Nanoarchitectonics toward Full Coverage of CdZnS Nanospheres by Layered Double Hydroxides for Enhanced Visible-Light-Driven H2 Evolution.

Nanoarchitectonics of semiconductors shed light on efficient photocatalytic hydrogen evolution by precisely controlling the surface microenvironment of cocatalysts. Taking cadmium zinc sulfide (CZS) nanoparticles as a target, the spontaneous modifications are conducted by interactions between surface Cd2+/Zn2+ atoms and thiol groups in thioglycolic acid. The capping ligand impacts the semiconductor surface with a negative electronic environment, contributing to the full coverage of CZS by nickel-cobalt hydroxides (NiCo-LDHs) cocatalysts. The obtained core-shell CZS@NiCo-LDHs, possessing a shell thickness of ≈20 nm, exhibits a distinguished topology (SBET = 87.65m2 g-1), long surface carrier lifetime, and efficient charge-hole separation. Further photocatalytic hydrogen evaluation demonstrates an enhanced H2 evolution rate of 18.75 mmol g-1 h-1 with an apparent quantum efficiency of 16.3% at 420 nm. The recorded catalytic performance of the core-shell sample is 44.6 times higher than that of pure CZS nanospheres under visible light irradiation. Further density functional theory simulations indicate that sulfur atoms play the role of charge acceptor and surface Ni/Co atoms are electron donors, as well as a built-in electric field effect can be established. Altogether, this work takes advantage of strong S affinity from surface metal atoms, revealing the interfacial engineering toward improved visible-light-driven photocatalytic hydrogen evolution (PHE) activity.

Common pathogenic bacteria-induced reprogramming of the host proteinogenic amino acids metabolism.

Apart from cancer, metabolic reprogramming is also prevalent in other diseases, such as bacterial infections. Bacterial infections can affect a variety of cells, tissues, organs, and bodies, leading to a series of clinical diseases. Common Pathogenic bacteria include Helicobacter pylori, Salmonella enterica, Mycobacterium tuberculosis, Staphylococcus aureus, and so on. Amino acids are important and essential nutrients in bacterial physiology and support not only their proliferation but also their evasion of host immune defenses. Many pathogenic bacteria or opportunistic pathogens infect the host and lead to significant changes in metabolites, especially the proteinogenic amino acids, to inhibit the host's immune mechanism to achieve its immune evasion and pathogenicity. Here, we review the regulation of host metabolism, while host cells are infected by some common pathogenic bacteria, and discuss how amino acids of metabolic reprogramming affect bacterial infections, revealing the potential adjunctive application of amino acids alongside antibiotics.

Inhibition of soluble epoxide hydrolase prevents diabetic retinopathy.

Diabetic retinopathy is an important cause of blindness in adults, and is characterized by progressive loss of vascular cells and slow dissolution of inter-vascular junctions, which result in vascular leakage and retinal oedema. Later stages of the disease are characterized by inflammatory cell infiltration, tissue destruction and neovascularization. Here we identify soluble epoxide hydrolase (sEH) as a key enzyme that initiates pericyte loss and breakdown of endothelial barrier function by generating the diol 19,20-dihydroxydocosapentaenoic acid, derived from docosahexaenoic acid. The expression of sEH and the accumulation of 19,20-dihydroxydocosapentaenoic acid were increased in diabetic mouse retinas and in the retinas and vitreous humour of patients with diabetes. Mechanistically, the diol targeted the cell membrane to alter the localization of cholesterol-binding proteins, and prevented the association of presenilin 1 with N-cadherin and VE-cadherin, thereby compromising pericyte-endothelial cell interactions and inter-endothelial cell junctions. Treating diabetic mice with a specific sEH inhibitor prevented the pericyte loss and vascular permeability that are characteristic of non-proliferative diabetic retinopathy. Conversely, overexpression of sEH in the retinal Müller glial cells of non-diabetic mice resulted in similar vessel abnormalities to those seen in diabetic mice with retinopathy. Thus, increased expression of sEH is a key determinant in the pathogenesis of diabetic retinopathy, and inhibition of sEH can prevent progression of the disease.

