinal cord of xenograft mice. Overall, our findings suggest that EA treatment ameliorated cancer-induced pain behaviors in the mouse xenograft model of cancer pain, possibly through inhibiting the expressions of neuropeptide-related and inflammation-related protein in central level following tumor cell xenografts.

Berberine-based self-assembly agents with enhanced synergistic antitumor efficacy.

Tumors are still a major threat to people worldwide. Nanodrug delivery and targeting systems can significantly improve the therapeutic efficacy of chemotherapeutic drugs for antitumor purposes. However, many nanocarriers are likely to exhibit drawbacks such as a complex preparation process, limited drug-loading capacity, untargeted drug release, and toxicity associated with nanocarriers. Therefore, new therapeutic alternatives are urgently needed to develop antitumor drugs. Natural products with abundant scaffold diversity and structural complexity, which are derived from medicinal plants, are important sources of new antitumor drugs. Here, two carrier-free berberine (BBR)-based nanoparticles (NPs) were established to increase the synergistic efficacy of tumor treatment. BBR can interact with glycyrrhetinic acid (GA) and artesunate (ART) to self-assemble BBR-GA and BBR-ART NPs without any nanocarriers, respectively, the formation of which is dominated by electrostatic and hydrophobic interactions. Moreover, BBR-GA NPs could lead to mitochondria-mediated cell apoptosis by regulating mitochondrial fission and dysfunction, while BBR-ART NPs induced ferroptosis in tumor cells. BBR-based NPs have been demonstrated to possess significant tumor targeting and enhanced antitumor properties compared with those of simple monomer mixes both in vitro and in vivo. These carrier-free self-assemblies based on natural products provide a strategy for synergistic drug delivery and thus offer broad prospects for developing enhanced antitumor drugs.

Extraction, purification, structural characterization, and bioactivities of the genus Schisandra polysaccharides: A review.

The genus Schisandra, a member of the Magnoliaceae family, is a well-known tonic traditional Chinese medicine with a long history of traditional medicinal and functional food used in China. Polysaccharides are one of its main active constituents, which have a wide range of bioactivities, such as anti-inflammatory, anti-tumor, neuroprotection, anti-diabetes, hepatoprotection, immunomodulation, and anti-fatigue. In this paper, we review the extraction, isolation, purification, structural characterization, bioactivities, as well as structure-activity relationship of polysaccharides from the genus Schisandra. In conclusion, we hope that this review could provide reference for the subsequent research on structural, bioactivities, development and application of the genus Schisandra polysaccharides.

Post-synthetic modified luminescent metal-organic framework for the detection of berberine hydrochloride in a traditional Chinese herb.

In this work, a novel fluorescence sensor UiO-66-PSM based on post-synthetic modified metal-organic frameworks was prepared for the detection of berberine hydrochloride (BBH) in the traditional Chinese herb Coptis. UiO-66-PSM was synthesized by a simple Schiff base reaction with UiO-66-NH2 and phthalaldehyde (PAD). The luminescence quenching can be attributed to the photo-induced electron transfer process from the ligand of UiO-66-PSM to BBH. The UiO-66-PSM sensor exhibited fast response time, low detection limit, and high selectivity to BBH. Moreover, the UiO-66-PSM sensor was successfully applied to the quantitative detection of BBH in the traditional Chinese herb Coptis, and the detection results obtained from the as-fabricated fluorescence sensing assay were consistent with those of high-performance liquid chromatography (HPLC), indicating that this work has potential applicability for the detection of BBH in traditional Chinese herbs.

Microwave-responsive gadolinium metal-organic frameworks nanosystem for MRI-guided cancer thermotherapy and synergistic immunotherapy.

