Machine Learning Model Based on the Neutrophil-to-Eosinophil Ratio Predicts the Recurrence of Hepatocellular Carcinoma After Surgery.

Background: Circulating eosinophils are associated with tumor development. An eosinophil-related index, the neutrophil to eosinophil ratio (NER), can be used to predict the prognosis of patients with tumors. However, there is still a lack of efficient prognostic biomarkers for HCC. In this study, we aimed to investigate the predictive value of the NER and develop an optimal machine learning model for the recurrence of HCC patients. Patients and methods: A retrospective collection of 562 patients who underwent hepatectomy with a pathologic diagnosis of HCC was performed. The relationship between NER and progression-free survival (PFS) was investigated. We developed a new machine learning framework with 10 machine learning algorithms and their 101 combinations to select the best model for predicting recurrence after hepatectomy. The performance of the model was assessed by the area under the curve (AUC) of characteristics and calibration curves, and clinical utility was evaluated by decision curve analysis (DCA). Results: Kaplan‒Meier curves showed that the PFS in the low NER group was significantly better than that in the high NER group. Multivariate Cox regression analysis showed that NER was an independent risk factor for recurrence after surgery. The random survival forests (RSF) model was selected as the best model that had good predictive efficacy and outperformed the TNM, BCLC, and CNLC staging systems. Conclusion: The NER has good predictive value for postoperative recurrence in patients with hepatocellular carcinoma. Machine learning model based on NER can be used for accurate predictions.

Microenvironment-regulated dual-hydrophilic coatings for glaucoma valve surface engineering.

Glaucoma valves (GVs) play an essential role in treating glaucoma. However, fibrosis after implantation has limited their long-term success in clinical applications. In this study, we aimed to develop a comprehensive surface-engineering strategy to improve the biocompatibility of GVs by constructing a microenvironment-regulated and dual-hydrophilic antifouling coating on a GV material (silicone rubber, SR). The coating was based on a superhydrophilic polydopamine (SPD) coating with good short-range superhydrophilicity and antifouling abilities. In addition, SPD coatings contain many phenolic hydroxyl groups that can effectively resist oxidative stress and the inflammatory microenvironment. Furthermore, based on its in situ photocatalytic free-radical polymerization properties, the SPD coating polymerized poly 2-methylacryloxyethylphosphocholine, providing an additional long-range hydrophilic and antifouling effect. The in vitro test results showed that the microenvironment-regulated and dual-hydrophilic coatings had anti-protein contamination, anti-oxidation, anti-inflammation, and anti-fiber proliferation capabilities. The in vivo test results indicated that this coating substantially reduced the fiber encapsulation formation of the SR material by inhibiting inflammation and fibrosis. This design strategy for dual hydrophilic coatings with microenvironmental regulation can provide a valuable reference for the surface engineering design of novel medical implantable devices. STATEMENT OF SIGNIFICANCE: Superhydrophilic polydopamine (SPD) coatings were prepared on silicone rubber (SR) by a two-electron oxidation method. Introduction of pMPC to SPD surface using photocatalytic radical polymerization to obtain a dual-hydrophilic coating. The dual-hydrophilic coating effectively modulates the oxidative and inflammatory microenvironment. This coating significantly reduced protein contamination and adhesion of inflammatory cells and fibroblasts in vitro. The coating-modified SR inhibits inflammatory and fibrosis responses in vivo, promising to serve the glaucoma valves.

Design, synthesis and antiproliferative evaluation of tetrahydro-ß-carboline histone deacetylase inhibitors bearing an aliphatic chain linker.

The use of histone deacetylase inhibitors (HDACis) is an effective approach for cancer treatment. In this work, a series of hydroxamic acid-based HDACis with a tetrahydro-ß-carboline core and aliphatic linker have been designed and synthesized. The optimal compound 13d potently inhibited HDAC1 and showed good antiproliferative activity against different tumor cell lines in vitro. Molecular docking of 13d was conducted to rationalize the high binding affinity for HDAC1. Therefore, this work provides a new structure design for HDAC inhibitors and also offers a promising treatment for solid tumors.

Frequency-Aware Degradation Modeling for Real-World Thermal Image Super-Resolution.

