Oxygen vacancy enhanced photocatalytic activity of Cu2O/TiO2 heterojunction.

In this study, a method was developed to create oxygen vacancies in Cu2O/TiO2 heterojunctions. By varying the amounts of ethylenediaminetetraacetic acid (EDTA), sodium citrate, and copper acetate, Cu2O/TiO2 with different Cu ratios were synthesized. Tests on CO2 photocatalytic reduction revealed that Cu2O/TiO2's performance is influenced by Cu content. The ideal Cu mass fraction in Cu2O/TiO2, determined by inductively coupled plasma (ICP), is between 0.075% and 0.55%, with the highest CO yield being 10.22 µmol g-1 h-1, significantly surpassing pure TiO2. High-resolution transmission electron microscopy and electron paramagnetic resonance studies showed optimal oxygen vacancy in the most effective heterojunction. Density functional theory (DFT) calculations indicated a 0.088 eV lower energy barrier for ∗CO2 to ∗COOH conversion in Cu2O/TiO2 with oxygen vacancy compared to TiO2, suggesting that oxygen vacancies enhance photocatalytic activity.

Bioinspired ginsenoside Rg3 PLGA nanoparticles coated with tumor-derived microvesicles to improve chemotherapy efficacy and alleviate toxicity.

Breast cancer, a pervasive malignancy affecting women, demands a diverse treatment approach including chemotherapy, radiotherapy, and surgical interventions. However, the effectiveness of doxorubicin (DOX), a cornerstone in breast cancer therapy, is limited when used as a monotherapy, and concerns about cardiotoxicity persist. Ginsenoside Rg3, a classic compound of traditional Chinese medicine found in Panax ginseng C. A. Mey., possesses diverse pharmacological properties, including cardiovascular protection, immune modulation, and anticancer effects. Ginsenoside Rg3 is considered a promising candidate for enhancing cancer treatment when combined with chemotherapy agents. Nevertheless, the intrinsic challenges of Rg3, such as its poor water solubility and low oral bioavailability, necessitate innovative solutions. Herein, we developed Rg3-PLGA@TMVs by encapsulating Rg3 within PLGA nanoparticles (Rg3-PLGA) and coating them with membranes derived from tumor cell-derived microvesicles (TMVs). Rg3-PLGA@TMVs displayed an array of favorable advantages, including controlled release, prolonged storage stability, high drug loading efficiency and a remarkable ability to activate dendritic cells in vitro. This activation is evident through the augmentation of CD86+CD80+ dendritic cells, along with a reduction in phagocytic activity and acid phosphatase levels. When combined with DOX, the synergistic effect of Rg3-PLGA@TMVs significantly inhibits 4T1 tumor growth and fosters the development of antitumor immunity in tumor-bearing mice. Most notably, this delivery system effectively mitigates the toxic side effects of DOX, particularly those affecting the heart. Overall, Rg3-PLGA@TMVs provide a novel strategy to enhance the efficacy of DOX while simultaneously mitigating its associated toxicities and demonstrate promising potential for the combined chemo-immunotherapy of breast cancer.

Regulating Sulfur Redox Kinetics by Coupling Photocatalysis for High-Performance Photo-Assisted Lithium-Sulfur Batteries.

Challenges such as shuttle effect have hindered the commercialization of lithium-sulfur batteries (LSBs), despite their potential as high-energy-density storage devices. To address these issues, we explore the integration of solar energy into LSBs, creating a photo-assisted lithium-sulfur battery (PA-LSB). The PA-LSB provides a novel and sustainable solution by coupling the photocatalytic effect to accelerate sulfur redox reactions. Herein, a perovskite quantum dot-loaded MOF material serves as a cathode for the PA-LSB, creating built-in electric fields at the micro-interface to extend the lifetime of photo-generated charge carriers. The band structure of the composite material aligns well with the electrochemical reaction potential of lithium-sulfur, enabling precise regulation of polysulfides in the cathode of the PA-LSB system. This is attributed to the selective catalysis of the liquid-solid reaction stage in the lithium-sulfur electrochemical process by photocatalysis. These contribute to the outstanding performance of PA-LSBs, particularly demonstrating a remarkably high reversible capacity of 679 mAh g-1 at 5 C, maintaining stable cycling for 1500 cycles with the capacity decay rate of 0.022% per cycle. Additionally, the photo-charging capability of the PA-LSB holds the potential to compensate for non-electric energy losses during the energy storage process, contributing to the development of lossless energy storage devices.

