Enhancing regenerative potential: A comprehensive review of stem cell transplantation for sports-related neuronal injuries, with a focus on spinal cord injuries and peripheral nervous system damage.

Neuronal injuries, as one of the consequences of sports-related incidents, exert a profound influence on the athletes' future, potentially leading to complete immobility and impeding their athletic pursuits. In cases of severe damage inflicted upon the spinal cord (SC) and peripheral nervous systems (PNS), the regenerative process is notably compromised, rendering it essentially inefficient. Among the pivotal therapeutic approaches for the enhancement and prevention of secondary SC injuries (SCI), stem cell transplantation (SCT) stands out prominently. Stem cells, whether directly involved in replacement and reconstruction or indirectly through modification and secretion of crucial bioenvironmental factors, engage in the intricate process of tissue regeneration. Stem cells, through the secretion of neurotrophic factors (NTFs) (aiming to modulate the immune system), reduction of inflammation, axonal growth stimulation, and myelin formation, endeavor to facilitate the regeneration of damaged SC tissue. The fundamental challenges of this approach encompass the proper selection of suitable stem cell candidates for transplantation and the establishment of an appropriate microenvironment conducive to SC repair. In this article, an attempt has been made to explore sports-related injuries, particularly SCI, to comprehensively review innovative methods for treating SCI, and to address the existing challenges. Additionally, some of the stem cells used in neural injuries and the process of their utilization have been discussed.

A hybrid deep learning approach to predict hourly riverine nitrate concentrations using routine monitored data.

With high-frequency data of nitrate (NO3-N) concentrations in waters becoming increasingly important for understanding of watershed system behaviors and ecosystem managements, the accurate and economic acquisition of high-frequency NO3-N concentration data has become a key point. This study attempted to use coupled deep learning neural networks and routine monitored data to predict hourly NO3-N concentrations in a river. The hourly NO3-N concentration at the outlet of the Oyster River watershed in New Hampshire, USA, was predicted through neural networks with a hybrid model architecture coupling the Convolutional Neural Networks and the Long Short-Term Memory model (CNN-LSTM). The routine monitored data (the river depth, water temperature, air temperature, precipitation, specific conductivity, pH and dissolved oxygen concentrations) for model training were collected from a nested high-frequency monitoring network, while the high-frequency NO3-N concentration data obtained at the outlet were not included as inputs. The whole dataset was separated into training, validation, and testing processes according to the ratio of 5:3:2, respectively. The hybrid CNN-LSTM model with different input lengths (1d, 3d, 7d, 15d, 30d) displayed comparable even better performance than other studies with lower frequencies, showing mean values of the Nash-Sutcliffe Efficiency 0.60-0.83. Models with shorter input lengths demonstrated both the higher modeling accuracy and stability. The water level, water temperature and pH values at monitoring sites were main controlling factors for forecasting performances. This study provided a new insight of using deep learning networks with a coupled architecture and routine monitored data for high-frequency riverine NO3-N concentration forecasting and suggestions about strategies about variable and input length selection during preprocessing of input data.

Recovery mechanism of heterotrophic ammonia assimilation system under chromium hexavalent stress.

Heterotrophic ammonia assimilation (HAA), an innovative technology for high-salinity wastewater treatment, demonstrates self-recovery capability following Cr (VI) stress. This study investigated the inhibitory effects and self-restoration mechanisms of Cr (VI) at various stress levels. The removal efficiencies of NH4+-N and Cr (VI) in the HAA gradually decreased with increasing influent Cr (VI) concentration. Exposure to Cr (VI) increased the amounts of high-molecular-weight proteins in soluble microbial products and stimulated the generation of extracellular polymeric substances. Heterotrophic functional microorganisms with Cr (VI) tolerance, such as Marinobacter and Planktosalinus, were enriched. An assimilation pathway gene (glnA) and a Cr (VI)-related gene (atoB) were also upregulated. After ceasing Cr (VI) addition, the HAA system demonstrated a 17.1 % increase in the removal efficiency of NH4+-N, which was attributable to its self-recovery ability. This study provides a scientific and theoretical foundation for the HAA process in resisting the impact of heavy-metal-containing wastewater and self-recovery.

Nutrients recovery by coupled bioreactor of heterotrophic ammonia assimilation and microbial fuel cell in saline wastewater.