The supervised super-resolution (SR) methods based on simple degradation assumptions (e.g., bicubic downsampling) have unsatisfactory generalization ability on real-world thermal images. To enhance the SR effect of real-world sceneries, we introduce an unsupervised SR framework for thermal images, incorporating degradation modeling and corresponding SR. Inspired by the physical prior that high frequency affects details and low frequency affects thermal contrast, we propose a frequency-aware degradation model, named TFADGAN. The model achieves image quality migration between thermal detectors of different resolutions by degrading different frequency components of the image from high-resolution (HR) to low-resolution (LR). Specifically, by adversarial learning with unpaired LR thermal images, the complex degradation processes of HR thermal images at low and high frequencies are modeled separately. Benefiting from the thermal characteristics mined from real-world images, the degraded images generated by TFADGAN are similar to LR thermal ones in terms of detail and contrast. Then, the SR model is trained based on the pseudo-paired data consisting of degraded images and HR images. Extensive experimental results demonstrate that the degraded images generated by TFADGAN provide reliable alternatives to real-world LR thermal images. In real-world thermal image experiments, the proposed SR framework can improve the peak signal-to-noise ratio (PSNR) and structural similarity degree (SSIM) by 1.28 dB and 0.02, respectively.

Two-electron oxidized polyphenol chemistry-inspired superhydrophilic drug-carrying coatings for the construction of multifunctional nasolacrimal duct stents.

Nasolacrimal duct obstruction due to infection, inflammation, or excessive fibroblast proliferation may result in persistent tearing, intraocular inflammation, or even blindness. In this study, surface engineering techniques are applied to nasolacrimal duct stents for the first time. Based on the functioning of marine mussels, "one-pot" and "stepwise" methods were employed to construct a novel multifunctional superhydrophilic PDA/RAP coating using dopamine and rapamycin. Micron-sized rapamycin crystals combined with nano-sized polydopamine particles form a micro-nano topographical structure. Therefore, acting synergistically with in situ-generated hydrophilic groups (amino, carboxyl, and phenolic hydroxyl), they impart excellent and long-lasting superhydrophilicity to the nasolacrimal duct stent. The PDA/RAP coating effectively maintained the stability of the initial microenvironment during stent implantation by inhibiting the onset of acute inflammation and infection during the early stages of implantation. Meanwhile, the rapamycin crystals, supported by the superhydrophilic platform, exhibited a sustained-release capability that helped them to better exert their anti-inflammatory, antibacterial, and anti-fibroblast proliferative properties, ensuring conducive conditions for the rapid repair of nasolacrimal duct epithelial cells, verified by a series of experiments. In conclusion, the PDA/RAP hydrophilic coating has anti-inflammatory, antifibrotic, antibacterial, and antithrombotic properties, offering a new strategy to address restenosis following clinical nasolacrimal duct stent implantation.

Molecular mechanisms of TACE refractoriness: Directions for improvement of the TACE procedure.

Transcatheter arterial chemoembolisation (TACE) is the standard of care for intermediate-stage hepatocellular carcinoma and selected patients with advanced hepatocellular carcinoma. However, TACE does not achieve a satisfactory objective response rate, and the concept of TACE refractoriness has been proposed to identify patients who do not fully benefit from TACE. Moreover, repeated TACE is necessary to obtain an optimal and sustained anti-tumour response, which may damage the patient's liver function. Therefore, studies have recently been performed to improve the effectiveness of TACE. In this review, we summarise the detailed molecular mechanisms associated with TACE responsiveness and relapse after this treatment to provide more effective targets for adjuvant therapy while helping to improve TACE regimens.

High-Efficiency Ultraviolet Electroluminescence from Multi-Resonance Phosphine Oxide Polycyclic Aromatics.

Efficient ultraviolet (UV) electroluminescent materials remain a great challenge, since short peak wavelength <400 nm and narrow full width at half maximum (FWHM) <50 nm are simultaneously required. In this sense, multi-resonance (MR) thermally activated delayed fluorescence (TADF) emitters featuring narrow-band emissions hold the promise for UV applications. Herein, a novel MR-TADF skeleton featuring carbazole-phosphine oxide (P=O) fused aromatics is developed to construct the first two UV MR emitters named CzP2PO and tBCzP2PO. In addition to synergistic resonance effects of P=O and N atom, sp3 -hybrid P atom renders the curved polycyclic planes of CzP2PO and tBCzP2PO, giving rise to their narrowband UV emissions with peak wavelengths <390 nm and FWHM<35 nm. Besides configuration quasi-planarization for radiation enhancement and quenching suppression, P=O moiety further enhances singlet-triplet coupling to facilitate reverse intersystem crossing, resulting in the state-of-the-art photoluminescence quantum yield of 62 % in tBCzP2PO doped films. As consequence, tBCzP2PO endowed its UV organic light-emitting diodes with the peak at 382 nm and FWHM of 32 nm, and especially the record-high external quantum efficiency (EQE) of 15.1 % among all kinds of UV devices. Our results demonstrate great potential of P=O based MR emitters in practical applications including optoelectronics, biology and medicine science.

