Selenium Utilization by GPX4 Is Required to Prevent Hydroperoxide-Induced Ferroptosis.

Selenoproteins are rare proteins among all kingdoms of life containing the 21st amino acid, selenocysteine. Selenocysteine resembles cysteine, differing only by the substitution of selenium for sulfur. Yet the actual advantage of selenolate- versus thiolate-based catalysis has remained enigmatic, as most of the known selenoproteins also exist as cysteine-containing homologs. Here, we demonstrate that selenolate-based catalysis of the essential mammalian selenoprotein GPX4 is unexpectedly dispensable for normal embryogenesis. Yet the survival of a specific type of interneurons emerges to exclusively depend on selenocysteine-containing GPX4, thereby preventing fatal epileptic seizures. Mechanistically, selenocysteine utilization by GPX4 confers exquisite resistance to irreversible overoxidation as cells expressing a cysteine variant are highly sensitive toward peroxide-induced ferroptosis. Remarkably, concomitant deletion of all selenoproteins in Gpx4cys/cys cells revealed that selenoproteins are dispensable for cell viability provided partial GPX4 activity is retained. Conclusively, 200 years after its discovery, a specific and indispensable role for selenium is provided.

H2O2 Photosynthesis from H2O and O2 under Weak Light by Carbon Nitrides with the Piezoelectric Effect.

Driven by the essential need of a green, safe, and low-cost approach to producing H2O2, a highly valuable multifunctional chemical, artificial photosynthesis emerges as a promising avenue. However, current catalyst systems remain challenging, due to the need of high-density sunlight, poor selectivity and activity, or/and unfavorable thermodynamics. Here, we reported that an indirect 2e- water oxidation reaction (WOR) in photocatalytic H2O2 production was unusually activated by C5N2 with piezoelectric effects. Interestingly, under ultrasonication, C5N2 exhibited an overall H2O2 photosynthesis rate of 918.4 µM/h and an exceptionally high solar-to-chemical conversion efficiency of 2.6% after calibration under weak light (0.1 sun). Mechanism studies showed that the piezoelectric effect of carbon nitride overcame the high uphill thermodynamics of *OH intermediate generation, which enabled a new pathway for 2e- WOR, the kinetic limiting step in the overall H2O2 production from H2O and O2. Benefiting from the outstanding sonication-assisted photocatalytic H2O2 generation under weak light, the concept was further successfully adapted to biomedical applications in efficient sono-photochemodynamic therapy for cancer treatment and water purification.

Dynamics of simplicial SEIRS epidemic model: global asymptotic stability and neural Lyapunov functions.

The transmission of infectious diseases on a particular network is ubiquitous in the physical world. Here, we investigate the transmission mechanism of infectious diseases with an incubation period using a networked compartment model that contains simplicial interactions, a typical high-order structure. We establish a simplicial SEIRS model and find that the proportion of infected individuals in equilibrium increases due to the many-body connections, regardless of the type of connections used. We analyze the dynamics of the established model, including existence and local asymptotic stability, and highlight differences from existing models. Significantly, we demonstrate global asymptotic stability using the neural Lyapunov function, a machine learning technique, with both numerical simulations and rigorous analytical arguments. We believe that our model owns the potential to provide valuable insights into transmission mechanisms of infectious diseases on high-order network structures, and that our approach and theory of using neural Lyapunov functions to validate model asymptotic stability can significantly advance investigations on complex dynamics of infectious disease.

Association between mixed metal exposure and stroke risk in Shanxi Province: a case-control study.

