A Non-Metallic Nanozyme Ameliorates Pulmonary Hypertension Through Inhibiting ROS/TGF-ß1 Signaling.

Pulmonary hypertension (PH) is a life-threatening cardiovascular disease with a lack of effective treatment options. Nanozymes, though promising for PH therapy, pose safety risks due to their metallic nature. Here, a non-metallic nanozyme is reported for the treatment of monocrotaline (MCT)-induced PH with a therapeutic mechanism involving the ROS/TGF-ß1 signaling. The synthesized melanin-polyvinylpyrrolidone-polyethylene glycol (MPP) nanoparticles showcase ultra-small size, excellent water solubility, high biocompatibility, and remarkable antioxidant capacity. The MPP nanoparticles are capable of effectively eliminating ROS in isolated pulmonary artery smooth muscle cells (PASMCs) from PH rats, and significantly reduce PASMC proliferation and migration. In vivo results from a PH model demonstrate that MPP nanoparticles significantly increase pulmonary artery acceleration time, decrease wall thickening and PCNA expression in lung tissues, as evidenced by echocardiograpy, histology and immunoblot analysis. Additionally, MPP nanoparticles treatment improve running capacity, decrease Fulton index, and attenuate right ventricular fibrosis in MCT-PH rats by using treadmill test, picrosirius red, and trichrome Masson staining. Further transcriptomic and biochemical analyses reveal that inhibiting ROS-driven activation of TGF-ß1 in the PA is the mechanism by which MPP nanoparticles exert their therapeutic effect. This study provides a novel approach for treating PH with non-metallic nanozymes based on a well-understood mechanism.

Low Rh doping accelerated HER/OER bifunctional catalytic activities of nanoflower-like Ni-Co sulfide for greatly boosting overall water splitting.

Facile synthesis of high-efficiency and stable bifunctional electrocatalyst is essential for producing clean hydrogen in energy storage systems. Herein, low Rh-doped flower-like Ni3S2/Co3S4 heterostructures were facilely prepared on porous nickel foam (labeled Rh-Ni3S2/Co3S4/NF) by a hydrothermal method. The correlation of the precursors types with the morphological structures and catalytic properties were rigorously investigated for oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) in the control groups. The low Rh doping within the catalyst played important role in boosting the catalytic characteristics. The resulting catalyst showed the smaller overpotentials of 197 and 78 mV to drive a current density of 10 mA cm-2 for the OER and HER in alkaline electrolyte, respectively. And the potential only required 1.71 V to drive a current density of 100 mA cm-2 in a water splitting device. It reflects excellent overall water splitting of the home-made Rh-Ni3S2/Co3S4/NF. This strategy shed some constructive light for preparing transition metal sulfide-based electrocatalysts in water splitting devices.

Influence and progress of tea pigment research: A comprehensive analysis of application of bibliometrics.

Tea pigment, as a natural pigment component in tea, has attracted much attention because of its unique health benefits. In recent years, with the deepening of scientific research, the research on biological activity, extraction technology and application of tea pigment has made remarkable progress. Through systematic bibliometrics analysis, this paper comprehensively combs and evaluates the research status of tea pigment. The propose is to provide valuable reference for future research and application. In this paper, the chemical structure of tea pigment is firstly summarized, and then its diverse biological activities, such as antioxidant, anti-inflammatory and anti-tumor, are deeply discussed, especially its potential application in the treatment of cardiovascular diseases and diabetes. In addition, the application prospect of tea pigment in food coloring, textile dyeing and other industrial fields is also discussed in detail. Through the collection and arrangement of a large number of research literatures, this paper analyzes the development trend, research methods and main achievements of tea pigment research, and pays special attention to the dosage and effect of tea pigment in practical application. These analyses not only contribute to a more comprehensive understanding of the characteristics and functions of tea pigments, but also provide scientific basis for the further development and application of tea pigments.

A Diketopyrrolopyrrole-Based All-in-One Nanoplatform for Self-Reinforcing Mild Photothermal Therapy Cascade Immunotherapy for Tumors.