Passivation protein-adhesion platform promoting stent reendothelialization using two-electron-assisted oxidation of polyphenols.

Superhydrophilic surfaces play an important role in nature. Inspired by this, scientists have designed various superhydrophilic materials that are widely used in the field of biomaterials, such as PEG molecular brushes and zwitterionic materials. However, superhydrophilic coatings with only anti-fouling properties do not satisfy the requirements for rapid reendothelialization of cardiovascular stent surfaces. Herein, a novel polyphenol superhydrophilic surface with passivated protein-adsorption properties was developed using two-electron oxidation of dopamine and polyphenols. This coating has a multiscale effects: 1) macroscopically: anti-fouling properties of superhydrophilic; 2) microscopically: protein adhesion properties of active groups (quinone-, amino-, hydroxyphenyl groups and aromatic ring). Polyphenols not only enhance the ability of coating to passivate protein-adsorption, but also make the coating have polyphenol-related biological functions. Therefore, the polyphenol and passivated protein-adsorption platform together maintain the stability of the scaffold microenvironment. This, in turn, provides favorable conditions for the growth of endothelial cells on the scaffold surface. In vivo implantation of the coated stents into the abdominal aorta resulted in uniform and dense endothelial cells covering the surface of the neointima. Moreover, new endothelial cells secreted large amounts of functional endothelial nitric oxide synthase like healthy endothelial cells. These results indicate that the polyphenol superhydrophilic coating potentially resists intra-stent restenosis and promotes surface reendothelialization. Hence, polyphenol superhydrophilic coatings with passivated protein-adsorption properties constructed by two-electron-assisted oxidation are a highly effective and versatile surface-modification strategy for implantable cardiovascular devices.

Effects of environmental and genetic interactions on job burnout in coal miners: interactions between occupational stress, coping styles, and NR3C2 gene polymorphisms.

Objectives: To investigate the current situation regarding occupational burnout among coal miners, explore the relationship between NR3C2 gene polymorphism and occupational burnout, and analyze the influence of the interaction between environment and gene on occupational burnout. This study provides a scientific basis for formulating health strategies to combat job burnout. Methods: A total of 1,500 first-line coal mine workers were selected by cluster random sampling, and the job burnout scale, job content questionnaire (JCQ), and simplified coping style questionnaire (SCSQ) were used for the questionnaire survey. A total of 150 workers were randomly selected from the high burnout group and the low burnout group, and a total of 300 workers were selected as the research objects to examine the relationship between gene polymorphism, environment-gene interactions and burnout. This study employed iMLDRTM genotyping technology for NR3C2 gene (rs5522, rs2070950) polymorphism analysis. The relationship between the occurrence of job burnout, occupational stress, coping styles and the NR3C2 gene was analyzed. Results: Finally, a total of 1,282 valid questionnaires were retrieved, with an effective recovery rate of 85.5%. The study included 128 participants (10%) with zero burnout, 400 (31.2%) with mild burnout, 649 (50.6%) with moderate burnout and 105 (8.2%) with severe burnout. There were significant differences in the rate of burnout among miners with respect to sex, age, working years, educational level, shifts, and marital status (P < 0.05). The difference in occupational stress between the different job burnout groups was statistically significant (P < 0.05). Compared with the GG genotype of rs2070950 of the NR3C2 gene, the CC genotype was identified as a susceptibility gene for occupational burnout (P < 0.05). In respect to rs5522, rs2070950, occupational stress, positive coping, and negative coping, the low-risk group was unlikely to suffer from job burnout compared with the high-risk group (OR = 0.103, 95%CI: 0.058-0.182). Conclusion: In addition to demographic characteristics, occupational stress and negative coping styles were also identified as risk factors for job burnout. The interaction between locus rs5522, locus rs2070950, occupational stress, positive response, and negative response were found to affect the incidence of occupational burnout.