Heterotrophic ammonia assimilation (HAA) process had been widely used in the treatment of high salt wastewater, but the electro enhanced coupling process and electron transfer process were rarely studied. In this study, a HAA process coupled microbial fuel cell (MFC) system was established to treat ammonia-containing wastewater under increasing salinity to achieve nitrogen recovery and electricity generation. Up to 95.4 % NH4+-N and 96.4 % COD removal efficiencies were achieved at 2 % salinity in HAA-MFC. The maximum power density and current density at 2 % salinity were 29.93 mW/m2 and 182.37 mA/m2, respectively. The residual organic matter in the cathode effluent was effectively removed by the anode. The increase of salinity not only enhanced the sludge settling performance and activity, but also promoted the enzyme activity and amino acid production of the ammonia assimilation pathway. Marinobacter and Halomonas were gradually enriched at the anode and cathode with increased salinity to promote ammonia assimilation and electron production. This research offered a promising solution to overcome salinity-related challenges in wastewater treatment and resource recovery.

Identification and validation of LINC01322 as a potential prognostic biomarker and oncogene promoting tumor progression in lung adenocarcinoma.

Our study identified a novel long noncoding RNA, LINC01322, that acts as an oncogene in lung adenocarcinoma progression. Cytoplasmic and nuclear RNA purification assays indicated that LINC01322 was localized in the cytoplasm and nucleus. Gene set enrichment analysis revealed the involvement of LINC01322 in the regulation of cell proliferation, migration, and the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway. LINC01322 may promote lung adenocarcinoma proliferation and migration through the Janus kinase/signal transducer and activator of transcription signaling pathway. In vitro experiments demonstrated that the knockdown of LINC01322 significantly suppressed lung adenocarcinoma cell proliferation, migration, and activation of the Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway, whereas overexpression had the opposite effects. Inhibition of the Janus kinase 2/signal transducer and activator of transcription 3 pathway activity partially reversed the enhancement of cell proliferation and migration caused by LINC01322 overexpression. In vivo experiments further verified the oncogene role of LINC01322. Altogether, our findings suggest that LINC01322 promotes lung adenocarcinoma progression by activating the Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway and that it could be a therapeutic target.

Novel strategy for treating high salinity oilfield produced water: Pyrite-activated peroxymonosulfate coupled with heterotrophic ammonia assimilation.

Existing conventional biological treatment techniques face numerous limitations in effectively removing total petroleum hydrocarbons (TPHs) and ammonia (NH4+-N) from oilfield-produced water (OPW), highlighting the pressing need for innovative pre-oxidation and biological treatment processes. In this study, a pyrite-activated peroxymonosulfate (PMS)-coupled heterotrophic ammonia assimilation (HAA) system was established to achieve satisfactory system performance for OPW treatment. Pyrite sustained-release Fe2+-activated PMS was used to produce SO4•- and •OH, and 71.0 % of TPHs were effectively removed from the oil wastewater. The average TPHs and NH4+-N removal efficiencies in the test group with pre-oxidation were 96.9 and 98.3 %, compared to 46.5 and 77.1 % in the control group, respectively. The maximum fluorescence intensities of tryptophan protein and aromatic protein in the test group declined by 83.7 %. Fourier transform ion cyclotron resonance mass spectrometry revealed that pre-oxidation degraded more long-chain hydrocarbons and aromatic family compound, whereas the HAA process produced more proteins and carbohydrates. Pyrite-PMS promoted the enrichment of ammonia-assimilating bacteria, alleviating the explosive increase in extracellular polymeric substances and reducing sludge settleability. The low cost, efficiency, green chemistry principles, and synergies of this approach make it a powerful solution for practical OPW treatment to reduce environmental impacts and promote sustainable wastewater treatment.

Hypoxic erythrocytes mediate cardioprotection through activation of soluble guanylate cyclase and release of cyclic GMP.

Red blood cells (RBCs) mediate cardioprotection via nitric oxide-like bioactivity, but the signaling and the identity of any mediator released by the RBCs remains unknown. We investigated whether RBCs exposed to hypoxia release a cardioprotective mediator and explored the nature of this mediator. Perfusion of isolated hearts subjected to ischemia-reperfusion with extracellular supernatant from mouse RBCs exposed to hypoxia resulted in improved postischemic cardiac function and reduced infarct size. Hypoxia increased extracellular export of cyclic guanosine monophosphate (cGMP) from mouse RBCs, and exogenous cGMP mimicked the cardioprotection induced by the supernatant. The protection induced by hypoxic RBCs was dependent on RBC-soluble guanylate cyclase and cGMP transport and was sensitive to phosphodiesterase 5 and activated cardiomyocyte protein kinase G. Oral administration of nitrate to mice to increase nitric oxide bioactivity further enhanced the cardioprotective effect of hypoxic RBCs. In a placebo-controlled clinical trial, a clear cardioprotective, soluble guanylate cyclase-dependent effect was induced by RBCs collected from patients randomized to 5 weeks nitrate-rich diet. It is concluded that RBCs generate and export cGMP as a response to hypoxia, mediating cardioprotection via a paracrine effect. This effect can be further augmented by a simple dietary intervention, suggesting preventive and therapeutic opportunities in ischemic heart disease.