The clinical application of cancer immunotherapy is unsatisfied due to low response rates and systemic immune-related adverse events. Microwave hyperthermia can be used as a synergistic immunotherapy to amplify the antitumor effect. Herein, we designed a Gd-based metal-organic framework (Gd-MOF) nanosystem for MRI-guided thermotherapy and synergistic immunotherapy, which featured high performance in drug loading and tumor tissue penetration. The PD-1 inhibitor (aPD-1) was initially loaded in the porous Gd-MOF (Gd/M) nanosystem. Then, the phase change material (PCM) and the cancer cell membrane were further sequentially modified on the surface of Gd/MP to obtain Gd-MOF@aPD-1@CM (Gd/MPC). When entering the tumor microenvironment (TME), Gd/MPC induces immunogenic death of tumor cells through microwave thermal responsiveness, improves tumor suppressive immune microenvironment and further enhances anti-tumor ability of T cells by releasing aPD-1. Meanwhile, Gd/MPC can be used for contrast-enhanced MRI. Transcriptomics data revealed that the downregulation of MSK2 in cancer cells leads to the downregulation of c-fos and c-jun, and ultimately leads to the apoptosis of cancer cells after treatment. In general, Gd/MPC nanosystem not only solves the problem of system side effect, but also achieves the controlled drug release via PCM, providing a promising theranostic nanoplatform for development of cancer combination immunotherapy.

Target Separation and Potential Anticancer Activity of Withanolide-Based Glucose Transporter Protein 1 Inhibitors from Physalis angulata var. villosa.

The glucose transporter 1 (GLUT1) protein is involved in the basal-level absorption of glucose in tumor cells. Inhibiting GLUT1 decreases tumor cell proliferation and induces tumor cell damage. Natural GLUT1 inhibitors have been studied only to a small extent, and the structures of known natural GLUT1 inhibitors are limited to a few classes of natural products. Therefore, discovering and researching other natural GLUT1 inhibitors with novel scaffolds are essential. Physalis angulata L. var. villosa is a plant known as Mao-Ku-Zhi (MKZ). Withanolides are the main phytochemical components of MKZ. MKZ extracts and the components of MKZ exhibited antitumor activity in recent pharmacological studies. However, the antitumor-active components of MKZ and their molecular mechanisms remain unknown. A cell membrane-biomimetic nanoplatform (CM@Fe3O4/MIL-101) was used for target separation of potential GLUT1 inhibitors from MKZ. A new withanolide, physagulide Y (2), together with six known withanolides (1, 3-7), was identified as a potential GLUT1 inhibitor. Physagulide Y was the most potent GLUT1 inhibitor, and its antitumor activity and possible mechanism of action were explored in MCF-7 human cancer cells. These findings advance the development of technologies for the targeted separation of natural products and identify a new molecular framework for the investigation of natural GLUT1 inhibitors.

Transcutaneous electrical acupoint stimulation for postoperative nausea and vomiting in patients undergoing craniotomy: A randomized controlled trial.

BACKGROUND: The incidence of nausea and vomiting following craniotomy is high, and pericardium 6 (P6; Neiguan) acupoint stimulation is an important strategy for treating postoperative nausea and vomiting (PONV). Here, we aimed to evaluate the efficacy of transcutaneous electrical acupoint stimulation (TEAS) at P6 as an adjunct to antiemetic drugs to prevent PONV after craniotomy. MATERIALS AND METHODS: This randomized placebo-controlled trial enrolled 120 patients scheduled for craniotomy. The enrolled patients were randomly assigned to a TEAS or sham TEAS group. The incidence of PONV, pain score, and postoperative remedial treatment with antiemetics and analgesics at 0-2, 2-6, and 6-24 h after craniotomy were assessed. RESULTS: The patient characteristics did not significantly differ between the two groups (P > 0.05). During 0-2 and 6-24 h after craniotomy, the incidence of vomiting was not significantly different between the two groups (P > 0.05). During 2-6 h, the incidence of vomiting was higher in the sham TEAS group than in the TEAS group (29.3 % vs. 14.0 %, P = 0.047). During 0-2 and 2-6 h, the pain scores did not differ significantly between the two groups (P > 0.05). During 6-24 h after craniotomy, the pain score was significantly higher in the sham TEAS group than in the TEAS group (P = 0.001). The degree of nausea and proportion of patients requiring antiemetic drugs were not significantly different between the two groups in each period (P > 0.05). CONCLUSION: TEAS at P6 may reduce vomiting incidence and pain scores following craniotomy.

