Selenium-GPX4 axis protects follicular helper T cells from ferroptosis.

Follicular helper T (TFH) cells are a specialized subset of CD4+ T cells that essentially support germinal center responses where high-affinity and long-lived humoral immunity is generated. The regulation of TFH cell survival remains unclear. Here we report that TFH cells show intensified lipid peroxidation and altered mitochondrial morphology, resembling the features of ferroptosis, a form of programmed cell death that is driven by iron-dependent accumulation of lipid peroxidation. Glutathione peroxidase 4 (GPX4) is the major lipid peroxidation scavenger and is necessary for TFH cell survival. The deletion of GPX4 in T cells selectively abrogated TFH cells and germinal center responses in immunized mice. Selenium supplementation enhanced GPX4 expression in T cells, increased TFH cell numbers and promoted antibody responses in immunized mice and young adults after influenza vaccination. Our findings reveal the central role of the selenium-GPX4-ferroptosis axis in regulating TFH homeostasis, which can be targeted to enhance TFH cell function in infection and following vaccination.

CHIP inhibits odontoblast differentiation through promoting DLX3 polyubiquitylation and degradation.

Dentin is the major hard tissue of teeth formed by differentiated odontoblasts. How odontoblast differentiation is regulated remains enigmatic. Here, we report that the E3 ubiquitin ligase CHIP is highly expressed in undifferentiated dental mesenchymal cells and downregulated after differentiation of odontoblasts. Ectopic expression of CHIP inhibits odontoblastic differentiation of mouse dental papilla cells, whereas knockdown of endogenous CHIP has opposite effects. Chip (Stub1) knockout mice display increased formation of dentin and enhanced expression of odontoblast differentiation markers. Mechanistically, CHIP interacts with and induces K63 polyubiquitylation of the transcription factor DLX3, leading to its proteasomal degradation. Knockdown of DLX3 reverses the enhanced odontoblastic differentiation caused by knockdown of CHIP. These results suggest that CHIP inhibits odontoblast differentiation by targeting its tooth-specific substrate DLX3. Furthermore, our results indicate that CHIP competes with another E3 ubiquitin ligase, MDM2, that promotes odontoblast differentiation by monoubiquitylating DLX3. Our findings suggest that the two E3 ubiquitin ligases CHIP and MDM2 reciprocally regulate DLX3 activity by catalyzing distinct types of ubiquitylation, and reveal an important mechanism by which differentiation of odontoblasts is delicately regulated by divergent post-translational modifications.

Bile metabolic fingerprints distinguish biliary tract cancer from benign biliary diseases.

BACKGROUND AND AIMS: Biliary tract cancers are aggressive gastrointestinal malignancies characterized by a dismal 5-year overall survival rate <20%. Current diagnostic modalities suffer from limitations regarding sensitivity and specificity. This study aimed to develop a bile metabolite-based platform for precise discrimination between malignant and benign biliary diseases. APPROACH AND RESULTS: Samples were collected from 336 patients with biliary tract cancer or benign biliary diseases across 3 independent cohorts. Untargeted metabolic fingerprinting was performed on 300 bile samples using novel nanoparticle-enhanced laser desorption/ionization mass spectrometry. Subsequently, a diagnostic assay was developed based on the exploratory cohort using a selected bile metabolic biomarker panel, with performance evaluated in the validation cohort. Further external validation of disease-specific metabolites from bile samples was conducted in a prospective cohort (n = 36) using quantitative analysis. As a result, we established a novel bile-based assay, BileMet, for the rapid and precise detection of malignancies in the biliary tract system with an AUC of 0.891. We identified 6-metabolite biomarker candidates and discovered the critical role of the chenodeoxycholic acid glycine conjugate as a protective metabolite associated with biliary tract cancer. CONCLUSIONS: Our findings confirmed the improved diagnostic capabilities of BileMet assay in a clinical setting. If applied, the BileMet assay enables intraoperative testing and fast medical decision-making for cases with suspected malignancy where brush cytology detection fails to support malignancy, ultimately reducing the economic burden by over 90%.