A case report of youth-onset lipoprotein glomerulopathy with APOE Chicago mutation.

BACKGROUND: This article reports an extremely rare case of lipoprotein glomerulopathy (LPG) with apolipoprotein E gene (APOE) Chicago mutation in a young Chinese male. Only five cases or families with APOE Chicago mutations have been reported in the literature. CASE PRESENTATION: The young male patient is manifested with nephrotic syndrome, accompanied by hyperlipidemia with a preferable increase in triglycerides and elevated ApoE level. Renal biopsy of the patient showed highly dilated glomerular capillaries filled with vacuolar lipids, segmentally fused podocyte foot processes, vacuolar degeneration of renal tubular epithelial cells and absence of electron-dense material, which indicates the diagnosis of LPG. Whole-exome gene sequencing identified the heterozygous mutation of NM_000041.4:c.494G > C (p.Arg165Pro), which is in the exon 4 of the APOE gene and also known as APOE Chicago mutation, a rare mutation of LPG. Further family pedigree gene analysis clarified that the mutation was inherited from the patient's mother, who does not have high ApoE levels or renal manifestations. This is also consistent with the incomplete penetrance of APOE gene mutations in LPG. Under lipid-lowering treatments, including a low-fat diet and fenofibrate, the patient's urinary protein was partially controlled, and the albumin level was recovered. CONCLUSION: Patients with nephrotic syndrome and elevated ApoE levels should be prompted into renal biopsy to avoid delay of appropriate treatment and unnecessary use of glucocorticoids. This case of LPG was diagnosed by renal biopsy and further verified with genetic sequencing. The timely diagnosis and treatment improved the patient's symptoms. This case is one of only six reported LPG cases or families with APOE Chicago mutation in the world.

Recent progress and prospects for chain elongation of transforming biomass waste into medium-chain fatty acids.

Chain elongation technology utilises microorganisms in anaerobic digestion to transform waste biomass into medium-chain fatty acids that have greater economic value. This innovative technology expands upon traditional anaerobic digestion methods, requiring abundant substrates that serve as electron donors and acceptors, and inoculating microorganisms with chain elongation functions. While this process may result in the production of by-products and elicit competitive responses, toxicity suppression of microorganisms by substrates and products remains a significant obstacle to the industrialisation of chain elongation technology. This study provides a comprehensive overview of existing research on widely employed electron donors and their synthetic reactions, competitive reactions, inoculum selection, toxicity inhibition of substrates and products, and increased chain elongation approaches. Additionally, it presents actionable recommendations for future research and development endeavours in this domain, intending to inspire and guide researchers in advancing the frontiers of chain elongation technology.

Se Alleviated Pb-Caused Neurotoxicity in Chickens: SPS2-GPx1-GSH-IL-2/IL-17-NO Pathway, Selenoprotein Suppression, Oxidative Stress, and Inflammatory Injury.

