The Role of Gaseous Molecules in Traumatic Brain Injury: An Updated Review

Traumatic brain injury (TBI) affects millions of people in China each year. TBI has a high mortality and often times a serious prognosis. The causative mechanisms of TBI during development and recovery from an injury remain vague, leaving challenges for the medical community to provide treatment options that improve prognosis and provide an optimal recovery. Biological gaseous molecules including nitric oxide (NO), carbon monoxide (CO), hydrogen sulfide (H2S), and molecular hydrogen (H2) have been found to play critical roles in physiological and pathological conditions in mammals. Accumulating evidence has found that these gaseous molecules can execute neuroprotection in many central nervous system (CNS) conditions due to their highly permeable properties allowing them to enter the brain. Considering the complicated mechanisms and the serious prognosis of TBI, effective and adequate therapeutic approaches are urgently needed. These four gaseous molecules can be potential attractive therapeutic intervention on TBI. In this review, we will present a comprehensive overview on the role of these four biological gasses in the development of TBI and their potential therapeutic applications

Contribution from the Western Pacific Subtropical High Index to a Deep Learning Typhoon Rainfall Forecast Model

In this study, a tropical cyclone or typhoon rainfall forecast model based on Random Forest is developed to forecast the daily rainfall at 133 weather stations in China. The input factors to the model training process include rainfall observations during 1960–2018, typhoon information (position and intensity), station information (position and altitude), and properties of the western Pacific subtropical high. Model evaluation shows that besides the distance between a station and cyclone, the subtropical high properties are ranked very high in the model’s feature importance, especially the subtropical ridgeline, and intensity. These aspects of the subtropical high influence the location and timing of typhoon landfall. The forecast model has a correlation coefficient of about 0.73, an Index of Agreement of nearly 0.8, and a mean bias of 1.28 mm based on the training dataset. Biases are consistently low, with both positive and negative signs, for target stations in the outer rainband (up to 1000 km, beyond which the model does not forecast) of typhoons. The range of biases is much larger for target stations in the inner-core (0–200 km) region. In this region, the model mostly overestimates (underestimates) the small (large) rain rates. Cases study of Typhoon Doksuri and Talim in 2023, as independent cases, shows the high performance of the model in forecasting the peak rain rates and timing of their occurrence of the two impactful typhoons

Timescale correlation of shallow trap states increases electrochemiluminescence efficiency in carbon nitrides

Abstract Highly efficient interconversion of different types of energy plays a crucial role in both science and technology. Among them, electrochemiluminescence, an emission of light excited by electrochemical reactions, has drawn attention as a powerful tool for bioassays. Nonetheless, the large differences in timescale among diverse charge-transfer pathways from picoseconds to seconds significantly limit the electrochemiluminescence efficiency and hamper their broad applications. Here, we report a timescale coordination strategy to improve the electrochemiluminescence efficiency of carbon nitrides by engineering shallow electron trap states via Au-N bond functionalization. Quantitative electrochemiluminescence kinetics measurements and theoretic calculations jointly disclose that Au-N bonds endow shallow electron trap states, which coordinate the timescale of the fast electron transfer in the bulk emitter and the slow redox reaction of co-reagent at diffusion layers. The shallow electron trap states ultimately accelerate the rate and kinetics of emissive electron-hole recombination, setting a new cathodic electrochemiluminescence efficiency record of carbon nitrides, and empowering a visual electrochemiluminescence sensor for nitrite ion, a typical environmental contaminant, with superior detection range and limit

Melatonin Ameliorates Hemorrhagic Transformation via Suppression of ROS-Induced NLRP3 Activation after Cerebral Ischemia in Hyperglycemic Rats

Melatonin is a strong antioxidant which beneficially protects against middle cerebral artery occlusion (MCAO) followed by hemorrhagic transformation in rats; protection includes the reduction of neurological deficits, infarction, and hematoma volume. The molecular mechanisms underlying these neuroprotective effects in the MCAO model have not been clearly identified. This study examined the influence and involved mechanism of melatonin on inflammation in hemorrhagic transformation following hyperglycemia MCAO rat model. Compared with the MCAO group, MCAO+dextrose (DX) group showed worse neurological function and higher infarction and hematoma volume. Interestingly, the protein expression of Nod-like receptor protein 3 (NLRP3) inflammasome increased in the MCAO+DX group compared with the MCAO group, which indicated that NLRP3 inflammasome may be involved in the DX-induced hemorrhagic transformation following MCAO. Then, three dosages of melatonin were intraperitoneally injected 2 h after MCAO induction. Melatonin treatment attenuated inflammatory response by inhibiting the reactive oxygen species (ROS) and NLRP3 inflammasome, alleviating neuronal injury, and reducing infarction and hematoma volume, finally improving neurological score. Melatonin also repressed cortical levels of proinflammatory cytokine IL-1β, which were increased 24 h after hyperglycemia MCAO. In order to identify the potential mechanisms, we further revealed that nigericin administration reversed the neuroprotective effect of melatonin by promoting NLRP3 inflammasome activation. In general, this present study reveals that melatonin prevents the occurrence of hyperglycemia-enhanced hemorrhagic transformation, and this effect might be beneficial to attenuate neurological dysfunction via suppressing the inflammatory response after MCAO which possibly associated with the inhibition of the ROS/NLRP3 inflammasome pathway

