Iodine Status of Infants and Toddlers under 2 Years of Age and Its Association with Feeding Behaviors and Maternal Iodine Status in Shanghai: A Quantile Regression Analysis.

It is crucial to provide adequate iodine nutrition to infants and toddlers for proper thyroid function and subsequent brain development. Infants are particularly vulnerable to iodine deficiency during the transition from a milk-based diet (breast milk and/or infant formula) to solid food. This study examines the current iodine levels of children during their first two years of life and investigates the association between these levels and feeding behaviors and the iodine status of their mothers in Shanghai, a city located in eastern China. A hospital-based cohort study was conducted to enroll mother-child pairs, where the child is aged 6-23 months, who visited community health service centers in the 16 districts of Shanghai, China. Data on socio-demographic factors and feeding behavior data were collected from the participants. The urinary iodine concentration (UIC) in both the young children and their mothers were analyzed. A total of 2282 mother-child pairs were included in this analysis. The median (p25-p75) UIC for lactating women, weaning women, and children were 121.3 µg/L (68.1-206.4 µg/L), 123.4 µg/L (58.4-227.2 µg/L), and 152.1 µg/L (75.8-268.3 µg/L), respectively. The UIC in children was found to be higher than that in their mothers (p < 0.001). Children who consumed less than 500 mL per day of formula milk in the last week had lower UICs compared with those who consumed 500 mL per day or more (p = 0.026). Furthermore, the children's UIC was positively correlated with the maternal UIC (rs = 0.285, p < 0.001). Multiple quantile regression analysis revealed a statistically significant positive association between maternal UIC and children's UIC between the 0.1 and 0.9 quantiles (all p < 0.001). We found that the iodine status of infants and toddlers, as well as of mothers, was sufficient. However, a large minority of children and mothers may be at risk of iodine deficiency. Furthermore, no associations between children's UIC and feeding behaviors were observed. Moreover, there was a positive correlation between the UIC of young children and their mothers.

Fabrication of Ceramic Microchannels with Periodic Corrugated Microstructures as Catalyst Support for Hydrogen Production via Diamond Wire Sawing.

Hydrogen energy is the clean energy with the most potential in the 21st century. The microchannel reactor for methanol steam reforming (MSR) is one of the effective ways to obtain hydrogen. Ceramic materials have the advantages of high temperature resistance, corrosion resistance, and high mechanical strength, and are ideal materials for preparing the catalyst support in microchannel reactors. However, the structure of ceramic materials is hard and brittle, and the feature size of microchannel is generally not more than 1 mm, which is difficult to process using traditional processing methods. Diamond wire saw processing technology is mainly used in the slicing of hard and brittle materials such as sapphire and silicon. In this paper, a microchannel with a periodic corrugated microstructure was fabricated on a ceramic plate using diamond wire sawing, and then as a catalyst support when used in a microreactor for MSR hydrogen production. The effects of wire speed and feed speed on the amplitude and period size of the periodic corrugated microstructure were studied using a single-factor experiment. The microchannel surface morphology was observed via SEM and a 3D confocal laser microscope under different processing parameters. The microchannel samples obtained under different processing parameters were supported by a multiple impregnation method. The loading strength of the catalyst was tested via a strong wind purge experiment. The experimental results show that the periodic corrugated microstructure can significantly enhance the load strength of the catalyst. The microchannel catalyst support with the periodic corrugated microstructure was put into the microreactor for a hydrogen production experiment, and a good hydrogen production effect was obtained. The experimental results have a positive guiding effect on promoting ceramic materials as the microchannel catalyst support for the development of hydrogen energy.

Comparative dosimetric study of h-IMRT and VMAT plans for breast cancer after breast-conserving surgery.