Antagonistic MADS-box transcription factors SEEDSTICK and SEPALLATA3 form a transcriptional regulatory network that regulates seed oil accumulation.

Transcriptional regulation is essential for balancing multiple metabolic pathways that influence oil accumulation in seeds. Thus far, the transcriptional regulatory mechanisms that govern seed oil accumulation remain largely unknown. Here, we identified the transcriptional regulatory network composed of MADS-box transcription factors SEEDSTICK (STK) and SEPALLATA3 (SEP3), which bridges several key genes to regulate oil accumulation in seeds. We found that STK, highly expressed in the developing embryo, positively regulates seed oil accumulation in Arabidopsis (Arabidopsis thaliana). Furthermore, we discovered that SEP3 physically interacts with STK in vivo and in vitro. Seed oil content is increased by the SEP3 mutation, while it is decreased by SEP3 overexpression. The chromatin immunoprecipitation, electrophoretic mobility shift assay, and transient dual-luciferase reporter assays showed that STK positively regulates seed oil accumulation by directly repressing the expression of MYB5, SEP3, and SEED FATTY ACID REDUCER 4 (SFAR4). Moreover, genetic and molecular analyses demonstrated that STK and SEP3 antagonistically regulate seed oil production and that SEP3 weakens the binding ability of STK to MYB5, SEP3, and SFAR4. Additionally, we demonstrated that TRANSPARENT TESTA 8 (TT8) and ACYL-ACYL CARRIER PROTEIN DESATURASE 3 (AAD3) are direct targets of MYB5 during seed oil accumulation in Arabidopsis. Together, our findings provide the transcriptional regulatory network antagonistically orchestrated by STK and SEP3, which fine tunes oil accumulation in seeds.

[Hyperspectral imaging technology distinguishes between Puerariae Lobatae Radix and Puerariae Lobatae Caulis].

Puerariae Lobatae Radix, the dried root of Pueraria lobata, is a traditional Chinese medicine with a long history. Puerariae Lobatae Caulis as an adulterant is always mixed into Puerariae Lobatae Radix for sales in the market. This study employed hyperspectral imaging(HSI) to distinguish between the two products. VNIR lens(spectral scope of 410-990 nm) and SWIR lens(spectral scope of 950-2 500 nm) were used for image acquiring. Multi-layer perceptron(MLP), partial least squares discriminant analysis(PLS-DA), and support vector machine(SVM) were employed to establish the full-waveband models and select the effective wavelengths for the distinguishing between Puerariae Lobatae Caulis and Puerariae Lobatae Radix, which provided technical and data support for the development of quick inspection equipment based on HSI. The results showed that MLP model outperformed PLS-DA and SVM models in the accuracy of discrimination with full wavebands in VNIR, SWIR, and VNIR+SWIR lens, which were 95.26%, 99.11%, and 99.05%, respectively. The discriminative band selection(DBS) algorithm was employed to select the effective wavelengths, and the discrimination accuracy was 93.05%, 98.05%, and 98.74% in the three different spectral scopes, respectively. On this basis, the MLP model combined with the effective wavelengths within the range of 2 100-2 400 nm can achieve the accuracy of 97.74%, which was close to that obtained with the full waveband. This waveband can be used to develop quick inspection devices based on HSI for the rapid and non-destructive distinguishing between Puerariae Lobatae Radix and Puerariae Lobatae Caulis.

Efficacy of Jiao's scalp acupuncture in combination with Xiangshao granules on chronic tension-type headache with concomitant nonalcoholic fatty liver disease in climacteric women.