Stem-cell-expressed DEVIL-like small peptides maintain root growth under abiotic stress via abscisic acid signaling.

Stem cells are essential to plant growth and development. Through data mining, we identified five DEVIL-like (DVL) small peptide genes that are preferentially expressed in the quiescent center of Arabidopsis (Arabidopsis thaliana) root but whose functions are unknown. When overexpressed, these genes caused a dramatic decrease in root length and pleiotropic phenotypes in the shoot. No root-growth defect was observed in the single-gene mutants, but the quintuple mutant exhibited slightly longer roots than the wild type (WT). Through transcriptome analysis with DVL20-overexpressing plants, we found that many genes involved in abscisic acid (ABA) signaling were regulated by these peptides. Consistent with this finding, we demonstrated that, relative to the WT, DVL20-overexpressing plants were more tolerant whereas the quintuple mutant was more sensitive to ABA. Using RT-qPCR, we showed that ABA signaling-associated genes were affected in an opposite manner when the plants were grown in normal or ABA-containing medium. Strikingly, ectopic expression of ABA signaling genes such as PYRABACTIN RESISTANCE 1-LIKE (PYL) 4, 5, or 6 or suppression of HIGHLY ABA-INDUCED 2 (HAI2) and MITOGEN-ACTIVATED PROTEIN KINASE KINASE KINASE 18 (MAPKKK18) not only largely rescued the root growth defects in DVL20-overexpressing plants in normal growth condition but also conferred tolerance to ABA. Based on these results, we propose that DVL1, 2, 5, 8 and 20 function redundantly in root stem-cell maintenance under abiotic stress, and this role is achieved via ABA signaling.

The PLETHORA Homolog In Marchantia polymorpha is Essential To Meristem Maintenance, Developmental Progression, And Redox Homeostasis.

To adapt to a terrestrial habitat, the ancestors of land plants must make several morphological and physiological modifications, such as a meristem allowing for three-dimensional growth, rhizoids for water and nutrient uptake, air pore complexes or stomata that permit air exchange, and a defense system to cope with oxidative stress that occurs frequently in a terrestrial habitat. To understand how meristem is determined during land plant evolution, we characterized the function of the closest PLETHORA homolog in the liverwort Marchantia polymorpha, which we named MpPLT. Through transgenic approach, we showed that MpPLT is expressed not only in the stem cells at the apical notch but also in the proliferation zone of the meristem, as well as cells that form the air-pore complex and rhizoids. Using the CRISPR method we then created mutants for MpPLT and found that the mutants are not only defective in meristem maintenance but also compromised in air-pore complex and rhizoid development. Strikingly, at later developmental stages, numerous gemma-like structures were formed in Mpplt mutants, suggesting developmental arrest. Further experiments indicate that MpPLT promotes plant growth by regulating MpWOX, which shared a similar expression pattern as MpPLT, and genes involved in auxin and cytokinin signaling pathways. Through transcriptome analyses, we found that MpPLT also has a role in redox homeostasis and that this role is essential to plant growth. Together, these results suggest that MpPLT has a crucial role in liverwort growth and development and hence may have played a crucial role in early land plant evolution.

Balance of Gata3 and Ramp2 in hepatocytes regulates hepatic vascular reconstitution in postoperative liver regeneration.