Stimulation of Erythrocyte Soluble Guanylyl Cyclase Induces cGMP Export and Cardioprotection in Type 2 Diabetes.

Reduced nitric oxide (NO) bioactivity in red blood cells (RBCs) is critical for augmented myocardial ischemia-reperfusion injury in type 2 diabetes. This study identified the nature of "NO bioactivity" by stimulating the intracellular NO receptor soluble guanylyl cyclase (sGC) in RBCs. sGC stimulation in RBCs from patients with type 2 diabetes increased export of cyclic guanosine monophosphate from RBCs and activated cardiac protein kinase G, thereby attenuating ischemia-reperfusion injury. These results provide novel insight into RBC signaling by identifying cyclic guanosine monophosphate from RBC as a mediator of protection against cardiac ischemia-reperfusion injury induced by sGC stimulation in RBCs.

A review of microbial nitrogen transformations and microbiome engineering for biological nitrogen removal under salinity stress.

The osmotic stress caused by salinity exerts severe inhibition on the process of biological nitrogen removal (BNR), leading to the deterioration of biosystems and the discharge of nitrogen with saline wastewater. Feasible strategies to solve the bottleneck in saline wastewater treatment have attracted great attention, but relevant studies to improve nitrogen transformations and enhance the salt-tolerance of biosystems in terms of microbiome engineering have not been systematically reviewed and discussed. This work attempted to provide a more comprehensive explanation of both BNR and microbiome engineering approaches for saline wastewater treatment. The effect of salinity on conventional BNR pathways, nitrification-denitrification and anammox, was summarized at cellular and metabolic levels, including the nitrogen metabolic pathways, the functional microorganisms, and the inhibition threshold of salinity. Promising nitrogen transformations, such as heterotrophic nitrification-aerobic denitrification, ammonium assimilation and the coupling of conventional pathways, were introduced and compared based on advantages and challenges in detail. Strategies to improve the salt tolerance of biosystems were proposed and evaluated from the perspective of microbiome engineering. Finally, prospects of future investigation and applications on halophilic microbiomes in saline wastewater treatment were discussed.

Responses of halophilic microbial communities to changes in salt composition: Comparison between autotrophic nitrification and heterotrophic ammonia assimilation biosystems.

The concentration and proportion of chlorine (Cl-) and sulfate ions (SO42-) in actual high salinity wastewater exhibit significant fluctuations due to their diverse sources. This study compared the response of halophilic autotrophic nitrification (AN) and heterotrophic ammonia assimilation (HAA) sludges to changes in salt composition. The results demonstrated that both the AN and HAA systems maintained high ammonia removal efficiency even when exposed to mixed salt ions or pure sulfate conditions. Increasing the concentration of SO42- resulted in an increase in extracellular polymeric substances content, sludge settleability, sludge hydrophobicity, and the relative abundance of Nitrosomonas in the AN system (from 2.3% to 10.4%). The dominant heterotrophic bacteria in the HAA system underwent turnover in response to changes in salt composition conditions. The robustness and the cooperation between microorganisms of the HAA system surpassed those of the AN system. This study provides scientific foundation for treating multi-ion high salinity wastewater.

The red blood cell as a mediator of endothelial dysfunction in patients with familial hypercholesterolemia and dyslipidemia.

