Quality assessment of videos on social media platforms related to gestational diabetes mellitus in China: A cross-section study.

Purpose: This study aimed to systematically evaluate the quality of content and information in videos related to gestational diabetes mellitus on Chinese social media platforms. Methods: The videos on various platforms, TikTok, Bilibili, and Weibo, were searched with the keyword "gestational diabetes mellitus" in Chinese, and the first 50 videos with a comprehensive ranking on each platform were included for subsequent analysis. Characteristic information of video was collected, such as their duration, number of days online, number of likes, comments, and number of shares. DISCREN, JAMA (The Journal of the American Medical Association) Benchmark Criteria, and GQS (Global Quality Scores) were used to assess the quality of all videos. Finally, the correlation analysis was performed among video features, video sources, DISCERN scores, and JAMA scores. Results: Ultimately, 135 videos were included in this study. The mean DISCERN total score was 31.84 ± 7.85, the mean JAMA score was 2.33 ± 0.72, and the mean GQS was 2.00 ± 0.40. Most of the videos (52.6%) were uploaded by independent medical professionals, and videos uploaded by professionals had the shortest duration and time online (P < 0.001). The source of the video was associated with numbers of "likes", "comments", and "shares" for JAMA scores (P < 0.001), but there was no correlation with DISCERN scores. Generally, videos on TikTok with the shortest duration received the most numbers of "likes", "comments", and "shares", but the overall quality of videos on Weibo was higher. Conclusion: Although the majority of the videos were uploaded by independent medical professionals, the overall quality appeared to be poor. Therefore, more efforts and actions should be taken to improve the quality of videos related to gestational diabetes mellitus.

Dual Interactive Mode Human-Machine Interfaces Based on Triboelectric Nanogenerator and IGZO/In2O3 Heterojunction Synaptic Transistor.

Imitating human neural networks via bio-inspired electronics advances human-machine interfaces (HMI), overcoming von Neumann limitations and enabling efficient, low-energy data processing in the big data era. However, single-contact mode HMIs have inherent limitations in terms of their capabilities and performances, such as constrained adaptability to dynamic environments, and reduced cognitive processing capabilities. Here, a dual-interactive-mode HMI system based on a triboelectric nanogenerator (TENG) and heterojunction synaptic transistor (HJST) is proposed for both contact and non-contact applications. The TENG incorporates a poly-methyl meth-acrylate (PMMA)-NiCo2S4/S film, in which the NiCo2S4/S composite traps and blocks electrons to optimize charge generation and storage. The heterojunction structure, mitigates the Debye screening effect, thereby improving transistor characteristics and reliability. The integrated TENG-HJST system exhibits synaptic functions, including excitatory/inhibitory postsynaptic current (EPSC/IPSC), paired-pulse facilitation/depression (PPF/PPD), and synaptic plasticity, enabling emulation of neural behavior and advanced information processing. Moreover, neural morphology manipulation is demonstrated in practical tasks, such as controlling international chess games. By integrating the TENG-HJST device with a robotic hand, conscious artificial responses are generated, enhancing event accuracy. This breakthrough in dual-interactive-mode interfacing holds promise for HMI systems and neural prostheses.

The association in diabetic retinopathy and stroke finding from NHANES evidence.

PURPOSE: Diabetic retinopathy and stroke are both vascular pathologies, and this study intends to investigate the relationship between diabetic retinopathy and stroke. METHODS: The NHANES database was used to find the relationship between diabetic retinopathy and stroke with 1948 individuals aged 40 years or older. The sensitivity of the data was verified by multiple interpolation, further analysis was done by subgroup analyses, and possible links were investigated with mediation studies. RESULTS: Diabetes retinopathy was found to be closely associated with stroke, with the PDR group having a higher stroke incidence than the NPDR group. After controlling for covariates, there were still substantial differences in the risk of stroke among patients with NPDR and PDR. Overall, subgroup analysis revealed DR group showed an important distinction, compared to the non-DR (OR = 1.76, 95% CI 1.15-2.64). The results of the mediation research indicated that the connection between DR and stroke was mediated by the frailty index and hypertension. CONCLUSION: This study demonstrated a statistically significant correlation between DR and stroke, which persisted even after DR staging and was more prevalent in PDR patients than in NPDR patients. Stroke prevention may benefit from DR health management.