AIM: To compare the dosimetric advantages and disadvantages between hybrid intensity-modulated radiation therapy (h-IMRT) and the volumetric modulated arc therapy (VMAT) technique in hypofractionated whole-breast irradiation (HF-WBI) for early-stage breast cancer (BC). METHODS: The dose distribution of h-IMRT and VMAT plans was compared in 20 breast cancer patients. This comparison included evaluation of dosimetric parameters using dose volume histograms (DVHs) for the planning target volume (PTV) and organs-at-risk (OARs). Additionally, the study examined the normal tissue complication probability (NTCP), the second cancer complication probability (SCCP) and the tumor control probability (TCP) based on different models. RESULTS: Significant differences were detected between the two plans, in terms of Machine units (MUs), the control points, 95 % volume (V95 %), dose homogeneity index (DHI) and conformity index (CI). The endpoint of grade II radiation pneumonitis and cardiac death due to ischemic heart disease were assessed. In h-IMRT plan, the NTCP values were marginally lower for radiation pneumonitis and slightly higher for cardiac death compared to VMAT plan, as determined by the Lyman-Kutcher-Burman model. The Schneider model was employed to predict the SCCP for both the bilateral lungs and contralateral breast, the results demonstrate that the h-IMRT plan outperforms the VMAT plan, with statistical significance. Additionally, the LQ-Poisson model was employed to forecast the TCP of the PTV, showing that the h-IMRT plan outperformed the VMAT plan (P > 0.05). CONCLUSION: The h-IMRT technique, offering superior dose coverage and better therapeutic efficacy with fewer side effects as calculated by models, is more suitable for HF-WBI compared to the VMAT technique.

Integrated network pharmacology and serum metabonomics analysis to explore the potential mechanism of Anemarrhena asphodeloides Bunge-Phellodendron chinense Schneid herb pair in the treatment of benign prostatic hyperplasia.

Anemarrhena asphodeloides Bunge-Phellodendron chinense Schneid (AAPC) is one of the most widely accepted herb pairs in Chinese medicine prescription for treating benign prostatic hyperplasia (BPH). However, the mechanisms underlying the combination of the two herbs for anti-BPH are still not completely clear. To uncover the potential mechanism of the AAPC herb pair in the treatment of BPH, chemical profiling, network pharmacology, serum metabonomics and experimental validation were integrated. UHPLC-Q-Exactive Orbitrap-MS was performed to characterize the chemical profiling of the herb pair extract, and network pharmacology was employed to forecast the potential effective components, core targets and key signaling pathways. Then, western blot and RT-PCR experiments were conducted to verify the PI3K/Akt/NF-κB signaling pathway predicted by network pharmacology. Finally, the serum differential metabolites and metabolic pathways were analyzed by serum non-targeted metabonomics, and these results were jointly analyzed by MetScape. 51 chemical components of the AAPC herb pair extract were identified, including phellodendrine, magnoflorine, berberine, mangiferin, anemarsaponin BIII, etc. In network pharmacology, the predicted core targets of these components include AKT1, TNF, EGFR, PTGS2, PIK3CA, etc. The KEGG pathway enrichment analysis indicated that PI3K-Akt, Rap1 and MAPK signaling pathways may play a key role in the AAPC herb pair for the treatment of BPH, and the results of animal experiments demonstrated that the herb pair could significantly inhibit the activation and expression of p-PI3K/PI3K, p-Akt/Akt, p-NF-κB/NF-κB in protein and mRNA levels. Furthermore, 31 serum differential metabolites and three main metabolic pathways were obtained by serum non-targeted metabonomics. And the crucial metabolic pathway of arachidonic acid (AA) was obtained by integrated analysis of network pharmacology and metabonomics results. In conclusion, the AAPC herb pair can improve BPH through inhibiting the activation and expression of the PI3K/Akt/NF-κB signaling pathway and AA metabolism.

Enhancement of Colorimetric pH-Sensitive Film Incorporating Amomum tsao-ko Essential Oil as Antibacterial for Mantis Shrimp Spoilage Tracking and Fresh-Keeping.