Lead (Pb), a heavy metal environmental pollutant, poses a threat to the health of humans and birds. Inflammation is one of the most common pathological phenomena in the case of illness and poisoning. However, the underlying mechanisms of inflammation remain unclear. The cerebellum and the thalamus are important parts of the nervous system. To date, there have been no reports of Pb inducing inflammation in animal cerebellums or thalami. Selenium (Se) can relieve Pb poisoning. Therefore, we aimed to explore the mechanism by which Se alleviates Pb toxicity to the cerebellums and thalami of chickens by establishing a chicken Pb or/and Se treatment model. Our results demonstrated that exposure to Pb caused inflammatory damage in cerebellums and thalami, evidenced by the characteristics of inflammation, the decrease in anti-inflammatory factors (interleukin (IL)-2 and interferon-γ (INF-γ)), and the increase in pro-inflammatory factors (IL-4, IL-6, IL-12ß, IL-17, and nitric oxide (NO)). Moreover, we found that the IL-2/IL-17-NO pathway took part in Pb-caused inflammatory injury. The above findings were reversed by the supplementation of dietary Se, meaning that Se relieved inflammatory damage caused by Pb via the IL-2/IL-17-NO pathway. In addition, an up-regulated oxidative index malondialdehyde (MDA) and two down-regulated antioxidant indices (glutathione (GSH) and total antioxidant capacity (TAC)) were recorded after the chickens received Pb stimulation, indicating that excess Pb caused an oxidant/antioxidant imbalance and oxidative stress, and the oxidative stress mediated inflammatory damage via the GSH-IL-2 axis. Interestingly, exposure to Pb inhibited four glutathione peroxidase (GPx) family members (GPx1, GPx2, GPx3, and GPx4), three deiodinase (Dio) family members (Dio1, Dio2, and Dio3), and fifteen other selenoproteins (selenophosphate synthetase 2 (SPS2), selenoprotein (Sel)H, SelI, SelK, SelM, SelO, SelP1, SelPb, SelS, SelT, SelU, and selenoprotein (Sep)n1, Sepw1, Sepx1, and Sep15), suggesting that Pb reduced antioxidant capacity and resulted in oxidative stress involving the SPS2-GPx1-GSH pathway. Se supplementation, as expected, reversed the changes mentioned above, indicating that Se supplementation improved antioxidant capacity and mitigated oxidative stress in chickens. For the first time, we discovered that the SPS2-GPx1-GSH-IL-2/IL-17-NO pathway is involved in the complex inflammatory damage mechanism caused by Pb in chickens. In conclusion, this study demonstrated that Se relieved Pb-induced oxidative stress and inflammatory damage via the SPS2-GPx1-GSH-IL-2/IL-17-NO pathway in the chicken nervous system. This study offers novel insights into environmental pollutant-caused animal poisoning and provides a novel theoretical basis for the detoxification effect of Se against oxidative stress and inflammation caused by toxic pollutants.

Gaussian Process-Gated Hierarchical Mixtures of Experts.

In this paper, we propose novel Gaussian process-gated hierarchical mixtures of experts (GPHMEs). Unlike other mixtures of experts with gating models linear in the input, our model employs gating functions built with Gaussian processes (GPs). These processes are based on random features that are non-linear functions of the inputs. Furthermore, the experts in our model are also constructed with GPs. The optimization of the GPHMEs is performed by variational inference. The proposed GPHMEs have several advantages. They outperform tree-based HME benchmarks that partition the data in the input space, and they achieve good performance with reduced complexity. Another advantage is the interpretability they provide for deep GPs, and more generally, for deep Bayesian neural networks. Our GPHMEs demonstrate excellent performance for large-scale data sets, even with quite modest sizes.

Comparison of the mesodermal differentiation potential between embryonic stem cells and scalable induced pluripotent stem cells.

BACKGROUND: Mesenchymal stem cells (MSCs) have promising potential in clinical application whereas their limited amount and sources hinder their bioavailability. Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have become prominent options in regenerative medicine as both possess the ability to differentiate into MSCs. METHODS: Recently, our research team has successfully developed human leukocyte antigen (HLA)-homozygous iPSC cell lines with high immune compatibility, covering 13.5% of the Taiwanese population. As we deepen our understanding of the differences between these ESCs and HLA-homozygous iPSCs, our study focused on morphological observations and flow cytometry analysis of specific surface marker proteins during the differentiation of ESCs and iPSCs into MSCs. RESULTS: The results showed no significant differences between the two pluripotent stem cells, and both of them demonstrated the equivalent ability to further differentiate into adipose, cartilage, and bone cells. CONCLUSION: Our research revealed that these iPSCs with high immune compatibility exhibit the same differentiation potential as ESCs, enhancing the future applicability of highly immune-compatible iPSCs.

Dysregulation of the circRNA_0087207/miR-548c-3p/PLSR1-TGFB2 axis in Leber hereditary optic neuropathy in vitro.

