Characterization of cancer-associated fibroblasts (CAFs) and development of a CAF-based risk model for triple-negative breast cancer.

Triple-negative breast Cancer (TNBC) is a highly malignant cancer with unclear pathogenesis. Within the tumor microenvironment (TME), cancer-associated fibroblasts (CAFs) vitally influence tumor onset and progression. Thus, this research aimed to identify distinct subgroups of CAF using single-cell and TNBC-related information from the GEO and TCGA databases, respectively. The primary aim was to establish a novel predictive model based on the CAF features and their clinical relevance. Moreover, the CAFs were analyzed for their immune characteristics, response to immunotherapy, and sensitivity to different drugs. The developed predictive model demonstrated significant effectiveness in determining the prognosis of patients with TNBC, TME, and the immune landscape of the tumor. Of note, the expression of GPR34 was significantly higher in TNBC tissues compared to that in other breast cancer (non-TNBC) tissues, indicating that GPR34 plays a crucial role in the onset and progression of TNBC. In summary, this research has yielded a novel predictive model for TNBC that holds promise for the accurate prediction of prognosis and response to immunotherapy in patients with TNBC.

A Highly Sensitive Model Based on Graph Neural Networks for Enzyme Key Catalytic Residue Prediction.

Determining the catalytic site of enzymes is a great help for understanding the relationship between protein sequence, structure, and function, which provides the basis and targets for designing, modifying, and enhancing enzyme activity. The unique local spatial configuration bound to the substrate at the active center of the enzyme determines the catalytic ability of enzymes and plays an important role in the catalytic site prediction. As a suitable tool, the graph neural network can better understand and identify the residue sites with unique local spatial configurations due to its remarkable ability to characterize the three-dimensional structural features of proteins. Consequently, a novel model for predicting enzyme catalytic sites has been developed, which incorporates a uniquely designed adaptive edge-gated graph attention neural network (AEGAN). This model is capable of effectively handling sequential and structural characteristics of proteins at various levels, and the extracted features enable an accurate description of the local spatial configuration of the enzyme active site by sampling the local space around candidate residues and special design of amino acid physical and chemical properties. To evaluate its performance, the model was compared with existing catalytic site prediction models using different benchmark datasets and achieved the best results on each benchmark dataset. The model exhibited a sensitivity of 0.9659, accuracy of 0.9226, and area under the precision-recall curve (AUPRC) of 0.9241 on the independent test set constructed for evaluation. Furthermore, the F1-score of this model is nearly four times higher than that of the best-performing similar model in previous studies. This research can serve as a valuable tool to help researchers understand protein sequence-structure-function relationships while facilitating the characterization of novel enzymes of unknown function.

New Type of Dynamically "Solid-Liquid" Interconvertible Electrolyte for High-Rate Zn Metal Battery.

The practical application of aqueous high-rate Zn metal battery (ZMB) is limited due to accelerated dendrite formation at high current densities. It is urgent to find an electrolyte, which could not only be mechanically stiff to clamp down dendrites but also not sacrifice ionic conductivity and interfacial compatibility. Herein, a new type of dynamically "solid-liquid" interconvertible electrolyte based on non-Newtonian fluid (NNFE) is proposed. Liquidity characteristic of NNFE is favorable for electrochemical kinetics and interfacial compatibility. Furthermore, in an area with high current rate NNFE would respond and mechanically stiffen to dissuade localized increase in Zn dendrite growth. Even at a current density of 50 mA cm-2, NNFE enables reversible and stable operation of a Zn symmetrical cell over 20 000 cycles. For Zn//Na5V12O32 (NVO) full cell, the NNFE also realizes lengthy cycling for 5000 periods at 5 A g-1. This research opens up new inspirations to high-rate Zn metal even other metal batteries.

Effects of Persimmon (Diospyros kaki L. cv. Mopan) Polysaccharide and Their Carboxymethylated Derivatives on Lactobacillus Strains Proliferation and Gut Microbiota: A Comparative Study.

