Tirofiban for Stroke without Large or Medium-Sized Vessel Occlusion.

BACKGROUND: The effects of the glycoprotein IIb/IIIa receptor inhibitor tirofiban in patients with acute ischemic stroke but who have no evidence of complete occlusion of large or medium-sized vessels have not been extensively studied. METHODS: In a multicenter trial in China, we enrolled patients with ischemic stroke without occlusion of large or medium-sized vessels and with a National Institutes of Health Stroke Scale score of 5 or more and at least one moderately to severely weak limb. Eligible patients had any of four clinical presentations: ineligible for thrombolysis or thrombectomy and within 24 hours after the patient was last known to be well; progression of stroke symptoms 24 to 96 hours after onset; early neurologic deterioration after thrombolysis; or thrombolysis with no improvement at 4 to 24 hours. Patients were assigned to receive intravenous tirofiban (plus oral placebo) or oral aspirin (100 mg per day, plus intravenous placebo) for 2 days; all patients then received oral aspirin until day 90. The primary efficacy end point was an excellent outcome, defined as a score of 0 or 1 on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]) at 90 days. Secondary end points included functional independence at 90 days and a quality-of-life score. The primary safety end points were death and symptomatic intracranial hemorrhage. RESULTS: A total of 606 patients were assigned to the tirofiban group and 571 to the aspirin group. Most patients had small infarctions that were presumed to be atherosclerotic. The percentage of patients with a score of 0 or 1 on the modified Rankin scale at 90 days was 29.1% with tirofiban and 22.2% with aspirin (adjusted risk ratio, 1.26; 95% confidence interval, 1.04 to 1.53, P = 0.02). Results for secondary end points were generally not consistent with the results of the primary analysis. Mortality was similar in the two groups. The incidence of symptomatic intracranial hemorrhage was 1.0% in the tirofiban group and 0% in the aspirin group. CONCLUSIONS: In this trial involving heterogeneous groups of patients with stroke of recent onset or progression of stroke symptoms and nonoccluded large and medium-sized cerebral vessels, intravenous tirofiban was associated with a greater likelihood of an excellent outcome than low-dose aspirin. Incidences of intracranial hemorrhages were low but slightly higher with tirofiban. (Funded by the National Natural Science Foundation of China; RESCUE BT2 Chinese Clinical Trial Registry number, ChiCTR2000029502.).

Emerging Nanomaterials toward Uranium Extraction from Seawater: Recent Advances and Perspectives.

Nuclear energy holds great potential to facilitate the global energy transition and alleviate the increasing environmental issues due to its high energy density, stable energy output, and carbon-free emission merits. Despite being limited by the insufficient terrestrial uranium reserves, uranium extraction from seawater (UES) can offset the gap. However, the low uranium concentration, the complicated uranium speciation, the competitive metal ions, and the inevitable marine interference remarkably affect the kinetics, capacity, selectivity, and sustainability of UES materials. To date, massive efforts have been made with varying degrees of success to pursue a desirable UES performance on various nanomaterials. Nevertheless, comprehensive and systematic coverage and discussion on the emerging UES materials presenting the fast-growing progress of this field is still lacking. This review thus challenges this position and emphatically focuses on this topic covering the current mainstream UES technologies with the emerging UES materials. Specifically, this review elucidates the causality between the physiochemical properties of UES materials induced by the intellectual design strategies and the UES performances and further dissects the relationships of materials-properties-activities and the corresponding mechanisms in depth. This review is envisaged to inspire innovative ideas and bring technical solutions for developing technically and economically viable UES materials.

Methylprednisolone as Adjunct to Endovascular Thrombectomy for Large-Vessel Occlusion Stroke: The MARVEL Randomized Clinical Trial.