BACKGROUND & AIMS: Post-hepatectomy liver failure (PHLF) leads to poor prognosis in patients undergoing hepatectomy, with hepatic vascular reconstitution playing a critical role. However, the regulators of hepatic vascular reconstitution remain unclear. In this study, we aimed to investigate the regulatory mechanisms of hepatic vascular reconstitution and identify biomarkers predicting PHLF in patients undergoing hepatectomy. METHODS: Candidate genes that were associated with hepatic vascular reconstitution were screened using adeno-associated virus vectors in Alb-Cre-CRISPR/Cas9 mice subjected to partial hepatectomy. The biological activities of candidate genes were estimated using endothelial precursor transfusion and associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) models. The level of candidates was detected in biopsies from patients undergoing ALPPS. Risk factors for PHLF were also screened using retrospective data. RESULTS: Downregulation of Gata3 and upregulation of Ramp2 in hepatocytes promoted the proliferation of liver sinusoidal endothelial cells and hepatic revascularization. Pigment epithelium-derived factor (PEDF) and vascular endothelial growth factor A (VEGFA) played opposite roles in regulating the migration of endothelial precursors from bone marrow and the formation of new sinusoids after hepatectomy. Gata3 restricted endothelial cell function in patient-derived hepatic organoids, which was abrogated by a Gata3 inhibitor. Moreover, overexpression of Gata3 led to higher mortality in ALPPS mice, which was improved by a PEDF-neutralizing antibody. The expression of Gata3/RAMP and PEDF/VEGFA tended to have a negative correlation in patients undergoing ALPPS. A nomogram incorporating multiple factors, such as serum PEDF/VEGF index, was constructed and could efficiently predict the risk of PHLF. CONCLUSIONS: The balance of Gata3 and Ramp2 in hepatocytes regulates the proliferation of liver sinusoidal endothelial cells and hepatic revascularization via changes in the expression of PEDF and VEGFA, revealing potential targets for the prevention and treatment of PHLF. IMPACT AND IMPLICATIONS: In this study, we show that the balance of Gata3 and Ramp2 in hepatocytes regulates hepatic vascular reconstitution by promoting a shift from pigment epithelium-derived factor (PEDF) to vascular endothelial growth factor A (VEGFA) expression during hepatectomy- or ALLPS (associating liver partition and portal vein ligation for staged hepatectomy)-induced liver regeneration. We also identified serum PEDF/VEGFA index as a potential predictor of post-hepatectomy liver failure in patients who underwent hepatectomy. This study improves our understanding of how hepatocytes contribute to liver regeneration and provides new targets for the prevention and treatment of post-hepatectomy liver failure.

Bi-allelic missense variants in MEI4 cause preimplantation embryonic arrest and female infertility.

Preimplantation embryonic arrest is an important pathogenesis of female infertility, but little is known about the genetic factors behind this phenotype. MEI4 is an essential protein for DNA double-strand break formation during meiosis, and Mei4 knock-out female mice are viable but sterile, indicating that MEI4 plays a crucial role in reproduction. To date, MEI4 has not been found to be associated with any human reproductive diseases. Here, we identified six compound heterozygous and homozygous MEI4 variants-namely, c.293C > T, p.(Ser98Leu), c.401C > G, p.(Pro134Arg), c.391C > G, p.(Pro131Ala), c.914A > T, p.(Tyr305Phe), c.908C > G, p.(Ala303Gly), and c.899A > T, p.(Gln300Leu)-in four independent families that were responsible for female infertility mainly characterized by preimplantation embryonic arrest. In vitro, we found that these variants reduced the interaction between MEI4 and DNA. In vivo, we generated a knock-in mouse model and demonstrated that female mice were infertile and were characterized by developmental defects during oogenesis. Our findings reveal the important roles of MEI4 in human reproduction and provide a new diagnostic marker for genetic counseling of clinical infertility patients.

Live Birth with or without Preimplantation Genetic Testing for Aneuploidy.