Exosomal Tenascin-C primes macrophage pyroptosis amplifying aberrant inflammation during sepsis-induced acute lung injury.

Sepsis-induced acute lung injury (ALI) is a serious complication of sepsis and the predominant cause of death. Exosomes released by lung tissue cells critically influence the progression of ALI during sepsis by modulating the inflammatory microenvironment. However, the molecular mechanisms by which exosome-mediated intercellular signaling exacerbates ALI in septic infection remain undefined. Our study found increased levels of exosomal Tenascin-C (TNC) in the plasma of both patients and mice with ALI, showing a strong association with disease progression. By integrating exosomal proteomics with transcriptome sequencing and experimental validation, we elucidated that LPS induce unresolved endoplasmic reticulum stress (ERs) in alveolar epithelial cells (AECs), ultimately leading to the release of exosomal TNC through the activation of PERK-eIF2α and the transcription factor CHOP. In the sepsis mouse model with TNC knockout, we noted a marked reduction in macrophage pyroptosis. Our detailed investigations found that exosomal TNC binds to TLR4 on macrophages, resulting in an augmented production of ROS, subsequent mitochondrial damage, activation of the NF-κB signaling pathway, and induction of DNA damage response. These interconnected events culminate in macrophage pyroptosis, thereby amplifying the release of inflammatory cytokines. Our findings demonstrate that exosomal Tenascin-C, released from AECs under unresolved ER stress, exacerbates acute lung injury by intensifying sepsis-associated inflammatory responses. This research provides new insights into the complex cellular interactions underlying sepsis-induced ALI.

EGFR of platelet regulates macrophage activation and bacterial phagocytosis function.

BACKGROUND: Beyond their crucial role in hemostasis, platelets possess the ability to regulate inflammation and combat infections through various mechanisms. Stringent control of macrophage activation is essential during innate immune responses in sepsis. Macrophages are considered crucial phagocytic cells that aid in the elimination of pathogens. Platelet interactions with monocytes-macrophages are known to be significant in the response against bacterial infections, but the primary mediator driving these interactions remains unclear. EGFR plays critical role in the regulation of inflammation and infection through various mechanisms. RESULTS: The overexpression of platelets by thrombopoietin (TPO) leads to the sequestration of both pro-inflammatory (IL-6/IL-1) and anti-inflammatory (IL-10) cytokines in the organ tissue of septic mice. Epidermal growth factor receptor (EGFR) is critical for platelet activation in sepsis. EGFR-licensed platelets enhance macrophage immune function, including the production of reactive oxygen species (ROS) and the clearance of bacteria. Platelet EGFR also induces M1 macrophage polarization by increasing the expression of inducible nitric oxide synthase (iNOS) and CD64. CONCLUSION: EGFR can activate platelet immune function. Moreover, activated platelets efficiently regulate bacterial phagocytosis and pro-inflammatory function of macrophages through an EGFR-dependent pathway.

Listeria-vectored cervical cancer vaccine candidate strains reduce MDSCs via the JAK-STAT signaling pathway.

BACKGROUND: Immunosuppressive status is prevalent in cancer patients and increases the complexity of tumor immunotherapy. It has been found that Listeria-vectored tumor vaccines had the potential ability of two-side regulatory effect on the immune response during immunotherapy. RESULTS: The results show that the combined immunotherapy with the LM∆E6E7 and LI∆E6E7, the two cervical cancer vaccine candidate strains constructed by our lab, improves the antitumor immune response and inhibits the suppressive immune response in tumor-bearing mice in vivo, confirming the two-sided regulatory ability of the immune response caused by Listeria-vectored tumor vaccines. The immunotherapy reduces the expression level of myeloid-derived suppressor cells (MDSCs)-inducing factors and then inhibits the phosphorylation level of STAT3 protein, the regulatory factor of MDSCs differentiation, to reduce the MDSCs formation ability. Moreover, vaccines reduce the expression of functional molecules associated with MDSCs may by inhibiting the phosphorylation level of the JAK1-STAT1 and JAK2-STAT3 pathways in tumor tissues to attenuate the immunosuppressive function of MDSCs. CONCLUSIONS: Immunotherapy with Listeria-vectored cervical cancer vaccines significantly reduces the level and function of MDSCs in vivo, which is the key point to the destruction of immunosuppression. The study for the first to elucidate the mechanism of breaking the immunosuppression.

