Scalable Customization of Crystallographic Plane Controllable Lithium Metal Anodes for Ultralong-Lasting Lithium Metal Batteries.

A formidable challenge to achieve the practical applications of rechargeable lithium (Li) metal batteries (RLMBs) is to suppress the uncontrollable growth of Li dendrites. One of the most effective solutions is to fabricate Li metal anodes with specific crystal plane, but still lack of a simple and high-efficient approach. Herein, a facile and controllable way for the scalable customization of polished Li metal anodes with highly preferred (110) and (200) crystallographic orientation (donating as polished Li(110) and polished Li(200), respectively) by regulating the times of accumulative roll bonding, is reported. According to the inherent characteristics of polished Li(110)/Li(200), the influence of Li atomic structure on the electrochemical performance of RLMBs is deeply elucidated by combining theoretical calculations with relative experimental proofs. In particular, a polished Li(110) crystal plane is demonstrated to induce Li+ uniform deposition, promoting the formation of flat and dense Li deposits. Impressively, the polished Li(110)||LiFePO4 full cells exhibit unprecedented cycling stability with 10 000 cycles at 10 C almost without capacity degradation, indicating the great potential application prospect of such textured Li metal. More valuably, this work provides an important reference for low-cost, continued, and large-scale production of Li metal anodes with highly preferred crystal orientation through roll-to-roll manufacturability.

Specific Knockout of Notch-1 in Macrophages Modulate the Progression of Hepatic Insulin Resistance in HFD Fed Mice via Regulating IRE1α-XBP1 Signals.

OBJECTIVE: To develop an intervention based on Notch-1 signalling pathway blockade by investigating the potential application of the neurogenic locus notch homologue protein 1(Notch-1) signalling pathway as a key regulator of chronic inflammation and adipogenesis in the treatment of hepatic insulin resistance (HIR). STUDY DESIGN: Experimental study. Place and Duration of the Study: Animal Laboratory of the Fourth Hospital of Hebei Medical University, Shijiazhuang, China, from April 2021 to June 2022. METHODOLOGY: HIR models were established in Notch-1WT and Notch-1MAC-KO mice by high fat diet (HFD) for 16 weeks. Haematoxylin and eosin (HE) staining and oil red O (ORO) staining were used to detect inflammatory infiltration and lipid accumulation in each group. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of TNF-α and IL-6. Free fatty acid (FFA) and total cholesterol (TC) were measured with relevant kits. Moreover, real-time quantitative polymerase chain reaction (PCR) was performed to detect the relative expressions of F4/80, Mcp1, and CD11b in hepatic tissues. Mass spectrometry was used to analyse the levels of triglyceride (TG), diacylglycerol (DAG) and conformite europeenne (CE) in liver tissue. Western blotting was used to detect the expression of related proteins. RESULTS: Specific knockdown of Notch-1 in macrophages decreases the relative fluorescence intensity of CD68 and attenuates inflammatory infiltration and lipid degeneration. There was no difference in plasma levels of FFA and TG. Specific knockdown of Notch-1 in macrophages decreases the expression of F4/80, Mcp1, and CD11b, as well as the levels of TG, DAG, CE, IL-6, and TNF-α. CONCLUSION: Specific knockout of Notch-1 in macrophages may reduce HIR by inhibiting the IRE1α-XBP1 signalling pathway. KEY WORDS: Hepatic insulin resistance, Macrophages, Notch-1, IRE1α, XBP1.

Identification and functional characterization of ABC transporters for selenium accumulation and tolerance in soybean.