BACKGROUND: Stroke is the second leading cause of death for all human beings and poses a serious threat to human health. Environmental exposure to a mixture of metals may be associated with the occurrence and development of stroke, but the evidence in the Chinese population is not yet conclusive. OBJECTIVES: This study evaluated the association between stroke risk and 13 metals METHODS: Metal concentrations in whole blood samples from 100 stroke cases and 100 controls were measured by ICP-MS. The cumulative impact of mixed metal on stroke risk was investigated by using three statistical models, BKMR, WQS and QGC. RESULTS: The case group had higher concentrations of Mg, Mn, Zn, Se, Sn, and Pb than the control group (p<0.05). BKMR model indicated a correlation between the risk of stroke and exposure to mixed metals. WQS model showed that Mg (27.2 %), Se (25.1 %) and Sn (14.8 %) were positively correlated with stroke risk (OR=1.53; 95 %Cl: 1.03-2.37, p=0.013). The QGC model showed that Mg (49.2 %) was positively correlated with stroke risk, while Ti (31.7 %) was negatively correlated with stroke risk. CONCLUSIONS: Mg may be the largest contributor to the cumulative effect of mixed metal exposure on stroke risk, and the interaction between metals requires more attention. These findings could provide scientific basis for effectively preventing stroke by managing metals in the environment.

Regulating Intermolecular Interactions and Film Formation Kinetics for Record Efficiency in Difluorobenzothiadizole-Based Organic Solar Cells.

The difluorobenzothiadizole (ffBT) unit is one of the most classic electron-accepting building blocks used to construct D-A copolymers for applications in organic solar cells (OSCs). Historically, ffBT-based polymers have achieved record power conversion efficiencies (PCEs) in fullerene-based OSCs owing to their strong temperature-dependent aggregation (TDA) characteristics. However, their excessive miscibility and rapid aggregation kinetics during film formation have hindered their performance with state-of-the-art non-fullerene acceptors (NFAs). Herein, we synthesized two ffBT-based copolymers, PffBT-2T and PffBT-4T, incorporating different π-bridges to modulate intermolecular interactions and aggregation tendencies. Experimental and theoretical studies revealed that PffBT-4T exhibits reduced electrostatic potential differences and miscibility with L8-BO compared to PffBT-2T. This facilitates improved phase separation in the active layer, leading to enhanced molecular packing and optimized morphology. Moreover, PffBT-4T demonstrated a prolonged nucleation and crystal growth process, leading to enhanced molecular packing and optimized morphology. Consequently, PffBT-4T-based devices achieved a remarkable PCE of 17.5 %, setting a new record for ffBT-based photovoltaic polymers. Our findings underscore the importance of conjugate backbone modulation in controlling aggregation behavior and film formation kinetics, providing valuable insights for the design of high-performance polymer donors in organic photovoltaics.

Synthesis and modification mechanism of vanadium oxide coated LiFePO4cathode materials with excellent electrochemical performance.

In an era of rapid industrial development, such that the demand for energy is increasing daily, lithium-ion batteries are playing a dominant role in energy storage devices due to their high safety and low cost. However, it is still a challenge for the preparation of advanced cathodes, which can determine the battery performance, with stable structures and fast diffusion of Li+. This is especially the case for lithium iron phosphate (LFP), a cathode material with severe limitations due to its low conductive efficiency. To improve its conductivity, LFP was compounded with defect-modified V2O5to prepare LFP/V/C materials with excellent electrochemical properties, which exhibited an initial capacity of 138.85 mAh g-1and 95% retention after 500 charge/discharge cycles at a current density of 5 C. Also, the effect of defects on ionic diffusion was discussed in detail by means of density function theor (DFT) calculations, confirming that the improvement of electrochemical performance is closely related to the introduction of hybrid conductive layers of surface cladding.

Fe-doped V2O5layered nanowire cathode material with high lithium storage performance.

As a lithium-ion battery cathode material with high theoretical capacity, the application of V2O5is limited by its unstable structure and low intrinsic conductivity. In this paper, we report a Fe doped V2O5nanowire with a layered structure of 200-300 nm diameter prepared by electrostatic spinning technique. The 3Fe-V2O5electrode exhibited a superb capacity of 436.9 mAh g-1in the first cycle when tested in the voltage range of 2.0-4.0 V at current density of 100 mA g-1, far exceeding its theoretical capacity (294 mAh g-1), and the high capacity of 312 mAh g-1was still maintained after 50 cycles. The superb performance is mainly attributed to its unique layered nanowire structure and the enhanced electrical conductivity as well as optimized structure brought by Fe-doping. This work made the homogeneous doping and nanosizing of the material easily achieved through electrostatic spinning technology, leading to an increase in the initial capacity of the V2O5cathode material and the cycling stability compared to the pure V2O5, which is an extremely meaningful exploration.