From 2D to 3D: Automatic measurement of the Cobb angle in adolescent idiopathic scoliosis with the weight-bearing 3D imaging.

BACKGROUND CONTEXT: Adolescent idiopathic scoliosis (AIS) necessitates accurate spinal curvature assessment for effective clinical management. Traditional two-dimensional (2D) Cobb angle measurements have been the standard, but the emergence of three-dimensional (3D) automatic measurement techniques, such as those using weight-bearing 3D imaging (WR3D), presents an opportunity to enhance the accuracy and comprehensiveness of AIS evaluation. PURPOSE: This study aimed to compare traditional 2D Cobb angle measurements with 3D automatic measurements utilizing the WR3D imaging technique in patients with AIS. STUDY DESIGN/SETTING: A cohort of 53 AIS patients was recruited, encompassing 88 spinal curves, for comparative analysis. PATIENT SAMPLE: The patient sample consisted of 53 individuals diagnosed with AIS. OUTCOME MEASURES: Cobb angles were calculated using the conventional 2D method and three different 3D methods: the Analytical Method (AM), the Plane Intersecting Method (PIM), and the Plane Projection Method (PPM). METHODS: The 2D cobb angle was manually measured by 3 experienced clinicians with 2D frontal whole-spine radiographs. For 3D cobb angle measurements, the spine and femoral heads were segmented from the WR3D images using a 3D-UNet deep-learning model, and the automatic calculations of the angles were performed with the 3D slicer software. RESULTS: AM and PIM estimates were found to be significantly larger than 2D measurements. Conversely, PPM results showed no statistical difference compared to the 2D method. These findings were consistent in a subgroup analysis based on 2D Cobb angles. CONCLUSION: Each 3D measurement method provides a unique assessment of spinal curvature, with PPM offering values closely resembling 2D measurements, while AM and PIM yield larger estimations. The utilization of WR3D technology alongside deep learning segmentation ensures accuracy and efficiency in comparative analyses. However, additional studies, particularly involving patients with severe curves, are required to validate and expand on these results. This study emphasizes the importance of selecting an appropriate measurement method considering the imaging modality and clinical context when assessing AIS, and it also underlines the need for continuous refinement of these techniques for optimal use in clinical decision-making and patient management.

Carbon capture in polymer-based electrolytes.

Nanoparticle organic hybrid materials (NOHMs) have been proposed as excellent electrolytes for combined CO2 capture and electrochemical conversion due to their conductive nature and chemical tunability. However, CO2 capture behavior and transport properties of these electrolytes after CO2 capture have not yet been studied. Here, we use a variety of nuclear magnetic resonance (NMR) techniques to explore the carbon speciation and transport properties of branched polyethylenimine (PEI) and PEI-grafted silica nanoparticles (denoted as NOHM-I-PEI) after CO2 capture. Quantitative 13C NMR spectra collected at variable temperatures reveal that absorbed CO2 exists as carbamates (RHNCOO- or RR'NCOO-) and carbonate/bicarbonate (CO32-/HCO3-). The transport properties of PEI and NOHM-I-PEI studied using 1H pulsed-field-gradient NMR, combined with molecular dynamics simulations, demonstrate that coulombic interactions between negatively and positively charged chains dominate in PEI, while the self-diffusion in NOHM-I-PEI is dominated by silica nanoparticles. These results provide strategies for selecting adsorbed forms of carbon for electrochemical reduction.

The Allostery and Modification of hGHRH Molecules and Specific Dimer Produced Significant Fertility Effect by Proliferating and Activating in-situ Ovarian Mesenchymal Stem Cells.