Prediction of Drug-Target Interactions with High-Quality Negative Samples and A Network-Based Deep Learning Framework.

Identification of drug-target interactions (DTIs) plays a crucial role in drug discovery. Compared to traditional experimental methods, computer-based methods for predicting DTIs can significantly reduce the time and financial burdens of drug development. In recent years, numerous machine learning-based methods have been proposed for predicting potential DTIs. However, a common limitation among these methods is the absence of high-quality negative samples. Moreover, the effective extraction of multisource information of drugs and proteins for DTI prediction remains a significant challenge. In this paper, we investigated two aspects: the selection of high-quality negative samples and the construction of a high-performance DTI prediction framework. Specifically, we found two types of hidden biases when randomly selecting negative samples from unlabeled drug-protein pairs and proposed a negative sample selection approach based on complex network theory. Furthermore, we proposed a novel DTI prediction method named HNetPa-DTI, which integrates topological information from the drug-protein-disease heterogeneous network and gene ontology (GO) and pathway annotation information of proteins. Specifically, we extracted topological information of the drug-protein-disease heterogeneous network using heterogeneous graph neural networks, and obtained GO and pathway annotation information of proteins from the GO term semantic similarity networks, GO term-protein bipartite networks, and pathway-protein bipartite network using graph neural networks. Experimental results show that HNetPa-DTI outperforms the baseline methods on four types of prediction tasks, demonstrating the superiority of our method. Our code and datasets are available at https://github.com/study-czx/HNetPa-DTI.

Noble metal-free ternary cobalt-nickel phosphides for enhanced photocatalytic dye-sensitized hydrogen evolution and catalytic mechanism investigation.

Transition metal phosphides have emerged as compelling alternatives to noble metal catalysts for photocatalytic hydrogen evolution, owing to their high efficiency, stability, ease of preparation, and low-cost-effectiveness. This study investigates a series of binary and ternary phosphides predominantly composed of cobalt and nickel employed for photocatalytic dye-sensitized hydrogen evolution. Under the optimal dye-to-catalyst mass ratio, CoNiP exhibited the highest hydrogen evolution activity (12.96 mmol g-1 h-1), demonstrating more significant and satisfactory performance than a variety of other reported materials. This can be attributed to the high conductivity and low hydrogen evolution overpotential of phosphides, which result from their metallic characteristics and the presence of free electrons, which promote efficient electron transfer between the catalyst and sensitizer. Density functional theory calculations revealed that the cobalt incorporation into the binary phosphides causes a negative shift in the average d-band center for CoNiP, weakening the adsorption affinity of the catalyst towards H2 molecules, thus effectively improving the hydrogen evolution rate compared to the pure binary phosphides. This work provides valuable insights for the development of low-cost and high-performance ternary phosphide photocatalysts.

Anterior Umbilication of Lens in a Family with Congenital Cataracts Associated with a Missense Mutation of MIP Gene.

Congenital cataracts (CCs) have significant genotypic and phenotypic heterogeneity. The major intrinsic protein (MIP) gene, one of the causative genes of CCs, plays a vital role in maintaining the homeostasis and transparency of the lens. In this study, we identified a unique phenotype of anterior umbilication of the lens in a four-generation pedigree with CCs. All patients in the observed family had nystagmus, nuclear cataracts, and elongated axial lengths compared with their healthy counterparts except for patient I:2, whose axial length was unavailable, and patientII:4, who had total cataracts. We confirmed, using Sanger sequencing based on whole-exon sequencing (WES) data, that all patients carried a heterozygous variant NM_012064.4:c.97C > T (NP_036196.1:p.R33C) in their MIP gene. To our knowledge, 29 variants of the human MIP gene and the relative phenotypes associated with CCs have been identified. Nevertheless, this is the first report on the anterior umbilication of the lens with nuclear or total opacity caused by the c.97C > T (p.R33C) variant in the MIP gene. These results also provide evidence that the elongated axial length might be associated with this variant. This study further confirms the phenotypic heterogeneity of CCs.

αB-Crystallin Alleviates Endotoxin-Induced Retinal Inflammation and Inhibits Microglial Activation and Autophagy.

