Nomogram construction and evaluation for predicting non-remission after a single radioactive iodine therapy for Graves' hyperthyroidism: a retrospective cohort study.

Background: Radioactive iodine (RAI) therapy is a widely used treatment for Graves' Hyperthyroidism (GH). However, various factors can impact the non-remission rate of GH after single RAI therapy. This study aimed to develop an online dynamic nomogram to assist physicians in providing personalized therapy for GH. Methods: Data from 454 GH patients who received RAI therapy were retrospectively reviewed and included in the present study. The univariate and multivariate analysis were conducted to investigate and identify independent influencing factors. The nomogram was developed based on the training cohort to explore non-remission rates. Finally, the reliability and accuracy of the constructed nomogram model were verified in the validation cohort via the calibration, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA). Results: 24-hours radioactive iodine uptake (RAIU24h), effective half-life (Teff), total iodine dose (TID) and iodine dose per gram of thyroid tissue (IDPG) were independent predictors. The nomogram had a high C-index 0.922 (95% CI: 0.892-0.953), for predicting non-remission. The calibration curves demonstrated excellent consistency between the predicted and the actual probability of non-remission. ROC analysis showed that the AUC of the nomogram model and the four independent factors in the training cohort were 0.922, 0.673, 0.760, 0.761, and 0.786, respectively. The optimal cutoff value for the total nomogram scores was determined to be 155. A total score of ≥155 indicates a higher likelihood of non-remission after a single RAI therapy for GH, whereas a score below 155 suggests a greater likelihood of remission. Additionally, the DCA curve indicated that this nomogram had good clinical utility in predicting non-remission. Conclusion: An online nomogram was constructed with good predictive performance, which can be used as a practical approach to predict and assist physicians in making personalized therapy decisions for GH patients.

Prospective Study Comparing [99mTc]Tc-DP-FAPI Quantitative SPECT/CT with [68Ga]Ga-FAPI-04 PET/CT in Patients with Gastrointestinal Tumors.

Over the past decade, [68Ga]Ga-FAPI-04 positron emission tomography (PET)/CT imaging has been widely used for the treatment of various tumors. However, the application of 99mTC-labeled fibroblast activation protein inhibitors in tumors has been less studied. Our team previously demonstrated the safe biological distribution of [99mTc]Tc-DP-FAPI in the human body. Based on this, this study reports the accuracy of [99mTc]Tc-DP-FAPI in the imaging diagnosis of gastrointestinal tumors and compares it with that of [68Ga]Ga-FAPI-04 to evaluate the differences. A total of 24 patients with clinically diagnosed gastrointestinal tumors were prospectively included. All patients received [99mTc]Tc-DP-FAPI quantitative SPECT/CT imaging on the first day and [68Ga]Ga-FAPI-04 PET/CT imaging on the second day. And the effectiveness of the two imaging probes in detecting suspicious lesions was analyzed and compared. The primary tumors of all 24 patients were well detected by two imaging probes, and the sensitivity of [99mTc]Tc-DP-FAPI and [68Ga]Ga-FAPI-04 to the primary lesions was 100%. [99mTc]Tc-DP-FAPI examined 21 lymph nodes with a sensitivity and specificity of 32.8% and 10.9%, and [68Ga]Ga-FAPI-04 detected 57 lymph nodes with a sensitivity and specificity of 89.1% and 67.2%, respectively. Three distant metastases were detected by [99mTc]Tc-DP-FAPI and nine metastases by [68Ga]Ga-FAPI-04. The study showed that [99mTc]Tc-DP-FAPI is highly sensitive to detecting primary lesions of gastrointestinal tumors. Compared with [68Ga]Ga-FAPI-04, [99mTc]Tc-DP-FAPI has the same sensitivity in detecting primary tumors but has certain limitations in detecting metastases. [99mTc]Tc-DP-FAPI is of great value for preliminary screening of tumor lesions and early diagnosis of disease in patients who are suspected of having gastrointestinal tumors.