The negative coordination of growth hormone secretagogue receptor (GHS-R) and growth hormone-releasing hormone receptor (GHRH-R) involves in the repair processes of cellular injury. The allosteric U- or H-like modified GHRH dimer Grinodin and 2Y were comparatively evaluated in normal Kunming mice and hamster infertility models induced by CPA treatment. 1-3-9 µg of Grinodin or 2Y per hamster stem-cell-exhaustion model was subcutaneously administered once a week, respectively inducing 75-69-46 or 45-13-50% of birth rates. In comparison, the similar mole of human menopausal gonadotropin (hMG) or human growth hormone (hGH) was administered once a day but caused just 25 or 20% of birth rates. Grinodin induced more big ovarian follicles and corpora lutea than 2Y, hMG, hGH. The hMG-treated group was observed many distorted interstitial cells and more connective tissues and the hGH-treated group had few ovarian follicles. 2Y had a plasma lifetime of 21 days and higher GH release in mice, inducing lower birth rate and stronger individual specificity in reproduction as well as only promoting the proliferation of mesenchymal-stem-cells (MSCs) in the models. In comparison, Grinodin had a plasma lifetime of 30 days and much lower GH release in mice. It significantly promoted the proliferation and activation of ovarian MSCs together with the development of follicles in the models by increasing Ki67 and GHS-R expressions, and decreasing GHRH-R expression in a dose-dependent manner. However, the high GH and excessive estrogen levels in the models showed a dose-dependent reduction in fertility. Therefore, unlike 2Y, the low dose of Grinodin specifically shows low GHS-R and high GHRH-R expressions thus evades GH and estrogen release and improves functions of organs, resulting in an increase of fertility.

[Immunoadjuvant Effect of Chitosan Oligosaccharide and Its Feasibility of Being Used as an Adjuvant for Attenuated Live Bacteria Vector Vaccines]. / å£³å¯¡ç³–çš„å ç–«ä½å‰‚æ•ˆæžœåŠä½œä¸ºå‡æ¯’æ´»èŒè½½ä½“ç–«è‹—ä½å‰‚çš„å¯è¡Œæ€§æŽ¢ç´¢.

Objective: To study the immunoadjuvant effects of chitosan oligosaccharide (COS), including the immune activation and the triggering of lysosomal escape, and to explore whether COS can be used as an adjuvant for attenuated live bacteria vector vaccines. Methods: 1) Mouse macrophages RAW264.7 cells were cultured with COS at 0 mg/mL (the control group) and 0.1-4 mg/mL for 24 h and the effect on cell viability was measured by CCK8 assay. Mouse macrophages RAW264.7 were treated with COS at 0 (the control group), 1, 2, and 4 mg/mL for 24 h. Then, the mRNA expression levels of the cytokines, including IFN-γ, IL-10, TGF-ß, and TLR4, were determined by RT-qPCR assay. 2) RAW264.7 cells were treated with 1 mL of PBS containing different components, including calcein at 50 µg/mL, COS at 2 mg/mL, and bafilomycin A1, an inhibitor, at 1 µmol/mL, for culturing. The cells were divided into the Calcein group, Calcein+COS group, and Calcein+COS+Bafilomycin A1 group accordingly. Laser scanning confocal microscopy was used to observe the phagocytosis and the intracellular fluorescence distribution of calcein, a fluorescent dye, in RAW264.7 cells in the presence or absence of COS intervention to determine whether COS was able to trigger lysosomal escape. 3) LM∆E6E7 and LI∆E6E7, the attenuated Listeria vector candidate therapeutic vaccines for cervical cancer, were encapsulated with COS at the mass concentrations of 0.5 mg/mL, 1 mg/mL, 2 mg/mL , 4 mg/mL, and 8 mg/mL. Then, the changes in zeta potential were measured to select the concentration of COS that successfully encapsulated the bacteria. Phagocytosis of the vaccine strains by RAW264.7 cells was measured before and after LM∆E6E7 and LI∆E6E7 were coated with COS at 2 mg/mL. Results: 1) CCK8 assays showed that, compared with the findings for the control group, the intervention of RAW264.7 cells with COS at different concentrations for 24 h was not toxic to the cells and promoted cell proliferation, with the difference being statistically significant (P<0.05). According to the RT-qPCR results, compared with those of the control group, the COS intervention up-regulated the mRNA levels of TLR4 and IFN-γ in RAW264.7 cells, while it inhibited the mRNA expression levels of TGF-ß and IL-10, with the most prominent effect being observed in the 4 mg/mL COS group (P<0.05). 2) Laser scanning confocal microscopy revealed that the amount of fluorescent dye released from lysosomes into the cells was greater in the Calcein+COS group than that in the Calcein group. In other words, a greater amount of fluorescent dye was released from lysosomes into the cells under COS intervention. Furthermore, this process could be blocked by bafilomycin A1. 3) The zeta potential results showed that COS could successfully encapsulate the surface of bacteria when its mass concentration reached 2 mg/mL. Before and after the vaccine strain was encapsulated by COS, the phagocytosis of LM∆E6E7 by RAW264.7 cells was 5.70% and 22.00%, respectively, showing statistically significant differences (P<0.05); the phagocytosis of LI∆E6E7 by RAW264.7 cells was 1.55% and 6.12%, respectively, showing statistically significant differences (P<0.05). Conclusion: COS has the effect of activating the immune response of macrophages and triggering lysosomal escape. The candidates strains of coated live attenuated bacterial vector vaccines can promote the phagocytosis of bacteria by macrophages. Further research is warranted to develop COS into an adjuvant for bacterial vector vaccine.