ATP-binding cassette (ABC) transporters were crucial for various physiological processes like nutrition, development, and environmental interactions. Selenium (Se) is an essential micronutrient for humans, and its role in plants depends on applied dosage. ABC transporters are considered to participate in Se translocation in plants, but detailed studies in soybean are still lacking. We identified 196 ABC genes in soybean transcriptome under Se exposure using next-generation sequencing and single-molecule real-time sequencing technology. These proteins fell into eight subfamilies: 8 GmABCA, 51 GmABCB, 39 GmABCC, 5 GmABCD, 1 GmABCE, 10 GmABCF, 74 GmABCG, and 8 GmABCI, with amino acid length 121-3022 aa, molecular weight 13.50-341.04 kDa, and isoelectric point 4.06-9.82. We predicted a total of 15 motifs, some of which were specific to certain subfamilies (especially GmABCB, GmABCC, and GmABCG). We also found predicted alternative splicing in GmABCs: 60 events in selenium nanoparticles (SeNPs)-treated, 37 in sodium selenite (Na2SeO3)-treated samples. The GmABC genes showed differential expression in leaves and roots under different application of Se species and Se levels, most of which are belonged to GmABCB, GmABCC, and GmABCG subfamilies with functions in auxin transport, barrier formation, and detoxification. Protein-protein interaction and weighted gene co-expression network analysis suggested functional gene networks with hub ABC genes, contributing to our understanding of their biological functions. Our results illuminate the contributions of GmABC genes to Se accumulation and tolerance in soybean and provide insight for a better understanding of their roles in soybean as well as in other plants.

Effects of Apatinib combined with Temozolomide on levels of sPD-1 and sPD-L1 in patients with drug-resistant recurrent glioblastoma.

OBJECTIVE: This study aimed to explore the effects of Apatinib combined with Temozolomide (TMZ) on the levels of Soluble PD-1 (sPD-1) and Soluble Programmed Death-1 Ligand (sPD-L1) in patients with drug-resistant recurrent Glioblastoma (GB). STUDY DESIGN: A total of 69 patients with recurrent GB from September 2020 to March 2022 were recruited and assigned to the control group (n = 34) and observation group (n = 35) according to different treatment options after tumor recurrence. The control group was treated with TMZ, and the observation group was treated with Apatinib combined with TMZ. Levels of sPD-1 and spd-l1, clinical efficacy, survival time and adverse reactions were observed and compared between the two groups. RESULTS: General data including gender, age, body mass index, and combined diseases indicated no statistical significance between groups (p > 0.05). Before the intervention, sPD-1 and sPD-L1 levels were not significantly different in the two groups (p > 0.05). After interventions, levels of PD-1 and sPD-L1 levels decreased significantly (p < 0.05). The objective remission rate and clinical benefit rate of the observation group were higher and overall survival and progression-free survival were longer than those of the control group (p < 0.05). No significant difference was observed in major adverse reactions among patients (p > 0.05). CONCLUSIONS: Apatinib combined with TMZ is safe and effective in the treatment of recurrent GB. The combined application of the two can reduce the levels of sPD-1 and sPD-L1, which has important clinical application value.

miR-455-3p regulates lymphangiogenesis in silicosis by regulating VEGF-C/VEGFR3.

Silicosis is a disease characterized by lung inflammation and fibrosis caused by long-term inhalation of free silicon dioxide (SiO2). Recent studies have found that a large number of lymphatic hyperplasia occurs during the occurrence and development of silicosis. miRNAs play an important role in lymphangiogenesis. However, the regulation and mechanism of miRNAs on lymphangiogenesis in silicosis remain unclear. In this study, lymphangiogenesis was observed in silicosis rats, and VEGF-C-targeted miRNAs were screened, and the effect of miRNAs on the formation of human lymphatic endothelial cells (HLECs) tubular structure was investigated in vitro. The results showed that SiO2 promoted the expressions of Collagen Ι and α-SMA, TNF-α, IL-6 and VEGF-C increased first and then decreased, and promoted the formation of lymphatic vessels. Bioinformatics methods screened miR-455-3p for targeted binding to VEGF-C, and dual luciferase reporter genes confirmed VEGF-C as the target gene of miR-455-3p, and miR-455-3p was down-regulated in the lung tissue of silicosis rats. Transfection of miR-455-3p Inhibitors down-regulated the expression level of miR-455-3p and up-regulated the expression levels of VEGF-C and VEGFR-3 in HLECs, enhanced migration ability and increased tube formation. Transfection of miR-455-3p Mimics showed an opposite trend. These results suggest that miR-455-3p further regulates the tubular structure formation of HLECs by regulating VEGF-C/VEGFR3. Therefore, targeting miR-455-3p may provide a new therapeutic strategy for SiO2-induced silicosis injury.