OBJECTIVE: This study aimed to assess the efficacy of Jiao's scalp acupuncture in combination with Xiangshao granules on chronic tension-type headache (CTTH) with concomitant nonalcoholic fatty liver disease (NAFLD) in climacteric women. METHODS: In this study, we enrolled 150 climacteric women with CTTH and concomitant NAFLD. The participants were divided into three groups based on the random number table: medication group, acupuncture group, and acupuncture-medication group. Treatment continued for 2 months. The efficacy of CTTH was assessed based on the visual analog scale/score (VAS). The influence on NAFLD was assessed based on body mass index (BMI), controlled attenuation parameter (CAP), and the ratio of hepatic-splenic computed tomography (CT) value. The Participant Health Questionnaire-9 (PHQ-9) score was compared among the three groups. RESULTS: A total of 123 participants completed the trial, including 37 participants in the medication group, 41 participants in the acupuncture group, and 45 participants in the acupuncture-medication group. Results are summarized hereinafter. (1) The total clinical efficiency rates of the medication group, acupuncture group, and acupuncture-medication group were 89.19% (33 of 37), 90.24% (37 of 41), and 95.65% (44 of 46), respectively. (2) Except for the BMI of the medication group ( P = 0.063), a significant difference in VAS, BMI, CAP, the ratio of hepatic-splenic CT value, and PHQ-9 score was found in the three groups ( P < 0.01). (3) There was a significant difference in VAS, BMI, CAP, and PHQ-9 among the three groups ( P < 0.01), with those in the acupuncture-medication group being superior. No difference in the ratio of hepatic-splenic CT value was found ( P = 0.440). (4) The efficacy differed significantly among the three groups ( χ2 = 8.130, P = 0.017), and it was significantly superior in the acupuncture-medication group ( P = 0.008, P = 0.013). CONCLUSIONS: Jiao's scalp acupuncture, in combination with Xiangshao granules, was superior in treating CTTH in climacteric women compared with either acupuncture or medication. Jiao's scalp acupuncture, in combination with Xiangshao granules, was superior in subsiding the negative moods in participants with CTTH and concomitant NAFLD.

Ethnic, Botanic, Phytochemistry and Pharmacology of the Acorus L. Genus: A Review.

The genus Acorus, a perennial monocotyledonous-class herb and part of the Acoraceae family, is widely distributed in the temperate and subtropical zones of the Northern and Southern Hemispheres. Acorus is rich in biological activities and can be used to treat various diseases of the nervous system, cardiovascular system, and digestive system, including Alzheimer's disease, depression, epilepsy, hyperlipidemia, and indigestion. Recently, it has been widely used to improve eutrophic water and control heavy-metal-polluted water. Thus far, only three species of Acorus have been reported in terms of chemical components and pharmacological activities. Previously published reviews have not further distinguished or comprehensively expounded the chemical components and pharmacological activities of Acorus plants. By carrying out a literature search, we collected documents closely related to Acorus published from 1956 to 2022. We then performed a comprehensive and systematic review of the genus Acorus from different perspectives, including botanical aspects, ethnic applications, phytochemistry aspects, and pharmacological aspects. Our aim was to provide a basis for further research and the development of new concepts.

[Effect of electroacupuncture on myocardial fibrosis in spontaneously hypertensive rats based on cholinergic anti-inflammatory pathway].

OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Neiguan" (PC 6) on myocardial fibrosis in spontaneously hypertensive rats (SHR), and explore preliminarily the mediating role of cholinergic anti-inflammatory pathway (CAP) and its downstream nuclear factor κB (NF-κB) signaling pathway. METHODS: Six 12-week-old WKY male rats were employed as the normal group. Eighteen 12-week-old SHR were randomly divided into 3 groups, i.e. a model group, an EA group and a blocking group (EA after blocking α7 nicotinic acetylcholine receptor [α7nAchR]), with 6 rats in each one. In the EA group, EA was delivered at "Neiguan"(PC 6) and the site 0.5 cm from its left side, with disperse-dense wave, 2 Hz/15 Hz in frequency and 1 mA in current intensity. One intervention took 30 min and was given once every 2 days, lasting 8 weeks. In the blocking group, prior to each EA, the α7nAchR specific blocker, α-bungartoxin was injected intravenously in the tails of the rats. After EA intervention, the systolic blood pressure (SBP), the diastolic blood pressure (DBP) and the mean arterial pressure (MAP) were measured with non-invasive blood pressure monitor. Using echocardiogram, the left ventricular (LV) anterior wall end-diastolic thickness (LVAWd) , LV posterior wall end-diastolic thickness (LVPWd) and the LV end-diastolic internal diameter (LVIDd) were measured. The level of hydroxyproline (Hyp) in the myocardial tissue was determined by using alkaline hydrolysis, and that of acetylcholine (Ach) was detected by ELISA. With the real-time PCR adopted, the mRNA expression of NF-κB p65, tumor necrosis factor α (TNF-α), interleukin (IL)-1ß and IL-6 were determined. RESULTS: Compared with the normal group, SBP, DBP, MAP, LVAWd and LVPWd were increased (P<0.01), and LVIDd was decreased (P<0.01) in the rats of the model group. SBP, DBP, MAP and LVAWd were dropped (P<0.01, P<0.05), and LVIDd rose (P<0.01) in the EA group when compared with those in the model group. The differences in the above indexes were not statistically significant between the blocking group and the model group (P>0.05). Compared with the normal group, Hyp level and the mRNA expression of NF-κB p65, TNF-α, IL-1ß and IL-6 in the myocardial tissue increased (P<0.01, P<0.05) and Ach level decreased (P<0.01) in the model group. Hyp level, the mRNA expression of NF-κB p65, TNF-α, IL-1ß and IL-6 in the myocardial tissue were reduced (P<0.05, P<0.01) and Ach level rose (P<0.01) in the EA group when compared with those in the model group. These indexes were not different statistically between the blocking group and the model group (P>0.05). CONCLUSION: CAP may be involved in ameliorating the pathological damage of myocardial fibrosis during EA at "Neiguan"(PC 6). The underlying effect mechanism is associated with up-regulating the neurotransmitter, Ach and down-regulating mRNA expression of NF-κB p65 and pro-inflammatory factors such as TNF-α, IL-1ß and IL-6 in myocardial tissue.

Revealing the hidden burden for lake management: the sediment phosphorus storage pools in Eastern Plain Lake Zone, China.

As one of the essential components in ecosystems, lakes play a major role in the global phosphorus (P) cycle. It is helpful for further understanding of the inside lake P geochemical cycle to research P pollution and storage in lakes, which is of positive significance for lake eutrophication restoration. In this study, we investigated the total phosphorus concentrations (TPC) of water and sediments from 37 lakes in the Eastern Plain Lake Zone (EPL) of China, evaluated the P pollution degree of lakes, and estimated P storage in lake sediments with quantitative data of lake area and number. The results indicate that the total phosphorus concentrations of water (TPCW) and total phosphorus concentrations of the surface sediments (0-1 cm, TPCSS) in EPL were high, the mean values were 0.11 mg·L-1 and 869.85 mg·kg-1 respectively, with obvious differences between urban and rural areas, as well as between different river basins. Over half (56.76% and 70.27% respectively) of the lakes reached severe pollution levels in water and surface sediments. There were 16224 lakes (> 0.01 km2) with a total area of 21662.37 km2 in the EPL, and the P storage in the lake sediments (0-30 cm) was about 4.87 ± 2.08 Tg (1 Tg = 1 × 1012 g), accounting for about 2.74% of the basin soil. TPCW and TPCSS of lakes in the EPL were significantly positively correlated, may suggest a close nutrient cycling relationship between the lake water and the sediment. During periods of high winds and waves, the stored P in the top sediments in the EPL may continue to participate in the internal P geochemical cycle and migrate to the overlying water, posing a potential pollution hazard. Therefore, it is crucial to take into account the sediment P pools when formulating effective lake phosphorus management strategies.

Low phosphorus promotes NSP1-NSP2 heterodimerization to enhance strigolactone biosynthesis and regulate shoot and root architecture in rice.