Importance: It is uncertain whether intravenous methylprednisolone improves outcomes for patients with acute ischemic stroke due to large-vessel occlusion (LVO) undergoing endovascular thrombectomy. Objective: To assess the efficacy and adverse events of adjunctive intravenous low-dose methylprednisolone to endovascular thrombectomy for acute ischemic stroke secondary to LVO. Design, Setting, and Participants: This investigator-initiated, randomized, double-blind, placebo-controlled trial was implemented at 82 hospitals in China, enrolling 1680 patients with stroke and proximal intracranial LVO presenting within 24 hours of time last known to be well. Recruitment took place between February 9, 2022, and June 30, 2023, with a final follow-up on September 30, 2023. Interventions: Eligible patients were randomly assigned to intravenous methylprednisolone (n = 839) at 2 mg/kg/d or placebo (n = 841) for 3 days adjunctive to endovascular thrombectomy. Main Outcomes and Measures: The primary efficacy outcome was disability level at 90 days as measured by the overall distribution of the modified Rankin Scale scores (range, 0 [no symptoms] to 6 [death]). The primary safety outcomes included mortality at 90 days and the incidence of symptomatic intracranial hemorrhage within 48 hours. Results: Among 1680 patients randomized (median age, 69 years; 727 female [43.3%]), 1673 (99.6%) completed the trial. The median 90-day modified Rankin Scale score was 3 (IQR, 1-5) in the methylprednisolone group vs 3 (IQR, 1-6) in the placebo group (adjusted generalized odds ratio for a lower level of disability, 1.10 [95% CI, 0.96-1.25]; P = .17). In the methylprednisolone group, there was a lower mortality rate (23.2% vs 28.5%; adjusted risk ratio, 0.84 [95% CI, 0.71-0.98]; P = .03) and a lower rate of symptomatic intracranial hemorrhage (8.6% vs 11.7%; adjusted risk ratio, 0.74 [95% CI, 0.55-0.99]; P = .04) compared with placebo. Conclusions and Relevance: Among patients with acute ischemic stroke due to LVO undergoing endovascular thrombectomy, adjunctive methylprednisolone added to endovascular thrombectomy did not significantly improve the degree of overall disability. Trial Registration: ChiCTR.org.cn Identifier: ChiCTR2100051729.

Nanoscale Borate Coating Network Stabilized Iron Oxide Anode for High-Energy-Density Bipolar Lithium-Ion Batteries.

High-capacity metal oxides based on non-toxic earth-abundant elements offer unique opportunities as advanced anodes for lithium-ion batteries (LIBs). But they often suffer from large volumetric expansion, particle pulverization, extensive side reactions, and fast degradations during cycling. Here, an easy synthesis method is reported to construct amorphous borate coating network, which stabilizes conversion-type iron oxide anode for the high-energy-density semi-solid-state bipolar LIBs. The nano-borate coated iron oxide anode has high tap density (1.6 g cm-3 ), high capacity (710 mAh g-1 between 0.5 - 3.0 V, vs Li/Li+ ), good rate performance (200 mAh g-1 at 50 C), and excellent cycling stability (≈100% capacity resention over 1,000 cycles at 5 A g-1 ). When paired with high-voltage cathode LiCoO2 , it enables Cu current collector-free pouch-type classic and bipolar full cells with high voltage (7.6 V with two stack layers), achieving high energy density (≈350 Wh kg-1 ), outstanding power density (≈6,700 W kg-1 ), and extended cycle life (75% capacity retention after 2,000 cycles at 2 C), superior to the state-of-the-art high-power LIBs using Li4 Ti5 O12 anode. The design and methodology of the nanoscale polyanion-like coating can be applied to other metal oxides electrode materials, as well as other electrochemical materials and devices.

The association between liver fibrosis and depression in patients after ischemic stroke.