Urbanization promotes carbon storage or not? The evidence during the rapid process of China.

China's commitment to attaining carbon neutrality by 2060 has galvanized research into carbon sequestration, a critical approach for mitigating climate change. Despite the rapid urbanization observed since the turn of the millennium, a comprehensive analysis of how urbanization influences urban carbon storage throughout China remains elusive. Our investigation delves into the nuanced effects of urbanization on carbon storage, dissecting both the direct and indirect influences by considering urban-suburban gradients and varying degrees of urban intensity. We particularly scrutinize the roles of climatic and anthropogenic factors in mediating the indirect effects of urbanization on carbon storage. Our findings reveal that urbanization in China has precipitated a direct reduction in carbon storage by approximately 13.89 Tg of carbon (Tg C). Remarkably, urban sprawl has led to a diminution of vegetation carbon storage by 8.65 Tg C and a decrease in soil carbon storage by 5.24 Tg C, the latter resulting from the sequestration of impervious surfaces and the elimination of organic matter inputs following vegetation removal. Meanwhile, carbon storage in urban greenspaces has exhibited an increase of 6.90 Tg C and offsetting 49.70% of the carbon loss induced by direct urbanization effects. However, the indirect effects of urbanization predominantly diminish carbon storage in urban greenspaces by an average of 5.40%. The degree of urban vegetation management emerges as a pivotal factor influencing the indirect effects of urbanization on carbon storage. To bolster urban carbon storage, curbing urban sprawl and augmenting urban green spaces are imperative strategies. Insights from this study are instrumental in steering sustainable urban planning and advancing towards the goal of carbon neutrality.

The application of large language models in medicine: A scoping review.

This study systematically reviewed the application of large language models (LLMs) in medicine, analyzing 550 selected studies from a vast literature search. LLMs like ChatGPT transformed healthcare by enhancing diagnostics, medical writing, education, and project management. They assisted in drafting medical documents, creating training simulations, and streamlining research processes. Despite their growing utility in assisted diagnosis and improving doctor-patient communication, challenges persisted, including limitations in contextual understanding and the risk of over-reliance. The surge in LLM-related research indicated a focus on medical writing, diagnostics, and patient communication, but highlighted the need for careful integration, considering validation, ethical concerns, and the balance with traditional medical practice. Future research directions suggested a focus on multimodal LLMs, deeper algorithmic understanding, and ensuring responsible, effective use in healthcare.

Involvement of H2A variants in DNA damage response of zygotes.

Phosphorylated H2AX, known as γH2AX, forms in response to genotoxic insults in somatic cells. Despite the high abundance of H2AX in zygotes, the level of irradiation-induced γH2AX is low at this stage. Another H2A variant, TH2A, is present at a high level in zygotes and can also be phosphorylated at its carboxyl end. We constructed H2AX- or TH2A-deleted mice using CRISPR Cas9 and investigated the role of these H2A variants in the DNA damage response (DDR) of zygotes exposed to γ-ray irradiation at the G2 phase. Our results showed that compared to irradiated wild-type zygotes, irradiation significantly reduced the developmental rates to the blastocyst stage in H2AX-deleted zygotes but not in TH2A-deleted ones. Furthermore, live cell imaging revealed that the G2 checkpoint was activated in H2AX-deleted zygotes, but the duration of arrest was significantly shorter than in wild-type and TH2A-deleted zygotes. The number of micronuclei was significantly higher in H2AX-deleted embryos after the first cleavage, possibly due to the shortened cell cycle arrest of damaged embryos and, consequently, the insufficient time for DNA repair. Notably, FRAP analysis suggested the involvement of H2AX in chromatin relaxation. Moreover, phosphorylated CHK2 foci were found in irradiated wild-type zygotes but not in H2AX-deleted ones, suggesting a critical role of these foci in maintaining cell cycle arrest for DNA repair. In conclusion, H2AX, but not TH2A, is involved in the DDR of zygotes, likely by creating a relaxed chromatin structure with enhanced accessibility for DNA repair proteins and by facilitating the formation of pCHK2 foci to prevent premature cleavage.