Anthocyanin-based smart packaging has been widely used for food freshness monitoring, but it cannot meet the requirements of smart films with antibacterial properties. This study aimed to enhance the antibacterial properties of intelligent films by incorporating Amomum tsao-ko essential oil (AEO) for mantis shrimp spoilage tracking and keeping the product fresh. A smart film was designed by introducing AEO and purple potato anthocyanin (PPA) to a polyvinyl alcohol/cellulose nanocrystal (PVA/CNC) polymer matrix. Our findings revealed that APP and AEO imparted the smart film with a favorable oxygen barrier, UV protection, mechanical properties, and antioxidant and pH/NH3-sensitive functions. Interestingly, the PVA/CNC-AEO-PPA film achieved 45.41% and 48.25% bactericidal efficacy against S. putrefaciens and V. parahaemolyticus, respectively. Furthermore, a visual observation confirmed that the target film (PVA/CNC-AEO-PPA) changed color significantly during mantis shrimp spoilage: rose red-light red-pink-light gray-dark gray. Meanwhile, the PVA/CNC-AEO-PPA film retarded the quality deterioration of the mantis shrimp effectively. The PVA/CNC-AEO-PPA film shows great application potential in mantis shrimp preservation and freshness monitoring; it is expected to become a rapid sensor for detecting seafood quality non-destructively and a multifunctional film for better preservation of product quality.

Cell-Impermeable Buffering Fluorogenic Probes for Live-Cell Super-Resolution Imaging of Plasma Membrane Morphology Dynamics.

Super-resolution fluorescence imaging has emerged as a potent tool for investigating the nanoscale structure and function of the plasma membrane (PM). Nevertheless, the challenge persists in achieving super-resolution imaging of PM dynamics due to limitations in probe photostability and issues with cell internalization staining. Herein, we report assembly-mediated buffering fluorogenic probes BMP-14 and BMP-16 exhibiting fast PM labeling and extended retention time (over 2 h) on PM. The incorporation of alkyl chains proves effective in promoting the aggregation of BMP-14 and BMP-16 into nonfluorescent nanoparticles to realize fluorogenicity and regulate the buffering capacity to rapidly replace photobleached probes ensuring stable long-term super-resolution imaging of PM. Utilizing these PM-buffering probes, we observed dynamic movements of PM filopodia and continuous shrinkage, leading to the formation of extracellular vesicles (EVs) using structured illumination microscopy (SIM). Furthermore, we discovered two distinct modes of EV fusion: one involving fusion through adjacent lipids and the other through filamentous lipid traction. The entire process of EV fusion outside the PM was dynamically tracked. Additionally, BMP-16 exhibited a unique capability of inducing single-molecule fluorescence blinking when used for cell membrane staining. This property makes BMP-16 suitable for the PAINT imaging of cell membranes.

DNA Molecular Glue Assisted Bacterial Conjugative Transfer.

Bacterial conjugation, a commonly used method to horizontally transfer functional genes from donor to recipient strains, plays an important role in the genetic manipulation of bacteria for basic research and industrial production. Successful conjugation depends on the donor-recipient cell recognition and a tight mating junction formation. However, the efficiency of conjugative transfer is usually very low. In this work, we developed a new technique that employed DNA molecule "glue" to increase the match frequency and the interaction stability between the donor and recipient cells. We used two E. coli strains, ETZ and BL21, as a model system, and modified them with the complementary ssDNA oligonucleotides by click chemistry. The conjugation efficiency of the modified bacteria was improved more than 4 times from 10% to 46%. This technique is simple and generalizable as it only relies on the active amino groups on the bacterial surface. It is expected to have broad applications in constructing engineered bacteria.

The role of circadian rhythms and sleep in the aetiology of autism spectrum disorder and attention-deficit/hyperactivity disorder: New evidence from bidirectional two-sample Mendelian randomization analysis.