BACKGROUND AND OBJECTIVE: Liver fibrosis has been considered a predictor of cardiovascular disease. This study aimed to evaluate whether the degree of liver fibrosis is related to post-stroke depression (PSD) at 3 months follow-up. METHODS: We prospectively and continuously enrolled patients with first-ever ischemic stroke from June 2020 to January 2022. Liver fibrosis was measured after admission by calculating the Fibrosis-4 index (FIB-4) and stratified into two categories (< 2.67 versus ≥ 2.67). Patients with a 17-item Hamilton Depression Scale score > 7 were further evaluated using the Chinese version of the structured clinical interview of DSM-IV, for diagnosing PSD at 3 months. RESULTS: A total of 326 patients (mean age 66.6 years, 51.5% male) were recruited for the study. As determined by the FIB-4 score, 80 (24.5%) patients had advanced liver fibrosis. During the follow-up, PSD was observed in 91 patients, which accounted for 27.9% (95% confidence interval [CI] 25.5%-30.5%) of the cohort. The prevalence of advanced liver fibrosis was higher in PSD patients than those without PSD (40.0% versus 24.0%; P = 0.006). After adjustment for covariates in the multivariate logistic analysis, advanced fibrosis was significantly associated with PSD (odds ratio [OR], 1.88; 95% CI, 1.03-3.42; P = 0.040). Similar results were found when the FIB-4 was analyzed as a continuous variable. CONCLUSIONS: This study found that advanced liver fibrosis was associated with an increased risk of 3-month PSD. FIB-4 score may be valuable for screening depressive symptoms in ischemic stroke patients.

Predictors and outcome of malignant cerebral edema after successful reperfusion in anterior circulation stroke.

BACKGROUND AND OBJECTIVE: Risk factors and predictors of malignant cerebral edema (MCE) after successful endovascular thrombectomy (EVT) were not fully explored. This study aimed to evaluate the incidence and risk factors of MCE after successful reperfusion. METHODS: We retrospectively analyzed consecutive ischemic stroke patients who underwent EVT in our institution from November 2015 to April 2022. Patients who failed to achieve successful reperfusion (modified thrombolysis in cerebral infarction [mTICI]<2b) were excluded. Based on multivariate logistic models, the best-fit monogram was established. The discriminative performance was assessed by the receiver operating characteristics curve (ROC). RESULTS: A total of 307 patients were included and 48 (15.6%) were diagnosed with MCE after successful reperfusion. Patients with MCE after successful reperfusion had a lower 3-month favorable outcome (15.2% versus 59.6%; p<0.001), a lower 3-month good outcome (17.4% versus 68.4%; p<0.001), and a higher rate of mortality at 3-month (54.3% versus 8.8%; p<0.001) compared with patients without MCE. Predictors of MCE after successful reperfusion included admission glucose level, baseline National Institutes of Health Stroke Scale (NIHSS) score, stroke etiology, occlusion site and puncture-to-reperfusion (PTR) time>120 min. The area under the curve (AUC) of the nomogram was 0.805 (95% CI, 0.756-0.847). CONCLUSIONS: MCE after successful reperfusion is associated with poor outcome and mortality. A nomogram containing admission glucose level, baseline NIHSS score, stroke etiology, occlusion site and PTR time>120 min may predict the risk of MCE after successful reperfusion in patients with acute ischemic stroke and treated successfully with EVT.

Molecular mechanisms of doxorubicin-induced cardiotoxicity: novel roles of sirtuin 1-mediated signaling pathways.

Doxorubicin (DOX) is an anthracycline chemotherapy drug used in the treatment of various types of cancer. However, short-term and long-term cardiotoxicity limits the clinical application of DOX. Currently, dexrazoxane is the only approved treatment by the United States Food and Drug Administration to prevent DOX-induced cardiotoxicity. However, a recent study found that pre-treatment with dexrazoxane could not fully improve myocardial toxicity of DOX. Therefore, further targeted cardioprotective prophylaxis and treatment strategies are an urgent requirement for cancer patients receiving DOX treatment to reduce the occurrence of cardiotoxicity. Accumulating evidence manifested that Sirtuin 1 (SIRT1) could play a crucially protective role in heart diseases. Recently, numerous studies have concentrated on the role of SIRT1 in DOX-induced cardiotoxicity, which might be related to the activity and deacetylation of SIRT1 downstream targets. Therefore, the aim of this review was to summarize the recent advances related to the protective effects, mechanisms, and deficiencies in clinical application of SIRT1 in DOX-induced cardiotoxicity. Also, the pharmaceutical preparations that activate SIRT1 and affect DOX-induced cardiotoxicity have been listed in this review.