Development and validation of a lung metastases-predicting nomogram for intermediate- to high-risk differentiated thyroid carcinoma patients.

Aim: This research aimed to construct a clinical model for forecasting the likelihood of lung metastases in differentiated thyroid carcinoma (DTC) with intermediate- to high-risk. Methods: In this study, 375 DTC patients at intermediate to high risk were included. They were randomly divided into a training set (70%) and a validation set (30%). A nomogram was created using the training group and then validated in the validation set using calibration, decision curve analysis (DCA) and receiver operating characteristic (ROC) curve. Results: The calibration curves demonstrated excellent consistency between the predicted and the actual probability. ROC analysis showed that the area under the curve in the training cohort was 0.865 and 0.845 in the validation cohort. Also, the DCA curve indicated that this nomogram had good clinical utility. Conclusion: A user-friendly nomogram was constructed to predict the lung metastases probability with a high net benefit.

[Box: see text].

Polystyrene microplastics exacerbated the toxicity of okadaic acid to the small intestine in mice.

Microplastics (MPs) and okadaic acid (OA) are known to coexist in marine organisms, potentially impacting humans through food chain. However, the combined toxicity of OA and MPs remains unknown. In this study, mice were orally administered OA at 200 µg/kg bw and MPs at 2 mg/kg bw. The co-exposure group showed a significant increase in malondialdehyde (MDA) content and significant decreases in superoxide dismutase (SOD) activity and glutathione (GSH) level compared to the control, MPs and OA groups (p < 0.05). Additionally, the co-exposure group exhibited significantly higher levels of IL-1ß and IL-18 compared to other groups (p < 0.05). These results demonstrated that co-exposure to MPs and OA induces oxidative stress and exacerbates inflammation. Histological and cellular ultrastructure analyses suggested that this combined exposure may enhance gut damage and compromise barrier integrity. Consequently, the concentration of OA in the small intestine of the co-exposure group was significantly higher than that in the OA group. Furthermore, MPs were observed in the lamina propria of the gut in the co-exposure group. Transcriptomic analysis revealed that the co-exposure led to increased expression of certain genes related to the NF-κB/NLRP3 pathway compared to the OA and MPs groups. Overall, this combined exposure may disrupt the intestinal barrier, and promote inflammation through the NF-κB/NLRP3 pathway. These findings provide precious information for the understanding of health risks associated with MPs and phycotoxins.

Landscape of Nuclear Medicine in China and Its Progress on Theranostics.

Nuclear medicine in China started in 1956 and, with the rapid development of the economy and continuous breakthroughs in precision medicine, has made significant progress in recent years. Almost 13,000 staff members in nearly 1,200 hospitals serve more than 3.9 million patients each year. Over the past decade, the radiopharmaceutical industry has developed rapidly, with the initial formation of a complete industrial chain of production of various radiopharmaceuticals for both clinical use and basic research. Advanced equipment such as PET/CT scanners is being manufactured domestically and even installed abroad. Recently, research into screening and synthesizing new target probes and their translation into the clinic has gained more attention, with various new tracers with potential clinical value being thoroughly studied. Simultaneously, 68Ga- and 177Lu-labeled tumor-targeted probes and others have been implemented for theranostics in an increasing number of hospitals and would be helped by approval from the National Medical Products Administration. Over the next 10-20 y, with the launch of the Mid- and Long-Term Development Plan for Medical Isotopes (2021-2035) by the Chinese government, there is great potential for nuclear medicine in China. With the rise in independent innovation in manufacturing, the shortage of radiopharmaceuticals will be effectively curtailed. We anticipate that the scale of nuclear medicine will at least double by 2035, covering all high-grade hospitals and leading to the aim of "one county, one department" in China.