LAY ABSTRACT: Research shows that people with autism spectrum disorder and attention-deficit/hyperactivity disorder often have sleep issues and problems with the body's natural daily rhythms, known as circadian rhythms. By exploring the genetic variants associated with these rhythms and the conditions, this study reveals that these rhythm changes and sleep patterns are directly linked to autism spectrum disorder and attention-deficit/hyperactivity disorder. It found that the timing of one's most active hours can increase the likelihood of having both autism spectrum disorder and attention-deficit/hyperactivity disorder. Importantly, it also shows that good sleep quality might protect against autism spectrum disorder, while disturbed sleep in people with attention-deficit/hyperactivity disorder seems to be a result rather than the cause of the condition. This understanding can help doctors and researchers develop better treatment approaches that focus on the specific ways sleep and body rhythms affect those with autism spectrum disorder and attention-deficit/hyperactivity disorder, considering their unique associations with circadian rhythms and sleep patterns. Understanding these unique links can lead to more effective, personalized care for those affected by these conditions.

Development and validation of a LASSO prediction model for cisplatin induced nephrotoxicity: a case-control study in China.

BACKGROUND: Early identification of high-risk individuals with cisplatin-induced nephrotoxicity (CIN) is crucial for avoiding CIN and improving prognosis. In this study, we developed and validated a CIN prediction model based on general clinical data, laboratory indications, and genetic features of lung cancer patients before chemotherapy. METHODS: We retrospectively included 696 lung cancer patients using platinum chemotherapy regimens from June 2019 to June 2021 as the traing set to construct a predictive model using Absolute shrinkage and selection operator (LASSO) regression, cross validation, and Akaike's information criterion (AIC) to select important variables. We prospectively selected 283 independent lung cancer patients from July 2021 to December 2022 as the test set to evaluate the model's performance. RESULTS: The prediction model showed good discrimination and calibration, with AUCs of 0.9217 and 0.8288, sensitivity of 79.89% and 45.07%, specificity of 94.48% and 94.81%, in the training and test sets respectively. Clinical decision curve analysis suggested that the model has value for clinical use when the risk threshold ranges between 0.1 and 0.9. Precision-Recall (PR) curve shown in recall interval from 0.5 to 0.75: precision gradually declines with increasing Recall, up to 0.9. CONCLUSIONS: Predictive models based on laboratory and demographic variables can serve as a beneficial complementary tool for identifying high-risk populations with CIN.

Activated partial thromboplastin time predicts mortality in patients with severe fever with thrombocytopenia syndrome: A multicenter study in north China.

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with high lethality. This study aimed to determine whether prolonged activated partial thromboplastin time (APTT) predicted SFTS mortality. Methods: SFTS patients were enrolled from 6 hospitals in the north China. Subjects were divided into training cohort and 5 externally validation cohorts. The least absolute shrinkage and selection operator Cox regression model was performed to screen potential prognostic factors. Risk factors were analyzed using multivariable regression models. Prognostic models were established by Cox regression and random survival forest (RSF) methods, and evaluated regarding discrimination, validity and clinical benefit. Time-dependent receiver operating characteristic (ROC) curve was used to evaluate the predictive effectiveness of variables. Results: 1332 SFTS cases were included, in which 211 patients died. Six potential prognostic factors were screened, and pulse, breath, APTT and aspartic transaminase (AST) were independently associated with mortality in both training cohort (Yantai, N = 791) and external validation cohort (N = 541). APTT was steadily correlated with the fatality (HR: 1.039-1.144; all P < 0.01) in each five sub-validation cohorts (Dandong, Dalian, Tai'an, Qingdao and Beijing). RSF model with variables of APTT, AST, pulse and breath had considerable prognostic effectiveness, which APTT showed the highest prognostic ability with the area under the curve of 0.848 and 0.787 for 7-day and 14-day survival, respectively. Survival differences were found between high and low levels of APTT for mortality using 50s as the optimal cut-off. Conclusions: SFTS patients have prolonged APTT, which is an independent risk factor for fatality. APTT≥50s was recommended as a biomarker to remind physicians to monitor and treat patients more aggressively to improve clinical prognosis.

Artemisinins ameliorate polycystic ovarian syndrome by mediating LONP1-CYP11A1 interaction.