Use of oral glucose tolerance testing and HbA1c at 6-14 gestational weeks to predict gestational diabetes mellitus in high-risk women.

PURPOSE: To study the prediction of gestational diabetes mellitus (GDM) in high-risk pregnant women by testing fasting blood glucose, 1-h(1hPG) and 2-h plasma glucose (2hPG) after an oral glucose tolerance test, and glycated hemoglobin (HbA1c) in early pregnancy (6-14 weeks). METHODS: We recruited 1311 pregnant women at high risk for diabetes from the Obstetrics Clinic of Daxing District People's Hospital between June 2017 and December 2019. The tests performed during the first trimester included fasting blood glucose (FPG), HbA1c, and 75-g oral glucose tolerance test (OGTT) with 1hPG and 2hPG. Seventy-three pregnant women diagnosed with pregestational diabetes mellitus (PGDM) early in pregnancy and 36 who were missed in the second trimester were excluded. A total of 1202 women were followed up until 24-28 weeks for GDM. The receiver operating characteristic (ROC) and area under the ROC curve (AUC) were calculated to determine the predictive values of FPG, 1hPG, 2hPG, and HbA1c for GDM in early pregnancy in high-risk pregnant women. RESULTS: The AUC for 1hPG for the prediction of GDM in high-risk pregnant women was greater than those for FPG, 2hPG, and HbA1c. All differences were significant. The AUCs for the predictive values of FPG, 1hPG, 2hPG, and HbA1c in high-risk pregnant women were 0.63, 0.76, 0.71, and 0.67, respectively. The prevalence of PGDM among pregnant women at high risk of diabetes was 5.6%. CONCLUSION: First-trimester levels of FPG, 1hPG, 2hPG, and HbA1c in high-risk women are significant predictors of GDM, with 1hPG having the most significant predictive value.

Extended Conjugation Tuning Carbon Nitride for Non-sacrificial H2 O2 Photosynthesis and Hypoxic Tumor Therapy.

Artificial photocatalysis offers a clean approach for producing H2 O2 . However, the poor selectivity and activity of H2 O2 production hamper traditional industrial applications and emerging photodynamic therapy (PDT)/chemodynamic therapy (CDT). Herein, we report a C5 N2 photocatalyst with a conjugated C=N linkage for selective and efficient non-sacrificial H2 O2 production in both normoxic and hypoxic systems. The strengthened delocalization of π-electrons by linkers in C5 N2 downshifted the band position, thermodynamically eliminating side H2 evolution reaction and kinetically promoting water oxidation. As a result, C5 N2 had a competitive solar-to-chemical conversion efficiency of 0.55 % in overall H2 O2 production and exhibited by far the highest activity under hypoxic conditions (698 µM h-1 ). C5 N2 was further applied to hypoxic PDT/CDT with outstanding performance in apparent cancer cell death and synchronous bioimaging. The study sheds light on the photosynthesis of H2 O2 by carbon nitrides for health applications.

Green synthesis of fluorescent carbon dots using chloroplast dispersions as precursors and application for Fe3+ ion sensing.

Water-soluble carbon dots (CDs) were synthesized using a one-step hydrothermal treatment of chloroplast dispersions extracted from fresh leaves as a green carbon source. The CD solution showed an emission peak centred at 445 nm when excited at 300 nm. The synthesized CDs were uniform and monodispersed with an average size of 5.6 nm. When adding ferric(III) ions (Fe3+ ) to the solution of the original CDs, the fluorescence intensity decreased significantly. Based on the linear relationship between fluorescence intensity and concentration of Fe3+ ions, an effective method for rapid, sensitive and selective Fe3+ sensing in aqueous solution could be established. Under optimum conditions, the extent of the fluorescence quenching of prepared CDs strongly depended on the Fe3+ ions over a wide concentration range 1.0-100.0 µM with a detection limit (3σ/k) of 0.3 µM. Furthermore, the quantitative determination of Fe3+ ions in environmental water samples was realized.