BACKGROUND: Embryo selection with preimplantation genetic testing for aneuploidy (PGT-A) may improve pregnancy outcomes after initial embryo transfer. However, it remains uncertain whether PGT-A improves the cumulative live-birth rate as compared with conventional in vitro fertilization (IVF). METHODS: In this multicenter, randomized, controlled trial, we randomly assigned subfertile women with three or more good-quality blastocysts to undergo either PGT-A or conventional IVF; all the women were between 20 and 37 years of age. Three blastocysts were screened by next-generation sequencing in the PGT-A group or were chosen by morphologic criteria in the conventional-IVF group and then were successively transferred one by one. The primary outcome was the cumulative live-birth rate after up to three embryo-transfer procedures within 1 year after randomization. We hypothesized that the use of PGT-A would result in a cumulative live-birth rate that was no more than 7 percentage points higher than the rate after conventional IVF, which would constitute the noninferiority margin for conventional IVF as compared with PGT-A. RESULTS: A total of 1212 patients underwent randomization, and 606 were assigned to each trial group. Live births occurred in 468 women (77.2%) in the PGT-A group and in 496 (81.8%) in the conventional-IVF group (absolute difference, -4.6 percentage points; 95% confidence interval [CI], -9.2 to -0.0; P<0.001). The cumulative frequency of clinical pregnancy loss was 8.7% and 12.6%, respectively (absolute difference, -3.9 percentage points; 95% CI, -7.5 to -0.2). The incidences of obstetrical or neonatal complications and other adverse events were similar in the two groups. CONCLUSIONS: Among women with three or more good-quality blastocysts, conventional IVF resulted in a cumulative live-birth rate that was noninferior to the rate with PGT-A. (Funded by the National Natural Science Foundation of China and others; ClinicalTrials.gov number, NCT03118141.).

SCARECROW maintains the stem cell niche in Arabidopsis roots by ensuring telomere integrity.

Stem cells are the ultimate source of cells for various tissues and organs and thus are essential for postembryonic plant growth and development. SCARECROW (SCR) is a plant-specific transcription regulator well known for its role in stem cell renewal in plant roots, but the mechanism by which SCR exerts this function remains unclear. To address this question, we carried out a genetic screen for mutants that no longer express SCR in the stem cell niche of Arabidopsis (Arabidopsis thaliana) roots and characterized 1 of these mutants. Molecular genetics methods allowed us to pinpoint the causal mutation in this mutant in TELOMERIC PATHWAYS IN ASSOCIATION WITH STN 1 (TEN1), encoding a factor that protects telomere ends. Interestingly, TEN1 expression was dramatically reduced in the scr mutant. Telomerase and STN1 and CONSERVED TELOMERE MAINTENANCE COMPONENT 1 (CTC1), components of the same protein complex as TEN1, were also dramatically downregulated in scr. Loss of STN1, CTC1, and telomerase caused defects in root stem cells. These results together suggest that SCR maintains root stem cells by promoting expression of genes that ensure genome integrity. Supporting this conclusion, we demonstrated that the scr mutant accumulates more DNA damage than wild-type Arabidopsis and that this problem is aggravated after exposure to zeocin, a DNA damage reagent. Finally, we identified 2 previously uncharacterized motifs in TEN1 and provide evidence that a conserved amino acid residue in 1 of the motifs is indispensable for TEN1 function. SCR thus provides a connection between genome integrity and stem cell maintenance in Arabidopsis roots.

The protective effects of ruscogenin against lipopolysaccharide-induced myocardial injury in septic mice.

ABSTRACT: Sepsis-induced myocardial dysfunction (SIMD) commonly occurs in individuals with sepsis and is a severe complication with high morbidity and mortality rates. The current study aimed to investigate the effects and potential mechanisms of the natural steroidal sapogenin ruscogenin (RUS) against lipopolysaccharide (LPS)-induced myocardial injury in septic mice. We found that RUS effectively alleviated myocardial pathological damage, normalized cardiac function, and increased survival in septic mice. RNA sequencing (RNA-seq) demonstrated that RUS administration significantly inhibited the activation of the NOD-like receptor signaling pathway in the myocardial tissues of septic mice. Subsequent experiments further confirmed that RUS suppressed myocardial inflammation and pyroptosis during sepsis. Additionally, cultured HL-1 cardiomyocytes were challenged with LPS, and we observed that RUS could protect these cells against LPS-induced cytotoxicity by suppressing inflammation and pyroptosis. Notably, both the in vivo and in vitro findings indicated that RUS inhibited NLRP3 upregulation in cardiomyocytes stimulated with LPS. As expected, knockdown of NLRP3 blocked the LPS-induced activation of inflammation and pyroptosis in HL-1 cells. Furthermore, the cardioprotective effects of RUS on HL-1 cells under LPS stimulation were abolished by the novel NLRP3 agonist BMS-986299. Taken together, our results suggest that RUS can alleviate myocardial injury during sepsis, at least in part by suppressing NLRP3-mediated inflammation and pyroptosis, highlighting the potential of this molecule as a promising candidate for SIMD therapy.