BACKGROUND: Leber hereditary optic neuropathy (LHON) is mainly the degeneration of retinal ganglion cells (RGCs) associated with high apoptosis and reactive oxygen species (ROS) levels, which is accepted to be caused by the mutations in the subunits of complex I of the mitochondrial electron transport chain. The treatment is still infant while efforts of correcting genes or using antioxidants do not bring good and consistent results. Unaffected carrier carries LHON mutation but shows normal phenotype, suggesting that the disease's pathogenesis is complex, in which secondary factors exist and cooperate with the primary complex I dysfunction. METHODS: Using LHON patient-specific induced pluripotent stem cells (iPSCs) as the in vitro disease model, we previously demonstrated that circRNA_0087207 had the most significantly higher expression level in the LHON patient-iPSC-derived RGCs compared with the unaffected carrier-iPSC-derived RGCs. To elaborate the underlying pathologies regulated by circRNA_008720 mechanistically, bioinformatics analysis was conducted and elucidated that circRNA_0087207 could act as a sponge of miR-548c-3p and modulate PLSCR1/TGFB2 levels in ND4 mutation-carrying LHON patient-iPSC-derived RGCs. RESULTS: Using LHON iPSC-derived RGCs as the disease-based platform, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis on targeted mRNA of miR-548c-3p showed the connection with apoptosis, suggesting downregulation of miR548c-3p contributes to the apoptosis of LHON patient RGCs. CONCLUSION: We showed that the downregulation of miR548c-3p plays a critical role in modulating cellular dysfunction and the apoptotic program of RGCs in LHON.

Understanding Water Diffusion Behaviors in Epoxy Resin through Molecular Simulations and Experiments.

The unclear understanding of the water diffusion behavior posts a big challenge to the manipulation of water absorption properties in epoxy resins. Herein, we investigated the water diffusion behavior and its relationship with molecule structures inside an epoxy resin mainly by the nonequilibrium molecular dynamics and experiments. It is found that at the initial rapid water absorption stage, bound water and free water both contribute, while at the later slow water absorption stage, free water plays a dominant role. The observed evolution of free water and bound water cannot be explained by the traditional Langmuir model. In addition, molecule polarity, free volume, and segment mobility can all influence the water diffusion process. Hence, the epoxy resin with low polarity and high molecular segment mobility is endowed with higher diffusion coefficients. The saturated water absorption content is almost dependent on the polarity. The understanding of how water diffuses and what decides the diffusion process is critical to the rational design of molecule structures for improving the water resistance in epoxy resin.

Salmonellosis outbreak archive in China: data collection and assembly.

Infectious disease outbreaks transcend the medical and public health realms, triggering widespread panic and impeding socio-economic development. Considering that self-limiting diarrhoea of sporadic cases is usually underreported, the Salmonella outbreak (SO) study offers a unique opportunity for source tracing, spatiotemporal correlation, and outbreak prediction. To summarize the pattern of SO and estimate observational epidemiological indicators, 1,134 qualitative reports screened from 1949 to 2023 were included in the systematic review dataset, which contained a 506-study meta-analysis dataset. In addition to the dataset comprising over 50 columns with a total of 46,494 entries eligible for inclusion in systematic reviews or input into prediction models, we also provide initial literature collection datasets and datasets containing socio-economic and climate information for relevant regions. This study has a broad impact on advancing knowledge regarding epidemic trends and prevention priorities in diverse salmonellosis outbreaks and guiding rational policy-making or predictive modeling to mitigate the infringement upon the right to life imposed by significant epidemics.

Hydrogen Fertilization with Hydrogen Nanobubble Water Improves Yield and Quality of Cherry Tomatoes Compared to the Conventional Fertilizers.

Although hydrogen gas (H2)-treated soil improves crop biomass, this approach appears difficult for field application due to the flammability of H2 gas. In this report, we investigated whether and how H2 applied in hydrogen nanobubble water (HNW) improves the yield and quality of cherry tomato (Lycopersicon esculentum var. cerasiforme) with and without fertilizers. Two-year-long field trials showed that compared to corresponding controls, HNW without and with fertilizers improved the cherry tomato yield per plant by 39.7% and 26.5% in 2021 (Shanghai), respectively, and by 39.4% and 28.2% in 2023 (Nanjing), respectively. Compared to surface water (SW), HNW increased the soil available nitrogen (N), phosphorus (P), and potassium (K) consumption regardless of fertilizer application, which may be attributed to the increased NPK transport-related genes in roots (LeAMT2, LePT2, LePT5, and SlHKT1,1). Furthermore, HNW-irrigated cherry tomatoes displayed a higher sugar-acid ratio (8.6%) and lycopene content (22.3%) than SW-irrigated plants without fertilizers. Importantly, the beneficial effects of HNW without fertilizers on the yield per plant (9.1%), sugar-acid ratio (31.1%), and volatiles (20.0%) and lycopene contents (54.3%) were stronger than those achieved using fertilizers alone. In short, this study clearly indicated that HNW-supplied H2 not only exhibited a fertilization effect on enhancing the tomato yield, but also improved the fruit's quality with a lower carbon footprint.