Siglec-F+ neutrophils in the spleen induce immunosuppression following acute infection.

Background: The mechanisms underlying the increased mortality of secondary infections during the immunosuppressive phase of sepsis remain elusive. Objectives: We sought to investigate the role of Siglec-F+ neutrophils on splenic T lymphocytes in the immunosuppressed phase of sepsis and on secondary infection in PICS mice, and to elucidate the underlying mechanisms. Methods: We established a mouse model of sepsis-induced immunosuppression followed by secondary infection with LPS or E. coli. The main manifestation of immunosuppression is the functional exhaustion of splenic T lymphocytes. Treg depletion reagent Anti-IL-2, IL-10 blocker Anti-IL-10R, macrophage depletion reagent Liposomes, neutrophil depletion reagent Anti-Ly6G, neutrophil migration inhibitor SB225002, Siglec-F depletion reagent Anti-Siglec-F are all used on PICS mice. The function of neutrophil subsets was investigated by adoptive transplantation and the experiments in vitro. Results: Compared to other organs, we observed a significant reduction in pro-inflammatory cytokines in the spleen, accompanied by a marked increase in IL-10 production, primarily by infiltrating neutrophils. These infiltrating neutrophils in the spleen during the immunosuppressive phase of sepsis undergo phenotypic change in the local microenvironment, exhibiting high expression of neutrophil biomarkers such as Siglec-F, Ly6G, and Siglec-E. Depletion of neutrophils or specifically targeting Siglec-F leads to enhance the function of T lymphocytes and a notable improvement in the survival of mice with secondary infections. Conclusions: We identified Siglec-F+ neutrophils as the primary producers of IL-10, which significantly contributed to T lymphocyte suppression represents a novel finding with potential therapeutic implications.

Role of protein degradation systems in colorectal cancer.

Protein degradation is essential for maintaining protein homeostasis. The ubiquitin‒proteasome system (UPS) and autophagy-lysosome system are the two primary pathways responsible for protein degradation and directly related to cell survival. In malignant tumors, the UPS plays a critical role in managing the excessive protein load caused by cancer cells hyperproliferation. In this review, we provide a comprehensive overview of the dual roles played by the UPS and autolysosome system in colorectal cancer (CRC), elucidating their impact on the initiation and progression of this disease while also highlighting their compensatory relationship. Simultaneously targeting both protein degradation pathways offers new promise for enhancing treatment efficacy against CRC. Additionally, apoptosis is closely linked to ubiquitination and autophagy, and caspases degrade proteins. A thorough comprehension of the interplay between various protein degradation pathways is highly important for clarifying the mechanism underlying the onset and progression of CRC.

Upregulation of PGC-1α expression by pioglitazone mediates prevention of sepsis-induced acute lung injury.