Mild photothermal therapy (PTT) has attracted attention for effectively avoiding the severe side effects associated with high-temperature tumor ablation. However, its progress is hindered by the limited availability of high-performance photothermal agents (PTAs) and the thermoresistance of cancer cells induced by heat shock reactions. Herein, this work proposes a new strategy to expand the library of high-performance organic small-molecule PTAs and utilize it to construct a multifunctional nano-theranostic platform. By incorporating additional acceptors and appropriate π-bridges, a diketopyrrolopyrrole-based dye BDB is developed, which exhibits strong absorption and bright fluorescence emission in the near-infrared (NIR) region. Subsequently, BDB is co-coated with the heat shock protein (HSP) inhibitor tanespimycin (17-AAG) using the functional amphiphilic polymers DSPE-Hyd-PEG2000-cRGD to form an all-in-one nanoplatform BAG NPs. As a result, BAG NPs can precisely target tumor tissue, guide the treatment process in real-time through NIR-II fluorescence/photoacoustic/photothermal imaging, and release 17-AAG on demand to enhance mild PTT. Additionally, the mild PTT has been demonstrated to induce immunogenic cell death (ICD) and activate a systemic anti-tumor immune response, thereby suppressing both primary and distant tumors. Overall, this study presents a multifunctional nanoplatform designed for precise mild PTT combined with immunotherapy for effective tumor treatment.

Regulating donor configuration to develop AIE-active type I photosensitizers for lipid droplet imaging and high-performance photodynamic therapy under hypoxia.

Type I photodynamic therapy is considered to be a more promising cancer treatment than type II photodynamic therapy due to its non-oxygen-dependent characteristics. In this work, three D-A structure N,N'-dihydrophenazine (DHP)-based photosensitizers DP-CNPY, SMP-CNPY and DMP-CNPY were designed and synthesized by introducing different numbers of methyl groups in the backbone neighbor of DHP as the donor and combined with the typical strong electron acceptor 2-(pyridin-4-yl)acetonitrile. Among the three photosensitizers, SMP-CNPY with one methyl modification showed the best type I ROS (O2-˙, ˙OH) generation capacity and AIE performance. By encapsulation, SMP-CNPY was fabricated into nanoparticles, and SMP-CNPY NPs exhibited lipid droplet targeting ability with near-infrared (NIR) emission. Cell experiments have proved that SMP-CNPY NPs can effectively kill different kinds of cancer cells under normal oxygen conditions. Even under hypoxic and extreme hypoxic conditions, SMP-CNPY NPs can still produce ROS and kill cancer cells. This work holds significant potential in the field of type I AIE-active photosensitizers and provides a new strategy for overcoming the hypoxic dilemma in the malignant tumor microenvironment.

Exosomal lncRNA-MIAT promotes neovascularization via the miR-133a-3p/MMP-X1 axis in diabetic retinopathy.

Diabetic retinopathy (DR), a most common microangiopathy of diabetes, causes vision loss and even blindness. The mechanisms of exosomal lncRNA remain unclear in the development of DR. Here, we first identifed the pro-angiogenic effect of exosomes derived from vitreous humor of proliferative diabetic retinopathy patients, where lncRNA-MIAT was enriched inside. Secondly, lncRNA-MIAT was demonstrated significantly increased in exosomes from high glucose induced human retinal vascular endothelial cell, and can regulate tube formation, migration and proliferation ability to promote angiogenesis in vitro and in vivo. Mechanistically, the pro-angiogenic effect of lncRNA-MIAT was via the lncRNA-MIAT/miR-133a-3p/MMP-X1 axis. The reduced level of lncRNA-MIAT in this axis mitigated the generation of retinal neovascular in mouse model of oxygen-induced retinopathy (OIR), providing crucial evidence for lncRNA-MIAT as a potential clinical target. These findings enhance our understanding of the role of exosomal lncRNA-MIAT in retinal angiogenesis, and propose a promising therapeutic strategy against diabetic retinopathy.

Identification, pathogenicity and molecular characterization of a novel fowl adenovirus 8b strain.