Vitamin K2 protects mice against non-alcoholic fatty liver disease induced by high-fat diet.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide and there is a huge unmet need to find safer and more effective drugs. Vitamin K has been found to regulate lipid metabolism in the liver. However, the effects of vitamin K2 on NAFLD is unclear. This study aims to evaluate the preventive and therapeutic effects of vitamin K2 in the process of fatty liver formation and to explore molecular mechanisms the associated with lipid metabolism. A non-alcoholic fatty liver model was established by high-fat diet administration for three months. Vitamin K2 significantly reduced the body weight, abdominal circumference and body fat percentage of NAFLD mice. Vitamin K2 also showed histological benefits in reducing hepatic steatosis. NAFLD mice induced by high-fat diet showed increased HMGR while vitamin K2 intervention could reverse the pathological lterations. Adiponectin (APN) is an endogenous bioactive polypeptide or protein secreted by adipocytes. We detected APN, SOD, AlaDH and other indicators that may affect the state of high-fat diet mice, but the experimental results showed that the above indicators did not change significantly. It is worth noting that the effect of vitamin K2 supplementation on the lipid-lowering effect of uc OC in vivo needs to be further explored. This study first reported the protective effect of vitamin K2 on high-fat diet-induced NAFLD in mice. The protective effect of vitamin K2 may be related to the improvement of lipid metabolism disorder in NAFLD.

First-in-human validation of enzymolysis clearance strategy for decreasing renal radioactivity using modified [68Ga]Ga-HER2 Affibody.

PURPOSE: Enzymolysis clearance strategy, characterized by releasing the non-reabsorbable radioactive fragment under the specific cleavage of enzymes, is confirmed to be a safe and effective way to reduce the renal radioactivity accumulation in mice. However, the effectiveness of this strategy in humans remains unknown. Human epidermal growth factor receptor 2 (HER2) is overexpressed in various types of tumors, and radiolabeled HER2 Affibody is believed to be an attractive tool for HER2-targeted theranostics. However, its wide application is limited by the high and persistent renal uptake. In this study, we intend to validate the effectiveness of enzymolysis clearance strategy in reducing renal accumulation by using a modified HER2 Affibody. MATERIALS AND METHODS: A new HER2 Affibody ligand, NOTA-MVK-ZHER2:2891, containing a cleavable Met-Val-Lys (MVK) linker was synthesized and labeled with 68Ga. The microPET imaging study was performed in SKOV-3 tumor mice to assess the uptakes of the control ligand and the MVK one in tumors and kidneys. Seven healthy volunteers were included for biodistribution and dosimetric studies with both the control and MVK ligands performed 1 week apart. Urine and blood samples from healthy volunteers were collected for in vivo metabolism study of the two ligands. Four HER2-positive and two HER2-negative patients were recruited for [68Ga]Ga-NOTA-MVK-ZHER2:2891 PET/CT imaging at 2 and 4 h post-injection (p.i.). RESULTS: [68Ga]Ga-NOTA-MVK-ZHER2:2891 was stable both in PBS and in mouse serum. MicroPET images showed that the tumor uptake of [68Ga]Ga-NOTA-MVK-ZHER2:2891 was comparable to that of [68Ga]Ga-NOTA-ZHER2:2891 at all the time points, while the kidney uptake was significantly reduced 40 min p.i. (P < 0.05). The biodistribution study in healthy volunteers showed that the kidney uptake of MVK ligand was significantly lower than that of the control ligand at 1 h p.i. (P < 0.05), with the SUVmean of 34.3 and 45.8, respectively, while the uptakes of the two ligands in the other organs showed negligible difference. The effective doses of the MVK ligand and the control one were 26.1 and 28.7 µSv/MBq, respectively. The enzymolysis fragment of [68Ga]Ga-NOTA-Met-OH was observed in the urine samples of healthy volunteers injected with the MVK ligand, indicating that the enzymolysis clearance strategy worked in humans. The PET/CT study of patients showed that the range of SUVmax of HER2-positive lesions was 9.4-21, while that of HER2-negative lesions was 2.7-6.2, which suggested that the MVK modification did not affect the ability of ZHER2:2891 structure to bind with HER2. CONCLUSION: We for the first time demonstrated that enzymolysis clearance strategy can effectively reduce renal radioactivity accumulation in humans. This strategy is expected to decrease renal radiation dose of peptide and small protein-based radiotracers, especially in the field of radionuclide therapy.