Simultaneous Determination and Health Risk Assessment of Four High Detection Rate Pesticide Residues in Pu'er Tea from Yunnan, China.

Four pesticides with a high detection rate in Pu'er tea have been determined by a QuEChERS (quick, easy, cheap, effective, rugged, safe) method with multiwalled carbon nanotubes (MWCNTs), and combined ultrahigh-performance liquid chromatography-triple quadrupole linear ion trap-tandem mass spectrometry (UHPLC-QTRAP-MS/MS). MWCNs have been compared with other common purification materials, and found to be superior. The matrix effect was systematically studied, and the results show that the MWCNs can quickly and effectively reduce matrix interference values, which were in the range from -17.8 to 13.8. The coefficients (R2) were greater than 0.99, with the limit of quantification ranging from 0.1 to 0.5 µg/kg, and the recovery rate ranging from 74.8% to 105.0%, while the relative standard deviation (RSD) ranged from 3.9% to 6.6%. A total of 300 samples, taken from three areas in which Yunnan Pu'er tea was most commonly produced, tested for four pesticides. The results show that the detection rate of tolfenpyrad in Pu'er tea was 35.7%, which is higher than other pesticides, and the lowest was indoxacarb, with 5.2%. The residual concentrations of chlorpyrifos, triazophos, tolfenpyrad and indoxacarb ranged from 1.10 to 5.28, 0.014 to 0.103, 1.02 to 51.8, and 1.07 to 4.89 mg/kg, respectively. By comparing with China's pesticide residue limits in tea (GB 2763-2021), the over standard rates of chlorpyrifos, tolfenpyrad, and indoxacarb were 4.35%, 0.87% and 0%, respectively. The risk assessment result obtained with the hazard quotient (HQ) method shows that the HQ of the four pesticides was far less than one, indicating that the risk is considered acceptable for the four pesticides in Pu'er tea. The largest HQ was found for tolfenpyrad, 0.0135, and the smallest was found for indoxacarb, 0.000757, but more attention should be paid to tolfenpyrad in daily diets in the future, because its detection rate, and residual and residual median were all relatively high.

Regulatory role of endogenous and exogenous fibroblast growth factor 1 in the cardiovascular system and related diseases.

Fibroblast growth factor 1 (FGF1) has a critical regulatory role in the development of the cardiovascular system (CVS) and is strongly associated with the progression or treatment of cardiovascular diseases (CVDs). However, the regulatory mechanisms of FGF1 in CVS and CVDs have not yet been fully elucidated. Therefore, this review article summarized the existing literature reports on the role of FGF1 in CVS under physiological and pathological conditions. First, the expression and physiological functions of endogenous FGF1 is fully demonstrated. Then, we analyzed the role of exogenous FGF1 in normal CVS and related pathological processes. Specifically, the potential signaling pathways might be mediated by FGF1 in CVDs treatment is discussed in detail. In addition, the barriers and feasible solutions for the application of FGF1 are further analyzed. Finally, we highlight therapeutic considerations of FGF1 for CVDs in the future. Thus, this article may be as a reference to provide some ideas for the follow-up research.

Regulatory mechanisms of Sesn2 and its role in multi-organ diseases.

Sestrin2 (Sesn2) is a powerful anti-oxidant that can prevent acute and chronic diseases. The role of Sesn2 has been thoroughly reviewed in liver, nervous system, and immune system diseases. However, there is a limited number of reviews that have summarized the effects of Sesn2 in heart and vascular diseases, and very less literature-based information is available on involvement of Sesn2 in renal and respiratory pathologies. This review summarizes the latest research on Sesn2 in multi-organ stress responses, with a particular focus on the protective role of Sesn2 in cardiovascular, respiratory, and renal diseases, emphasizing the potential therapeutic benefit of targeting Sesn2 in stress-related diseases.