Since 2012, there has been a noticeable upward trend in the global incidence of inclusion body hepatitis (IBH) cases, leading to substantial economic losses in the poultry industry. In response to this trend, the current study aimed to investigate the phylogenetic information, genetic mutations, and pathogenicity of the highly pathogenic fowl adenovirus (FAdV) strain HN1472, which was isolated from liver samples obtained from a laying flock affected by IBH. This investigation was carried out using 1-day-old specific pathogen-free (SPF) chickens. Recombination and phylogenetic analyses confirmed that HN1472 is a recombinant strain derived from FAdV-8a and FAdV-8b, and exhibited significant genetic divergence in the hexon, fiber, and ORF19 genes. Notably, the phylogenetic analysis identified recombination events in these regions. Furthermore, animal experiments revealed that HN1472 is a highly pathogenic isolate, causing 80% mortality and manifesting clinical signs of IBH in SPF chickens. Furthermore, the recombinant FAdV serotype 8b (FAdV-8b) was found to be widely distributed in various tissues, with a higher concentration in the livers and gizzard tissue at 3 d postchallenge (dpc). Collectively, these findings contribute to our current understanding of the factors influencing the pathogenicity and genetic diversity of FAdV serotype 8b (FAdV-8b) in China.

Variation in the affinity of three representative avian adenoviruses for the cellular coxsackievirus and adenovirus receptor.

According to previous studies, three representative avian adenoviral strains utilize coxsackievirus-adenovirus receptor (CAR) as a receptor and seem to exhibit diverse binding affinities and modes. Thus, further revealing the exact molecular mechanism underlying the interaction between different FAdVs and the attachment receptor CAR is necessary. In this study, we successfully solved the crystal structure of the FAdV-4 fiber1 knob at 1.6 Šresolution. The interaction between the fibre knob and different domains of CAR was verified by confocal microscopy, coimmunoprecipitation and surface plasmon resonance (SPR) analysis. The fibre knobs of the three representative fowl adenoviruses specifically recognized CAR domain 1 (D1), but the recognition of CAR domain 2 (D2) by chicken embryo lethal orphan (CELO) strains was weak. These results provide insights into the differences in adenovirus‒host cell interactions and have important implications for the exploration of viral invasion mechanisms.

Development and implementation of a prognostic model for clear cell renal cell carcinoma based on heterogeneous TLR4 expression.

Objective: Clear cell renal cell carcinoma (ccRCC) is the most common subtype among renal cell carcinomas and has the worst prognosis, originating from renal tubular epithelial cells. Toll-like receptor 4 (TLR4) plays a crucial role in ccRCC proliferation, infiltration, and metastasis. The aim of this study was to construct a prognostic scoring model for ccRCC based on TLR4 expression heterogeneity and to explore its association with immune infiltration, thereby providing insights for the treatment and prognostic evaluation of ccRCC. Methods: Using R software, a differential analysis was conducted on normal samples and ccRCC samples, and in conjunction with the KEGG database, a correlation analysis for the clear cell renal cell carcinoma pathway (hsa05211) was carried out. We observed the expression heterogeneity of TLR4 in the TCGA-KIRC cohort and identified its related differential genes (TRGs). Based on the expression levels of TRGs, consensus clustering was employed to identify TLR4-related subtypes, and further clustering heatmaps, principal component, and single-sample gene set enrichment analyses were conducted. Overlapping differential genes (ODEGs) between subtypes were analysed, and combined with survival data, univariate Cox regression, LASSO, and multivariate Cox regression were used to establish a prognostic risk model for ccRCC. This model was subsequently evaluated through ROC analysis, risk factor correlation analysis, independent prognostic factor analysis, and intergroup differential analysis. The ssGSEA model was employed to explore immune heterogeneity in ccRCC, and the performance of the model in predicting patient prognosis was evaluated using box plots and the oncoPredict software package. Results: In the TCGA-KIRC cohort, TLR4 expression was notably elevated in ccRCC samples compared to normal samples, correlating with improved survival in the high-expression group. The study identified distinct TLR4-related differential genes and categorized ccRCC into three subtypes with varied survival outcomes. A risk prognosis model based on overlapping differential genes was established, showing significant associations with immune cell infiltration and key immune checkpoints (PD-1, PD-L1, CTLA4). Additionally, drug sensitivity differences were observed between risk groups. Conclusion: In the TCGA-KIRC cohort, the expression of TLR4 in ccRCC samples exhibited significant heterogeneity. Through clustering analysis, we identified that the primary immune cells across subtypes are myeloid-derived suppressor cells, central memory CD4 T cells, and regulatory T cells. Furthermore, we successfully constructed a prognostic risk model for ccRCC composed of 17 genes. This model provides valuable references for the prognosis prediction and treatment of ccRCC patients.