Phosphorus is an essential macronutrient for plant development and metabolism, and plants have evolved ingenious mechanisms to overcome phosphate (Pi) starvation. However, the molecular mechanisms underlying the regulation of shoot and root architecture by low phosphorus conditions and the coordinated utilization of Pi and nitrogen remain largely unclear. Here, we show that Nodulation Signaling Pathway 1 (NSP1) and NSP2 regulate rice tiller number by promoting the biosynthesis of strigolactones (SLs), a class of phytohormones with fundamental effects on plant architecture and environmental responses. We found that NSP1 and NSP2 are induced by Oryza sativa PHOSPHATE STARVATION RESPONSE2 (OsPHR2) in response to low-Pi stress and form a complex to directly bind the promoters of SL biosynthesis genes, thus markedly increasing SL biosynthesis in rice. Interestingly, the NSP1/2-SL signaling module represses the expression of CROWN ROOTLESS 1 (CRL1), a newly identified early SL-responsive gene in roots, to restrain lateral root density under Pi deficiency. We also demonstrated that GR244DO treatment under normal conditions inhibits the expression of OsNRTs and OsAMTs to suppress nitrogen absorption but enhances the expression of OsPTs to promote Pi absorption, thus facilitating the balance between nitrogen and phosphorus uptake in rice. Importantly, we found that NSP1p:NSP1 and NSP2p:NSP2 transgenic plants show improved agronomic traits and grain yield under low- and medium-phosphorus conditions. Taken together, these results revealed a novel regulatory mechanism of SL biosynthesis and signaling in response to Pi starvation, providing genetic resources for improving plant architecture and nutrient-use efficiency in low-Pi environments.

Effects of nanoscale zinc oxide treatment on growth, rhizosphere microbiota, and metabolism of Aconitum carmichaelii.

Trace elements play a crucial role in the growth and bioactive substance content of medicinal plants, but their utilization efficiency in soil is often low. In this study, soil and Aconitum carmichaelii samples were collected and measured from 22 different locations, followed by an analysis of the relationship between trace elements and the yield and alkaloid content of the plants. The results indicated a significant positive correlation between zinc, trace elements in the soil, and the yield and alkaloid content of A. carmichaelii. Subsequent treatment of A. carmichaelii with both bulk zinc oxide (ZnO) and zinc oxide nanoparticles (ZnO NPs) demonstrated that the use of ZnO NPs significantly enhanced plant growth and monoester-type alkaloid content. To elucidate the underlying mechanisms responsible for these effects, metabolomic analysis was performed, resulting in the identification of 38 differentially expressed metabolites in eight metabolic pathways between the two treatments. Additionally, significant differences were observed in the rhizosphere bacterial communities, with Bacteroidota and Actinobacteriota identified as valuable biomarkers for ZnO NP treatment. Covariation analysis further revealed significant correlations between specific microbial communities and metabolite expression levels. These findings provide compelling evidence that nanoscale zinc exhibits much higher utilization efficiency compared to traditional zinc fertilizer.

Hyodeoxycholic acid ameliorates nonalcoholic fatty liver disease by inhibiting RAN-mediated PPARα nucleus-cytoplasm shuttling.

Nonalcoholic fatty liver disease (NAFLD) is usually characterized with disrupted bile acid (BA) homeostasis. However, the exact role of certain BA in NAFLD is poorly understood. Here we show levels of serum hyodeoxycholic acid (HDCA) decrease in both NAFLD patients and mice, as well as in liver and intestinal contents of NAFLD mice compared to their healthy counterparts. Serum HDCA is also inversely correlated with NAFLD severity. Dietary HDCA supplementation ameliorates diet-induced NAFLD in male wild type mice by activating fatty acid oxidation in hepatic peroxisome proliferator-activated receptor α (PPARα)-dependent way because the anti-NAFLD effect of HDCA is abolished in hepatocyte-specific Pparα knockout mice. Mechanistically, HDCA facilitates nuclear localization of PPARα by directly interacting with RAN protein. This interaction disrupts the formation of RAN/CRM1/PPARα nucleus-cytoplasm shuttling heterotrimer. Our results demonstrate the therapeutic potential of HDCA for NAFLD and provide new insights of BAs on regulating fatty acid metabolism.

Joint effect of whole blood metals exposure with dyslipidemia in representative US adults in NHANES 2011-2020.