BACKGROUND: Patients with familial hypercholesterolemia (FH) display high levels of low-density lipoprotein cholesterol (LDL-c), endothelial dysfunction, and increased risk of premature atherosclerosis. We have previously shown that red blood cells (RBCs) from patients with type 2 diabetes induce endothelial dysfunction through increased arginase 1 and reactive oxygen species (ROS). OBJECTIVE: To test the hypothesis that RBCs from patients with FH (FH-RBCs) and elevated LDL-c induce endothelial dysfunction. METHODS AND RESULTS: FH-RBCs and LDL-c >5.0 mM induced endothelial dysfunction following 18-h incubation with isolated aortic rings from healthy rats compared to FH-RBCs and LDL-c <2.5 mM or RBCs from healthy subjects (H-RBCs). Inhibition of vascular but not RBC arginase attenuated the degree of endothelial dysfunction induced by FH-RBCs and LDL-c >5.0 mM. Furthermore, arginase 1 but not arginase 2 was elevated in the vasculature of aortic segments after incubation with FH-RBCs and LDL-c >5.0 mM. A superoxide scavenger, present throughout the 18-h incubation, attenuated the degree of endothelial dysfunction induced by FH-RBCs and LDL-c >5.0 mM. ROS production was elevated in these RBCs in comparison with H-RBCs. Scavenging of vascular ROS through various antioxidants also attenuated the degree of endothelial dysfunction induced by FH-RBCs and LDL-c >5.0 mM. This was corroborated by an increase in the lipid peroxidation product 4-hydroxynonenal. Lipidomic analysis of RBC lysates did not reveal any significant changes across the groups. CONCLUSION: FH-RBCs induce endothelial dysfunction dependent on LDL-c levels via arginase 1 and ROS-dependent mechanisms.

Analysis of genetic variants in a child with Intellectual developmental disorder with behavioral abnormalities and craniofacial dysmorphism without seizures / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical phenotype and genetic characteristics of a child with Intellectual developmental disorder with behavioral abnormalities and craniofacial malformations without epilepsy (IDDBCS).@*METHODS@#A child who had visited the Lianyungang Maternal and Child Health Care Hospital in April 2021 was selected as the study subject. Clinical data of the child were collected. Genomic DNA was extracted from peripheral blood samples of the child and his parents and subjected to whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing of his family members.@*RESULTS@#The child, a 3-year-and-4-month-old male, had presented with global developmental delay and cranial malformation. Genetic testing revealed that he has harbored a heterozygous c.1703delA (p.K568Sfs9) variant of the PHF21A gene, for which both of his parents were of the wild type. This low-frequency variant may alter the structure and function of the protein product. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), it was classified as a pathogenic variant (PVS1+PS2+PM2_Supporting).@*CONCLUSION@#The heterozygous c.1703delA (p.K568Sfs9) variant of the PHF21A gene probably underlay the IDDBCS in this patient.

Erythrocytes from patients with ST-elevation myocardial infarction induce cardioprotection through the purinergic P2Y13 receptor and nitric oxide signaling.

Red blood cells (RBCs) are suggested to play a role in cardiovascular regulation by exporting nitric oxide (NO) bioactivity and ATP under hypoxia. It remains unknown whether such beneficial effects of RBCs are protective in patients with acute myocardial infarction. We investigated whether RBCs from patients with ST-elevation myocardial infarction (STEMI) protect against myocardial ischemia-reperfusion injury and whether such effect involves NO and purinergic signaling in the RBCs. RBCs from patients with STEMI undergoing primary coronary intervention and healthy controls were administered to isolated rat hearts subjected to global ischemia and reperfusion. Compared to RBCs from healthy controls, RBCs from STEMI patients reduced myocardial infarct size (30 ± 12% RBC healthy vs. 11 ± 5% RBC STEMI patients, P < 0.001), improved recovery of left-ventricular developed pressure and dP/dt and reduced left-ventricular end-diastolic pressure in hearts subjected to ischemia-reperfusion. Inhibition of RBC NO synthase with L-NAME or soluble guanylyl cyclase (sGC) with ODQ, and inhibition of cardiac protein kinase G (PKG) abolished the cardioprotective effect. Furthermore, the non-selective purinergic P2 receptor antagonist PPADS but not the P1 receptor antagonist 8PT attenuated the cardioprotection induced by RBCs from STEMI patients. The P2Y13 receptor was expressed in RBCs and the cardioprotection was abolished by the P2Y13 receptor antagonist MRS2211. By contrast, perfusion with PPADS, L-NAME, or ODQ prior to RBCs administration failed to block the cardioprotection induced by RBCs from STEMI patients. Administration of RBCs from healthy subjects following pre-incubation with an ATP analog reduced infarct size from 20 ± 6 to 7 ± 2% (P < 0.001), and this effect was abolished by ODQ and MRS2211. This study demonstrates a novel function of RBCs in STEMI patients providing protection against myocardial ischemia-reperfusion injury through the P2Y13 receptor and the NO-sGC-PKG pathway.

Albedo changes caused by future urbanization contribute to global warming.