Acute visual impairment as a main presenting symptom of non-convulsive status epilepticus: a case report.

BACKGROUND: Nonconvulsive status epilepticus (NCSE) is a state of ongoing seizure activity without convulsions. The heterogeneous and subtle clinical features of NCSE make diagnosis and treatment challenging. Here, we report a patient with NCSE who showed a main presenting symptom of acute visual impairment, which is a rare and atypical clinical symptom of NCSE. CASE PRESENTATION: A 62-year-old man was admitted to the neurology department after complaining of an inability to see in the right eye for 2 days and progressive headache. He had a history of poststroke epilepsy and vascular dementia. Physical examination revealed right visual field hemianopia, visual neglect and cognitive impairment. T2 and diffusion-weighted magnetic resonance imaging showed high signal intensity in the left temporal, parietal and occipital lobes. Electroencephalography monitoring was performed, which found continuous sharp wave discharges, especially in the regions of the left temporal, parietal and occipital lobes. These findings were most consistent with the diagnosis of NCSE. Thus, a treatment of intravenous pumping of diazepam and an oral antiepileptic drug was added immediately. After that, the visual loss in the patient recovered quickly, and electroencephalography did not find epileptiform waves. On day 11, a follow-up MRI was performed, which showed that the abnormal signals of the left temporal, parietal and occipital lobes were markedly attenuated, and the patient returned to his premorbid state with a modified Rankin Scale score of 3. CONCLUSIONS: Acute visual impairment can be seen in NCSE, and it can be reversed by administering effective antiepileptic treatment. Meanwhile, transient peri-ictal MRI abnormalities can be observed in NCSE.

Dexmedetomidine alleviates cerebral ischemia-reperfusion injury in rats via inhibition of hypoxia-inducible factor-1α.

Dexmedetomidine (Dex) was reported to reduce ischemia-reperfusion (I/R) injury in kidney and brain tissues. Thus, we aimed to study the role and mechanism of Dex in cerebral I/R injury by inhibiting hypoxia-inducible factor-1α (HIF-1α) and apoptosis. First, I/R injury models were established. Six groups were assigned after different treatments: sham, I/R, I/R+Dex, I/R+2-methoxyestradiol (2ME2) (HIF-1α inhibitor), I/R+CoCl 2 (HIF-1α activator), and I/R+Dex+CoCl 2 groups. Neurological function, cerebral infarction volume, survival, and apoptosis of brain cells were then analyzed. Besides, immunohistochemistry and Western blot analysis were used to detect the expression of HIF-1α, BCL-2[B-cell leukemia/lymphoma 2] adenovirus E1B interacting protein 3 (BNIP3), B-cell leukemia/lymphoma 2 (BCL2), BCL2[B-cell leukemia/lymphoma 2] associated X (Bax), and cleaved-caspase3 proteins in brain tissues. I/R rats showed cerebral infarction, increased neurological function score, number of terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL)-positive cells and HIF-1α-positive cells as well as decreased neurons. Inhibition of HIF-1α can reduce the apoptosis induced by I/R, and overexpression of HIF-1α can aggravate apoptosis in brain tissue of I/R rats. Furthermore, activation of HIF-1α expression blocks the inhibitory effect of Dex on neuronal apoptosis in I/R rats. Dex may inhibit the neuronal apoptosis of I/R rats by inhibiting the HIF-1α pathway and then improve the cerebral I/R injury in rats.

Association between procalcitonin levels and carotid atherosclerosis in acute ischemic stroke patients.