Mechanistic insights into the effects of diuron exposure on Alexandrium pacificum.

Diuron (N-(3,4-dichlorophenyl)-N,N­dimethylurea, DCMU), a ureic herbicide, is extensively used in agriculture to boost crop productivity; however, its extensive application culminates in notable environmental pollution, especially in aquatic habitats. Therefore, the present study investigated the effect of diuron on the dinoflagellate Alexandrium pacificum, which is known to induce harmful algal blooms (HAB), and its potential to biodegrade DCMU. Following a four-day DCMU exposure, our results revealed that A. pacificum proficiently assimilated DCMU at concentrations of 0.05 mg/L and 0.1 mg/L in seawater, attaining a complete reduction (100 % efficiency) after 96 h for both concentrations. Moreover, evaluations of paralytic shellfish toxins content indicated that cells subjected to higher DCMU concentrations (0.1 mg/L) exhibited reductions of 73.4 %, 86.7 %, and 75 % in GTX1, GTX4, and NEO, respectively. Exposure to DCMU led to a notable decrease in A. pacificum's photosynthetic efficacy, accompanied by increased levels of reactive oxygen species (ROS) and suppressed cell growth, with a growth inhibition rate of 41.1 % at 72 h. Proteomic investigations pinpointed the diminished expression levels of specific proteins like SxtV and SxtW, linked to paralytic shellfish toxins (PSTs) synthesis, as well as key proteins associated with Photosystem II, namely PsbA, PsbD, PsbO, and PsbU. Conversely, proteins central to the cysteine biosynthesis pathways exhibited enhanced expression. In summary, our results preliminarily resolved the molecular mechanisms underlying the response of A. pacificum to DCMU and revealed that DCMU affected the synthesis of PSTs. Meanwhile, our data suggested that A. pacificum has great potential in scavenging DCMU.

Diallyl trisulfide improves spinal cord ischemia-reperfusion injury damage by activating AMPK to stabilize mitochondrial function.

BACKGROUND: Spinal cord ischemia-reperfusion injury (SCII) is a catastrophic event, which can cause paraplegia in severe cases. In the reperfusion stage, oxidative stress was up-regulated, which aggravated the injury and apoptosis of neurons. As the main active ingredient of garlic, diallyl trisulfide (DATS) displays strong antioxidant capacity. However, it is unknown whether DATS can protect the neurons of SCII. MATERIALS AND METHODS: In this study, the descending aorta at the distal end of the left subclavian artery was ligated and perfused again after 14 min. Samples including blood and spinal cord (L2-L5) were taken 24 h later for morphological and biochemical examination. RESULTS: After SCII, the rats showed motor dysfunction, increase apoptosis, malondialdehyde content, mitochondrial biogenesis and dynamic balance disorder. After the application of DATS, the adenosine monophosphate activated protein kinase (AMPK) was activated, the mitochondrial damage was improved, the oxidative stress was weakened, and the neuronal damage was recovered to some extent. However, the addition of compound C significantly weakened the protective effect of DATS. CONCLUSION: Oxidative stress caused by mitochondrial damage was one of the important mechanisms of neuronal damage in SCII. DATS could activate AMPK, stabilize mitochondrial biogenesis and dynamic balance, and reduce neuronal damage caused by oxidative stress.

First-in-Humans PET Imaging of KRASG12C Mutation Status in Non-Small Cell Lung and Colorectal Cancer Patients Using [18F]PFPMD.