The replacement of natural lands with urban structures has multiple environmental consequences, yet little is known about the magnitude and extent of albedo-induced warming contributions from urbanization at the global scale in the past and future. Here, we apply an empirical approach to quantify the climate effects of past urbanization and future urbanization projected under different shared socioeconomic pathways (SSPs). We find an albedo-induced warming effect of urbanization for both the past and the projected futures under three illustrative scenarios. The albedo decease from urbanization in 2018 relative to 2001 has yielded a 100-year average annual global warming of 0.00014 [0.00008, 0.00021] °C. Without proper mitigation, future urbanization in 2050 relative to 2018 and that in 2100 relative to 2018 under the intermediate emission scenario (SSP2-4.5) would yield a 100-year average warming effect of 0.00107 [0.00057,0.00179] °C and 0.00152 [0.00078,0.00259] °C, respectively, through altering the Earth's albedo.

Pretreatment HDL-C and ApoA1 are predictive biomarkers of progression-free survival in patients with EGFR mutated advanced non-small cell lung cancer treated with TKI.

BACKGROUND: We aimed to explore the correlation between blood lipids (high density lipoprotein cholesterol [HDL-C] and apolipoprotein A1 [ApoA1]) and epidermal growth factor receptor (EGFR) T790M mutation, as well as its predictive role in clinical efficacy and progression-free survial (PFS) in advanced non-small cell lung cancer (NSCLC) patients treated with EGFR tyrosine kinase inhibitors (EGFR-TKI). METHODS: We retrospectively collected information of 153 patients with advanced NSCLC harboring exon EGFR mutation and receiving EGFR-TKI. RESULTS: The best cutoff value for HDL-C and ApoA1 was determined to be 1.15 and 1.14 mmol/l. The overall response rate (ORR) was 67.7% in the high HDL-C group and 46.6% in the low HDL-C group, respectively. The ORR of the high ApoA1 group showed a significant increase than that of the low ApoA1 group (68.1% vs. 38.5%). The mean ApoA1 level of the EGFR T790M mutation-positive group was significantly higher than that of the EGFR T790M mutation-negative group (1.13 g/l vs. 1.01 g/l). Patients with high ApoA1 levels were related to the EGFR T790M mutation (r = 0.324). (3) The median progression-free survival (PFS) of the high HDL-C group and low HDL-C group were 13.00 months and 10.20 months. The median PFS of the high ApoA1 group and the low ApoA1 group were 12.10 and 10.00 months, respectively. Multivariate Cox stepwise regression model analysis demonstrated ECOG PS, pathological type and HDL-C were confirmed as critical and independent predictors of PFS. CONCLUSIONS: Patients with EGFR T790M mutations often show higher ApoA1 levels. Peripheral serum HDL-C and ApoA1 before treatment can be used as potential significant factors for predicting clinical efficacy and PFS in advanced NSCLC patients treated with EGFR-TKI.

Erythrocytes Induce Vascular Dysfunction in COVID-19.

Current knowledge regarding mechanisms underlying cardiovascular complications in patients with COVID-19 is limited and urgently needed. We shed light on a previously unrecognized mechanism and unravel a key role of red blood cells, driving vascular dysfunction in patients with COVID-19 infection. We establish the presence of profound and persistent endothelial dysfunction in vivo in patients with COVID-19. Mechanistically, we show that targeting reactive oxygen species or arginase 1 improves vascular dysfunction mediated by red blood cells. These translational observations hold promise that restoring the redox balance in red blood cells might alleviate the clinical complications of COVID-19-associated vascular dysfunction.

Mendelian randomization study on the causal effects of tumor necrosis factor inhibition on coronary artery disease and ischemic stroke among the general population.

BACKGROUND: Tumor necrosis factor (TNF) is a potent inflammatory cytokine that has been causally associated with coronary artery disease (CAD) and ischemic stroke (IS), implying opportunities for disease prevention by anti-TNF therapeutics. METHODS: Leveraging summary statistics of several genome-wide association studies (GWAS), we assessed the repurposing potential of TNF inhibitors for CAD and IS using drug-target Mendelian randomization (MR) design. Pharmacologic blockade of the pro-inflammatory TNF signalling mediated by TNF receptor 1 (TNFR1) was instrumented by four validated variants. Causal effects of TNF/TNFR1 blockade on CAD (Ncase/control upto 122,733/424,528) and IS (Ncase/control upto 60,341/454,450) were then estimated via various MR estimators using circulating C-reactive protein (CRP; NGWAS=204,402) as downstream biomarker to reflect treatment effect. Associations of a functional variant, rs1800693, with CRP, CAD and IS were also examined. FINDINGS: No protective effect of TNF/TNFR1 inhibition on CAD or IS was observed. For every 10% decrease of circulating CRP achieved by TNF/TNFR1 blockade, odds ratio was 0.98 (95% confidence interval [CI]: 0.60-1.60) for CAD and 0.77 (95% CI: 0.36-1.63) for IS. Findings remained null in all supplement analyses. INTERPRETATION: Our findings do not support TNFR1 as a promising target for CAD or IS prevention among the general population. Future research is warranted to investigate whether the detrimental effect of circulating TNF on CAD and IS might be counteracted by modulating other relevant drug targets. FUNDING: No.