With little knowledge on the joint effects of metal exposure on dyslipidemia, we aimed to investigate the relationship between exposure to metal and dyslipidemia among US adults based on the National Health and Nutrition Examination Survey (NHANES). Based on the five NHANES waves (2011-2020), we selected five metals in blood as exposure, namely, cadmium (Cd), lead (Pb), total mercury (Hg), manganese (Mn), and selenium (Se), which were detected by inductively coupled plasma mass spectrometry. Survey-multivariable logistic regression, generalized weighted quantile sum (WQS), and Bayesian kernel machine regression (BKMR) were performed to determine whether dyslipidemia was associated with single metals or mixed metals. Our study included 12,526 participants aged from 20 to 80, representing 577.1 million non-institutionalized US adults. We found a positive association between several metals including Pb [adjusted odds ratio (AOR) = 1.332, 95%CI: 1.165, 1.522], total Hg (AOR = 1.264, 95%CI: 1.120, 1.427), Mn (AOR = 1.181, 95%CI: 1.046, 1.334), and Se (AOR = 1.771, 95%CI: 1.576, 1.992) and dyslipidemia. According to the WQS approach, metal mixtures were positively associated with dyslipidemia (AOR: 1.310, 95%CI: 1.216, 1.411) after a full-model adjustment. As is shown in the BKMR model, mixed metals tended to be positively associated with dyslipidemia ratios in a significant manner. Females, non-Hispanic White populations, people aged over 60, and those who did a little physical activity had a greater risk for dyslipidemia. Our findings suggest metals including Cd, Pb, Hg, Mn, and Se and their combinations may adversely affect dyslipidemia among US adults. Due to the cross-sectional nature of the study, it is possible that reverse causation may exist.

Nicotinamide riboside intervention alleviates hematopoietic system injury of ionizing radiation-induced premature aging mice.

Radiotherapy destroys cancer cells and inevitably harms normal human tissues, causing delayed effects of acute radiation exposure (DEARE) and accelerating the aging process in most survivors. However, effective methods for preventing premature aging induced by ionizing radiation are lacking. In this study, the premature aging mice of DEARE model was established after 6 Gy total body irradiation (TBI). Then the therapeutic effects and mechanism of nicotinamide riboside on the premature aging mice were evaluated. The results showed that 6 Gy TBI induced premature aging of the hematopoietic system in mice. Nicotinamide riboside treatment reversed aging spleen phenotypes by inhibiting cellular senescence and ameliorated serum metabolism profiles. Further results demonstrated that nicotinamide riboside supplementation alleviated the myeloid bias of hematopoietic stem cells and temporarily restored the regenerative capacity of hematopoietic stem cells probably by mitigating the reactive oxygen species activated GCN2/eIF2α/ATF4 signaling pathway. The results of this study firstly indicate that nicotinamide riboside shows potential as a DEARE therapeutic agent for radiation-exposed populations and patients who received radiotherapy.

Ferroptosis and mitochondrial dysfunction in acute central nervous system injury.

Acute central nervous system injuries (ACNSI), encompassing traumatic brain injury (TBI), non-traumatic brain injury like stroke and encephalomeningitis, as well as spinal cord injuries, are linked to significant rates of disability and mortality globally. Nevertheless, effective and feasible treatment plans are still to be formulated. There are primary and secondary injuries occurred after ACNSI. Most ACNSIs exhibit comparable secondary injuries, which offer numerous potential therapeutic targets for enhancing clinical outcomes. Ferroptosis, a newly discovered form of cell death, is characterized as a lipid peroxidation process that is dependent on iron and oxidative conditions, which is also indispensable to mitochondria. Ferroptosis play a vital role in many neuropathological pathways, and ACNSIs may induce mitochondrial dysfunction, thereby indicating the essentiality of the mitochondrial connection to ferroptosis in ACNSIs. Nevertheless, there remains a lack of clarity regarding the involvement of mitochondria in the occurrence of ferroptosis as a secondary injuries of ACNSIs. In recent studies, anti-ferroptosis agents such as the ferroptosis inhibitor Ferrostain-1 and iron chelation therapy have shown potential in ameliorating the deleterious effects of ferroptosis in cases of traumatic ACNSI. The importance of this evidence is extremely significant in relation to the research and control of ACNSIs. Therefore, our review aims to provide researchers focusing on enhancing the therapeutic outcomes of ACNSIs with valuable insights by summarizing the physiopathological mechanisms of ACNSIs and exploring the correlation between ferroptosis, mitochondrial dysfunction, and ACNSIs.