ZFYVE19 deficiency: a ciliopathy involving failure of cell division, with cell death.

BACKGROUND AND AIMS: Variants in ZFYVE19 underlie a disorder characterised by progressive portal fibrosis, portal hypertension and eventual liver decompensation. We aim to create an animal model to elucidate the pathogenic mechanism. METHODS: Zfyve19 knockout (Zfyve19-/- ) mice were generated and exposed to different liver toxins. Their livers were characterised at the tissue, cellular and molecular levels. Findings were compared with those in wild-type mice and in ZFYVE19-deficient patients. ZFYVE19 knockout and knockdown retinal pigment epithelial-1 cells and mouse embryonic fibroblasts were generated to study cell division and cell death. RESULTS: The Zfyve19-/- mice were normal overall, particularly with respect to hepatobiliary features. However, when challenged with α-naphthyl isothiocyanate, Zfyve19-/- mice developed changes resembling those in ZFYVE19-deficient patients, including elevated serum liver injury markers, increased numbers of bile duct profiles with abnormal cholangiocyte polarity and biliary fibrosis. Failure of cell division, centriole and cilia abnormalities, and increased cell death were observed in knockdown/knockout cells. Increased cell death and altered mRNA expression of cell death-related signalling pathways was demonstrated in livers from Zfyve19-/- mice and patients. Transforming growth factor-ß (TGF-ß) and Janus kinase-Signal Transducer and Activator of Transcription 3 (JAK-STAT3) signalling pathways were upregulated in vivo, as were chemokines such as C-X-C motif ligands 1, 10 and 12. CONCLUSIONS: Our findings demonstrated that ZFYVE19 deficiency is a ciliopathy with novel histological features. Failure of cell division with ciliary abnormalities and cell death activates macrophages and may thus lead to biliary fibrosis via TGF-ß pathway in the disease.

Low-intensity pulsed ultrasound promotes the osteogenesis of mechanical force-treated periodontal ligament cells via Piezo1.

Background: Low-intensity pulsed ultrasound (LIPUS) can accelerate tooth movement and preserve tooth and bone integrity during orthodontic treatment. However, the mechanisms by which LIPUS affects tissue remodeling during orthodontic tooth movement (OTM) remain unclear. Periodontal ligament cells (PDLCs) are pivotal in maintaining periodontal tissue equilibrium when subjected to mechanical stimuli. One notable mechano-sensitive ion channel, Piezo1, can modulate cellular function in response to mechanical cues. This study aimed to elucidate the involvement of Piezo1 in the osteogenic response of force-treated PDLCs when stimulated by LIPUS. Method: After establishing rat OTM models, LIPUS was used to stimulate rats locally. OTM distance and alveolar bone density were assessed using micro-computed tomography, and histological analyses included hematoxylin and eosin staining, tartrate-resistant acid phosphatase staining and immunohistochemical staining. GsMTx4 and Yoda1 were respectively utilized for Piezo1 functional inhibition and activation experiments in rats. We isolated human PDLCs (hPDLCs) in vitro and evaluated the effects of LIPUS on the osteogenic differentiation of force-treated hPDLCs using real-time quantitative PCR, Western blot, alkaline phosphatase and alizarin red staining. Small interfering RNA and Yoda1 were employed to validate the role of Piezo1 in this process. Results: LIPUS promoted osteoclast differentiation and accelerated OTM in rats. Furthermore, LIPUS alleviated alveolar bone resorption under pressure and enhanced osteogenesis of force-treated PDLCs both in vivo and in vitro by downregulating Piezo1 expression. Subsequent administration of GsMTx4 in rats and siPIEZO1 transfection in hPDLCs attenuated the inhibitory effect on osteogenic differentiation under pressure, whereas LIPUS efficacy was partially mitigated. Yoda1 treatment inhibited osteogenic differentiation of hPDLCs, resulting in reduced expression of Collagen Ⅰα1 and osteocalcin in the periodontal ligament. However, LIPUS administration was able to counteract these effects. Conclusion: This research unveils that LIPUS promotes the osteogenesis of force-treated PDLCs via downregulating Piezo1.

Low-intensity pulsed ultrasound reduces alveolar bone resorption during orthodontic treatment via Lamin A/C-Yes-associated protein axis in stem cells.

BACKGROUND: The bone remodeling during orthodontic treatment for malocclusion often requires a long duration of around two to three years, which also may lead to some complications such as alveolar bone resorption or tooth root resorption. Low-intensity pulsed ultrasound (LIPUS), a noninvasive physical therapy, has been shown to promote bone fracture healing. It is also reported that LIPUS could reduce the duration of orthodontic treatment; however, how LIPUS regulates the bone metabolism during the orthodontic treatment process is still unclear. AIM: To investigate the effects of LIPUS on bone remodeling in an orthodontic tooth movement (OTM) model and explore the underlying mechanisms. METHODS: A rat model of OTM was established, and alveolar bone remodeling and tooth movement rate were evaluated via micro-computed tomography and staining of tissue sections. In vitro, human bone marrow mesenchymal stem cells (hBMSCs) were isolated to detect their osteogenic differentiation potential under compression and LIPUS stimulation by quantitative reverse transcription-polymerase chain reaction, Western blot, alkaline phosphatase (ALP) staining, and Alizarin red staining. The expression of Yes-associated protein (YAP1), the actin cytoskeleton, and the Lamin A/C nucleoskeleton were detected with or without YAP1 small interfering RNA (siRNA) application via immunofluorescence. RESULTS: The force treatment inhibited the osteogenic differentiation potential of hBMSCs; moreover, the expression of osteogenesis markers, such as type 1 collagen (COL1), runt-related transcription factor 2, ALP, and osteocalcin (OCN), decreased. LIPUS could rescue the osteogenic differentiation of hBMSCs with increased expression of osteogenic marker inhibited by force. Mechanically, the expression of LaminA/C, F-actin, and YAP1 was downregulated after force treatment, which could be rescued by LIPUS. Moreover, the osteogenic differentiation of hBMSCs increased by LIPUS could be attenuated by YAP siRNA treatment. Consistently, LIPUS increased alveolar bone density and decreased vertical bone absorption in vivo. The decreased expression of COL1, OCN, and YAP1 on the compression side of the alveolar bone was partially rescued by LIPUS. CONCLUSION: LIPUS can accelerate tooth movement and reduce alveolar bone resorption by modulating the cytoskeleton-Lamin A/C-YAP axis, which may be a promising strategy to reduce the orthodontic treatment process.