Genetic, virulence, and antimicrobial resistance characteristics associated with distinct morphotypes in ST11 carbapenem-resistant Klebsiella pneumoniae.

ST11 is the most common lineage among carbapenem-resistant Klebsiella pneumoniae (CRKP) infections in Asia. Diverse morphotypes resulting from genetic mutations are associated with significant differences in microbial characteristics among K. pneumoniae isolates. Here, we investigated the genetic determinants and critical characteristics associated with distinct morphotypes of ST11 CRKP. An ST11-KL47 CRKP isolate carrying a pLVPK-like virulence plasmid was isolated from a patient with a bloodstream infection; the isolate had the "mcsw" morphotype. Two distinct morphotypes ("ntrd" and "msdw") were derived from this strain during in vitro passage. Whole genome sequencing was used to identify mutations that cause the distinct morphotypes of ST11 CRKP. Transmission electron microscopy, antimicrobial susceptibility tests, growth assays, biofilm formation, virulence assays, membrane permeability assays, and RNA-seq analysis were used to investigate the specific characteristics associated with different morphotypes of ST11 CRKP. Compared with the parental mcsw morphotype, the ntrd morphotype resulted from mutation of genes involved in capsular polysaccharide biosynthesis (wza, wzc, and wbaP), a result validated by gene knockout experiments. This morphotype showed capsule deficiency and lower virulence potential, but higher biofilm production. By contrast, the msdw morphotype displayed competition deficiency and increased susceptibility to chlorhexidine and polymyxin B. Further analyses indicated that these characteristics were caused by interruption of the sigma factor gene rpoN by insertion mutations and deletion of the rpoN gene, which attenuated membrane integrity presumably by downregulating the phage shock protein operon. These data expand current understanding of genetic, virulence, and antimicrobial resistance characteristics associated with distinct morphotypes in ST11 CRKP.

Androgens and erectile dysfunction: from androgen deficiency to treatment.

INTRODUCTION: Androgens play important roles in regulating the growth and development of the male reproductive system and maintaining libido and erectile function. The specific mechanisms by which androgen deficiency leads to erectile dysfunction (ED) are not yet fully understood. OBJECTIVES: To understand the mechanisms and treatment of androgen deficiency-related ED. METHODS: A literature search in the past 10 years was conducted in PubMed and Google Scholar to determine the effects of androgen deficiency on erectile function and the treatment of androgen deficiency. RESULTS: Androgen deficiency can be caused by hypothalamic-pituitary lesions and injuries, testicular-related diseases and injuries, endocrine and metabolic disorders, the side effects of medication, and age. Androgen deficiency can lead to ED by inhibiting the NOS/NO/cGMP pathway (nitric oxide synthase/nitric oxide/cyclic guanosine monophosphate) and altering the expression of ion channel proteins, as well as by inducing oxidative stress, death, and fibrosis in penile corpus cavernosum cells. Testosterone replacement therapy is effective at improving the serum testosterone levels and erectile function in patients with androgen deficiency. For patients who need to maintain a low androgenic state, erectile function can be improved by lifestyle changes, treatment with phosphodiesterase type 5 inhibitors, low-intensity extracorporeal shock wave therapy, and stem cell therapy. CONCLUSIONS: Androgen deficiency can affect the structure and function of the penile corpus cavernosum, leading to ED. Areas of further study include how androgen replacement therapy can improve erectile function and how to improve the maintenance of erectile function in patients with hypoandrogenic status.