Sesame bacterial wilt significantly alters rhizosphere soil bacterial community structure, function, and metabolites in continuous cropping systems.

Bacterial wilt is the leading disease of sesame and alters the bacterial community composition, function, and metabolism of sesame rhizosphere soil. However, its pattern of change is unclear. Here, the purpose of this study was to investigate how these communities respond to three differing severities of bacterial wilt in mature continuously cropped sesame plants by metagenomic and metabolomic techniques, namely, absence (WH), moderate (WD5), and severe (WD9) wilt. The results indicated that bacterial wilt could significantly change the bacterial community structure in the rhizosphere soil of continuously cropped sesame plants. The biomarker species with significant differences will also change with increasing disease severity. In particular, the gene expression levels of Ralstonia solanacearum in the WD9 and WD5 treatments increased by 25.29% and 33.61%, respectively, compared to those in the WH treatment (4.35 log10 copies g-1). The occurrence of bacterial wilt significantly altered the functions of the bacterial community in rhizosphere soil. KEEG and CAZy functional annotations revealed that the number of significantly different functions in WH was greater than that in WD5 and WD9. Bacterial wilt significantly affected the relative content of metabolites, especially acids, in the rhizosphere soil, and compared with those in the rhizosphere soil from WH, 10 acids (including S-adenosylmethionine, N-acetylleucine, and desaminotyrosine, etc.) in the rhizosphere soil from WD5 or WD9 significantly increased. In comparison, the changes in the other 10 acids (including hypotaurine, erucic acid, and 6-hydroxynicotinic acid, etc.) were reversed. The occurrence of bacterial wilt also significantly inhibited metabolic pathways such as ABC transporter and amino acid biosynthesis pathways in rhizosphere soil and had a significant impact on two key enzymes (1.1.1.11 and 2.6.1.44). In conclusion, sesame bacterial wilt significantly alters the rhizosphere soil bacterial community structure, function, and metabolites. This study enhances the understanding of sesame bacterial wilt mechanisms and lays the groundwork for future prevention and control strategies against this disease.

Promoting the Near-Infrared-II Fluorescence of Diketopyrrolopyrrole-Based Dye for In Vivo Imaging via Donor Engineering.

Small-molecule dyes for fluorescence imaging in the second near-infrared region (NIR-II, 900-1880 nm) hold great promise in clinical applications. Constructing donor-acceptor-donor (D-A-D) architectures has been recognized to be a feasible strategy to achieve NIR-II fluorescence. However, the development of NIR-II dyes via such a scheme is hampered by the lack of high-performance electron acceptors and donors. Diketopyrrolopyrrole (DPP), as a classic organic optoelectronic material, enjoys strong light absorption, high fluorescence quantum yield (QY), and facile derivatization. Nevertheless, its application in the NIR-II imaging field has been hindered by its limited electron-withdrawing ability and the aggregation-caused quenching (ACQ) effect resulting from the planar structure of DPP. Herein, with DPP as an electron acceptor and through donor engineering, we have successfully designed and synthesized a DPP-based dye named T-27, in which the strong D-A interaction confers excellent NIR absorption and high-brightness NIR-II fluorescence tail emission. By strategically introducing long alkyl chains on the donor unit to increase intermolecular spacing and reduce the influence of solvent molecules, T-27 exhibits an improved anti-ACQ effect in aqueous solutions. After being encapsulated into DSPE-PEG2000, T-27 nanoparticles (NPs) show a relative NIR-II fluorescence QY of 3.4% in water, representing the highest value among the DPP-based NIR-II dyes reported to date. The outstanding photophysical properties of T-27 NPs enable multimode NIR-IIa bioimaging under 808 nm excitation. As such, the T-27 NPs can distinguish mouse femoral vein and artery and achieve cerebral vascular microscopic imaging with a penetrating depth of 800 µm, demonstrating the capability for high-resolution deep-tissue imaging. This work holds significant potential in the field of bioimaging and provides a new strategy for developing bright NIR-II dyes.