Resveratrol reduces ROS-induced ferroptosis by activating SIRT3 and compensating the GSH/GPX4 pathway.

BACKGROUND: Intestinal ischemia-reperfusion injury occurs in acute intestinal obstruction, intussusception, acute mesenteric artery embolism, and other diseases and can lead to local intestinal necrosis, distant organ involvement, or systemic reactions, with high morbidity and mortality. Ferroptosis plays a crucial role in intestinal ischemia-reperfusion injury, and inhibition of ferroptosis may provide new approaches for treating the disease. SIRT3 protects cells from oxidative stress and may be involved in the process of ferroptosis. We hypothesized that resveratrol, an agonist of SIRT3, could ameliorate intestinal ischemia-reperfusion injury by compensating the GSH/GPX4 pathway. METHODS: Intestinal ischemia-reperfusion (I/R) and Caco-2 hypoxia-reoxygenation models were established. Transmission electron microscopy was used to assess mitochondrial function; the Chiu's score was used to evaluate the degree of intestinal mucosal injury based on HE staining; and Western blot was used to detect the SIRT3/FoxO3a pathway, tight junction proteins and ferroptosis-related protein expression. Sirt3-/- C57, shSIRT3-Caco-2 cells and siFoxO3a-Caco-2 cells were established. C11-BODIPY was used to detect lipid peroxide in cells; FD4 and IFABP were used to detect intestinal permeability; MitoSOX was used to detect ROS levels; and MitoTracker and immunofluorescence colocalization were used to detect SIRT3 levels. RESULTS: In the intestinal I/R model, I/R injury occurs mainly during the reperfusion period and leads to ferroptosis through the GSH/GPX4 pathway. Resveratrol could reduce ferroptosis and ameliorate I/R injury by activating SIRT3. In Sirt3-/- mice, more intestinal mucosal cells underwent ferroptosis, I/R injury was more severe, and resveratrol lost the ability to ameliorate I/R injury. In addition, hypoxia-reoxygenation increased RSL3-induced ferroptosis sensitivity in Caco-2 cells in vitro. In the presence of shSIRT3 or RSL3 alone, resveratrol could ameliorate Caco-2 ferroptosis, but not RSL3-induced shSIRT3-Caco-2 ferroptosis. Furthermore, resveratrol might activate the SIRT3/FoxO3a pathway, increase the expression of SOD2 and catalase, and inhibit ROS generation, thus reducing lipid peroxidation and ferroptosis. CONCLUSION: To date, this is the first study to show that resveratrol ameliorates intestinal ischemia-reperfusion injury by activating SIRT3 and reducing ferroptosis. Resveratrol can reduce intestinal ischemia-reperfusion injury by activating the SIRT3/FoxO3a pathway, increasing the expression of SOD2 and catalase, reducing ROS and LPO production, compensating for the GSH/GPX4 pathway and inhibiting ferroptosis. Resveratrol increases the expression of SOD2 and catalase, reduces the production of ROS and LPO, compensates for the GSH/GPX4 pathway and inhibits ferroptosis by activating the SIRT3/FoxO3a pathway.

Levosimendan improves cardiac function, hemodynamics, and body inflammation in patients with acute myocardial infarction and heart failure.

OBJECTIVE: To examine the effects of levosimendan on cardiac function, hemodynamics, and body inflammation of patients with acute myocardial infarction and heart failure. METHODS: A retrospective analysis was conducted on 113 acute myocardial infarction patients with heart failure (admitted to Xianyang First People's Hospital from September 2018 to January 2022). According to the treatment plan, patients were categorized into a control group (n = 53) (treated with conventional diuresis and vasodilation) and observation group (n = 60) (treated with levosimendan in addition to the treatment of the control group). Indexes were compared between the two groups before and after treatment, including effectiveness rate, mean pulmonary arterial pressure (PAMP) and pulmonary capillary wedge pressure (PCWP). Left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD) and left ventricular ejection fraction (LVEF) were monitored before and after treatment by color Doppler ultrasonography. Serum high-sensitivity C-reactive protein (hs-CRP) levels were measured before and after treatment. Logistic analysis was applied to screen independent factors affecting treatment efficacy. Adverse reactions and life quality after 6 months of treatment were compared between the two groups. RESULTS: The overall response rate of the observation group was higher than that of the control group (P<0.05). Changes in PAMP and PCWP in the two groups before and after treatment were significantly different. Patients in the observation group had improved indicators compared with the control group (all P<0.05). After treatment, the cardiac function indexes and inflammation-related factors of the observation group were improved more than those of the control group (P<0.05). Patients in the observation group had a lower incidence of adverse reactions and a higher life quality 6 months after treatment compared to the control group (P<0.05). Diabetes and treatment regimen were independent risk factors affecting treatment efficacy by logistic regression analysis. CONCLUSION: The administration of levosimendan helps improve cardiac function, hemodynamics, and body inflammation in patients with acute myocardial infarction and heart failure, with fewer adverse reactions and higher safety.