Carbon dots synthesized by the m-trihydroxybenzene as the carbon source and its application on the detection of pH value.

New carbon dots (CDs) were prepared by a microwave method using m-trihydroxybenzene and dilute sulphuric acid as raw materials. The as-prepared CDs exhibited excellent water solubility and photoluminesence properties. The optimum excitation and emission wavelengths of the new CDs were at 365 nm and 465 nm, respectively. The fluorescence of the new CDs experienced remarkable changes in the presence of Britton-Robinson (BR) buffer solution with different pH values under 4°C after reacting for 70 min. In addition, a linear relationship between the logarithm of the relative fluorescence intensity ratio [lg(IF /IFo )] of CDs and the pH values of the sensing system ranging 1.81-5.72 was obtained, with a correlation coefficient of 0.9933. Thus, a sensitive and simple method to detect the pH value of solution was developed. Furthermore, the analytical application of detecting the concentration of acetic acid in vinegar was investigated. The detection values were found similar to the reference values, fully demonstrating a good linear relationship between the logarithm of the relative fluorescence intensity ratio of the CDs and the pH value of the system. Hence, the method could be used to detect the concentration of acetic acid in vinegar.

Spectrofluorometric determination of berberine using a novel Au nanocluster with large Stokes shift.

Berberine hydrochloride (BHC), a natural isoquinoline alkaloid, is widely applied as a an agent in traditional Chinese medicine. Almost all the traditional methods for BHC detection require complicated preprocessing steps or expensive instruments. In this article, we report a simple, rapid, sensitive, and selective method for BHC detection using fluorescent gold nanoclusters (F-AuNCs) as the fluorescent probe with a large Stokes shift of 237 nm. The F-AuNCs prepared with citrate-stabilized stannous chloride and hydrogen tetrachloroaurate(III) as raw materials in an aqueous medium display strong and stable fluorescence at 566 nm. When F-AuNCs are mixed with BHC, the fluorescence of F-AuNCs is effectively quenched. Under optimized conditions, this method allows sensitive and selective measurements of BHC in a concentration ranging from 1.0 × 10-6 to 1.0 × 10-4 mol L-1 with a detection limit of 7.5 × 10-8 mol L-1, which is relatively low among reported spectral methods. This method provides excellent selectivity for the detection of BHC against inorganic anions and natural amino acids. In addition, the BHC content in two different types of berberine tablets was successfully determined by this method and the results showed high accuracy. Graphical Abstract ᅟ.

Giant Serpentine Middle Cerebral Artery Aneurysm.

Giant serpentine aneurysms are rare entity, which have unique presentations and distinct angiographic features, with poor prognosis if not treated. In this paper, a patient with a giant serpentine aneurysm originated from right middle cerebral artery was reported. A 38-year-old woman suffered from progressively headache and vision declined. The computed tomography and magnetic resonance image revealed a partially calcified, large mass (approximately 80 × 70 × 60 mm sized) in the right frontal-temple lobe. On computed tomography angiography, an unruptured, giant, partially thrombosed, serpentine aneurysm was confirmed. After treatment by craniotomy, the patient was rehabilitation. Operation is an effective method for the treatment of giant serpentine aneurysms. In addition, cerebral angiography and balloon test occlusion are the crucial way of preoperative assessment.

Risk of Stroke in Patients with Herpes Zoster: A Systematic Review and Meta-Analysis.