Kirsten rat sarcoma (KRAS) mutations are an important marker for tumor-targeted therapy. In this study, we sought to develop a KRASG12C oncoprotein-targeted PET tracer and to evaluate its translational potential for noninvasive imaging of the KRASG12C mutation in non-small cell lung cancer (NSCLC) and colorectal cancer (CRC) patients. Methods: [18F]PFPMD was synthesized on the basis of AMG510 (sotorasib) by attaching a polyethylene glycol chain to the quinazolinone structure. The binding selectivity and imaging potential of [18F]PFPMD were verified by cellular uptake, internalization, and blocking (H358: KRASG12C mutation; A549: non-KRASG12C mutation) studies, as well as by a small-animal PET/CT imaging study on tumor-bearing mice. Five healthy volunteers were enrolled to assess the safety, biodistribution, and dosimetry of [18F]PFPMD. Subsequently, 14 NSCLC or CRC patients with or without the KRASG12C mutation underwent [18F]PFPMD and [18F]FDG PET/CT imaging. The SUVmax of tumor uptake of [18F]PFPMD was measured and compared between patients with and without the KRASG12C mutation. Results: [18F]PFPMD was obtained with a high radiochemical yield, radiochemical purity, and stability. The protein-binding assay showed that [18F]PFPMD selectively binds to the KRASG12C protein. [18F]PFPMD uptake was significantly higher in H358 than in A549 and was decreased by pretreatment with AMG510 (H358 vs. A549: 3.22% ± 0.28% vs. 2.50% ± 0.25%, P < 0.05; block: 2.06% ± 0.13%, P < 0.01). Similar results were observed in tumor-bearing mice on PET imaging (H358 vs. A549: 3.93% ± 0.24% vs. 2.47% ± 0.26% injected dose/g, P < 0.01; block: 2.89% ± 0.29% injected dose/g; P < 0.05). [18F]PFPMD was safe in humans and was excreted primarily by the gallbladder and intestines. The whole-body effective dose was comparable to that of [18F]FDG. The accumulation of [18F]PFPMD in KRASG12C mutation tumors was significantly higher than that in non-KRASG12C mutation tumors (SUVmax: 3.73 ± 0.58 vs. 2.39 ± 0.22, P < 0.01) in NSCLC and CRC patients. Conclusion: [18F]PFPMD is a safe and promising PET tracer for noninvasive screening of the KRASG12C mutation status in NSCLC and CRC patients.

Systematic dissection of genomic features determining the vast diversity of conotoxins.

BACKGROUND: Conus, a highly diverse species of venomous predators, has attracted significant attention in neuroscience and new drug development due to their rich collection of neuroactive peptides called conotoxins. Recent advancements in transcriptome, proteome, and genome analyses have facilitated the identification of conotoxins within Conus' venom glands, providing insights into the genetic features and evolutionary patterns of conotoxin genes. However, the underlying mechanism behind the extraordinary hypervariability of conotoxins remains largely unknown. RESULTS: We analyzed the transcriptomes of 34 Conus species, examining various tissues such as the venom duct, venom bulb, and salivary gland, leading to the identification of conotoxin genes. Genetic variation analysis revealed that a subset of these genes (15.78% of the total) in Conus species underwent positive selection (Ka/Ks > 1, p < 0.01). Additionally, we reassembled and annotated the genome of C. betulinus, uncovering 221 conotoxin-encoding genes. These genes primarily consisted of three exons, with a significant portion showing high transcriptional activity in the venom ducts. Importantly, the flanking regions and adjacent introns of conotoxin genes exhibited a higher prevalence of transposon elements, suggesting their potential contribution to the extensive variability observed in conotoxins. Furthermore, we detected genome duplication in C. betulinus, which likely contributed to the expansion of conotoxin gene numbers. Interestingly, our study also provided evidence of introgression among Conus species, indicating that interspecies hybridization may have played a role in shaping the evolution of diverse conotoxin genes. CONCLUSIONS: This study highlights the impact of adaptive evolution and introgressive hybridization on the genetic diversity of conotoxin genes and the evolution of Conus. We also propose a hypothesis suggesting that transposable elements might significantly contribute to the remarkable diversity observed in conotoxins. These findings not only enhance our understanding of peptide genetic diversity but also present a novel approach for peptide bioengineering.