Extended Conjugation Refining Carbon Nitride for Non-sacrificial H2O2 Photosynthesis and Hypoxic Tumor Therapy

Artificial photocatalysis offers a clean approach for producing H2O2. However, the poor selectivity and activity of H2O2 production hamper traditional industrial applications and emerging photodynamic therapy (PDT)/chemodynamic therapy (CDT). Here, we report a well-defined C5N2 photocatalyst with a conjugated C=N linkage for highly selective and efficient non-sacrificial H2O2 production both in normoxic and hypoxic systems. The strengthened delocalization of π-electrons by linkers in C5N2 significantly downshifted the band position, which eliminated the side photoreduction reaction of H2 evolution in thermodynamics and promoted water oxidation ability in kinetics. As a result, C5N2 had a competitive overall H2O2 production with solar-to-chemical conversion efficiency of 0.55% and more interestingly, exhibited the highest activity so far in hypoxic condition (698 μM/h). C5N2 was further applied to hypoxic PDT/CDT, exhibiting outstanding performance in conspicuous cancer cell death and synchronous bioimaging. It shed light on unlocking linker functions in electronic structure engineering of carbon nitrides for highly efficient overall photosynthesis of H2O2 and expanded the scope of their prospective application in health care

Identifying tumor cell-released extracellular vesicles as biomarkers for breast cancer diagnosis by a three-dimensional hydrogel-based electrochemical immunosensor

Abstract Tumor cell-released LC3+ extracellular vesicles (LC3+ EVs) participate in immunosuppression during autophagy and contribute to the occurrence and development of breast cancer. In view of the strong association between the LC3+ EVs and breast cancer, developing an effective strategy for the quantitative detection of LC3+ EVs levels with high sensitivity to identify LC3+ EVs as new biomarkers for accurate diagnosis of breast cancer is crucial, but yet not been reported. Herein, an ultrasensitive electrochemical immunosensor is presented for the quantitative determination of LC3+ EVs using a three-dimensional graphene oxide hydrogel-methylene blue composite as a redox probe, showing a low detection limit and a wide linear range. With this immunosensor, the expression levels of LC3+ EVs in various practical sample groups including different cancer cell lines, the peripheral blood of tumor-bearing mice before and after immunotherapy, and the peripheral blood from breast cancer patients with different subtypes and stages were clearly distinguished. This study demonstrated that LC3+ EVs were superior as biomarkers for the accurate diagnosis of breast cancer compared to traditional biomarkers, particularly for cancer subtype discrimination. This work would provide a new noninvasive detection tool for the early diagnosis and prognosis assessment of breast cancer in clinics

NIR-Responsive Carbon Nitride of Five-Membered Rings (C3N2) for Photoelectrochemical Biosensing

Polymeric carbon nitrides (pCN) have garnered immense attention, ranging from super-hard materials to artificial photosynthesis, due to their exceptional chemical and optoelectronic properties. The most studied C3N4 along with other stoichiometric pCN, such as C3N, C2N and C3N5, commonly employed a six-membered ring as the basic units; while the five-membered rings are also popular in a myriad of natural and artificial molecules with a more polarized framework and intriguing functionalities. Here, we report a facile synthesis of C3N2 with a topological structure of five-membered rings, endowing by far the narrowest the first electronic transition energy (0.81 eV) in pCN family. The basic imidazole unit with dangling bonds, resulting in an unusual electronic band of p-π conjugation and split molecular orbitals, was revealed in C3N2 by both experiments and density functional theory calculations. Moreover, a NIR-responsive photoelectrochemical (PEC) biosensor for non-transparent biosamples was constructed for the first time using C3N2 with outstanding performance. This work would not only open a new vista of pCN with different topological structures but also broaden the horizon of their application, such as prospective in vivo PEC bioassay