Three-Dimensional Reconstruction of Computed Tomography Imaging Is Not Reliable in Assessing Acetabular Rim Osteophytes or Acetabular Rim Pathology in Patients With Femoroacetabular Impingement.

Purpose: To determine the reliability of 3-dimensional (3D) reconstruction of computed tomography (CT) imaging in evaluating acetabular rim morphology or acetabular rim osteophyte (ARO) existence and to group patients with femoroacetabular impingement (FAI) by ARO extent on coronal sections of CT and further compare clinical differences among groups. Methods: Patients who underwent primary hip arthroscopy for FAI by the same surgeon between August 2016 and December 2018 with minimum 2-year follow-up were enrolled. The ARO was evaluated both on the acetabular gross anatomy (AGA) and coronal sections of CT, for its position, width (unit: mm), area (unit: mm2), and CT value (unit: HU). Patients were divided into 4 groups based on the extent of ARO on coronal CT: group A (ARO anterior to 12 o'clock), group P (ARO posterior to 12 o'clock), group AP (ARO across 12 o'clock), and group N (no ARO). Inter- and intraobserver correlation was analyzed. Demographic data, FAI deformity indicators on imaging, quantitative measurements of ARO, and pre- and postoperative patient-reported outcomes were compared among groups. Results: There were 229 patients (229 hips) enrolled in total, 122 male (53.3%) and 107 female (46.7%), with a mean age of 37.2 ± 10.2 years. The correlation between 2 observers for grouping ARO using AGA was positive but poor (Kendall Tau-b coefficient = 0.157, P = .008). Moderate correlation was found between grouping based on AGA and coronal CT by the same observer (Kendall Tau-b coefficient = 0.482, P = .000). The patients were divided into 4 groups: 84 patients (36.7%) in group N, 2 patients (0.9%) in group A, 69 patients (30.1%) in group P, and 74 patients (32.3%) in group AP. Group N was younger in age (35.4 ± 10.7 years) than group P (39.6 ± 10.2 years) (P = 0.012) and had a larger proportion of women (57.1%) than group AP (36.5%) (χ2 = 6.869, P = .032). There was a greater proportion of positive posterior wall sign in group P (52.2%) than 48.6% for group AP and 33.3% for group N (χ2 = 6.397, P = .041). Group N had 61 (72.6%) Tönnis grade 0 hips compared with 37 (50%) in group AP (P = .014). No statistical significance was found among groups in pre- and postoperative α angle, lateral center-edge angle, and patient-reported outcomes. The widths of ARO in group AP for the 3 marked points from anterior to posterior were 3.88 ± 1.86, 4.84 ± 2.72, and 6.66 ± 3.18, separately (P＜.001); 15.73 ± 21.46, 19.22 ± 18.86, and 29.96 ± 17.05 for area (P＜.01); and 652.67 ± 214.12, 677.10 ± 274.81, and 728.84 ± 232.39 for CT value (P＜.05). For the ARO posterior to 12 o'clock, the group AP showed a larger width (6.66 ± 3.18), area (29.96 ± 17.05), and CT value (728.84 ± 232.39) than group P of (4.70 ± 2.25), (20.15 ± 12.91), and (641.84 ± 183.33) (P＜.001). Conclusions: The evaluation of ARO on AGA is poor consistent with definite double-rim sign on coronal CT. There is a tendency of size-enlarging and density-increasing for ARO from anterior to posterior along the acetabular rim. Younger age, female gender, lower Tönnis grade, and negative posterior wall sign showed lower rate of ARO development. Level of Evidence: Level IV, diagnostic case series.