Prognostic Value of Fibrinogen-to-Albumin Ratio in Coronary Three-Vessel Disease.

Objective: To investigate the prognostic value of fibrinogen-to-albumin ratio (FAR) in the adverse outcomes of patients with coronary three-vessel disease (TVD). Methods: A total of 4061 patients with TVD between 2013 and 2018 were analyzed in this retrospective cohort study. The best cut­off value of the FAR determined by receiver operating characteristic (ROC) curve analysis was 0.084. 2782 (68.5%) patients were in the low FAR group (FAR < 0.084) and 1279 (31.5%) patients were in the high FAR group (FAR ≥ 0.084), respectively. Three multivariate Cox proportional hazards models were applied to determine the associations of FAR with clinical outcomes. The concordance index (C-index), net reclassification index (NRI), and integrated discrimination improvement (IDI) were used to assess the incremental predictive value of the FAR and baseline models with respect to the additive effects of the established traditional risk factors on the discrimination of clinical outcomes. The primary endpoint was all-cause mortality. The secondary endpoint was major adverse cardiac and cerebrovascular events (MACCEs). Results: The median follow-up duration was 2.4 years (range 1.1-4.1 years). Multivariate Cox regression analyses showed that the incidence of all-cause mortality (4.7% vs 2.2%, adjusted hazard ratio [HR] 1.68, 95% confidence interval [CI] 1.12-2.52, p=0.011) and MACCE (34.6% vs 27.3%, HR 1.28, 95% CI 1.13-1.46, p<0.001) were significantly higher in the high FAR group compared to the low FAR group. The C-index was 0.72 (p < 0.001), the value of NRI was 0.3778 (p < 0.001), and the value of IDI was 0.0098 (p < 0.001) for those with FAR. After FAR was added to the traditional model, the discrimination and risk reclassification ability can be significantly improved for all-cause mortality. The similar results were found for MACCE. Conclusion: Higher level of FAR was associated with all-cause mortality and MACCE among patients with TVD. FAR could help to improve the prognostic performance of the traditional risk factors for TVD patients.

A systematic review of tea pigments: Prevention of major diseases, protection of organs, and potential mechanisms and applications.

With the growing awareness of a healthy life, tea pigments (TPGs) are in focus for their health benefits. TPGs not only provide specific color to tea liquor but also possess health benefits such as anti-obesity, anti-tumor, anti-inflammatory, anti-viral, anti-oxidative, and bacteriostatic properties. Also, TPGs can benefit bone, liver, kidney, cardiovascular, gut microbiome, and sleep health. Based on previous reports, this review provides a brief introduction to the health benefits of TPGs, focusing on the prevention of human diseases and the protection of organs. Also, the latest research on the functional mechanism(s), practical application, and development strategies of TPGs is discussed.

Diagnostic accuracy of a novel optical coherence tomography-based fractional flow reserve algorithm for assessment of coronary stenosis significance.

BACKGROUND: This study aimed to introduce a novel optical coherence tomography-derived fractional flow reserve (FFR) computational approach and assess the diagnostic performance of the algorithm for assessing physiological function. METHODS: The fusion of coronary optical coherence tomography and angiography was used to generate a novel FFR algorithm (AccuFFRoct) to evaluate functional ischemia of coronary stenosis. In the current study, a total of 34 consecutive patients were included, and AccuFFRoct was used to calculate the FFR for these patients. With the wire-measured FFR as the reference standard, we evaluated the performance of our approach by accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). RESULTS: Per vessel accuracy, sensitivity, specificity, PPV, and NPV for AccuFFRoct in identifying hemodynamically significant coronary stenosis were 93.8%, 94.7%, 92.3%, 94.7%, and 92.3%, respectively, were found. Good correlation (Pearson's correlation coefficient r = 0.80, p < 0.001) between AccuFFRoct and FFR was observed. The Bland-Altman analysis showed a mean difference value of -0.037 (limits of agreement: -0.189 to 0.115). The area under the receiver-operating characteristic curve (AUC) of AccuFFRoct in identifying physiologically significant stenosis was 0.94, which was higher than the minimum lumen area (MLA, AUC = 0.91) and significantly higher than the diameter stenosis (%DS, AUC = 0.78). CONCLUSIONS: This clinical study shows the efficiency and accuracy of AccuFFRoct for clinical implementation when using invasive FFR measurement as a reference. It could provide important insights into coronary imaging superior to current methods based on the degree of coronary artery stenosis.