Polycystic ovary syndrome (PCOS), a prevalent reproductive disorder in women of reproductive age, features androgen excess, ovulatory dysfunction, and polycystic ovaries. Despite its high prevalence, specific pharmacologic intervention for PCOS is challenging. In this study, we identified artemisinins as anti-PCOS agents. Our finding demonstrated the efficacy of artemisinin derivatives in alleviating PCOS symptoms in both rodent models and human patients, curbing hyperandrogenemia through suppression of ovarian androgen synthesis. Artemisinins promoted cytochrome P450 family 11 subfamily A member 1 (CYP11A1) protein degradation to block androgen overproduction. Mechanistically, artemisinins directly targeted lon peptidase 1 (LONP1), enhanced LONP1-CYP11A1 interaction, and facilitated LONP1-catalyzed CYP11A1 degradation. Overexpression of LONP1 replicated the androgen-lowering effect of artemisinins. Our data suggest that artemisinin application is a promising approach for treating PCOS and highlight the crucial role of the LONP1-CYP11A1 interaction in controlling hyperandrogenism and PCOS occurrence.

An Asymmetric NIR-II Organic Fluorophore with an Ultra-Large Stokes Shift for Imaging-Guided and Targeted Phototherapy.

NIR-II imaging-guided phototherapy is an attractive, yet challenging, tumor treatment strategy. By monitoring the accumulation of phototherapy reagents at the tumor site through imaging and determining the appropriate therapy window, the therapeutic effect could be significantly improved. Probes with NIR-II (1000-1700 nm) fluorescence emission and a large Stokes shift hold great promise for fluorescence imaging with deep penetration, minimized self-quenching, and high spatiotemporal resolution. However, due to the lack of a suitable molecular framework, the design of a simple small-molecule dye with a large Stokes shift and NIR-II fluorescence emission has rarely been reported. Herein, we prepare an asymmetric D-π-A type NIR-II fluorescence probe (TBy). The probe is incapsulated in an amphiphilic polymer and modified with a fibronectin targeting peptide CREKA, which could recognize the fibrin-fibronectin complex overexpressed in multiple malignant tumors. The nanoparticles thus constructed (TByC-NPs) have maximum fluorescence emission at 1037 nm with a large Stokes shift of 426 nm, which is the largest Stokes shift among organic NIR-II fluorescent dyes reported in the literature. The TByC-NPs exhibit a good NIR-II imaging performance, active tumor targeting, and good photothermal and photodynamic capabilities. In vitro and in vivo studies verify that the TByC nanoplatform shows outstanding biocompatibility for NIR-II imaging-guided phototherapy and provides an excellent antitumor effect.

Sex-specific associations of adolescent motherhood with cognitive function, behavioral problems, and autistic-like traits in offspring and the mediating roles of family conflict and altered brain structure.

BACKGROUND: Previous studies have linked adolescent motherhood to adverse neurodevelopmental outcomes in offspring, yet the sex-specific effect and underlying mechanisms remain unclear. METHODS: This study included 6952 children aged 9-11 from the Adolescent Brain Cognitive Development study. The exposed group consisted of children of mothers < 20 years at the time of birth, while the unexposed group was composed of children of mothers aged 20-35 at birth. We employed a generalized linear mixed model to investigate the associations of adolescent motherhood with cognitive, behavioral, and autistic-like traits in offspring. We applied an inverse-probability-weighted marginal structural model to examine the potential mediating factors including adverse perinatal outcomes, family conflict, and brain structure alterations. RESULTS: Our results revealed that children of adolescent mothers had significantly lower cognitive scores (ß, - 2.11, 95% CI, - 2.90 to - 1.31), increased externalizing problems in male offspring (mean ratio, 1.28, 95% CI, 1.08 to 1.52), and elevated internalizing problems (mean ratio, 1.14, 95% CI, 0.99 to 1.33) and autistic-like traits (mean ratio, 1.22, 95% CI, 1.01 to 1.47) in female. A stressful family environment mediated ~ 70% of the association with internalizing problems in females, ~ 30% with autistic-like traits in females, and ~ 20% with externalizing problems in males. Despite observable brain morphometric changes related to adolescent motherhood, these did not act as mediating factors in our analysis, after adjusting for family environment. No elevated rate of adverse perinatal outcomes was observed in the offspring of adolescent mothers in this study. CONCLUSIONS: Our results reveal distinct sex-specific neurodevelopmental outcomes impacts of being born to adolescent mothers, with a substantial mediating effect of family environment on behavioral outcomes. These findings highlight the importance of developing sex-tailored interventions and support the hypothesis that family environment significantly impacts the neurodevelopmental consequences of adolescent motherhood.