68Ga-FAPI-04 PET for Surveillance of Anastomotic Recurrence in Postoperative Patients with Gastrointestinal Cancer: a Comparative Study with 18F-FDG PET.

PURPOSE: This study aims to compare the diagnostic efficacy of 68Ga-FAPI-04 PET and 18F-FDG PET for detecting anastomotic recurrence in postoperative patients with gastrointestinal cancer, and to characterize the signal pattern over time at surgical wounds on both PET imaging. METHODS: Gastrointestinal cancer patients who planned to 68Ga-FAPI-04 and 18F-FDG PET/CT imaging for postoperative surveillance were involved. The SUVmax at surgical wounds were assessed. Endoscopic pathology confirmed anastomotic recurrence or it was ruled out by imaging and clinical follow-up. The sensitivity, specificity, positive and negative predictive values (PPV and NPV), and accuracy of the two PET imaging in detecting anastomotic recurrence were compared. Relationships between tracer uptake at surgical wounds and postoperative time were also analyzed. RESULTS: Compared with non-recurrent patients, the recurrent patients exhibited a significantly higher anastomotic SUVmax on 68Ga-FAPI-04 PET (SUVmax: 9.92 ± 4.36 vs. 2.81 ± 1.86, P = 0.002). Sensitivity, specificity, PPV, NPV, and accuracy of detecting anastomotic recurrence were 100.0%, 87.3%, 41.7%, 100.0%, and 88.3% for 68Ga-FAPI-04 PET, and 60.0%, 81.8%, 23.1%, 95.7%, and 80.0% for 18F-FDG PET, respectively. Although 68Ga-FAPI-04 PET signal at surgical wounds showed a slight trend to decrease with time, no statistical difference was observed over months post-surgery (P > 0.05). CONCLUSIONS: Both tracers displayed high NPVs in identifying anastomotic recurrence with a higher sensitivity to 68Ga-FAPI-04. Tracer uptake at anastomotic sites does not decrease significantly over time, which results in low PPVs for both PET. Therefore, it is difficult to differentiate anastomotic recurrence from inflammation on either PET imaging.

Chromium-Based Complexes Bearing Aminophosphine and Phosphine-Imine-Pyrryl Ligands for Selective Ethylene Tri/Tetramerization.

A series of Cr-based complexes 6-10 bearing aminophosphine (P,N) ligands Ph2P-L-NH2 [L = CH2CH2 (1), L = CH2CH2CH2 (2), and L = C6H4CH2 (3)] and phosphine-imine-pyrryl (P,N,N) ligands 2-(Ph2P-L-N=CH)C4H3NH [L = CH2CH2CH2 (4) and L = C6H4CH2 (5)] were prepared, and their catalytic properties were examined for ethylene tri/tetramerization. X-ray crystallographic analysis of complex 8 indicated the κ2-P,N bidentate coordination mode at the Cr(III) center and the distorted octahedral geometry of monomeric P,N-CrCl3. Upon activation by methylaluminoxane (MAO), complexes 7-8 bearing P,N (PC3N backbone) ligands 2-3 showed good catalytic reactivity for ethylene tri/tetramerization. On the other hand, complex 6 bearing the P,N (PC2N backbone) ligand 1 was found active for non-selective ethylene oligomerization, while complexes 9-10 bearing P,N,N ligands 4-5 only produced polymerization products. In particular, the high catalytic activity of 458.2 kg/(g·Cr·h), excellent selectivity of 90.9% (1-hexene and 1-octene combined), and extremely low PE content of 0.1% were obtained with complex 7 in toluene at 45 °C and 45 bar. These results suggest that rational control of P,N and P,N,N ligand backbones, including a carbon spacer and rigidity of a carbon bridge, can lead to the high-performance catalyst for the ethylene tri/tetramerization process.

Preparation of Neohesperidin-Taro Starch Complex as a Novel Approach to Modulate the Physicochemical Properties, Structure and In Vitro Digestibility.