Persimmon is a fruit that contains sugars, vitamins, phenolic compounds, and various other nutrients. The aim of this study was to explore the structure of carboxymethylated persimmon polysaccharide (CM-PFP) and its interaction with the human gut microbiota. Carboxymethyl modification of the persimmon polysaccharide (PFP) increased both the Mw and Mn, enhanced dispersion stability, and decreased thermal stability. Both PFP and CM-PFP promoted the proliferation of Lactobacillus while inhibiting the proliferation of Staphylococcus aureus and Escherichia coli. In the simulated fecal fermentation, the pH of PFP- and CM-PFP-containing media decreased, the content of short-chain fatty acids increased, and the abundance of intestinal flora at the phylum and genus levels changed. The relative abundance of harmful intestinal bacteria was significantly reduced in both PFP and CM-PFP groups. Furthermore, it was found that CM-PFP was more easily metabolized than PFP, glucose, and fructo-oligosaccharide (FOS) and had a proliferation increase effect on Lactobacillus. Therefore, CM-PFP has a significant positive effect on both Lactobacillus proliferation and the human gut microbiota.

Aberrant Exon 8/8a Splicing by Downregulated PTBP (Polypyrimidine Tract-Binding Protein) 1 Increases CaV1.2 Dihydropyridine Resistance to Attenuate Vasodilation.

OBJECTIVE: Calcium channel blockers, such as dihydropyridines, are commonly used to inhibit enhanced activity of vascular CaV1.2 channels in hypertension. However, patients who are insensitive to such treatments develop calcium channel blocker-resistant hypertension. The function of CaV1.2 channel is diversified by alternative splicing, and the splicing factor PTBP (polypyrimidine tract-binding protein) 1 influences the utilization of mutually exclusive exon 8/8a of the CaV1.2 channel during neuronal development. Nevertheless, whether and how PTBP1 makes a role in the calcium channel blocker sensitivity of vascular CaV1.2 channels, and calcium channel blocker-induced vasodilation remains unknown. Approach and Results: We detected high expression of PTBP1 and, inversely, low expression of exon 8a in CaV1.2 channels (CaV1.2E8a) in rat arteries. In contrast, the opposite expression patterns were observed in brain and heart tissues. In comparison to normotensive rats, the expressions of PTBP1 and CaV1.2E8a channels were dysregulated in mesenteric arteries of hypertensive rats. Notably, PTBP1 expression was significantly downregulated, and CaV1.2E8a channels were aberrantly increased in dihydropyridine-resistant arteries compared with dihydropyridine-sensitive arteries of rats and human. In rat vascular smooth muscle cells, PTBP1 knockdown resulted in shifting of CaV1.2 exon 8 to 8a. Using patch-clamp recordings, we demonstrated a concomitant reduction of sensitivity of CaV1.2 channels to nifedipine, due to the higher expression of CaV1.2E8a isoform. In vascular myography experiments, small interfering RNA-mediated knockdown of PTBP1 attenuated nifedipine-induced vasodilation of rat mesenteric arteries. CONCLUSIONS: PTBP1 finely modulates the sensitivities of CaV1.2 channels to dihydropyridine by shifting the utilization of exon 8/8a and resulting in changes of responses in dihydropyridine-induced vasodilation.

Strongly trapping soluble lithium polysulfides using polar cysteamine groups for highly stable lithium sulfur batteries.

Sulfur has become one of the most promising positive electrode materials for lithium sulfur batteries due to its high theoretical capacity and high energy density (2500 Wh kg-1). The use of common nonpolar carbon/sulfur composites has proved to be a good way to improve the performance, but they still cannot efficiently trap highly polar lithium polysulfides due to the weak interactions between nonpolar carbon and polar polysulfides. Herein, we report a new strategy of using polar cysteamine groups to trap polar polysulfides, leading to greatly enhanced capacity of ∼920 mAh g-1 at 1 C with a high Coulombic efficiency of ∼99.1%, and a long cycle life of over 600 cycles with a capacity retention higher than 80%. Importantly, in situ UV/Vis spectroscopy was employed to identify intermediates during cycling, which demonstrates the constructed unique polar cysteamine functionalized carbon nanotubes (CNTs) can greatly reduce the production of polysulfides and suppress the shuttle effect. The broken-bond model of linear polysulfane during cycling was further demonstrated by density functional theory calculations. The present strategy of using polar cysteamine-functionalized CNTs to trap soluble intermediates is promising and has significant potential for the development of highly efficient lithium sulfur batteries.

Combination of NGAL and Cystatin C for Prediction of Preeclampsia at 10-14 Weeks of Gestation.