Room-Temperature Synthesis of Carbon-Nanotube-Interconnected Amorphous NiFe-Layered Double Hydroxides for Boosting Oxygen Evolution Reaction.

The oxygen evolution reaction (OER) is a key half-reaction in electrocatalytic water splitting. Large-scale water electrolysis is hampered by commercial noble-metal-based OER electrocatalysts owing to their high cost. To address these issues, we present a facile, one-pot, room-temperature co-precipitation approach to quickly synthesize carbon-nanotube-interconnected amorphous NiFe-layered double hydroxides (NiFe-LDH@CNT) as cost-effective, efficient, and stable OER electrocatalysts. The hybrid catalyst NiFe-LDH@CNT delivered outstanding OER activity with a low onset overpotential of 255 mV and a small Tafel slope of 51.36 mV dec-1, as well as outstanding long-term stability. The high catalytic capability of NiFe-LDH@CNT is associated with the synergistic effects of its room-temperature synthesized amorphous structure, bi-metallic modulation, and conductive CNT skeleton. The room-temperature synthesis can not only offer economic feasibility, but can also allow amorphous NiFe-LDH to be obtained without crystalline boundaries, facilitating long-term stability during the OER process. The bi-metallic nature of NiFe-LDH guarantees a modified electronic structure, providing additional catalytic sites. Simultaneously, the highly conductive CNT network fosters a nanoporous structure, facilitating electron transfer and O2 release and enriching catalytic sites. This study introduces an innovative approach to purposefully design nanoarchitecture and easily synthesize amorphous transition-metal-based OER catalysts, ensuring their cost effectiveness, production efficiency, and long-term stability.

Predictive value of machine learning algorithm of coronary artery calcium score and clinical factors for obstructive coronary artery disease in hypertensive patients.

BACKGROUND: The addition of coronary artery calcium score (CACS) to prediction models has been verified to improve performance. Machine learning (ML) algorithms become important medical tools in an era of precision medicine, However, combined utility by CACS and ML algorithms in hypertensive patients to forecast obstructive coronary artery disease (CAD) on coronary computed tomography angiography (CCTA) is rare. METHODS: This retrospective study was composed of 1,273 individuals with hypertension and without a history of CAD, who underwent dual-source computed tomography evaluation. We applied five ML algorithms, coupled with clinical factors, imaging parameters, and CACS to construct predictive models. Moreover, 80% individuals were randomly taken as a training set on which 5-fold cross-validation was done and the remaining 20% were regarded as a validation set. RESULTS: 16.7% (212 out of 1,273) of hypertensive patients had obstructive CAD. Extreme Gradient Boosting (XGBoost) posted the biggest area under the receiver operator characteristic curve (AUC) of 0.83 in five ML algorithms. Continuous net reclassification improvement (NRI) was 0.55 (95% CI (0.39-0.71), p < 0.001), and integrated discrimination improvement (IDI) was 0.04 (95% CI (0.01-0. 07), p = 0.0048) when the XGBoost model was compared with traditional Models. In the subgroup analysis stratified by hypertension levels, XGBoost still had excellent performance. CONCLUSION: The ML model incorporating clinical features and CACS may accurately forecast the presence of obstructive CAD on CCTA among hypertensive patients. XGBoost is superior to other ML algorithms.

Lens epithelial cell-derived exosome inhibits angiogenesis in ocular pathological neovascularization through its delivery of miR-146a-5p.