Molecular mechanism of selenium against lead-induced apoptosis in chicken brainstem relating to heat shock protein, selenoproteins, and inflammatory cytokines.

Extensive application of lead (Pb) brought about environmental pollution and toxic reactions of organisms. Selenium (Se) has the effect of antagonizing Pb poisoning in humans and animals. However, it is still unclear how Pb causes brainstem toxicity. In the present study, we wanted to investigate whether Se can alleviate Pb toxicity in chicken brainstems by reducing apoptosis. One hundred and eighty chickens were randomly divided into four groups, namely the control group, the Se group, the Pb group, and the Se/Pb group. Morphological examination, ultrastructural observation, relative mRNA expressions of genes on heat shock proteins (HSPs); selenoproteins; inflammatory cytokines; and apoptosis-related factors were investigated. The results showed that Pb exposure led to tissue damage and apoptosis in chicken brainstems. Furthermore, an atypical expression of HSPs (HSP27, HSP40, HSP60, HSP70, and HSP90); selenoprotein family glutathione peroxidase (GPx) 1, GPx2, GPx3, and GPx4), thioredoxin reductases (Txnrd) (Txnrd1, Txnrd2, and Txnrd3), dio selenoprotein famliy (diodothyronine deiodinases (Dio)1, Dio2, and Dio3), as well as other selenoproteins (selenoprotein (Sel)T, SelK, SelS, SelH, SelM, SelU, SelI, SelO, Selpb, selenoprotein n1 (Sepn1), Sepp1, Sepx1, Sepw1, 15-kDa selenoprotein (Sep15), and selenophosphate synthetases 2 (SPS2)); inflammatory cytokines (Interleukin 2 (IL-2), IL-4, IL-6, IL-12ß, IL-17, and Interferon-γ (IFN-γ)); and apoptosis-related genes (B-cell lymphoma-2 (Bcl-2), tumor protein 53 (p53), Bcl-2 Associated X (Bax), Cytochrome c (Cyt c), and Caspase-3) were identified. An inflammatory reaction and apoptosis were induced in chicken brainstems after exposure to Pb. Se alleviated the abnormal expression of HSPs, selenoproteins, inflammatory cytokines, and apoptosis in brainstem tissues of chickens treated with Pb. The results indicated that HSPs, selenoproteins, inflammatory, and apoptosis were involved in Se-resisted Pb poisoning. Overall, Se had resistance effect against Pb poisoning, and can be act as an antidote for Pb poisoning in animals.

Efficient induction of pluripotent stem cells differentiated into mesenchymal stem cell lineages.

BACKGROUND: Mesenchymal stem cells (MSCs) have garnered significant attention in the field of cell-based therapy owing to their remarkable capabilities for differentiation and self-renewal. However, primary tissue-derived MSCs are plagued by various limitations, including constrained tissue sources, arduous and invasive retrieval procedures, heterogeneous cell populations, diminished purity, cellular senescence, and a decline in self-renewal and proliferative capacities after extended expansion. Addressing these challenges, our study focuses on establishing a robust differentiation platform to generate mesenchymal stem cells derived from induced pluripotent stem cells (iMSCs). METHODS: To achieve this, we used a comprehensive methodology involving the differentiation of induced pluripotent stem cells into MSCss. The process was meticulously designed to ensure the expression of key MSC positive markers (CD73, CD90, and CD105) at elevated levels, coupled with the minimal expression of negative markers (CD34, CD45, CD11b, CD19, and HLA-DR). Moreover, the stability of these characteristics was evaluated across 10th generations. RESULTS: Our findings attest to the success of this endeavor. iMSCs exhibited robust expression of positive markers and limited expression of negative markers, confirming their MSC identity. Importantly, these characteristics remained stable even up to the 10th generation, signifying the potential for sustained use in therapeutic applications. Furthermore, our study demonstrated the successful differentiation of iMSCs into osteocytes, chondrocytes, and adipocytes, showcasing their multilineage potential. CONCLUSION: In conclusion, the establishment of induced pluripotent stem cell-derived mesenchymal stem cells (iMSCs) presents a significant advancement in overcoming the limitations associated with primary tissue-derived MSCs. The remarkable stability and multilineage differentiation potential exhibited by iMSCs offer a strong foundation for their application in regenerative medicine and tissue engineering. This breakthrough paves the way for further research and development in harnessing the full therapeutic potential of iMSCs.