BACKGROUND: Preeclampsia (PE) is a severe pregnancy complication and is an important cause for maternal and child death, premature delivery, and limited intrauterine growth and development. The aim of this study was to investigate the role of NGAL and cystatin C, alone and in combination, for early prediction of PE at 10 - 14 weeks of gestation. METHODS: Serum levels of NGAL and cystatin C were assessed in women at 10 - 14 weeks of gestation who subsequently developed PE (n = 128) and normal pregnancy outcome (n = 183). Comparison of clinical characteristics, NGAL, and cystatin C levels between normal pregnancy and PE groups were analyzed using Mann-Whitney test. The receiver operating characteristic curve (ROC curve) was used to analyze the value of serum NGAL and cystatin C levels in predicting PE. RESULTS: The levels of cystatin C and NGAL in the serum were significantly higher in the PE group [0.64 mg/L (0.52 - 0.78)] and [34.9 ng/mL (24.4 - 55.2), respectively] than in the normal pregnancy group [0.56 mg/L (0.49 - 0.65)] and [20.2 ng/mL (13.8 - 26.9), respectively]. ROC curve analysis showed that serum NGAL levels predicted the area under the curve in the PE period 0.739 (95% CI: 0.618 to 0.860). Serum cystatin C levels predicted the area under the curve in the PE period 0.722 (95% CI: 0.592 to 0.853). The combination of serum NGAL and cystatin C levels predicted the area under the curve in the PE period 0.877 (95% CI: 0.811 to 0.943). CONCLUSIONS: NGAL and cystatin C levels in serum appear to be ideal biomarkers for PE prediction at 10 - 14 weeks. The combination of NGAL and cystatin C will also be more valuable in discriminating patients at risk of developing PE from other pregnancy complications early in gestation.

Establishing the chromatographic fingerprint of traditional Chinese medicine standard decoction based on quality by design approach: A case study of Licorice.

A novel analytical quality by design approach for developing a chromatographic fingerprint was established for analyzing complex traditional Chinese medicine, using a licorice standard decoction as an example. Considering the characteristics of integrity and ambiguity, the resolution of eight common peaks, total peak number, capacity factor distributions, and peak purity were selected as potential critical method attributes for assessing the quality of the chromatographic fingerprint. A central composite design was used to evaluate the relationship between critical method attributes and critical method parameters, including column temperature, wavelength, flow rate, formic-acid concentration, and gradient parameters. A standard probability method was employed to calculate the design space of the fingerprint analysis parameters and evaluate the robustness of the methodology. The optimized high-performance liquid chromatography fingerprint conditions were acetonitrile and 0.1% formic acid water gradient elution (0-5 min, 5-19% A; 5-10 min, 19% A; 10-50 min, 19-42% A; 50-54 min, 42-100% A; 54-60 min, 100% A), column temperature 25±5°C, detection wavelength 265 nm. The design space of fingerprint analytical method based on the analytical quality by design approach not only met the requirements of the fingerprint analysis, but also improved the robustness and applicability of the fingerprint method.

Patterns, perceptions, and perceived barriers to physical activity in adult cancer survivors.

PURPOSE: Physical activity (PA) during and after cancer treatment is associated with improved cancer- and non-cancer-related outcomes. We assessed for predictors of change in PA levels among cancer survivors. METHODS: Adult cancer survivors from a comprehensive cancer center completed a one-time questionnaire retrospectively assessing PA levels before, during, and after cancer treatment along with their perceptions of PA. Multivariable logistic regression models evaluated the association of clinico-demographics variables and perceptions of PA with changes in whether patients were meeting PA guidelines after cancer diagnosis. RESULTS: Among the 1003 patients, 319 (32%) met moderate to vigorous PA (MVPA) guidelines before diagnosis. Among those meeting guidelines before diagnosis, 50% still met guidelines after treatment; 12% not meeting MVPA guidelines initially met them after treatment/at follow-up. Among patients meeting guidelines before diagnosis, better ECOG performance status at follow-up, receiving curative therapy, and spending a longer time on PA initially were each associated with meeting guidelines at follow-up. After controlling for other variables, perceiving that PA improves quality of life (adjusted odds ratio, aOR = 11.09, 95%CI [1.42-86.64], P = 0.02) and overall survival (aOR = 8.52, 95%CI [1.12-64.71], P = 0.04) was each associated with meeting MVPA guidelines during/after treatment, in patients who did not meet guidelines initially. Only 13% reported receiving counseling, which was not associated with PA levels. Common reported barriers to PA included fatigue, lacking motivation, and being too busy. CONCLUSIONS: Patient perceptions of PA benefits are strongly associated with improving PA levels after a cancer diagnosis. Clinician counseling should focus on patient education and changing patient perceptions.