Validating the Baveno Elastography Criteria of Advanced Liver Fibrosis in Two-Dimensional Shear Wave Elastography: A Prospective Pathology-Based Study.

INTRODUCTION: The Baveno criteria for assessing advanced liver fibrosis were mainly determined by transient elastography (TE), and its pathology-based validation studies in two-dimensional shear wave elastography (2D-SWE) remain limited. We aimed to validate the Baveno criteria through use of 2D-SWE. METHOD: Consecutive patients who underwent liver biopsies for various benign liver diseases were prospectively recruited. Liver stiffness measurement (LSM) was simultaneously evaluated by TE and 2D-SWE. The optimal cutoff value to predict advanced liver fibrosis was determined by the Youden Index, and the diagnostic performance was estimated using area under the receiver operating characteristic (AUROC) analysis. RESULTS: A total of 101 patients were enrolled having a median age of 55.0 (IQR: 46.0-63.5) years, with 53 (52.48%) of them being male. Using <9 and >14 kPa as the optimal dual cutoffs, the AUROC values in TE and 2D-SWE were 0.92 (95% CI: 0.83-0.97) and 0.93 (95% CI: 0.84-0.98), respectively (p = 0.61). The sensitivity and specificity of LSM by TE/2D-SWE achieved rates of 94.44%/94.44% and 86.00%/88.00%, respectively. However, using the Baveno criteria, the AUROC values in TE and 2D-SWE could remain achieving 0.91 (95% CI: 0.82-0.97) and 0.93 (95% CI: 0.84-0.98), respectively (p = 0.36). The sensitivity and specificity in TE/2D-SWE were 88.24%/88.24% and 86.79%/90.57%, respectively. CONCLUSION: This study establishes the compatibility of the Baveno dual cutoff criteria with 2D-SWE, positioning it as an easily used criteria in clinical practice and research.

Inflammation-related molecular signatures involved in the anticancer activities of brigatinib as well as the prognosis of EML4-ALK lung adenocarcinoma patient.

Although ALK tyrosine kinase inhibitors (ALK-TKIs) have shown remarkable benefits in EML4-ALK positive NSCLC patients compared to conventional chemotherapy, the optimal sequence of ALK-TKIs treatment remains unclear due to the emergence of primary and acquired resistance and the lack of potential prognostic biomarkers. In this study, we systematically explored the validity of sequential ALK inhibitors (alectinib, lorlatinib, crizotinib, ceritinib and brigatinib) for a heavy-treated patient with EML4-ALK fusion via developing an in vitro and in vivo drug testing system based on patient-derived models. Based on the patient-derived models and clinical responses of the patient, we found that crizotinib might inhibit proliferation of EML4-ALK positive tumors resistant to alectinib and lorlatinib. In addition, NSCLC patients harboring the G1269A mutation, which was identified in alectinib, lorlatinib and crizotinib-resistant NSCLC, showed responsiveness to brigatinib and ceritinib. Transcriptomic analysis revealed that brigatinib suppressed the activation of multiple inflammatory signaling pathways, potentially contributing to its anti-tumor activity. Moreover, we constructed a prognostic model based on the expression of IL6, CXCL1, and CXCL5, providing novel perspectives for predicting prognosis in EML4-ALK positive NSCLC patients. In summary, our results delineate clinical responses of sequential ALK-TKIs treatments and provide insights into the mechanisms underlying the superior effects of brigatinib in patients harboring ALKG1269A mutation and resistant towards alectinib, lorlatinib and crizotinib. The molecular signatures model based on the combination of IL6, CXCL1 and CXCL5 has the potential to predict prognosis of EML4-ALK positive NSCLC patients.