A deep neural network predictor to predict the sensitivity of neoadjuvant chemoradiotherapy in locally advanced rectal cancer.

Neoadjuvant chemoradiotherapy (NCRT) is widely used for locally advanced rectal cancer (LARC). This study aimed to conduct an effective model to predict NCRT sensitivity and provide guidance for clinical treatment. Biomarkers for NCRT sensitivity were identified by applying transcriptome profiles using logistic regression and subsequently screened out by Spearman correlation analysis and four machine learning algorithms. A deep neural network (DNN) predictor was constructed by using in-house dataset and validated in two independent datasets. Additionally, a web-based program was developed. Wnt/ß-catenin signaling and linoleic acid metabolism (LA) pathways were associated with NCRT sensitivity and prognosis in LARC, antagonistically. A DNN predictor with an 18-gene signature was conducted within in-house datasets. In two validation cohorts, area under ROC curve (AUC) achieved 0.706 and 0.897. The DNN subtypes were significantly associated with NCRT sensitivity, survival status et al. Moreover, NK and cytotoxic T cells were observed contribution to NCRT sensitivity while regulatory T, myeloid-derived suppressor cells and dysfunction of CD4 T effector memory cells could impede NCRT response. A DNN predictor could predict NCRT sensitivity in LARC and stratify LARC patients with different clinical and immunity characteristic.

Unveiling the Morphology of Carbon-Supported Ru Nanoparticles by Multiscale Modeling.

Simulating the behavior of metal nanoparticles on supports is crucial for boosting their catalytic performance and various nanotechnology applications; however, such simulations are limited by the conflicts between accuracy and efficiency. Herein, we introduce a multiscale modeling strategy to unveil the morphology of Ru supported on pristine and N-doped graphene. Our multiscale modeling started with the electronic structures of a supported Ru single atom, revealing the strong metal-support interaction around pyridinic nitrogen sites. To determine the stable configurations of Ru2-13 clusters on three different graphene supports, global energy minimum searches were performed. The sintering of the global minimum Ru13 clusters on supports was further simulated by ab initio molecular dynamics (AIMD). The AIMD data set was then collected for deep potential molecular dynamics to study the melting of Ru nanoparticles. This study presents comprehensive descriptions of carbon-supported Ru and develops modeling approaches that bridge different scales and can be applied to various supported nanoparticle systems.

Comparison of different prediction tools for the risk of intravesical recurrence after radical nephroureterectomy for upper tract urothelial carcinoma: a propensity-matched analysis

Objective To compare the predictive performance of the current clinical prediction models for predicting intravesical recurrence (IVR) after radical nephroureterectomy (RNU) in patients with upper tract urothelial carcinoma (UTUC). Methods We retrospectively analysed upper tract urothelial carcinoma patients who underwent radical nephroureterectomy in our centre from January 2009 to December 2019. We used the propensity score matching (PSM) method to adjust the confounders between the IVR and non-IVR groups. Additionally, Xylinas’ reduce model and full model, Zhang’s model, and Ishioka’s risk stratification model were used to retrospectively calculate predictions for each patient. Receiver operating characteristic (ROC) curves were generated, and the areas under the curves (AUCs) were compared to identify the method with the highest predictive value. Zesults We included 217 patients with a median follow-up of 41 months, of which 57 had IVR. After PSM analysis, 52 pairs of well-matched patients were included in the comparative study. No significant difference was found in clinical indicators besides hydronephrosis. The model comparison showed that the AUCs of the reduced Xylinas’ model for 12 months, 24 months, and 36 months were 0.69, 0.73, and 0.74, respectively, and those of the full Xylinas’ model were 0.72, 0.75, and 0.74, respectively. The AUC of Zhang’s model for 12 months, 24 months, and 36 months was 0.63, 0.71, and 0.71, respectively, the performance of Ishioka’s model is that the AUC of 12 months, 24 months and 36 months was 0.66, 0.71, and 0.74, respectively. Conclusion The external verification results of the four models show that more comprehensive data and a larger sample size of patients are needed to strengthen the models’ derivation and updating procedure, to better apply them to different populations (AU)

The Preserved Thickness Ratio of the Femoral Head Contributes to the Collapse Predictor of Osteonecrosis.