[Application of fingerprint technology in quality evaluation and process control of traditional Chinese medicine formula granules].

The fingerprint technology could reflect the internal chemical characteristics of Chinese herbal medicine or preparation, which has the characteristics of "wholeness" and "fuzziness". It is suitable for evaluating the quality of intermediate and finished products in the production process of traditional Chinese medicine formula granules. In this paper, the applications of high performance liquid chromatography (HPLC), thin layer chromatography (TLC), gas chromatography (GC) and infrared spectrum (IR) fingerprint technology in the quality control of traditional Chinese medicine formula granules were reviewed, and their advantages and disadvantages were analyzed. The aim of this article is to enhance the combined application of various fingerprint technologies in traditional Chinese medicine formula granules. It could provide technical reference for realizing the stability of production process and improving the overall quality of formula granules.

Stabilized Lithium-Sulfur Batteries by Covalently Binding Sulfur onto the Thiol-Terminated Polymeric Matrices.

Despite the low competitive cost and high theoretical capacity of lithium-sulfur battery, its practical application is severely hindered by fast capacity fading and limited capacity retention mainly caused by the polysulfide dissolution problem. Here, this paper reports a new strategy of using thiol-terminated polymeric matrices to prevent polysulfide dissolution, which exhibits an initial capacity of 829.1 mAh g-1 , and the exceptionally stable capacity retention of ≈84% at 1 C after 200 cycles, and excellent cycling stability with a low mean decay rate of 0.048% after 600 cycles. Significantly, in situ UV/vis spectroscopy analysis of the electrolyte upon battery cycling is performed to verify the function of preventing polysulfide dissolution by means of strongly anchoring discharge products of lithium sulphides. Moreover, density functional theory calculations reveal that the breakage of the linear sulfur chains results in the less soluble short-chain polysulfides due to the formation of the covalently crosslinked discharge products, which avoids the production of soluble long-chain polysulfide and minimizes the shuttle effect. These results exhibit an alternative for the stabilization of the electrochemical performance of lithium-sulfur batteries.

Prognostic value of pretreatment circulating neutrophils, monocytes, and lymphocytes in oropharyngeal cancer stratified by human papillomavirus status.

BACKGROUND: The objective of this study was to investigate the prognostic value of the pretreatment circulating neutrophil count (CNC), circulating monocyte count (CMC), and circulating lymphocyte count (CLC) in human papillomavirus (HPV)-related (HPV+) and HPV-unrelated (HPV-) oropharyngeal cancer (OPC). METHODS: All p16-confirmed HPV+ and HPV- OPC cases treated with chemoradiotherapy from 2000 to 2010 were included. Overall survival (OS) and recurrence-free survival (RFS) were compared for high and low CNCs, CMCs, and CLCs (dichotomized by median values). A multivariate analysis (MVA) confirmed their prognostic value in HPV+ and HPV- tumors, respectively. RESULTS: Five hundred ten HPV+ OPC cases and 192 HPV- OPC cases were included. The HPV+ cohort had lower CNC and CMC values but a CLC similar to that of the HPV- patients (P < .01). The median follow-up was 4.8 years. In the HPV+ cohort, a high CNC or CMC correlated with reduced OS and RFS in comparison with a low CNC or CMC (P < .01 for all), but no difference was evident in OS (P = .30) or RFS (P = .10) with the CLC. MVA confirmed that a higher CNC or CMC independently predicted lower OS (hazard ratio [HR] for CNC, 1.14, P < .01; HR for CMC, 2.95, P < .01) and lower RFS (HR for CNC, 1.11, P < .01; HR for CMC, 3.39, P < .01), whereas a higher CLC was associated with higher RFS (HR, 0.66, P = .03) and marginally higher OS (HR, 0.80, P = .08). In the HPV- cohort, CNC, CMC, and CLC were not predictive of OS (P = .16, P = .86, and P = .14) or RFS (P = .61, P = .59, and P = .62). CONCLUSIONS: This relatively large cohort study demonstrates that a high CNC and a high CMC independently predict inferior OS and RFS, whereas a high CLC predicts better RFS and marginally better OS in HPV+ OPC patients. This association was not apparent in HPV- patients.