BACKGROUND: Several observational studies suggest that herpes zoster (HZ) may increase the risk of stroke, but the results are inconsistent. Our study was designed to assess the association between HZ and the risk of stroke through a meta-analysis of cohort studies. METHODS: The electronic databases PubMed and EMBASE were searched from inception to May 31, 2016 to identify relevant cohort studies that assess the risk of stroke in patients with HZ. Reference lists were also reviewed to identify potential studies. The random-effects model and fixed-effects model were used to calculate the summary relative risks (RRs) with 95% confidence intervals (CIs). RESULTS: Six cohort studies (251,076 HZ patients and 8462 cases of stroke) were identified in the study. The result showed that HZ was significantly correlated with increased risk of stroke, and the pooled RR was 1.36 (95% confidence interval [CI]: 1.10, 1.67) (P = .004). In the subgroup analysis, the significant association was observed except for stroke type (hemorrhage group). In the sensitivity analysis, excluding 1 study, the pooled RR was 1.45 (95% CI: 1.17, 1.80) (P = .001) for HZ, and 4.42 (95% CI: 2.75, 7.11) (P = .000) for herpes zoster ophthalmicus. Considerable heterogeneity was observed in our study. CONCLUSION: Our study furnishes evidence of a positive association between HZ and the risk of stroke.

A rare solitary neurofibroma of the frontal sinus.

Neurofibromas are common peripheral nerve sheath tumors related to Schwann cell's proliferation and are usually associated with neurofibromatosis type 1. Although solitary neurofibroma that occurs in the paranasal sinus is reported occasionally, neurofibroma located in the frontal sinus is extremely rare. Here, we report a case of a young woman who had a heterogeneous lesion in the left frontal sinus, eroding its anterior and posterior wall with signs of intracranial invasion. Postoperatively, results of the histologic examination confirmed the diagnosis of solitary neurofibroma. In conclusion, solitary neurofibroma should be considered in the differential diagnosis of frontal sinus masses.

Vim-PSA Double-Target DBS for the Treatment of Holmes Tremor Secondary to Brainstem Hemorrhage: A Case Report.

We report the case of a 53-year-old man who was diagnosed with Holmes tremor and underwent deep brain stimulation of the ventro-intermediate thalamic nucleus and posterior subthalamic area. We assessed the patients' tremor with the Fahn-Tolosa-Marin Tremor Rating Scale at 1, 3, 6, 12 and 24 months after deep brain stimulation. Deep brain stimulation relieved the patient's tremor during the 24-month follow-up period.

Efficient and Stable Air-Processed Organic Solar Cells Enabled by an Antioxidant Additive.

Current high-efficiency organic solar cells (OSCs) are generally fabricated in an inert atmosphere that limits their real-world scalable manufacturing, while the efficiencies of air-processed OSCs lag far behind. The impacts of ambient factors on solar cell fabrication remain unclear. In this work, the effects of ambient factors on cell fabrication are systematically investigated, and it is unveiled that the oxidation and doping of organic light absorbers are the dominant reasons causing cell degradation when fabricated in air. To address this issue, a new strategy for fabricating high-performance air-processed OSCs by introducing an antioxidant additive (4-bromophenylhydrazine, BPH) into the precursor solutions, is developed. BPH can effectively inhibit oxygen infiltration from the ambient to the photoactive layer and suppress trap formation caused by oxidation. Compared with conventional air-processed OSCs, this strategy remarkably increases the cell power conversion efficiency (PCE) from 16.7% to 19.3% (independently certified as 19.2%), representing the top value of air-processed OSCs. Furthermore, BPH significantly improves the operational stability of the cells in air by two times with a T80 lifetime of over 500 h. This study highlights the potential of using antioxidant additives to fabricate high-efficiency and stable OSCs in air, significantly promoting the industrialization of OSCs.

Thiophosphate and selenite conversely modulate cell death induced by glutathione depletion or cisplatin: effects related to activity and Sec contents of thioredoxin reductase.