Applying the Wake-Up-like Effect to Enhance the Capabilities of Two-Dimensional Ferroelectric Field-Effect Transistors.

For traditional ferroelectric field-effect transistors (FeFETs), enhancing the polarization domain of bulk ferroelectric materials is essential to improve device performance. However, there has been limited investigation into the enhancement of polarization field in two-dimensional (2D) ferroelectric material such as CuInP2S6 (CIPS). In this study, similar to bulk ferroelectric materials, CIPS exhibited enhanced polarization field upon application of external cyclic voltage. Moreover, unlike traditional ferroelectric materials, the polarization enhancement of CIPS is not due to redistribution of the defect but rather originates from a mechanism: the long-distance migration of Cu ions. We termed this mechanism the "wake-up-like effect". After incorporating the wake-up-like effect into the graphene/CIPS/WSe2 FeFET device, we successfully increased the hysteresis window and enhanced the current on/off ratio by 4 orders of magnitude. Moreover, the FeFET yielded remarkable achievements, such as multilevel nonvolatile memory with 21 distinct conductance levels, a high on/off ratio exceeding 106, a long retention time exceeding 103 s, and neuromorphic computing with 93% accuracy at recognizing handwritten digits. Introducing the wake-up-like effect to 2D CIPS may pave the way for innovative approaches to achieve advanced multilevel nonvolatile memory and neuromorphic computing capabilities for next-generation micro-nanoelectronic devices.

Prognostic significance of preoperative lymphocytes, albumin, and neutrophils (LANR) index in resectable pancreatic ductal adenocarcinoma.

PURPOSE: The index composed of preoperative lymphocytes, albumin, and neutrophils (LANR), a new composite score based on inflammatory response and nutritional status, has been reported to be associated with the prognosis of multiple types of cancer, but the role of LANR in the prognosis of resectable pancreatic ductal adenocarcinoma (PDAC) has not yet been elucidated. PATIENTS AND METHODS: The data of 142 patients with PDAC who underwent radical resection in the Affiliated Hospital of Jiangnan University from January 2015 to December 2018 were retrospectively analyzed. Receiver Operating Characteristic (ROC) curves were generated to determine the optimal cut-off values for these parameters, as well as the sensitivity and specificity of LANR in predicting survival. The Kaplan-Meier method was used to draw the survival curves. Log rank test was used for univariate analysis, and Cox proportional hazards regression model was used for multivariate analysis.  RESULTS: The optimal cut-off value of LANR was 18.145, and a low preoperative LANR was significantly correlated with the location of the tumor (p = 0.047). Multivariate analysis showed that tumor differentiation degree (HR:2.357, 95%CI:1.388-4.003,p = 0.002), lymph node metastasis (HR:1.755, 95%CI: 1.115-2.763, p = 0.015), TNM stage (HR:4.686, 95%CI: 2.958-7.425, p < 0.001), preoperative cancer antigen 19 - 9 levels (HR:1.001, 95%CI: 1.000-1.001, p < 0.001) and preoperative LANR (HR:0.221, 95%CI: 0.111-0.441, p < 0.001) were independent risk factors for a poor prognosis in patients undergoing radical resection of PDAC. CONCLUSION: This study found that preoperative LANR can be used to assess the prognosis of radical resection in patients with PDAC; those with low preoperative LANR had a worse outcome.

Chemoradiotherapy versus surgery after neoadjuvant chemoimmunotherapy in patients with stage III NSCLC: a real-world multicenter retrospective study.