On-chip supercapacitors with ultrahigh volumetric performance based on electrochemically co-deposited CuO/polypyrrole nanosheet arrays.

We introduce a new method for fabricating unique on-chip supercapacitors based on CuO/polypyrrole core/shell nanosheet arrays by means of direct electrochemical co-deposition on interdigital-like electrodes. The prepared all-solid-state device demonstrates exceptionally high specific capacitance of 1275.5 F cm(-3) (∼40 times larger than that of CuO-only supercapacitors) and high-energy-density of 28.35 mWh cm(-3), which are both significantly greater than other solid-state supercapacitors. More importantly, the device maintains approximately 100% capacity retention at 2.5 A cm(-3) after 3000 cycles. The in situ co-deposition of CuO/polypyrrole nanosheets on interdigital substrate enables effective charge transport, electrode fabrication integrity, and device integration. Because of their high energy, power density, and stable cycling stability, these newly developed on-chip supercapacitors permit fast, reliable applications in portable and miniaturized electronic devices.

SLC38A5 promotes glutamine metabolism and inhibits cisplatin chemosensitivity in breast cancer.

BACKGROUND: Solute carrier family 38 member 5 (SLC38A5), as an amino acid transporter, play a vital role in cellular biological processes. In this study, we analyzed the function of SLC38A5 and its potential mechanism in breast cancer (BC) progression. METHODS: The expression of SLC38A5 in cancer and adjacent-normal tissues was analyzed by qRT-PCR and Western blot, and its correlation with patient prognosis was analyzed. The immunohistochemical staining of cancer tissues and adjacent-normal tissues was performed on SLC38A5-positive specimens. BC mice were successfully applied to examine the role of SLC38A5 on tumor proliferation using the CCK-8 assay. In BC cells and mouse tumor tissues, SLC38A5 and PCNA expression were determined by Western blotting. RESULTS: The study found that SLC38A5 was highly expressed in BC patients and associated with a poor survival. SLC38A5 silencing inhibited BC cell viability and glutamine uptake. In addition, SLC38A5 overexpression promoted BC cell viability via the glutamine metabolism. SLC38A5 inhibited cisplatin chemosensitivity in BC cells. Importantly, SLC38A5 silencing inhibited tumor growth in vivo. CONCLUSION: Our findings suggest that SLC38A5 enhances BC cell viability by glutamine metabolism, inhibits the chemical sensitivity of cisplatin in BC cells, and promotes tumor growth, emphasizing the clinical relevance of SLC38A5 in BC management as a novel potential therapeutic target.

Neutrophil extracellular trap-induced ferroptosis promotes abdominal aortic aneurysm formation via SLC25A11-mediated depletion of mitochondrial glutathione.

BACKGROUND: Neutrophil extracellular traps (NETs) induce oxidative stress, which may initiate ferroptosis, an iron-dependent programmed cell death, during abdominal aortic aneurysm (AAA) formation. Mitochondria regulate the progression of ferroptosis, which is characterized by the depletion of mitochondrial glutathione (mitoGSH) levels. However, the mechanisms are poorly understood. This study examined the role of mitoGSH in regulating NET-induced ferroptosis of smooth muscle cells (SMCs) during AAA formation. METHODS: Concentrations of NET markers were tested in plasma samples. Western blotting and immunofluorescent staining were performed to detect the expression and localization of NET and ferroptosis markers in tissue samples. The role of NETs and SMC ferroptosis during AAA formation was investigated using peptidyl arginine deiminase 4 gene (Padi4) knockout or treatment with a PAD4 inhibitor, ferroptosis inhibitor or activator in an angiotensin II-induced AAA mouse model. The regulatory effect of SLC25A11, a mitochondrial glutathione transporter, on mitoGSH and NET-induced ferroptosis of SMCs was investigated using in vitro and in vivo experiments. Transmission electron microscopy was used to detect mitochondrial damage. Blue native polyacrylamide gel electrophoresis was used to analyze the dimeric and monomeric forms of the protein. RESULTS: Significantly elevated levels of NETosis and ferroptosis markers in aortic tissue samples were observed during AAA formation. Specifically, NETs promoted AAA formation by inducing ferroptosis of SMCs. Subsequently, SLC25A11 was identified as a potential biomarker for evaluating the clinical prognosis of patients with AAA. Furthermore, NETs decreased the stability and dimerization of SLC25A11, leading to the depletion of mitoGSH. This depletion induced the ferroptosis of SMCs and promoted AAA formation. CONCLUSION: During AAA formation, NETs regulate the stability of the mitochondrial carrier protein SLC25A11, leading to the depletion of mitoGSH and subsequent activation of NET-induced ferroptosis of SMCs. Preventing mitoGSH depletion and ferroptosis in SMCs is a potential strategy for treating AAA.