Effects of cycloplegia on crystalline lens morphology and location in acute acquired concomitant esotropia.

PURPOSE: The study aims to compare morphology and location of crystalline lens between acute acquired concomitant esotropia (AACE) patients and control subjects, both before and after cycloplegia. METHODS: This is a prospective and observational clinical study. Morphological and locational parameters of the crystalline lens in 53 AACE patients and 32 control subjects were assessed before and after cycloplegia using CASIA2 system, which represents the latest swept-source anterior segment optical coherence tomography. Cycloplegic refraction was recorded by administering 1% atropine in patients younger than 12 years and 1% cyclopentolate in those > 12 years old. Morphological parameters included anterior radius of curvature (ARC), posterior radius of curvature (PRC), lens thickness (LTH), and equivalent diameter of lens (LED). Locational parameters comprised lens decentration (LD) and lens tilt (LT). Comparison of these parameters before and after cycloplegia were conducted between AACE and controls. Additionally, the study analyzed and compared the changes in these parameter post-cycloplegia. RESULTS: Our findings suggest no significant difference in morphological parameters including ARC, PRC, LTH and LED between AACE patients and controls before or after cycloplegia. However, 2D-modeling data in the 0° meridian revealed that variation post-cycloplegia of LD (lens shift) in right eyes was different in AACE patients, measuring - 0.03(0.08) [median(interquartile range)] which was significantly distinct from the control group, exhibiting a measurement of 0.01(0.06) (z = - 2.373, p = 0.018). In left eyes, a similar trend was observed with lens shift in the 0° meridian being 0.02(0.06) in AACE, significantly differing from control group's measurement of - 0.02(0.08) (z = - 2.809, p = 0.005). Further, correlation analysis revealed that larger temporal shift of lens was associated with greater changes in ARC (r = 0.294, p = 0.006) and LTH (r = - 0.230, p = 0.031). CONCLUSIONS: The morphological features of the crystalline lens were similar in AACE patients and controls; however, the change of lens location by cycloplegia was observed only in AACE patients, suggesting an association with excessive accommodation.

Eyelid retraction during smiling in a patient with monocular congenital ptosis: a case report.

BACKGROUND: Blepharoptosis is a common symptom in ophthalmology clinic, but eyelid retraction when smiling in a ptosis eye is a rare manifestation. Here we report a novel manifestation that eyelid retraction during smiling in a patient with monocular congenital ptosis. CASE DESCRIPTION: A 10-year-old girl with isolated and mild unilateral congenital ptosis showed eyelid retraction in ptotsis eye when smiling together with a lid lag on downgaze. She didn't have any systematic and ocular diseases other than myopia and astigmatism.Eyelid retraction during smiling is 5 mm, resulting in a significant difference in the height of bilateral palpebral fissures.As for ptosis, is mild.The margin to reflex distance 1 is 1.0 mm on the right eye(ptosis eye) and 3.0 mm on the left eye. A lid lag of 1.0 mm on downward gaze was noted on the right, she could close her eyes fully while sleeping.The ice pack test, laboratory test for thyroid function, whole-exome sequencing (WES) and magnetic resonance imaging(MRI) of the orbital and ocular motor nerves showed normal results.Her symptoms alleviated after 6 months, with the retraction of the right upper eyelid when smiling was approximately 3 mm, thus the difference in the palpebral fissure height when smiling was smaller than that at the initial presentation. CONCLUSION: Blepharoptosis may accompanied with abnormal innervation like eyelid retraction, this phenomenon can be alleviated with age.The results of the levator muscle function test should be carefully examined to determine whether it is ptosis in an impaired innervation eyelid.