Abnormal ocular neovascularization, a major pathology of eye diseases, leads to severe visual loss. The role of lens epithelial cell (LEC)-derived exosomes (Lec-exo) is largely unknown. Thus, we aimed to investigate whether Lec-exo can inhibit abnormal ocular neovascularization and explore the possible mechanisms. In our study, we proved the first evidence that exosomes derived from LECs attenuated angiogenesis in both oxygen-induced retinopathy and laser-induced choroidal neovascularization mice models. Further in vitro experiments proved that Lec-exo inhibited proliferation, migration, and tube formation capability of human umbilical vein endothelial cells in high glucose condition. Further high-throughput miRNAs sequencing analysis detected that miR-146a-5p was enriched in Lec-exo. Mechanistically, exosomal miR-146a-5p was delivered to endothelial cells and bound to the NRAS coding sequence, which subsequently inactivated AKT/ERK signaling pathway. We successfully elucidated the function of Lec-exo in inhibiting abnormal ocular neovascularization, which may offer a promising strategy for treatment of abnormal ocular neovascularization.

TMEM175 downregulation participates in impairment of the autophagy related lysosomal dynamics following neonatal hypoxic-ischemic brain injury.

The mechanism underlying long-term cognitive impairment caused by neonatal hypoxic-ischemic brain injury (HIBI) remains unclear. Autophagy is a closely related mechanism and may play a role in this process. We aimed to investigate the role of lysosomal transmembrane protein 175 (TMEM175) in the autophagy-lysosome pathway in neonatal rats with HIBI. A neonatal rat model of HIBI was established, hypoxia was induced, followed by left common carotid artery ligation. Expression levels of TMEM175 and the corresponding proteins involved in autophagy flux and the endolysosomal system fusion process were measured. Rats were administered TMEM175 plasmid via intracerebroventricular injection to induce overexpression. Brain damage and cognitive function were then assessed. TMEM175 was downregulated in the hippocampal tissue, and the autophagy-lysosome pathway was impaired following HIBI in neonatal rats. Overexpression of TMEM175 significantly mitigated neuronal injury and improved long-term cognitive and memory function in neonatal rats with HIBI. We found that improvement in the autophagy-lysosome pathway and endolysosomal system homeostasis, which are TMEM175 related, occurred via regulation of lysosomal membrane dynamic fusion. TMEM175 plays a critical role in maintaining the autophagy-lysosome pathway and endolysosomal homeostasis, contributing to the amelioration of neuronal injury and impaired long-term cognitive function following neonatal HIBI.

A mechanistic and kinetic investigation on the oxidative thermal decomposition of decabromodiphenyl ether.

The thermal processes of materials containing decabromodiphenyl ether (BDE-209) normally result in the exposure of BDE-209 to high-temperature environments, generating a series of hazardous compounds. However, the evolution mechanisms of BDE-209 during oxidative thermal processes remain unclear. Thus, this paper presents a detailed investigation on the oxidative thermal decomposition mechanism of BDE-209 by utilizing density functional theory methods at the M06/cc-pVDZ theoretical level. The results show that the barrierless fission of the ether linkage dominates the initial degradation of BDE-209 at all temperatures, with branching ratio over 80%. The decomposition of BDE-209 in oxidative thermal processes is mainly along BDE-209 → pentabromophenyl and pentabromophenoxy radicals → pentabromocyclopentadienyl radicals → brominated aliphatic products. Additionally, the study results on the formation mechanisms of several hazardous pollutants indicate that the ortho-phenyl-type radicals created by ortho-C-Br bond fission (branching ratio reached 15.1% at 1600 K) can easily be converted into octabrominated dibenzo-p-dioxin and furan, which require overcoming the energy barriers of 99.0 and 48.2 kJ/mol, respectively. The O/ortho-C coupling of two pentabromophenoxy radicals also acts as a non-negligible pathway for the formation of octabrominated dibenzo-p-dioxin. The synthesis of octabromonaphthalene involves the self-condensation of pentabromocyclopentadienyl radicals, followed by an intricately intramolecular evolution. Results presented in this study can enhance our understanding of the transformation mechanism of BDE-209 in thermal processes, and offer an insight into controlling the emissions of hazardous pollutants.