Downregulation of Erythrocyte miR-210 Induces Endothelial Dysfunction in Type 2 Diabetes.

Red blood cells (RBC) act as mediators of vascular injury in type 2 diabetes mellitus (T2DM). miR-210 plays a protective role in cardiovascular homeostasis and is decreased in whole blood of T2DM mice. We hypothesized that downregulation of RBC miR-210 induces endothelial dysfunction in T2DM. RBC were coincubated with arteries and endothelial cells ex vivo and transfused in vivo to identify the role of miR-210 and its target protein tyrosine phosphatase 1B (PTP1B) in endothelial dysfunction. RBC from patients with T2DM and diabetic rodents induced endothelial dysfunction ex vivo and in vivo. miR-210 levels were lower in human RBC from patients with T2DM (T2DM RBC) than in RBC from healthy subjects. Transfection of miR-210 in human T2DM RBC rescued endothelial function, whereas miR-210 inhibition in healthy subjects RBC or RBC from miR-210 knockout mice impaired endothelial function. Human T2DM RBC decreased miR-210 expression in endothelial cells. miR-210 expression in carotid artery plaques was lower in T2DM patients than in patients without diabetes. Endothelial dysfunction induced by downregulated RBC miR-210 involved PTP1B and reactive oxygen species. miR-210 mimic attenuated endothelial dysfunction induced by RBC via downregulating vascular PTP1B and oxidative stress in diabetic mice in vivo. These data reveal that the downregulation of RBC miR-210 is a novel mechanism driving the development of endothelial dysfunction in T2DM.

Therapeutic Potential of Sunitinib in Ameliorating Endothelial Dysfunction in Type 2 Diabetic Rats.

INTRODUCTION: Sunitinib, a multi-targeted tyrosine kinase receptor inhibitor used to treat renal-cell carcinoma and gastrointestinal stromal tumor, was recently shown to have a beneficial effect on metabolism in type 2 diabetes (T2D). Endothelial dysfunction is a key factor behind macro- and microvascular complications in T2D. The effect of sunitinib on endothelial function in T2D remains, however, unclear. We therefore tested the hypothesis that sunitinib ameliorates endothelial dysfunction in T2D. METHODS: Sunitinib (2 mg/kg/day, by gavage) was administered to T2D Goto-Kakizaki (GK) rats for 6 weeks, while water was given to GK and Wistar rats as controls. Hemodynamic, inflammatory, and metabolic parameters as well as endothelial function were measured. RESULTS: Systolic, mean arterial blood pressures, plasma tumor necrosis factor α levels, kidney weight to body weight (BW) ratio, and glucose levels were higher, while BW was lower in GK rats than in Wistar rats. Six-week treatment with sunitinib in GK rats did not affect these parameters but suppressed the increase in glucose levels. Endothelium-dependent relaxations were reduced in both aortas and mesenteric arteries isolated from GK as compared to Wistar rats, which was markedly reversed in both types of arteries from GK rats treated with sunitinib. CONCLUSIONS: This study demonstrates that sunitinib has a glucose-lowering effect and ameliorates endothelial dysfunction in both conduit and resistance arteries of GK rats.

Key points of technical review for the registration of SARS-CoV-2 nucleic acid tests in China.

In response to the outbreak of COVID-19, in accordance with the principles of 'unified command, early involvement, prompt review and scientific approval' as well as the requirements of ensuring product safety, effectiveness and controllable quality, the Center for Medical Device Evaluation (CMDE) has issued Key Points of Technical Review for the Registration of SARS-CoV-2 Nucleic Acid Tests (Key Points) to provide the requirements of tests. Because of the sustainability of the pandemic, more efforts and attempts are needed for SARS-CoV-2 detection and control. This article interprets the Key Points issued by the CMDE and provides certain refinements to wider audiences.