PURPOSE: The optimal treatment after neoadjuvant chemoimmunotherapy for patients with stage III non-small cell lung cancer (NSCLC) is unclear. This study aimed at comparing the efficacy and safety of chemoradiotherapy and surgery after neoadjuvant chemoimmunotherapy in stage III NSCLC. MATERIALS AND METHODS: We conducted a real-world multicenter retrospective study on patients with stage III NSCLC who received surgery or chemoradiotherapy after neoadjuvant chemoimmunotherapy between October 2018 and December 2022. Progression-free survival (PFS) and overall survival (OS) were assessed from the initiation of neoadjuvant treatment and estimated by the Kaplan‒Meier method. Univariate and multivariate Cox regression models were used to examine potential prognostic factors. One-to-one propensity score matching (PSM) was used to further minimize confounding. RESULTS: A total of 239 eligible patients were enrolled, with 104 (43.5%) receiving surgery and 135 (56.5%) receiving CRT. After 1:1 PSM, 1- and 2-year PFS rates in patients receiving radical surgery (rSurgery group) vs. patients receiving definitive cCRT (dCCRT group) were 80.0% vs. 79.2% and 67.2% vs. 53.1%, respectively (P = 0.774). One- and 2-year OS rates were 97.5% vs. 97.4% and 87.3% vs. 89.9%, respectively (P = 0.558). Patients in the dCCRT group had a numerically lower incidence of distant metastases compared to those in the rSurgery group (42.9% vs. 70.6%, P = 0.119). The incidence of treatment-related adverse events was similar in both groups, except that the incidence of grade 3/4 hematological toxicity was significantly higher in the dCCRT group (30.0% vs. 10.0%, P = 0.025). CONCLUSION: Following neoadjuvant chemoimmunotherapy, definitive concurrent chemoradiotherapy may achieve noninferior outcomes to radical surgery in stage III NSCLC.

Anthocyanin gene enrichment in the distal region of cotton chromosome A07: mechanisms of reproductive organ coloration.

Introduction: The biosynthesis of secondary metabolites like anthocyanins is often governed by metabolic gene clusters (MGCs) in the plant ancestral genome. However, the existence of gene clusters specifically regulating anthocyanin accumulation in certain organs is not well understood. Methods and results: In this study, we identify MGCs linked to the coloration of cotton reproductive organs, such as petals, spots, and fibers. Through genetic analysis and map-based cloning, we pinpointed key genes on chromosome A07, such as PCC/GhTT19, which is involved in anthocyanin transport, and GbBM and GhTT2-3A, which are associated with the regulation of anthocyanin and proanthocyanidin biosynthesis. Our results demonstrate the coordinated control of anthocyanin and proanthocyanidin pathways, highlighting the evolutionary significance of MGCs in plant adaptation. The conservation of these clusters in cotton chromosome A07 across species underscores their importance in reproductive development and color variation. Our study sheds light on the complex biosynthesis and transport mechanisms for plant pigments, emphasizing the role of transcription factors and transport proteins in pigment accumulation. Discussion: This research offers insights into the genetic basis of color variation in cotton reproductive organs and the potential of MGCs to enhance our comprehension of plant secondary metabolism.

Fn-OMV potentiates ZBP1-mediated PANoptosis triggered by oncolytic HSV-1 to fuel antitumor immunity.

Oncolytic viruses (OVs) show promise as a cancer treatment by selectively replicating in tumor cells and promoting antitumor immunity. However, the current immunogenicity induced by OVs for tumor treatment is relatively weak, necessitating a thorough investigation of the mechanisms underlying its induction of antitumor immunity. Here, we show that HSV-1-based OVs (oHSVs) trigger ZBP1-mediated PANoptosis (a unique innate immune inflammatory cell death modality), resulting in augmented antitumor immune effects. Mechanistically, oHSV enhances the expression of interferon-stimulated genes, leading to the accumulation of endogenous Z-RNA and subsequent activation of ZBP1. To further enhance the antitumor potential of oHSV, we conduct a screening and identify Fusobacterium nucleatum outer membrane vesicle (Fn-OMV) that can increase the expression of PANoptosis execution proteins. The combination of Fn-OMV and oHSV demonstrates potent antitumor immunogenicity. Taken together, our study provides a deeper understanding of oHSV-induced antitumor immunity, and demonstrates a promising strategy that combines oHSV with Fn-OMV.