BACKGROUND AND PURPOSES: Procalcitonin has been suggested as a new risk factor in atherosclerotic disease. However, whether procalcitonin levels are associated with the risk of carotid atherosclerosis remains unclear. This study aimed to investigate the relationship between procalcitonin levels and carotid atherosclerosis among patients with first-ever acute ischemic stroke. METHODS: Two hundred and thirty consecutive patients were prospectively enrolled in this study. Serum procalcitonin concentrations were measured at admission for all patients. We also performed ultrasound examination to detect the mean carotid intima-media thickness, presence of carotid-wall thickening, plaque and significant stenosis. Multiple regression analysis was used to estimate the association between procalcitonin levels and carotid atherosclerosis. RESULTS: The median procalcitonin concentration was 0.051 µg/L (interquartile range, 0.036-0.080 µg/L). Of the 230 patients, 102 (44.3%) had carotid-wall thickening, 113 (49.1%) had plaque and 77 (33.5%) had significant stenosis. After adjusting for all potential confounders by multiple logistic regression analysis, patients with procalcitonin levels in the fourth quartile, compared with the first quartile, were more likely to have carotid-wall thickening [odds ratio 2.288, 95% confidence intervals 1.042-5.021, P = 0.039] and significant stenosis [odds ratio 3.871, 95% confidence intervals 1.690-8.867, P = 0.003]. Furthermore, the linear regression analysis revealed a significant positive correlation between procalcitonin levels and the mean carotid intima-media thickness (ß = 0.162, P = 0.012). CONCLUSIONS: Higher procalcitonin concentrations at admission might be associated with carotid-wall thickening and significant stenosis in ischemic stroke patients.

New Graphene Form of Nanoporous Monolith for Excellent Energy Storage.

Extraordinary tubular graphene cellular material of a tetrahedrally connected covalent structure was very recently discovered as a new supermaterial with ultralight, ultrastiff, superelastic, and excellent conductive characteristics, but no high specific surface area will keep it from any next-generation energy storage applications. Herein, we prepare another new graphene monolith of mesoporous graphene-filled tubes instead of hollow tubes in the reported cellular structure. This graphene nanoporous monolith is also composed of covalently bonded carbon network possessing high specific surface area of ∼1590 m(2) g(-1) and electrical conductivity of ∼32 S cm(-1), superior to graphene aerogels and porous graphene forms self-assembled by graphene oxide. This 3D graphene monolith can support over 10 000 times its own weight, significantly superior to CNT and graphene cellular materials with a similar density. Furthermore, pseudocapacitance-active functional groups are introduced into the new nanoporous graphene monolith as an electrode material in electrochemical capacitors. Surprisingly, the electrode of 3D mesoporous graphene has a specific capacitance of 303 F g(-1) and maintains over 98% retention after 10 000 cycles, belonging to the list for the best carbon-based active materials. The macroscopic mesoporous graphene monolith suggests the great potential as an electrode for supercapacitors in energy storage areas.

The Establishment of Adult Reference Intervals on Fructosamine in Beijing.

BACKGROUND: Fructosamine (FRA) is widely used for diabetes monitor and control as a glycemic marker, especially in patients in whom the measurement of HbA1c may be biased or even unreliable. However, the FRA reference intervals based on Asian population features still keep seldom reported. The objective of this study was to establish the adult FRA reference intervals in Beijing, China. METHODS: A total of 1,497 healthy subjects were separated into three groups by gender and age. Subsequently, FRA levels in the collected serum samples from the reference individuals were tested by automatic chemical analyzer. The obtained data were statistically analyzed with SPSS. RESULTS: The serum FRA level in female group was slightly higher than that in male group without statistical significance. Meanwhile, further analysis indicated that the FRA level gradually increased along with the growth of the age. Compared with the age 20-45 group (248.83 ± 17.64 µmol/l) or the age 46-65 group (251.95 ± 19.63 µmol/l), the FRA level of the age >65 group (264.63± 23.05 µmol/l) was statistically significantly increased (P < 0.01). To better analyze the difference, the age 20-45 group and the age 46-65 group were combined into an age 20-65 group (249.88 ±18.39 µmol/l). In comparison to the age >65 group, the FRA level of age 20-65 group was significantly decreased (P <0.01). CONCLUSION: A novel FRA reference interval of the local healthy population in Beijing was established. The data demonstrated that there was no gender difference in FRA level, however, which was significantly increased in elder persons.