The imbalance between pro-inflammatory M1 and anti-inflammatory M2 macrophages plays a critical role in the pathogenesis of sepsis-induced acute lung injury (ALI). Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) may modulate macrophage polarization toward the M2 phenotype by altering mitochondrial activity. This study aimed to investigate the role of the PGC-1α agonist pioglitazone (PGZ) in modulating sepsis-induced ALI. A mouse model of sepsis-induced ALI was established using cecal ligation and puncture (CLP). An in vitro model was created by stimulating MH-S cells with lipopolysaccharide (LPS). qRT-PCR was used to measure mRNA levels of M1 markers iNOS and MHC-II and M2 markers Arg1 and CD206 to evaluate macrophage polarization. Western blotting detected expression of peroxisome proliferator-activated receptor gamma (PPARγ) PGC-1α, and mitochondrial biogenesis proteins NRF1, NRF2, and mtTFA. To assess mitochondrial content and function, reactive oxygen species levels were detected by dihydroethidium staining, and mitochondrial DNA copy number was measured by qRT-PCR. In the CLP-induced ALI mouse model, lung tissues exhibited reduced PGC-1α expression. PGZ treatment rescued PGC-1α expression and alleviated lung injury, as evidenced by decreased lung wet-to-dry weight ratio, pro-inflammatory cytokine secretion (tumor necrosis factor-α, interleukin-1ß, interleukin-6), and enhanced M2 macrophage polarization. Mechanistic investigations revealed that PGZ activated the PPARγ/PGC-1α/mitochondrial protection pathway to prevent sepsis-induced ALI by inhibiting M1 macrophage polarization. These results may provide new insights and evidence for developing PGZ as a potential ALI therapy.

Safety of non-ionic contrast media in CT examinations for out-patients: retrospective multicenter analysis of 473,482 patients.

OBJECTIVES: This study aimed to explore the incidence of and potential risk factors for adverse drug reactions (ADRs) after non-ionic iodinated contrast media (NICM) administration for CT exams in out-patient settings in China. MATERIALS AND METHODS: A total of 473,482 out-patients who underwent intravenous NICM between January 1st, 2017, and Dec 31st, 2021, were retrospectively enrolled from three institutions. The occurrence of ADRs and clinical information were recorded. Chi-square test, Poisson regression, and logistic regression analyses were used to evaluate potential ADR risk factors and correlation with demographics, season, and NICM type. RESULTS: Among the 473,482 patients (mean age 55.22 ± 14.85; 253,499 male) who received intravenous NICM, the overall ADR incidence was 0.110% (522 of 473,482), with 0.099% acute-related drug reactions (469 of 473,482) and 0.0004% serious ADRs (two of 473,482). Iopromide was associated with a higher risk of acute ADRs. Late ADRs were more frequently observed with iodixanol 320. Multi-level logistic regression of patients with acute ADRs and a control group (matched 1:1 for age, gender, NICM, prescriber department, and institution) showed that summer (adjusted OR = 1.579; p = 0.035) and autumn (adjusted OR = 1.925; p < 0.001) were risk factors of acute ADRs. However, underlying disease and scanned body area were not related to a higher ADR incidence. CONCLUSION: The use of NICM for out-patients is in general safe with a low ADR incidence. The type of contrast medium (iopromide) and the seasons (summer and autumn) were associated with a higher risk of acute ADRs. Late ADRs were more often observed with iodixanol. CLINICAL RELEVANCE STATEMENT: In comparison to in-patients, out-patients may be exposed to higher risk due to a lack of extensive risk screening, less nursing care, and higher throughput pressure. Safety data about NICM from a large population may complement guidelines and avoid ambiguity. KEY POINTS: • The incidence and risk factors for adverse events after using non-ionic iodinated contrast media are complex in out-patients. • Non-ionic iodinated contrast media are safe for out-patients and the overall incidence of adverse drug reactions was 0.110%. • There is a higher risk of acute adverse drug reactions in summer and autumn.

Long-term observation of V4c implantable collamer lenses implantation for moderate to extreme high myopia correction: five years follow-up.