αB-Crystallin, a member of the small heat shock protein (sHSP) family, plays an immunomodulatory and neuroprotective role by inhibiting microglial activation in several diseases. However, its effect on endotoxin-induced uveitis (EIU) is unclear. Autophagy may be associated with microglial activation, and αB-crystallin is involved in the regulation of autophagy in some cells. The role of αB-crystallin in microglial autophagy is unknown. This study aimed to explore the role of αB-crystallin on retinal microglial autophagy, microglial activation, and neuroinflammation in both cultured BV2 cells and the EIU mouse model. Our results show that αB-crystallin reduced the release of typical proinflammatory cytokines at both the mRNA and protein level, inhibited microglial activation in morphology, and suppressed the expression of autophagy-related molecules and the number of autophagolysosomes in vitro. In the EIU mouse model, αB-crystallin treatment alleviated the release of ocular inflammatory cytokines and the representative signs of inflammation, reduced the apoptosis of ganglion cells, and rescued retinal inflammatory structural and functional damage, as evaluated by optical coherence tomographic and electroretinography. Taken together, these results indicate that αB-crystallin inhibits the activation of microglia and supresses microglial autophagy, ultimately reducing endotoxin-induced neuroinflammation. In conclusion, αB-crystallin provides a novel and promising option for affecting microglial autophagy and alleviating symptoms of ocular inflammatory diseases.

Mesoporous Ternary Nitrides of Earth-Abundant Metals as Oxygen Evolution Electrocatalyst.

As sustainable energy becomes a major concern for modern society, renewable and clean energy systems need highly active, stable, and low-cost catalysts for the oxygen evolution reaction (OER). Mesoporous materials offer an attractive route for generating efficient electrocatalysts with high mass transport capabilities. Herein, we report an efficient hard templating pathway to design and synthesize three-dimensional (3-D) mesoporous ternary nickel iron nitride (Ni3FeN). The as-synthesized electrocatalyst shows good OER performance in an alkaline solution with low overpotential (259 mV) and a small Tafel slope (54 mV dec-1), giving superior performance to IrO2 and RuO2 catalysts. The highly active contact area, the hierarchical porosity, and the synergistic effect of bimetal atoms contributed to the improved electrocatalytic performance toward OER. In a practical rechargeable Zn-air battery, mesoporous Ni3FeN is also shown to deliver a lower charging voltage and longer lifetime than RuO2. This work opens up a new promising approach to synthesize active OER electrocatalysts for energy-related devices.

Comparison of expression profiling of circular RNAs in vitreous humour between diabetic retinopathy and non-diabetes mellitus patients.

AIMS: To compare circular (circRNA) expression levels in the vitreous humour between PDR (proliferative diabetic retinopathy) and the control groups. METHODS: The present study collected vitreous humour samples of both the PDR group and the control group (composed of rhegmatogenous retinal detachment, idiopathic macular hole and idiopathic macular epiretinal membrane). All the samples were subjected to circRNA and mRNA sequencing as well as bioinformatic analysis. RESULTS: The vitreous humour of the PDR and control groups was collected during PPV surgery. Compared to the control group, 122 upregulated and 9 downregulated circRNAs, and 818 upregulated mRNAs and 864 downregulated mRNAs were identified. We further selected 12 circRNAs to validate the RNA expression level by qPCR; results showed that with the exception of 2 downregulated circRNAs the remaining were significantly upregulated in the PDR group, which was consistent with RNA sequencing results. Bioinformatic analysis was conducted to predict possible miRNAs absorbed by circRNAs. Each circRNA could interact with at least five miRNAs. We randomly chose three miRNAs to test the expression level in the vitreous humour by qPCR and found these miRNAs were significantly downregulated in the PDR group. CONCLUSIONS: The changed profiling of circRNAs in the vitreous humour was reliable and may become a promising biomarker of DR and the circRNA-miRNA-mRNA network. It may also play an important role in the progression of DR.

[Relationship between ultrasound imaging and traditional Chinese medicine syndrome in limb lymphedema].