CRISPR/Cas-based gene editing in therapeutic strategies for beta-thalassemia.

Beta-thalassemia (ß-thalassemia) is an autosomal recessive disorder caused by point mutations, insertions, and deletions in the HBB gene cluster, resulting in the underproduction of ß-globin chains. The most severe type may demonstrate complications including massive hepatosplenomegaly, bone deformities, and severe growth retardation in children. Treatments for ß-thalassemia include blood transfusion, splenectomy, and allogeneic hematopoietic stem cell transplantation (HSCT). However, long-term blood transfusions require regular iron removal therapy. For allogeneic HSCT, human lymphocyte antigen (HLA)-matched donors are rarely available, and acute graft-versus-host disease (GVHD) may occur after the transplantation. Thus, these conventional treatments are facing significant challenges. In recent years, with the advent and advancement of CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated protein 9) gene editing technology, precise genome editing has achieved encouraging successes in basic and clinical studies for treating various genetic disorders, including ß-thalassemia. Target gene-edited autogeneic HSCT helps patients avoid graft rejection and GVHD, making it a promising curative therapy for transfusion-dependent ß-thalassemia (TDT). In this review, we introduce the development and mechanisms of CRISPR/Cas9. Recent advances on feasible strategies of CRISPR/Cas9 targeting three globin genes (HBB, HBG, and HBA) and targeting cell selections for ß-thalassemia therapy are highlighted. Current CRISPR-based clinical trials in the treatment of ß-thalassemia are summarized, which are focused on γ-globin reactivation and fetal hemoglobin reproduction in hematopoietic stem cells. Lastly, the applications of other promising CRISPR-based technologies, such as base editing and prime editing, in treating ß-thalassemia and the limitations of the CRISPR/Cas system in therapeutic applications are discussed.

Efficacy, Safety, Predictability, and Stability of LASIK for Presbyopia Correction: A Systematic Review and Meta-analysis.

PURPOSE: To determine the efficacy, safety, predictability, and stability of laser in situ keratomileusis (LASIK) in the treatment of presbyopia. METHODS: The databases of CNKI, VIP, Wan-Fang, CBM, Chinese Clinical Registry, PubMed, The Cochrane Library, Web of Science, Embase, and ClinicalTrials.gov were searched until March 2023. The authors chose the studies of LASIK in the treatment of presbyopia. Outcomes were efficacy, safety, predictability, and stability. The review was registered in the international platform of registered systematic review and meta-analysis protocols (INPLASY202350005). RESULTS: A total of 28 non-randomized controlled trials (15,861 eyes) were included. The results showed that after LASIK, (1) the distance efficacy decreased (mean difference [MD]: 0.02, 95% CI: 0.0 to 0.03, P < .05) and the near efficacy increased (MD: -0.01, 95% CI: -0.19 to-0.02, P < .05); (2) the distance safety decreased (MD: 0.07, 95% CI: 0.04 to 0.10, P < .0001) and near safety increased (MD: -0.19, 95% CI: -0.39 to 0.02, P > .05); (3) the predictability within ±1.00 and ±0.50 D was 94% (relative risk [RR]: 0.94, 95% CI: 0.90 to 0.98, P < .001) and 80% (RR: 0.80, 95% CI: 0.74 to 0.86, P < .001), respectively; and (4) 6 months postoperatively, the percentage of spherical equivalent changing within ±0.50 D was 95% (RR: 0.95, 95% CI: 0.89 to 0.99, P < .001). CONCLUSIONS: The near efficacy, predictability, and stability of LASIK for presbyopia correction were satisfactory; however, the distance efficacy and distance safety decreased. [J Refract Surg. 2023;39(9):627-638.].