Subcutaneous daratumumab in Chinese patients with relapsed or refractory multiple myeloma: an open-label, multicenter, phase 1 study (MMY1010).

Despite recent progress in multiple myeloma (MM) treatments, most patients will relapse and require additional treatment. Intravenous daratumumab, a human IgGκ monoclonal antibody targeting CD38, has shown good efficacy in the treatment of MM. A subcutaneous version of daratumumab was formulated to reduce the burden of intravenous infusions. We aimed to investigate the efficacy and safety of subcutaneous daratumumab in Chinese patients with relapsed/refractory MM based on the demonstrated noninferiority of subcutaneous daratumumab to intravenous daratumumab, with a shorter administration time and reduced infusion-related reaction rate in global studies. This phase 1, multicenter study (MMY1010; ClinicalTrials.gov Identifier: NCT04121260) evaluated subcutaneous daratumumab in Chinese patients with relapsed/refractory MM after 1 prior line (n = 1) or ≥2 prior lines (n = 20) of therapy, including a proteasome inhibitor and an immunomodulatory drug. Primary endpoints were pharmacokinetics and safety. Mean (standard deviation) maximum trough concentration of daratumumab was 826 (335) µg/mL, which was consistent with prior studies of subcutaneous daratumumab and intravenous daratumumab. Safety was consistent with safety profiles observed in other daratumumab studies, with no new safety concerns identified. Incidences of infusion-related reactions and injection-site reactions were low and consistent with other subcutaneous daratumumab studies. At a median follow-up of 7.5 months, the overall response rate was 57.1%, with a very good partial response or better rate of 38.1% and complete response or better rate of 19.0%. Our results demonstrate a favorable benefit/risk profile of subcutaneous daratumumab in Chinese patients with relapsed/refractory MM, potentially impacting clinical administration of daratumumab in this population.

SAMCF: Adaptive global style alignment and multi-color spaces fusion for joint optic cup and disc segmentation.

The optic cup (OC) and optic disc (OD) are two critical structures in retinal fundus images, and their relative positions and sizes are essential for effectively diagnosing eye diseases. With the success of deep learning in computer vision, deep learning-based segmentation models have been widely used for joint optic cup and disc segmentation. However, there are three prominent issues that impact the segmentation performance. First, significant differences among datasets collecting from various institutions, protocols, and devices lead to performance degradation of models. Second, we find that images with only RGB information struggle to counteract the interference caused by brightness variations, affecting color representation capability. Finally, existing methods typically ignored the edge perception, facing the challenges in obtaining clear and smooth edge segmentation results. To address these drawbacks, we propose a novel framework based on Style Alignment and Multi-Color Fusion (SAMCF) for joint OC and OD segmentation. Initially, we introduce a domain generalization method to generate uniformly styled images without damaged image content for mitigating domain shift issues. Next, based on multiple color spaces, we propose a feature extraction and fusion network aiming to handle brightness variation interference and improve color representation capability. Lastly, an edge aware loss is designed to generate fine edge segmentation results. Our experiments conducted on three public datasets, DGS, RIM, and REFUGE, demonstrate that our proposed SAMCF achieves superior performance to existing state-of-the-art methods. Moreover, SAMCF exhibits remarkable generalization ability across multiple retinal fundus image datasets, showcasing its outstanding generality.