Assessing the particulate matter emission reduction characteristics of small turbofan engine fueled with 100 % HEFA sustainable aviation fuel.

With the continuous increase in global air transportation, the impact of ultrafine particulate matter (PM) emissions from aviation on human health and environmental pollution is becoming increasingly severe. In addition to carbon reduction throughout the lifecycle, Sustainable Aviation Fuels (SAF) also represent a significant pathway for reducing PM emissions. However, due to issues such as airworthiness safety and adaptability, existing research has mostly focused on the emission performance of SAF when blended with traditional fuels at <50 %, leaving the emission characteristics of higher blending ratios to be explored. In this study, using measurement methods recommended by the International Civil Aviation Organization (ICAO), the PM emission reduction characteristics of small turbofan engines fueled with 100 % Hydroprocessed Esters and Fatty Acids (HEFA)-SAF were experimentally evaluated and compared with traditional fuels RP-3 and Diesel, while avoiding the interference of lubricant blending combustion. The results showed that the peak number concentration of particle size distribution (PSD), PM total number, as well as the number and mass concentration of non-volatile particulate matter (nvPM) decreased initially and then increased with rising thrust conditions. HEFA-SAF exhibits PSD with smaller diameters, and the Geometric Mean Diameter (GMD) ranges from 7.7 nm to 20.3 nm under all conditions. Both volatile particulates (vPM) and nvPM from HEFA-SAF are significantly reduced, with nvPM number emission index (EIn) being 92 % and 71 % lower than Diesel and RP-3, respectively. The nvPM mass emission index (EIm) also shows reductions of 96 % and 89 % compared to Diesel and RP-3. Microscopic characterization also indicated that using HEFA-SAF emitted fewer and smaller PMs. This study establishes a foundation for evaluating the effectiveness of 100 % SAF in reducing PM emissions within the aviation sector, and contributes to the airworthiness regulations development related to the use of SAF in a variety of application environments, alongside enhancing environmental protection measures.

Selectively "size-excluding" water molecules to enable a highly reversible zinc metal anode.

Significant water-related side reactions hinder the development of highly safe, low-cost aqueous zinc metal batteries (AZMBs) for grid-scale energy storage. Herein, by regulating the length of alkyl chains, we successfully adjust interstitial voids between the polymer chains of a metal soap interface between 1.48 Å (size of a zinc ion) and 4.0 Å (size of a water molecule). Therefore, water molecules are selectively "size-excluded," while smaller zinc ions are permitted to pass through. Consequently, water-related side reactions (including hydrogen evolution and corrosion) could be effectively inhibited. Furthermore, abundant zinc ion tunnels accompanied with zincophilic components facilitate the homogenization of the Zn2+ flux, thus preventing dendrite growth. Therefore, the Zn symmetric cell shows a lifespan of approximately 10 000 cycles at 20 mA cm-2 and 1 mA h cm-2, and the Zn//Na5V12O32 (NVO) full cell delivers much better cycling stability with much higher capacity retention of around 93% after 2000 cycles at 2 A g-1 compared to its bare Zn counterpart (19%). This work provides valuable insights for the utilization of metal soap interfaces and regulation of their channel size between perpendicular alkyl chains to realize precise water shielding, which is not only applicable in ZMBs but also in other aqueous batteries.

The requirement of the mitochondrial protein NDUFS8 for angiogenesis.