Six-month binocular stereopsis recovery and its influencing factors in children with intermittent exotropia.

OBJECTIVE: To investigate the recovery of binocular stereopsis recovery and its influencing factors in children with intermittent exotropia after successful correction of eye position. METHODS: Prospective clinical study. A total of 178 patients, aged 9 ∼ 14 (10.8 ± 1.7) years, who were successfully corrected after intermittent exotropia surgery at the Beijing Tongren Hospital Affiliated to Capital Medical University from October 2023 to September 2023 were collected, the follow-up duration was six-month or longer. Paired t test, Pearson correlation analysis and multivariable linear regression analysis were used to probe preoperative clinical features that may predict the stereopsis six months after surgery. RESULTS: Six months after surgery, the angle of deviation of the patients met the orthotopic standard, and there was significant difference compared with that before surgery (distant: -2.7△±3.2△ vs. -30.5△±8.4△, t=-25.3, P < 0.001. Near:-3.7△±4.1△ vs. -33.7△±8.0△, t=-26.1, P < 0.001). Distant stereopsis (3.0 ± 0.6 vs. 3.9 ± 0.4, t = 4.9, P < 0.05) and near stereopsis (2.3 ± 0.5 vs. 2.6 ± 0.4, t = 3.8, P < 0.05) were both significantly improved compared with that of before surgery. 17% and 22% patients rebuilt normal distant stereopsis and normal near stereopsis, respectively. Preoperative distant stereopsis (r=-0.26, P = 0.004) and near stereopsis (r=-0.23, P = 0.011) was significantly negatively correlated with convergence reserve. Multivariable analysis showed that patients' age (ß = 0.003, p = 0.037), anisometropia (ß = 0.015, p = 0.043), and preoperative distant stereopsis (ß = 0.456, p < 0.001) were significantly associated with postoperative distant stereopsis. Patients' age (ß = 0.005, p = 0.044), anisometropia (ß = 0.127, p = 0.034), angle of deviation (ß=-0.230, p = 0.020), and preoperative near stereopsis (ß = 0.136, p < 0.001) were significantly associated with postoperative near stereopsis. CONCLUSION: IXT patients could get eye position fixed after surgery, about 20% patients benefited from stereopsis improvement. Patient's age, binocular anisometropia, angle of deviation and preoperative stereopsis were independent factors influencing postoperative stereopsis.

Prevention of postoperative nausea and vomiting after orthognathic surgery: a scoping review.

INTRODUCTION: Postoperative nausea and vomiting (PONV) is one of the most common adverse events following orthognathic surgery. It's a distressing feeling for patients and continues to be the cause of postoperative complications such as bleeding, delayed healing, and wound infection. This scoping review aims to identify effective PONV prophylaxis strategies during orthognathic surgery that have emerged in the past 15 years. METHODS: We searched Pubmed, Cochrane Controlled Register of Trials, and Embase from 2008 to May 2023. Studies meeting the following criteria were eligible for inclusion: (1) recruited patients undergo any orthognathic surgery; (2) evaluated any pharmacologic or non-pharmacologic method to prevent PONV. Studies meeting the following criteria were excluded: (1) case series, review papers, or retrospective studies; (2) did not report our prespecified outcomes. RESULTS: Twenty-one studies were included in this review. Pharmacological methods for PONV prevention include ondansetron and dexamethasone (3 studies), peripheral nerve block technique (4 studies), dexmedetomidine (1 study), pregabalin (2 studies), nefopam (2 studies), remifentanil (1 study), propofol (2 studies), and penehyclidine (1 study). Non-pharmacologic methods include capsicum plaster (1 study), throat packs (2 studies) and gastric aspiration (2 studies). CONCLUSIONS: Based on current evidence, we conclude that prophylactic antiemetics like dexamethasone, ondansetron, and penehyclidine are the first defense against PONV. Multimodal analgesia with nerve block techniques and non-opioid analgesics should be considered due to their notable opioid-sparing and PONV preventive effect. For the non-pharmacological methods, throat packs are not recommended for routine use because of their poor effect and serious complications. More prospective RCTs are required to confirm whether gastric aspiration can prevent PONV effectively for patients undergoing orthognathic surgery.