Observation of dichotomic field-tunable electronic structure in twisted monolayer-bilayer graphene.

Twisted bilayer graphene (tBLG) provides a fascinating platform for engineering flat bands and inducing correlated phenomena. By designing the stacking architecture of graphene layers, twisted multilayer graphene can exhibit different symmetries with rich tunability. For example, in twisted monolayer-bilayer graphene (tMBG) which breaks the C2z symmetry, transport measurements reveal an asymmetric phase diagram under an out-of-plane electric field, exhibiting correlated insulating state and ferromagnetic state respectively when reversing the field direction. Revealing how the electronic structure evolves with electric field is critical for providing a better understanding of such asymmetric field-tunable properties. Here we report the experimental observation of field-tunable dichotomic electronic structure of tMBG by nanospot angle-resolved photoemission spectroscopy (NanoARPES) with operando gating. Interestingly, selective enhancement of the relative spectral weight contributions from monolayer and bilayer graphene is observed when switching the polarity of the bias voltage. Combining experimental results with theoretical calculations, the origin of such field-tunable electronic structure, resembling either tBLG or twisted double-bilayer graphene (tDBG), is attributed to the selectively enhanced contribution from different stacking graphene layers with a strong electron-hole asymmetry. Our work provides electronic structure insights for understanding the rich field-tunable physics of tMBG.

Segmentation of hyphae and yeast in fungi-infected tissue slice images and its application in analyzing anti-fungal blue light therapy.

Candida albicans (C. albicans) is a pathogenic fungus that undergoes morphological transitions between hyphal and yeast, adapting to diverse environmental stimuli and exhibiting distinct virulence. Existing researches on anti-fungal blue light (ABL) therapy have either focused solely on hyphae or neglected to differentiate between morphologies, obscuring potential differential effects. To address this gap, we established a novel dataset of 150 C. albicans-infected mouse skin tissue slice images with meticulously annotated hyphae and yeast. Eleven representative convolutional neural networks were trained and evaluated on this dataset using seven metrics to identify the optimal model for segmenting hyphae and yeast in original high pixel size images. Leveraging the segmentation results, we analyzed the differential impact of blue light on the invasion depth and density of both morphologies within the skin tissue. Comparison results demonstrated that U-Net-BN emerged as superior segmentation accuracy compared to other models, achieving the best overall performance. While both hyphae and yeast exhibited significant reductions in invasion depth and density at the highest ABL dose (180 J/cm2), only yeast was significantly inhibited at the lower dose (135 J/cm2). This novel finding emphasizes the importance of developing more effective treatment strategies for both morphologies.

We studied the effects of blue light therapy on hyphal and yeast forms of Candida albicans. Through image segmentation techniques, we discovered that the changes in invasion depth and density differed between these two forms after exposure to blue light.

Extravascular administration of IGF1R antagonists protects against aortic aneurysm in rodent and porcine models.

An abdominal aortic aneurysm (AAA) is a life-threatening cardiovascular disease. We identified plasma insulin-like growth factor 1 (IGF1) as an independent risk factor in patients with AAA by correlating plasma IGF1 with risk. Smooth muscle cell- or fibroblast-specific knockout of Igf1r, the gene encoding the IGF1 receptor (IGF1R), attenuated AAA formation in two mouse models of AAA induced by angiotensin II infusion or CaCl2 treatment. IGF1R was activated in aortic aneurysm samples from human patients and mice with AAA. Systemic administration of IGF1C, a peptide fragment of IGF1, 2 weeks after disease development inhibited AAA progression in mice. Decreased AAA formation was linked to competitive inhibition of IGF1 binding to its receptor by IGF1C and modulation of downstream alpha serine/threonine protein kinase (AKT)/mammalian target of rapamycin signaling. Localized application of an IGF1C-loaded hydrogel was developed to reduce the side effects observed after systemic administration of IGF1C or IGF1R antagonists in the CaCl2-induced AAA mouse model. The inhibitory effect of the IGF1C-loaded hydrogel administered at disease onset on AAA formation was further evaluated in a guinea pig-to-rat xenograft model and in a sheep-to-minipig xenograft model of AAA formation. The therapeutic efficacy of IGF1C for treating AAA was tested through extravascular delivery in the sheep-to-minipig model with AAA established for 2 weeks. Percutaneous injection of the IGF1C-loaded hydrogel around the AAA resulted in improved vessel flow dynamics in the minipig aorta. These findings suggest that extravascular administration of IGF1R antagonists may have translational potential for treating AAA.