Neohesperidin (NH), a natural flavonoid, exerts multiple actions, such as antioxidant, antiviral, antiallergic, vasoprotective, anticarcinogenic and anti-inflammatory effects, as well as inhibition of tumor progression. In this study, the NH-taro starch complex is prepared, and the effects of NH complexation on the physicochemical properties, structure and in vitro digestibility of taro starch (TS) are investigated. Results showed that NH complexation significantly affected starch gelatinization temperatures and reduced its enthalpy value (ΔH). The addition of NH increased the viscosity and thickening of taro starch, facilitating shearing and thinning. NH binds to TS via hydrogen bonds and promotes the formation of certain crystalline regions in taro starch. SEM images revealed that the surface of NH-TS complexes became looser with the increasing addition of NH. The digestibility results demonstrated that the increase in NH (from 0.1% to 1.1%, weight based on starch) could raise RS (resistant starch) from 21.66% to 27.75% and reduce RDS (rapidly digestible starch) from 33.51% to 26.76% in taro starch. Our work provided a theoretical reference for the NH-taro starch complex's modification of physicochemical properties and in vitro digestibility with potential in food and non-food applications.

Chromium-Based Complexes Bearing N-Substituted Diphosphinoamine Ligands for Ethylene Oligomerization.

A range of novel N-substituted diphosphinoamine (PNP) ligands Ph2PN(R)PPh2 [R = F2CHCH2 (1); R = Me2CHCH2 (2); R = Me2CHCH2CH2 (3)] have been synthesized via one-step salt elimination reaction. The ligand-coordinated chromium carbonyls [Ph2PN(R)PPh2]Cr(CO)4 (4-6) were further synthesized, and X-ray crystallography analysis of complex 6 revealed the κ2-P,P bidentate binding mode of Cr center and the molecular structure of PNP ligand 3. Then the catalytic ethylene oligomerization behaviors of PNP ligands 1-3 bridging chromium chloride complexes {[Ph2PN(R)PPh2]CrCl2(µ-Cl)}2 (7-9) were further discussed in depth. Experimental results showed that complex 7 with the strong electron-withdrawing F2CHCH2 group can promote the nonselective ethylene oligomerization, while both complex 8 and complex 9 with the electron-donating Me2CHCH2 and Me2CHCH2CH2 groups can significantly enhance the selective ethylene tri/tetramerization. The good catalytic activity of 198.3 kg/(g Cr·h), the selectivity toward 1-hexene and 1-octene of 76.4%, and the low PE content of 0.2% were simultaneously achieved with the Al/Cr molar ratio of 600 using the complex 8/MMAO system at 45 °C and 45 bar. These excellent results were mainly attributed to the fact that the ß-branching of bridging ligand 2 increased the steric bulk of the N-moiety for complex 8.

Pueraria montana (Kudzu vine) Ameliorate the Inflammation and Oxidative Stress against Fe-NTA Induced Renal Cancer.