Feasibility and safety of Post-Urgent PCI Same-DaY discharge (PUSDY Trial) in China: protocol for a multicentre randomised controlled trial.

INTRODUCTION: In the Chinese healthcare system, where there is overcrowding in hospitals, especially in tertiary care centres, adoption of same-day discharge (SDD) post-percutaneous coronary intervention (PCI) could potentially lead to significant savings of healthcare resources and costs. This study is a non-inferiority trial examining whether post-PCI SDD is feasible in China. The primary hypothesis is that patient outcomes in post-urgent PCI SDD patients are non-inferior to regular discharge patients. METHODS AND ANALYSIS: Post-Urgent PCI Same-DaY is an investigator-initiated multicentre randomised unblinded clinical non-inferiority trial, with 1:1 centralised randomisation to the SDD or usual care (UC) group. Based on sample size calculations, 1296 patients from at least three hospitals, with mild to moderate myocardial infarction, will be included, and acute coronary syndrome patients will be excluded. All patients will receive UC while patients assigned to the SDD group will be discharged on the same day or within 12 hours post-PCI. The primary outcome is major adverse cardiovascular and cerebrovascular events 30 days after discharge. The secondary outcomes are all-cause mortality, bleeding and access site complications. The outcome rates will be compared between groups with the absolute risk difference with a 95% CI. ETHICS AND DISSEMINATION: The study protocol V.2.0 has been approved on 21 January 2022 by the Ethics Committee of Beijing Anzhen Hospital, Capital Medical University (approval number: 2021 KLSD No. 23). The outcomes of this study will be disseminated through a peer-reviewed journal and presented at international conferences. TRIAL REGISTRATION NUMBER: ChiCTR 2200057065; China Clinical Trial Registration.

Dynamic human retinal pigment epithelium (RPE) and choroid architecture based on single-cell transcriptomic landscape analysis.

The retinal pigment epithelium (RPE) and choroid are located behind the human retina and have multiple functions in the human visual system. Knowledge of the RPE and choroid cells and their gene expression profiles are fundamental for understanding retinal disease mechanisms and therapeutic strategies. Here, we sequenced the RNA of about 0.3 million single cells from human RPE and choroids across two regions and seven ages, revealing regional and age differences within the human RPE and choroid. Cell-cell interactions highlight the broad connectivity networks between the RPE and different choroid cell types. Moreover, the transcription factors and their target genes change during aging. The coding of somatic variations increases during aging in the human RPE and choroid at the single-cell level. Moreover, we identified ELN as a candidate for improving RPE degeneration and choroidal structure during aging. The mapping of the molecular architecture of the human RPE and choroid improves our understanding of the human vision support system and offers potential insights into the intervention targets for retinal diseases.

Sesquiterpene lactones improve secretory diarrhea symptoms by inhibiting intestinal Ca2+-activated Cl- channel activities directly and indirectly.

Secretory diarrhea caused by bacteria and viruses is usually accompanied by activation of the cystic fibrosis transmembrane conductance regulator (CFTR) and calcium-activated Cl- channels (CaCCs) in the intestinal epithelium. Inhibition of CFTR and CaCCs activities significantly reduces fluid losses and intestinal motility in diarrheal diseases. For this reason, CFTR and CaCCs are potential targets of therapeutic drug screening. Here, we reported that the sesquiterpene lactones, alantolactone (AL) and isoalantolactone (iAL), significantly inhibited ATP and Eact-induced short-circuit currents in T84, HT-29 and Fischer rat thyroid (FRT) cells expressing transmembrane protein 16A (TMEM16A) in a concentration-dependent manner. AL and iAL also inhibited the CaCC-mediated short-circuit currents induced by carbachol in the mouse colons. Both compounds inhibited forskolin-induced currents in T84 cells but did not significantly affect mouse colons. In vivo studies indicated that AL and iAL attenuated gastrointestinal motility and decreased watery diarrhea in rotavirus-infected neonatal mice. Preliminary mechanism studies showed that AL and iAL inhibited CaCCs at least partially by inhibiting Ca2+ release and basolateral membrane K+ channels activity. These findings suggest a new pharmacological activity of sesquiterpene lactone compounds that might lead to the development of treatments for rotaviral secretory diarrhea.

The effect of EDTA solution on corneal endothelial cells in rabbits.