Role of RIPK3 in lipid metabolism and postnatal overfeeding-induced metabolic disorders in mice.

Postnatal overfeeding can increase the long-term risk of metabolic disorders, such as obesity, but the underlying mechanisms remain unclear and treatment approaches are limited. Receptor-interacting protein kinase 3 (RIPK3) is associated with several metabolic diseases. We investigated the effects of RIPK3 on neonatal overfeeding-related metabolic disorders. On postnatal day 3, litter sizes were adjusted to 9-10 (normal litters, NL) or 2-3 (small litters, SL) mice per dam to mimic postnatal overfeeding. After weaning, NL and SL mouse were fed normal diet. We generated an adeno-associated virus (AAV) carrying short hairpin RNA (shRNA) against Ripk3 and an empty vector as a control. The NL and SL groups were treated intravenously with 1×1012 vector genome of AAV vectors at week 6. The SL group showed a higher body weight than the NL group from week 3 of age through adulthood. At weeks 6 and 13, the SL group exhibited impaired glucose and insulin tolerance, RIPK3 up-regulation, and lipid accumulation in liver and adipose tissues. In the SL group, the genes involved in lipid synthesis and lipolysis were increased, whereas fatty acid ß-oxidation-related genes were weakened in adipose tissue and liver. At week 13, AAV-shRNA-Ripk3 ameliorated adipose tissue hypertrophy, hepatic steatosis, insulin resistance, and dysregulated lipid metabolism in the adipose tissue and liver of SL mice. These findings support a novel mechanism underlying the pathogenesis of postnatal overfeeding-related metabolic disorders and suggest potential therapeutic targets.

Multimode Ultrasound Model for Predicting the Early Treatment Response of Anti-VEGF Agents Plus Anti-PD-1 Antibody in Patients with Unresectable Hepatocellular Carcinoma.

OBJECTIVE: The purpose of the study described was to establish prediction models to initially screen the beneficiary patients with unresectable hepatocellular carcinoma (HCC) in the treatment of anti-vascular endothelial growth factor (VEGF) agents plus anti-programmed cell death-1 (PD-1) antibody. METHODS: A total of 62 patients were enrolled in this study. All patients underwent ultrasound (US), color ddoppler flowing imaging (CDFI), contrast-enhanced ultrasound (CEUS) and laboratory examinations within 2 wk before the treatment. Tumor response was assessed according to mRECIST criteria. Univariate and multivariate analyses were used to select the independent predictors. US + CDFI, CEUS and FULL models were established. Three models were displayed by nomography. Receiver operating characteristic (ROC) and calibration curves were drawn to evaluate the predictive ability of models. Decision curve analysis (DCA) was used to assess the clinical utility of models. RESULTS: On univariate and multivariate analysis, the US boundary (p = 0.037), halo (p = 0.002) and CDFI (p = 0.024) were included in the US + CDFI model. CEUS boundary (p = 0.001) and washout time (p < 0.001) were included in the CEUS model. The number of lesions (p = 0.104), halo on US (p = 0.014), CDFI (p = 0.057) and washout time on CEUS (p = 0.015) were incorporated into the FULL model. The C indices of the US + CDFI, CEUS and FULL models were 0.918, 0.920 and 0.973. CEUS and FULL models yielded a good net benefit for almost all threshold probabilities. CONCLUSION: Nomograms based on US, CDFI, CEUS and clinical characteristics could help to non-invasively predict the response to treatment with anti-PD-1 antibodies plus anti-VEGF agents.

FBP1 orchestrates keratinocyte proliferation/differentiation and suppresses psoriasis through metabolic control of histone acetylation.