Renal tissue plays a crucial function in maintaining homeostasis, making it vulnerable to xenobiotic toxicity. Pueraria montana has more beneficial potential against the various diseases and has long history used as a traditional Chinese medicine. But its effect against the renal cancer not scrutinize. The goal of this study is to see if Pueraria montana can protect rats from developing kidney tumors caused by diethylnitrosamine (DEN) and ferric nitrite (Fe-NTA). Wistar rats was selected for the current study and DEN (use as an inducer) and Fe-NTA (promoter) for induction the renal cancer. For 22 weeks, the rats were given orally Pueraria montana (12.5, 25, and 50 mg/kg) treatment. At regular intervals, the body weight and food intake were calculated. The rats were macroscopically evaluated for identification of cancer in the renal tissue. The renal tumor makers, renal parameters, antioxidant enzymes, phase I and II enzymes, inflammatory cytokines and mediators were estimated at end of the experimental study. Pueraria montana treated rats displayed the suppression of renal tumors, incidence of the tumors along with suppression of tumor percentage. Pueraria montana treated rats significantly (p < 0.001) increased body weight and suppressed the renal weight and food intake. It also reduced the level of renal tumor marker ornithine decarboxylase (ODC) and [3H] thymidine incorporation along with suppression of renal parameter such as uric acid, blood urea nitrogen (BUN), urea and creatinine. Pueraria montana treatment significantly (p < 0.001) altered the level of phase enzymes and antioxidant. Pueraria montana treatment significantly (p < 0.001) repressed the level of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and improved the level of interleukin-10 (IL-10). Pueraria montana treatment suppressed the level of prostaglandin (PGE2), cyclooxygenase-2 (COX-2), nuclear kappa B factor (NF-κB) and transforming growth factor beta 1 (TGF-ß1). Pueraria montana suppressed the inflammatory necrosis, size the bowman capsules in the renal histopathology. Pueraria montana exhibited the chemoprotective effect via dual mechanism such as suppression of inflammatory reaction and oxidative stress.

Arsenic retention in erythrocytes and excessive erythrophagocytosis is related to low selenium status by impaired redox homeostasis.

Arsenic (As) contamination in drinking water is a global public health problem. Epidemiological studies have shown that selenium (Se) deficiency is associated with an increasing risk of arsenism. However, the association between Se status and As retention in erythrocytes and mechanisms underlying this association have not been fully investigated. In the present study, a total of 165 eligible subjects were recruited and As was found to accumulate in blood mainly by retention in erythrocytes. Retention of As in erythrocytes was negatively correlated with Se status, antioxidant parameters related to Se and As methylation capacity, but positively correlated with the protein-binding capacity of As. Additionally, erythrocytes isolated from subjects with low Se status exhibited cellular damage along with lower protein levels of CD47, which could be aggravated by hydrogen peroxide treatment. Consistent with the human study, the erythrocytes from mice with sub-chronic As exposure exhibited similar cellular damage and shown to be phagocytosed by splenic macrophages, and these effects were mitigated by dietary Se supplementation. Furthermore, hydrogen peroxide treatment induced excessive phagocytosis of erythrocytes with As exposure by splenic macrophages, while co-treating erythrocytes with the reducing agent, N-Acetyl-l-cysteine, mitigated this excessive erythrophagocytosis. Hyperactivation of the NFκB pathway was also detected in splenic macrophages after excessive erythrophagocytosis. In conclusion, this study found that low Se status involving impaired redox homeostasis increased As retention in erythrocytes, which were subsequently phagocytosed by splenic macrophages and led to an increased inflammatory status of splenic macrophages. These findings provide insight into physiological features of arsenism related to Se status and redox homeostasis.

Fluvoxamine Confers Neuroprotection via Inhibiting Infiltration of Peripheral Leukocytes and M1 Polarization of Microglia/Macrophages in a Mouse Model of Traumatic Brain Injury.

Neuroinflammation is an important mediator of secondary injury pathogenesis that exerts dual beneficial and detrimental effects on pathophysiology of the central nervous system (CNS) after traumatic brain injury (TBI). Fluvoxamine is a serotonin selective reuptake inhibitor (SSRI) and has been reported to have the anti-inflammatory properties. However, the mechanisms and therapeutic effects of fluvoxamine in neuroinflammation after TBI have not be defined. In this study, we showed that fluvoxamine inhibited peripheral immune cell infiltration and glia activation at 3 days in mice subjected to TBI. Fluvoxamine treatment promoted microglial/macrophage phenotypic transformation from pro-inflammatory M1-phenotype to anti-inflammatory M2-phenotype in in vivo and in vitro experiments. In addition, fluvoxamine treatment attenuated neuronal apoptosis, blood-brain barrier (BBB) disruption, cerebrovascular damage, and post-traumatic edema formation, thereby improving neurological function of mice subjected to TBI. These findings support the clinical evaluation of fluvoxamine as a neuroprotective therapy for TBI.