Thiophosphate (SPO(3)) was recently shown to promote cysteine insertion at Sec (selenocysteine)-encoding UGA codons during selenoprotein synthesis. We reported previously that irreversible targeting by cDDP [cis-diamminedichloroplatinum(II) or cisplatin] of the Sec residue in TrxR1 (thioredoxin reductase 1) contributes to cDDP cytotoxicity. This effect could possibly be attenuated in cells expressing less reactive Sec-to-cysteine-substituted TrxR1 variants, or pronounced in cells with higher levels of Sec-containing TrxR1. To test this, we supplemented cells with either SPO(3) or selenium and subsequently determined total as well as specific activities of cellular TrxR1, together with extent of drug-induced cell death. We found that cDDP became less cytotoxic after incubation of A549 or HCT116 cells with lower SPO(3) concentrations (100-300 µM), whereas higher SPO(3) (>300 µM) had pronounced direct cytotoxicity. NIH 3T3 cells showed low basal TrxR1 activity and high susceptibility to SPO(3) cytotoxicity, or to glutathione depletion. Supplementing NIH 3T3 cells with selenite, however, gave increased cellular TrxR1 activity with concomitantly decreased dependence on glutathione, whereas the susceptibility to cDDP increased. The results suggest molecular mechanisms by which the selenium status of cells can affect their glutathione dependence while modulating the cytotoxicity of drugs that target TrxR1.

Spinal subdural hematoma in a patient with immune thrombocytopenic purpura following microvascular decompression: a rare case report.

This article reports a case of spontaneous spinal subdural hematoma (SSDH) after brain surgery in a patient with immune thrombocytopenic purpura (ITP), reviews the relevant literature, and discusses the etiology, pathogenesis, and clinical features of SSDH in patients with ITP. A male patient in his early 50 s with an 8-year history of ITP and suffering from coexistent hemifacial spasm and trigeminal neuralgia underwent microvascular decompression in our department. His preoperative corrected platelet count was within the normal range. On postoperative day 2, the patient complained of acute low back pain and sciatica. Lumbar magnetic resonance imaging demonstrated an SSDH extending from L3 to L4 with a significantly decreased platelet count (30.0 × 109/L). The pain was gradually relieved after 2 weeks of conservative treatment, and no neurological deficit occurred during the 1-year follow-up. Brain surgery may increase the risk of postoperative SSDH in patients with ITP. Clinicians planning brain surgery must conduct a rigorous assessment through detailed physical examination, laboratory tests, and medical history records and maintain perioperative platelet counts within the normal range to prevent various risks associated with spinal cord compression.

Inflammatory bowel disease and risk of Parkinson's disease: evidence from a meta-analysis of 14 studies involving more than 13.4 million individuals.

Background: The relationship between inflammatory bowel disease (IBD) and the risk of Parkinson's Disease (PD) has been investigated in several epidemiological studies. However, the results of these studies were inconclusive and inconsistent. We evaluated the potential relationship between IBD and PD risk by a meta-analysis. Methods: Search the electronic databases PubMed, Embase and Cochrane databases from inception to November 30, 2022, to identify relevant studies that assess the risk of PD in patients with IBD. The cohort, cross-sectional, mendelian randomization and case-control studies that reported risk estimates of PD and IBD were included in our analysis. The random-effect model and fixed-effects model were used to calculate the summary relative risks (RRs) with 95% confidence intervals (CIs). Results: In total, 14 studies (nine cohort studies, two cross-sectional studies, two mendelian randomization studies and one case-control study) involving more than 13.4 million individuals were analyzed in our analysis. Our results suggested that the risk of PD in IBD patients is moderately increased, with the pooled RR was 1.17 (95% CI: 1.03-1.33, P = 0.019). Omit of any single study from this analysis had little effect on the combined risk estimate. No evidence of publication bias was found. In the subgroup analysis, the combined RR was 1.04 (95% CI: 0.96, 1.12, P = 0.311) for Crohn's disease (CD), and 1.18 (95% CI: 1.06, 1.31, P = 0.002) for ulcerative colitis (UC). In addition, a significant association was identified in patients with IBD aged ≥ 60 years (RR = 1.22; 95% CI: 1.06-1.41, P = 0.007), but not in age < 60 years (RR = 1.19; 95% CI: 0.58-2.41, P = 0.639). Meanwhile, the meta-analysis results suggested a protective role for IBD medication use against PD development, with the RR was 0.88 (95% CI: 0.74, 1.04, P = 0.126). Conclusion: Our results indicated that patients with IBD had a moderately higher risk of PD compared to non-IBD individuals. Patients with IBD should be aware of the potential risks for PD, especially who were ≥ 60 years old.