Mitochondria are important for the activation of endothelial cells and the process of angiogenesis. NDUFS8 (NADH:ubiquinone oxidoreductase core subunit S8) is a protein that plays a critical role in the function of mitochondrial Complex I. We aimed to investigate the potential involvement of NDUFS8 in angiogenesis. In human umbilical vein endothelial cells (HUVECs) and other endothelial cell types, we employed viral shRNA to silence NDUFS8 or employed the CRISPR/Cas9 method to knockout (KO) it, resulting in impaired mitochondrial functions in the endothelial cells, causing reduction in mitochondrial oxygen consumption and Complex I activity, decreased ATP production, mitochondrial depolarization, increased oxidative stress and reactive oxygen species (ROS) production, and enhanced lipid oxidation. Significantly, NDUFS8 silencing or KO hindered cell proliferation, migration, and capillary tube formation in cultured endothelial cells. In addition, there was a moderate increase in apoptosis within NDUFS8-depleted endothelial cells. Conversely, ectopic overexpression of NDUFS8 demonstrated a pro-angiogenic impact, enhancing cell proliferation, migration, and capillary tube formation in HUVECs and other endothelial cells. NDUFS8 is pivotal for Akt-mTOR cascade activation in endothelial cells. Depleting NDUFS8 inhibited Akt-mTOR activation, reversible with exogenous ATP in HUVECs. Conversely, NDUFS8 overexpression boosted Akt-mTOR activation. Furthermore, the inhibitory effects of NDUFS8 knockdown on cell proliferation, migration, and capillary tube formation were rescued by Akt re-activation via a constitutively-active Akt1. In vivo experiments using an endothelial-specific NDUFS8 shRNA adeno-associated virus (AAV), administered via intravitreous injection, revealed that endothelial knockdown of NDUFS8 inhibited retinal angiogenesis. ATP reduction, oxidative stress, and enhanced lipid oxidation were detected in mouse retinal tissues with endothelial knockdown of NDUFS8. Lastly, we observed an increase in NDUFS8 expression in retinal proliferative membrane tissues obtained from human patients with proliferative diabetic retinopathy. Our findings underscore the essential role of the mitochondrial protein NDUFS8 in regulating endothelial cell activation and angiogenesis.

Dilemma of Low-Cost Filter Paper as Separator: Toughen Its Wet Strength for Robust Aqueous Zinc-Ion Batteries.

The industrialization of aqueous zinc-ion batteries (AZIBs) is hampered by poor-performance separators. Filter paper (FP), with mature production processes and low prices, has potential as a separator. However, its swelling and decline of mechanical durability in aqueous environments make it easily punctured by dendrites. In response, wet strength promotion is proposed to toughen FP for robust AZIBs, termed wet-strengthened FP (WSFP). Due to the self-cross-linking network formed on cellulose fibers, water molecules are prevented from easily permeating and disrupting the hydrogen bonds between cellulose molecules. Moreover, the positively charged network can anchor SO42-, thus increasing the Zn2+ transference number and facilitating uniform zinc deposition. Surprisingly, the half and full cells with the WSFP separator present much more stable cycling than untreated FP and glass fiber (GF) separators. These results suggest that robust and low-cost WSFP separators provide a new avenue for the development of high-performance AZIBs with potential for commercialization.

Extracorporeal shock wave lithotripsy is effective in treating single melamine induced urolithiasis in infants and young children.

PURPOSE: We evaluated the safety and efficacy of extracorporeal shock wave lithotripsy in the treatment of single melamine induced urolithiasis in infants and young children. MATERIALS AND METHODS: A total of 189 infants and young children with single melamine induced urolithiasis were referred to our center for treatment with extracorporeal shock wave lithotripsy between March 2009 and July 2010. Location of the calculus was proximal ureteral in 17 patients, mid ureteral in 5, distal ureteral in 26 and kidney in 141. Stone size ranged from 3.8 to 25 mm (mean ± SD 9.79 ± 3.83). RESULTS: All patients underwent extracorporeal shock wave lithotripsy using the same device with an energy ranging from 8 to 12 kV. Stone-free rate was 97.88%, clinically insignificant residual fragment rate was 1.59% and repeat treatment rate was 2.65%. A total of 180 patients (95.24%) required only 1 lithotripsy session and 5 (2.65%) required 2 sessions. Mean ± SD number of shock waves delivered per session was 580.36 ± 190.69 (range 65 to 950). Extracorporeal shock wave lithotripsy failed to fragment stones in only 1 infant, who had a proximal ureteral stone. A total of 181 specimens were collected and analyzed by infrared spectrum, with results demonstrating that the main composition was uric acid and melamine. All patients were followed for a mean of 28 months (range 20 to 36). No severe complication, such as renal subcapsular hemorrhage, hypertension, kidney rupture or lung injury, was observed. CONCLUSIONS: Extracorporeal shock wave lithotripsy with low energy can effectively disintegrate melamine induced calculi. This approach has become our preferred method for treating single melamine induced urolithiasis in infants and young children.