Keratinocyte proliferation and differentiation in epidermis are well-controlled and essential for reacting to stimuli such as ultraviolet light. Imbalance between proliferation and differentiation is a characteristic feature of major human skin diseases such as psoriasis and squamous cell carcinoma. However, the effect of keratinocyte metabolism on proliferation and differentiation remains largely elusive. We show here that the gluconeogenic enzyme fructose-1,6-bisphosphatase 1 (FBP1) promotes differentiation while inhibits proliferation of keratinocyte and suppresses psoriasis development. FBP1 is identified among the most upregulated genes induced by UVB using transcriptome sequencing and is elevated especially in upper epidermis. Fbp1 heterozygous mice exhibit aberrant epidermis phenotypes with local hyperplasia and dedifferentiation. Loss of FBP1 promotes proliferation and inhibits differentiation of keratinocytes in vitro. Mechanistically, FBP1 loss facilitates glycolysis-mediated acetyl-CoA production, which increases histone H3 acetylation at lysine 9, resulting in enhanced transcription of proliferation genes. We further find that the expression of FBP1 is dramatically reduced in human psoriatic lesions and in skin of mouse imiquimod psoriasis model. Fbp1 deficiency in mice facilitates psoriasis-like skin lesions development through glycolysis and acetyl-CoA production. Collectively, our findings reveal a previously unrecognized role of FBP1 in epidermal homeostasis and provide evidence for FBP1 as a metabolic psoriasis suppressor.

The promotion mechanism of different nitrogen doping types on the catalytic activity of activated carbon electro-Fenton cathode: Simultaneous promotion of H2O2 generation and phenol degradation ability.

Doping with nitrogen atoms can improve the catalytic activity of activated carbon cathodes in electro-Fenton systems, but currently there is a lack of understanding of the catalytic mechanism, which limits the further development of high-performance activated carbon cathodes. Here, a multi-scale exploration was conducted using density functional theory and experimental methods to investigate the mechanism of different nitrogen doping types promoting the redox performance of activated carbon cathodes and the degradation of phenol. The density functional theory results indicate that the introduction of nitrogen atoms enhances the binding ability between carbon substrates and oxygen-containing substances, promotes the localization of surrounding electrons, and makes it easier for O2 to bind with protons and catalyze the hydrogenation reaction of *OOH. Due to its weak binding ability with oxygen-containing substances, AC is difficult to form H2O2, resulting in a tendency towards the 4e-ORR pathway. The binding energy between graphite-N carbon substrate and pyridine-N carbon substrate with *OOH is closer to the volcano top, so graphite n and pyridine n can better promote the selectivity of activated carbon for 2e-ORR. In addition, the calculation results also indicate that pyrrole-N and graphite-N are more capable of catalyzing the reaction energy barrier between ·OH and phenol. Finally, the simulation results were used to guide the modification of nitrogen doped activated carbon and experimental verification was carried out. The degradation results of phenol confirmed the efficient synergistic effect between different types of nitrogen doping, and the NAC-800 electrode exhibited efficient and stable characteristics. This work provides a guiding strategy for further developing stable and highly selective activated carbon cathode materials.

Complex phenotype in Fanconi renotubular syndrome type 1: Hypophosphatemic rickets as the predominant presentation.

GATM-related Fanconi renotubular syndrome 1 (FRTS1) is a form of renal Fanconi syndrome (RFS), which is a disorder of solute and water reabsorption caused by defects in the function of the entire proximal tubule. Recent findings reveal the molecular basis of FRTS1: Intramitochondrial fiber aggregation triggered by mutant GATM provides a starting point for proximal tubule damage and drives disease progression. As a rare and newly recognized inherited kidney disease, the complex manifestations of FRTS1 are easily underdiagnosed or misdiagnosed. We discuss the complex phenotype of a 26-year-old woman with onset in infancy and a long history of hypophosphatemic rickets. We also identified a novel heterozygous missense variant in the GATM gene in this patient. The novel variant and phenotype we report expand the disease spectrum of FRTS1. We recommend screening for GATM in children with RFS, especially in patients with resistant rickets who have previously had negative genetic testing. In addition, we found pathological deposition of mutant GATM proteins within mitochondria in the patient's urinary sediment cells by a combination of electron microscopy and immunofluorescence. This unique urine cytology experiment has the potential to be a valuable tool for identifying patients with RRTS1.