Automated insulin delivery in children with type 1 diabetes during physical activity: a meta-analysis.

OBJECTIVES: The aim of this study was to evaluating the performance of the automated insulin delivery (AID) in adolescents, and children with type 1 diabetes (T1D) during physical activity. METHODS: Relevant studies were searched electronically in the Cochrane Library, PubMed, and Embase utilizing the key words "Child", "Insulin Infusion Systems", and "Diabetes Mellitus" from inception to 17th March 2024 to evaluate the performance of the AID in adolescents, and children with T1D during physical activity. RESULTS: Twelve studies involving 514 patients were identified. AID did not show a beneficial effect on duration of hypoglycemia<70 mg/dL during study period (p>0.05; I 2=96 %) and during the physical activity (p>0.99). Percentage of sensor glucose values in TIR was higher in AID than the non-AID pumps during study period (p<0.001; I 2=94 %). The duration of hyperglycemic time was significantly decreased in AID group compared to the non-AID pumps group during study period (p<0.05; I 2>50 %). CONCLUSIONS: AID improved TIR and decreased the duration of hyperglycemic time, but did not appear to have a significant beneficial effect on the already low post-exercise duration of hypoglycemia achievable by open loop or sensor-augmented pumps in adolescents and children with T1D during physical activity; further research is needed to confirm the beneficial effect of AID on duration of hypoglycemia.

Jerks are Useful: Extracting pulse rate from wrist-placed accelerometry jerk during sleep in children.

STUDY OBJECTIVES: Evaluate wrist-placed accelerometry predicted heartrate compared to electrocardiogram (ECG) heartrate in children during sleep. METHODS: Children (n=82, 61% male, 43.9% Black) wore a wrist-placed Apple Watch Series 7 (AWS7) and ActiGraph GT9X during a polysomnogram. 3-Axis accelerometry data was extracted from AWS7 and the GT9X. Accelerometry heartrate estimates were derived from jerk (the rate of acceleration change), computed using the peak magnitude frequency in short time Fourier Transforms of Hilbert transformed jerk computed from acceleration magnitude. Heartrates from ECG traces were estimated from R-R intervals using R-pulse detection. Lin's Concordance Correlation Coefficient (CCC), mean absolute error (MAE) and mean absolute percent error (MAPE) assessed agreement with ECG estimated heartrate. Secondary analyses explored agreement by polysomnography sleep stage and a signal quality metric. RESULTS: The developed scripts are available on Github. For the GT9X, CCC was poor at -0.11 and MAE and MAPE were high at 16.8 (SD=14.2) beats/minute and 20.4% (SD=18.5%). For AWS7, CCC was moderate at 0.61 while MAE and MAPE were lower at 6.4 (SD=9.9) beats/minute and 7.3% (SD=10.3%). Accelerometry estimated heartrate for AWS7 was more closely related to ECG heartrate during N2, N3 and REM sleep than lights on, wake, and N1 and when signal quality was high. These patterns were not evident for the GT9X. CONCLUSIONS: Raw accelerometry data extracted from AWS7, but not the GT9X, can be used to estimate heartrate in children while they sleep. Future work is needed to explore the sources (i.e., hardware, software, etc.) of the GT9X's poor performance.