Naphthalimide-based fluorescent probe for Hg2+ detection and imaging in living cells and zebrafish.

A simple naphthalimide-based fluorescent probe was designed and synthesized for the determination of mercury ion (Hg2+ ). The probe showed a noticeable fluorescence quenching response for Hg2+ . When added with Hg2+ , the fluorescence intensity of the probe at 560 nm was remarkably decreased with the color changed from yellow to colorless under ultraviolet (UV) light. The probe had a notable selectivity and sensitivity for Hg2+ and displayed an excellent sensing performance when detecting Hg2+ at low concentration (19.5 nM). The binding phenomenon between the probe and Hg2+ was identified by Job's method and high-resolution mass spectrometry (HRMS). Moreover, the probe was not only utilized to identify Hg2+ in real samples with satisfactory results (92.00%-110.00%) but also was successfully used for bioimaging in cells and zebrafish. The recognition mechanism has been verified by transmission electron microscopy (TEM) for the first time. All the results showed that the probe could be used as a potent useful tool for detection of Hg2+ .

Nanoscale Analysis of Frozen Water by Atom Probe Tomography Using Graphene Encapsulation and Cryo-Workflows.

There has been an increasing interest in atom probe tomography (APT) to characterize hydrated and biological materials. A major benefit of APT compared to microscopy techniques more commonly used in biology is its combination of outstanding three-dimensional (3D) spatial resolution and mass sensitivity. APT has already been successfully used to characterize biominerals, revealing key structural information at the atomic scale, however there are many challenges inherent to the analysis of soft hydrated materials. New preparation protocols, often involving specimen preparation and transfer at cryogenic temperature, enable APT analysis of hydrated materials and have the potential to enable 3D atomic scale characterization of biological materials in the near-native hydrated state. In this study, samples of pure water at the tips of tungsten needle specimens were prepared at room temperature by graphene encapsulation. A comparative study was conducted where specimens were transferred at either room temperature or cryo-temperature and analyzed by APT by varying the flight path and pulsing mode. The differences between the analysis workflows are presented along with recommendations for future studies, and the compatibility between graphene coating and cryogenic workflows is demonstrated.

Phentolamine and B vitamins for feeding intolerance in late preterm infants: a randomised trial.

BACKGROUND AND OBJECTIVES: Feeding intolerance (FI) is a common problem in late preterm infants (34 weeks ≤ gestational age < 37 weeks). This study aimed to evaluate the efficacy and safety of phentolamine combined with B vitamins in treating FI in late preterm infants and to explore its effects on gastrointestinal symptoms, inflammation and complications. METHODS AND STUDY DESIGN: We randomly assigned 118 late preterm infants with FI to a treatment group (n = 56) or a control group (n = 62). The treatment group received intravenous phentolamine and intramuscular B vitamins, whereas the control group received basic treatment only. We measured the time of disappearance of gastrointestinal symptoms, the time of basal at-tainment, the time of hospitalisation, the incidence of complications, the concentrations of inflammatory markers and the overall effective rate of treatment. RESULTS: The treatment group had a shorter duration of gastrointestinal symptoms than did the control group (p < 0.01). The treatment group also had lower concentrations of inflammatory markers and a higher overall effective rate than did the control group (p < 0.05). There was no difference between the two groups in the time of hospitalisation, basal attainment, weight re-covery and the incidence of complications (p > 0.05). CONCLUSIONS: Phentolamine and B vitamins can reduce gastrointestinal symptoms and inflammation in late preterm infants with FI but do not affect the occurrence of complications.