OBJECTIVES: The collapse of femoral head is a serious symptom of osteonecrosis of the femoral head (ONFH), resulting in hip pain and deformity. However, it is hardly possible to reestablish the femoral head nonoperatively once the collapse happens. Predicting femoral head collapse is of great value for the prognosis of ONFH. This study aimed to develop a new method to quantify the preserved thickness of femoral head and to assess its diagnostic contribution in predicting femoral head collapse on plain radiographs. METHODS: This was a single-center retrospective study. A total of 101 hips (85 patients) with ARCO stage II from January 2008 to December 2016 were included in this study. The preserved thickness was measured on standard anteroposterior (AP) and frog-leg (FL) radiographs. The anteroposterior view's preserved thickness ratio (APTR) and the frog-leg view's preserved thickness ratio (FPTR) were calculated to show the preserved thickness ratio of the femoral head anteriorly and laterally. Univariate and multivariate logistic regression was performed to determine the risk factors for collapse. Sensitivity, specificity, and cut-off values for APTR and FPTR were determined by the receiver operating characteristic (ROC) curve analysis. Kaplan-Meier (K-M) analysis was applied to determine femoral head survival in ONFH patients. RESULTS: The mean age of the 27 females and 58 males was 38.93 years old. The mean follow-up time was 74.62 (36-124) months in the non-collapse group and 18.66 (3-82) months in the collapse group. Femoral head collapse was observed in 62 hips during the follow-up period. Logistic regression analysis and ROC results showed that APTR <24.79% and FPTR <10.62% were significantly correlated with femoral head collapse. The Kaplan-Meier survival curve suggested that the overall survival rate of APTR ≥24.79% was 68.2% at 5 and 10 years and FPTR ≥10.62% was 71.63% at 5 and 10 years. At the last follow-up, 26 hips had collapse on the anterior side of the femoral head, 12 hips occurred on the lateral side, and 24 hips happened to collapse on both anterior and lateral sides. CONCLUSION: Femoral head collapse predominantly occurred anteriorly rather than laterally in ONFH patients. The measurements of APTR and FPTR have noticeable implications for the prediction of femoral head collapse, and contribute to the selection of treatment options for ONFH patients with types B and C1 according to the JIC classification.

The effects of Tripterygium wilfordii Hook F on renal outcomes in type 2 diabetic kidney disease patients with severe proteinuria: a single-center cohort study.

AIM: Tripterygium wilfordii Hook F (TwHF) has been shown to substantially reduce proteinuria in patients with diabetic kidney disease (DKD); however, the effect of TwHF on renal outcomes in DKD remains unknown. Accordingly, we aimed to establish the effects of TwHF on renal outcomes in patients with DKD. METHODS: Overall, 124 patients with DKD, induced by type 2 diabetes mellitus, with 24-h proteinuria > 2 g, and an estimated glomerular filtration rate > 30 mL/min/1.73 m2 were retrospectively investigated. The renal outcomes were defined as doubling serum creatinine levels or end-stage kidney disease. Kaplan-Meier curves and Cox regression analyses were performed to analyze prognostic factors for renal outcomes. RESULTS: By the end of the follow-up, renal outcomes were observed in 23 and 11 patients in the non-TwHF and TwHF groups, respectively (p = 0.006). TwHF significantly reduced the risk of renal outcomes (adjusted hazard ratio [HR] 0.271, 95% confidence interval [CI] 0.111-0.660, p = 0.004) in patients with chronic kidney disease (CKD) G3 (adjusted HR 0.274, 95%CI 0.081-0.932, p = 0.039). Based on the Kaplan-Meier analysis, 1- and 3-year proportions of patients without renal outcomes were significantly lower in the non-TwHF group than those in the TwHF group (92.8% vs. 95.5% and 47.2% vs. 76.8%, respectively; p = 0.0018). CONCLUSION: In DKD patients with severe proteinuria, TwHF could prevent DKD progression, especially in patients with CKD G3. A randomized clinical trial is needed to elucidate the benefits of TwHF on renal outcomes in patients with DKD.