A novel mutation in SORD gene associated with distal hereditary motor neuropathies.

BACKGROUND: Distal hereditary motor neuropathy (dHMN) is a heterogeneous group of hereditary diseases caused by the gradual degeneration of the lower motor neuron. More than 30 genes associated with dHMN have been reported, while 70-80% of those with the condition are still unable to receive a genetic diagnosis. METHODS: A 26-year-old man experiencing gradual weakness in his lower limbs was referred to our hospital, and data on clinical features, laboratory tests, and electrophysiological tests were collected. To identify the disease-causing mutation, we conducted whole exome sequencing (WES) and then validated it through Sanger sequencing for the proband and his parents. Silico analysis was performed to predict the pathogenesis of the identified mutations. A literature review of all reported mutations of the related gene for the disease was performed. RESULTS: The patient presented with dHMN phenotype harboring a novel homozygous variant c.361G > C (p.Ala121Pro) in SORD, inherited from his parents, respectively. A121 is a highly conserved site and the mutation was categorized as "likely pathogenic" according to the criteria and guidelines of the American College of Medical Genetics and Genomics (ACMG). A total of 13 published articles including 101 patients reported 18 SORD variants. Almost all described cases have the homozygous deletion variant c.757delG (p.A253Qfs*27) or compound heterozygous state of a combination of c.757delG (p.A253Qfs*27) with another variant. The variant c.361G > C (p.Ala121Pro) detected in our patient was the second homozygous variant in SORD-associated hereditary neuropathy. CONCLUSION: One novel homozygous variant c.361G > C (p.Ala121Pro) in SORD was identified in a Chinese patient with dHMN phenotype, which expands the mutation spectrum of SORD-associated hereditary neuropathy and underscores the significance of screening for SORD variants in patients with undiagnosed hereditary neuropathy patients.

Integration of dietary nutrition and TRIB3 action into diabetes mellitus.

Despite intensive studies for decades, the common mechanistic correlations among the underlying pathology of diabetes mellitus (DM), its complications, and effective clinical treatments remain poorly characterized. High-quality diets and nutrition therapy have played an indispensable role in the management of DM. More importantly, tribbles homolog 3 (TRIB3), a nutrient-sensing and glucose-responsive regulator, might be an important stress-regulatory switch, linking glucose homeostasis and insulin resistance. Therefore, this review aimed to introduce the latest research progress on the crosstalk between dietary nutrition intervention and TRIB3 in the development and treatment of DM. This study also summarized the possible mechanisms involved in the signaling pathways of TRIB3 action in DM, in order to gain an in-depth understanding of dietary nutrition intervention and TRIB3 in the pathogenesis of DM at the organism level.

Elevation of p53 sensitizes obese kidney to adriamycin-induced aberrant lipid homeostasis via repressing HNF4α-mediated FGF21 sensitivity.