BACKGROUND: This study aims to assess the long term effectiveness, safety, predictability and stability of V4c implantable collamer lenses (ICL) for correction of moderate to extreme high myopia. METHODS: We reviewed 125 eyes from 64 patients who implanted V4c ICL at the Refractive Surgery Center of West China Hospital in Chengdu, China, between May 2015 and January 2017. The median spherical equivalent was -11.50 D (interquartile range [IQR]: -13.00 to -9.00 D). We followed up with the patients over five years and evaluated several parameters, including uncorrected visual acuity (UDVA), corrected visual acuity (CDVA), axial length, refractive error, endothelial cell density (ECD), intraocular pressure (IOP), white-to-white distance (WTW), and vault. We performed a correlation analysis to explore the potential impacts on vault following implantation. RESULTS: The median safety index (postoperative CDVA/preoperative CDVA) during the last follow-up was 1.00 (interquartile range [IQR]: 1.00-1.20), and the efficacy indices (postoperative UDVA/preoperative CDVA) were 1.20 (IQR: 1.00-1.25), 1.20 (IQR: 1.00-1.33), and 0.8 (IQR: 0.65-1.00) at postoperative 1 week, 1 month, and 5 years, respectively. At the five-year mark, 16% of the eyes were within ±0.50 D of expected correction, and 73% were within ±2.00 D. No significant difference in ECD was observed between pre-operative and post-operative measurements. Compared to baseline, we observed a significant increase in IOP at the one-week follow-up, which decreased significantly at the one-month visit. Furthermore, we identified ICL size and spherical equivalent (SE) as independent variables in a multiple linear regression model that accurately predicted the five-year vault after surgery. CONCLUSION: In conclusion, V4c ICL implantation is an effective and safe treatment for moderate to extreme high myopia with good predictability and stability over the long-term.

Outline and background for the EU-OS solubility prediction challenge.

In June 2022, EU-OS came to the decision to make public a solubility data set of 100+K compounds obtained from several of the EU-OS proprietary screening compound collections. Leveraging on the interest of SLAS for screening scientific development it was decided to launch a joint EUOS-SLAS competition within the chemoinformatics and machine learning (ML) communities. The competition was open to real world computation experts, for the best, most predictive, classification model of compound solubility. The aim of the competition was multiple: from a practical side, the winning model should then serve as a cornerstone for future solubility predictions having used the largest training set so far publicly available. From a higher project perspective, the intent was to focus the energies and experiences, even if professionally not precisely coming from Pharma R&D; to address the issue of how to predict compound solubility. Here we report how the competition was ideated and the practical aspects of conducting it within the Kaggle framework, leveraging of the versatility and the open-source nature of this data science platform. Consideration on results and challenges encountered have been also examined.

The regulatory relationship between NAMPT and PD-L1 in cancer and identification of a dual-targeting inhibitor.

Cancer is a heterogeneous disease. Although both tumor metabolism and tumor immune microenvironment are recognized as driving factors in tumorigenesis, the relationship between them is still not well-known, and potential combined targeting approaches remain to be identified. Here, we demonstrated a negative correlation between the expression of NAMPT, an NAD+ metabolism enzyme, and PD-L1 expression in various cancer cell lines. A clinical study showed that a NAMPTHigh PD-L1Low expression pattern predicts poor prognosis in patients with various cancers. In addition, pharmacological inhibition of NAMPT results in the transcription upregulation of PD-L1 by SIRT-mediated acetylation change of NF-κB p65, and blocking PD-L1 would induce NAMPT expression through a HIF-1-dependent glycolysis pathway. Based on these findings, we designed and synthesized a dual NAMPT/PD-L1 targeting compound, LZFPN-90, which inhibits cell growth in a NAMPT-dependent manner and blocks the cell cycle, subsequently inducing apoptosis. Under co-culture conditions, LZFPN-90 treatment contributes to the proliferation and activation of T cells and blocks the growth of cancer cells. Using mice bearing genetically manipulated tumors, we confirmed that LZFPN-90 exerted target-dependent antitumor activities, affecting metabolic processes and the immune system. In conclusion, our results demonstrate the relevance of NAD+-related metabolic processes in antitumor immunity and suggest that co-targeting NAD+ metabolism and PD-L1 represents a promising therapeutic approach.