Corneal disease threatens vision globally. Among corneal diseases, calcific band keratopathy has severe effects on vision owing to its unique location. Currently, ethylene diamine tetraacetic acid (EDTA) chelation remains the most important treatment. However, only the safety of low-dose topical EDTA eye drops is well established in humans. Therefore, the purpose of this study was to determine the safe dose range of EDTA for calcific band keratopathy surgery and its toxic effects on rabbit eyes. Rabbits were administered different doses of EDTA solutions (0.50, 0.20, 0.10, 0.05, and 0.01 M) for twenty minutes. In day seven, the rabbits were euthanized and pathological examination was performed for cornea. We found severe corneal edema in 0.50 M group, while milder edema in lower-concentration treated groups. Followed by corneal thickness measurement, the measured values increase to the peak in post-operative three day (0.20 M group) or one day (lower-concentration groups), then decreased. Groups comparison shown significant difference between BSS control group and higher concentration groups (0.20 M and 0.10 M) (P < 0.001) in observation period, but no significance was observed between low concentration and control group in the day seven after surgery (P > 0.05). Confocal microscopy examination suggested, the number of corneal endothelial cells significantly decreased from 3428.6 ± 180.3 cells/mm2 to 2808 ± 80.6 cells/mm2 in the 0.50 M group, while the lower-concentration groups showed lesser toxic effects on corneal endothelial cells. Finally, our histological examination demonstrated inflammation in each experimental group and dose-dependent, compared with control group. Our study found 0.05 M and 0.01 M EDTA solutions had no obvious toxic effect on the corneal endothelium compared with higher concentration. However, further study of EDTA side effect by clinical trials, and therapeutic effect observation with different concentration are necessary.

Adenine transversion editors enable precise, efficient A•T-to-C•G base editing in mammalian cells and embryos.

Base editors have substantial promise in basic research and as therapeutic agents for the correction of pathogenic mutations. The development of adenine transversion editors has posed a particular challenge. Here we report a class of base editors that enable efficient adenine transversion, including precise A•T-to-C•G editing. We found that a fusion of mouse alkyladenine DNA glycosylase (mAAG) with nickase Cas9 and deaminase TadA-8e catalyzed adenosine transversion in specific sequence contexts. Laboratory evolution of mAAG significantly increased A-to-C/T conversion efficiency up to 73% and expanded the targeting scope. Further engineering yielded adenine-to-cytosine base editors (ACBEs), including a high-accuracy ACBE-Q variant, that precisely install A-to-C transversions with minimal Cas9-independent off-targeting effects. ACBEs mediated high-efficiency installation or correction of five pathogenic mutations in mouse embryos and human cell lines. Founder mice showed 44-56% average A-to-C edits and allelic frequencies of up to 100%. Adenosine transversion editors substantially expand the capabilities and possible applications of base editing technology.

Surface modification of quartz sand: A review of its progress and its effect on heavy metal adsorption.

Quartz sand (SiO2) is a prevalent filtration medium, boasting wide accessibility, superior stability, and cost-effectiveness. However, its utility is often curtailed by its sleek surface, limited active sites, and swift saturation of adsorption sites. This review outlines the prevalent strategies and agents for quartz sand surface modification and provides a comprehensive analysis of the various modification reagents and their operative mechanisms. It delves into the mechanism and utility of surface-modified quartz sand for adsorbing heavy metal ions (HMIs). It is found that the reported modifiers usually form connections with the surface of quartz sand through electrostatic forces, van der Waals forces, pore filling, chemical bonding, and/or molecular entanglement. The literature suggests that these modifications effectively address issues inherent to natural quartz sand, such as its low superficial coarseness, rapid adsorption site saturation, and limited adsorption capacity. Regrettably, comprehensive investigations into the particle size, regenerative capabilities, and application costs of surface-modified quartz sand and the critical factors for its wider adoption are lacking in most reports. The adsorption mechanisms indicate that surface-modified quartz sand primarily removes HMIs from aqueous solutions through surface complexation, ion exchange, and electrostatic and gravitational forces. However, these findings were derived under controlled laboratory conditions, and practical applications for treating real wastewater necessitate overcoming further laboratory-scale obstacles. Finally, this review outlines the limitations of partially surface modified quartz sand and suggests potential venues for future developments, providing a valuable reference for the advancement of cost-effective, HMI-absorbing, surface-modified quartz sand filter media.