INTRODUCTION: Lipid metabolism disorders have been confirmed to be closely related to kidney injury caused by adriamycin (ADR) and obesity, respectively. However, it has not been explored whether lipid metabolism disorders are related to kidney injury caused by ADR aggravated by obesity, and the specific molecular mechanism needs to be further clarified. OBJECTIVES: This study was designed to examine the role of p53-fibroblast growth factor 21 (FGF21) axis in ADR-induced renal injury aggravated by high fat diet (HFD). METHODS: We engineered Fgf21 KO mice and used long-term (4 months) and short-term (0.5 months) HFD feeding, and ADR-injected mice, as well as STZ-induced type 1 diabetic mice and type 2 (db/db) diabetic mice to produce a in vivo model of nephrotoxicity. The specific effects of p53/FGF21 on regulation of lipid metabolism disorders and its downstream mediators in kidney were subsequently elucidated using a combination of functional and pathological analysis, RNA-sequencing, molecular biology and in vitro approaches. RESULTS: Long-term HFD feeding mice exhibited compromised effects of FGF21 on alleviation of renal dysfunction and lipid accumulation following ADR administration. However, these impairments were reversed by p53 inhibitor (pifithrin-α, PFT-α). PFT-α sensitized FGF21 actions in kidney tissues, while knockout of Fgf21 impaired the protective effects of PFT-α on lipid metabolism. Mechanistically, p53 impaired the renal expression of FGF recepter-1 (FGFR1) and thereby developed gradually into FGF21 resistance via inhibiting hepatocyte nuclear factor alpha (HNF4α)-mediated transcriptional activation of Fgfr1. More importantly, exogenous supplementation of FGF21 or PFT-α could not only alleviate ADR-induced lipid metabolism disorder aggravated by HFD, but also reduce lipid accumulation caused by diabetic nephropathy. CONCLUSION: Given the difficulties in developing the long-acting recombinant FGF21 analogs for therapeutic applications, sensitizing obesity-impaired FGF21 actions by suppression of p53 might be a therapeutic strategy for maintaining renal metabolic homeostasis during chemotherapy.

Oxygen Vacancy-Driven Heterointerface Breaks the Linear-Scaling Relationship of Intermediates toward Electrocatalytic CO2 Reduction.

Smart metal-metal oxide heterointerface construction holds promising potentials to endow an efficient electron redistribution for electrochemical CO2 reduction reaction (CO2RR). However, inhibited by the intrinsic linear-scaling relationship, the binding energies of competitive intermediates will simultaneously change due to the shifts of electronic energy level, making it difficult to exclusively tailor the binding energies to target intermediates and the final CO2RR performance. Nonetheless, creating specific adsorption sites selective for target intermediates probably breaks the linear-scaling relationship. To verify it, Ag nanoclusters were anchored onto oxygen vacancy-rich CeO2 nanorods (Ag/OV-CeO2) for CO2RR, and it was found that the oxygen vacancy-driven heterointerface could effectively promote CO2RR to CO across the entire potential window, where a maximum CO Faraday efficiency (FE) of 96.3% at -0.9 V and an impressively high CO FE of over 62.3% were achieved at a low overpotential of 390 mV within a flow cell. The experimental and computational results collectively suggested that the oxygen vacancy-driven heterointerfacial charge spillover conferred an optimal electronic structure of Ag and introduced additional adsorption sites exclusively recognizable for *COOH, which, beyond the linear-scaling relationship, enhanced the binding energy to *COOH without hindering *CO desorption, thus resulting in the efficient CO2RR to CO.

Visualizing Electrochemical CO2 Conversion via the Emerging Scanning Electrochemical Microscope: Fundamentals, Applications and Perspectives.

With the rapid development and maturity of electrochemical CO2 conversion involving cathodic CO2 reduction reaction (CO2RR) and anodic oxygen evolution reaction (OER), conventional ex situ characterizations gradually fall behind in detecting real-time products distribution, tracking intermediates, and monitoring structural evolution, etc. Nevertheless, advanced in situ techniques, with intriguing merits like good reproducibility, facile operability, high sensitivity, and short response time, can realize in situ detection and recording of dynamic data, and observe materials structural evolution in real time. As an emerging visual technique, scanning electrochemical microscope (SECM) presents local electrochemical signals on various materials surface through capturing micro-current caused by reactants oxidation and reduction. Importantly, SECM holds particular potentials in visualizing reactive intermediates at active sites and obtaining instantaneous morphology evolution images to reveal the intrinsic reactivity of active sites. Therefore, this review focuses on SECM fundamentals and its specific applications toward CO2RR and OER, mainly including electrochemical behavior observation on local regions of various materials, target products and onset potentials identification in real-time, reaction pathways clarification, reaction kinetics exploration under steady-state conditions, electroactive materials screening and multi-techniques coupling for a joint utilization. This review undoubtedly provides a leading guidance to extend various SECM applications to other energy-related fields.