OBJECTIVE: To study the correlation between traditional Chinese medicine (TCM) syndrome type and the ultrasound imaging changes in patients with limb lymphedema, and to provide evidence for TCM syndrome differentiation. METHODS: Syndrome typing was done and ultrasonography was performed in 107 patients with limb lymphedema. The thickenings of derma, hypodermis and deep-fascia were measured. The ultrasound echo intensity and the morphology of the hypodermis were classified into five degrees according to the ultrasonogram. The ultrasound indexes in the limb lymphedema patients with different syndromes were compared, and the relationship between TCM syndromes and the ultrasound indexes was analyzed. RESULTS: There were specific ultrasound image features in different TCM syndromes of limb lymphedema. The thickenings of derma, hypodermis and deep-fascia in the limb lymphedema patients with downward migration of damp-heat or phlegm stagnation and blood stasis were more significant than those in the patients with collateral obstruction due to cold-dampness (P<0.05, P<0.01). The thickenings of derma and hypodermis in the patients with phlegm stagnation and blood stasis were obviously more severe than those in the patients with downward migration of damp-heat (P<0.01). The maximum and minimum ultrasound echo intensities of hypodermis were in phlegm stagnation and blood stasis and downward migration of damp-heat respectively (P<0.05), and there was a significant difference in the hypodermal morphology among the three syndrome types (P<0.05). The most obvious structure disturbance was observed in the patients with phlegm stagnation and blood stasis syndrome. CONCLUSION: TCM syndrome type of limb lymphedema is related to ultrasound image changes. The imaging data can be regarded as new objective indexes for TCM syndrome differentiation, and it has an important value for diagnosis and treatment of limb lymphedema.

Inhibition of Notch1 Signaling Alleviates Endotoxin-Induced Inflammation Through Modulating Retinal Microglia Polarization.

Microglial cells are resident immune cells and play an important role in various cerebral and retinal inflammatory diseases. Notch1 signaling is involved in the microglia polarization and the control of cerebral inflammatory reactions. However, its role in endotoxin-induced uveitis (EIU) remains unknown. This study aimed to investigate the role of Notch1 signaling on retinal microglia polarization and inflammation in the cultured retinal microglial cells and EIU rat model. We found that Notch1 signaling blockade with N-[N-(3, 5-difluorophenacetyl)-1-alany1-S-phenyglycine t-butyl ester (DAPT) shifted retinal microglia phenotype from pro-inflammatory M1 phenotype (COX2+ and iNOS+) to anti-inflammatory M2 phenotype (Arg-1+) and reduced the release of pro-inflammatory cytokines both in vivo and in vitro. Moreover, DAPT treatment contributed to prevent retinal ganglion cells from apoptosis, reduce the intraocular infiltrating cells, and attenuate the impairment of retinal function. Taken together, these results suggest that inhibition of Notch1 signaling could alleviate the inflammatory response in EIU rat mainly through regulating the polarization of retinal microglia. Therefore, Notch1 signaling might be a promising therapeutic target in the treatment of ocular inflammatory diseases.

Clinical Features and Visual Acuity Outcomes in Culture-Positive Endogenous Fungal Endophthalmitis in Southern China.

PURPOSE: To report the causative organisms, management strategies, and visual outcomes of culture-proven endogenous fungal endophthalmitis in a case series from southern China. METHODS: We reviewed the microbiological and medical records of patients with culture-positive endogenous fungal endophthalmitis visiting the Zhongshan Ophthalmic Center, Guangzhou, China, between January 1, 2006, and March 31, 2016. RESULTS: The inclusion criteria were met in 32 eyes of 29 patients. Molds were a common causative organism in 15 patients (51.7%), while yeasts appeared in 14 patients (48.3%). Initial visual acuity (VA) at the level of finger counting or better was significantly related to a good visual outcome (P = 0.002). Molds as a causative agent were significantly associated with worse visual outcome than yeasts (P = 0.020). CONCLUSION: Molds were a common cause of culture-proven fungal endophthalmitis. Endogenous fungal endophthalmitis is generally associated with poor VA outcomes, especially if caused by molds and if the patient's initial VA is too low to permit finger counting.