Exploring long-term changes and influencing factors of the upper airway in patients with a skeletal Class II relationship after mandibular advancement with maxillary setback surgery: A comprehensive 2-year follow-up investigation.

INTRODUCTION: The objective of this study was to investigate the 2-year postoperative change and influencing factors of the upper airway after mandibular advancement with maxillary setback surgery for patients with a skeletal Class II relationship. METHODS: Fifty-seven participants who underwent mandibular advancement with maxillary setback surgery were enrolled consecutively. Cone-beam computed tomography was performed preoperatively, 3 months postoperatively (T1), and 2 years (T2) postoperatively. All parameters were measured using Dolphin Imaging software (Dolphin Imaging and Management Solutions, Chatsworth, Calif). RESULTS: The total volume (V), minimum cross-sectional area (CSAmin), and glossopharynx increased significantly in both the short-term (V, 13.33%; CSAmin, 33.03%; glossopharynx, 26.73%) and long-term (V, 10.19%; CSAmin, 23.18%; glossopharynx, 18.27%) after the surgery. Mandibular advancement, mandibular width increase, preoperative CSAmin, and body mass index (BMI) significantly affected 2-year postoperative V increases. Mandibular advancement and BMI significantly affected 2-year postoperative glossopharynx increases. Backward movement of point PNS may lead to a reduction of the nasopharynx; however, downward movement of point PNS, upward movement of point A, and increased maxillary width may compensate for this effect by increasing the likelihood of the nasopharynx opening. Furthermore, mandibular body length at T1 is positively associated with relapse rate ([T2 - T1] / T1) of V and CSAmin. CONCLUSIONS: Mandibular advancement amount, mandibular width increase, preoperative CSAmin, and BMI are the 4 factors for long-term V changes. Patients with a longer mandibular body length might have a lower relapse rate.

High triglyceride-glucose (TyG) index is associated with poor prognosis of heart failure with preserved ejection fraction.

BACKGROUND: The impact of insulin resistance on the prognosis of heart failure with preserved ejection fraction (HFpEF) remains unknown. This study aimed to investigate the association between the triglyceride-glucose (TyG) index, an easily calculated marker of insulin resistance, and the long-term prognosis of HFpEF. METHODS: A total of 823 patients with HFpEF were enrolled in the study. The TyG index was determined using the formula ln(fasting triglycerides [mg/dL] × fasting glucose [mg/dL]/2). The primary endpoint was all-cause death. The secondary endpoints were cardiovascular (CV) death and heart failure (HF) rehospitalization. Restricted cubic spline, multivariate Cox proportional hazard models, and competing risk models were used for analyses. RESULTS: During a median follow-up period of 3.16 years, 147 (17.8%) all-cause deaths, 139 (16.8%) CV deaths, and 222 (27.0%) HF rehospitalizations occurred. Restricted cubic spline analysis revealed a J-shaped association between the TyG index and the mortality and rehospitalization rates. In the multivariate Cox proportional hazard models, compared with those in the lowest TyG index tertile, patients in the highest tertile exhibited the greatest susceptibility to all-cause death (HR 1.53, 95% CI 1.19-1.98) and CV death (HR 1.52, 95% CI 1.19-1.96). In the competing risk model, a significant association between the TyG index and HF rehospitalization was observed (HR 1.31, 95% CI, 1.07-1.61). CONCLUSION: A high TyG index is associated with an increased risk of mortality and rehospitalization in patients with HFpEF. The TyG index may serve as a promising prognostic marker for patients with HFpEF.

Effects of vertical control on anatomic and aerodynamic characteristics of the oropharyngeal airway during premolar extraction treatment of Class II hyperdivergent nonsevere crowding malocclusion.

INTRODUCTION: This study aimed to analyze the effects of premolar extraction treatment with vertical control on changes in the anatomy and aerodynamics of the oropharynx in Class II hyperdivergent malocclusion with nonsevere crowding. METHODS: Thirty-nine patients with Class II hyperdivergent malocclusion were enrolled consecutively. All the participants underwent 4 premolar extractions. The high-pull J-hook and mini-implants were used to provide vertical control. Cone-beam computed tomography was performed before and after treatment. The participants were divided into a decreased lower vertical facial height group (n = 23) and an increased lower vertical facial height group (n = 16) on the basis of superimposition. The aerodynamic characteristics, including airway resistance (inspiration, Rin; expiration, Rex) and maximum velocity (inspiration, Vmaxin; expiration, Vmaxex) at inspiration and expiration, were calculated using computational fluid dynamics. Anatomic characteristics, including volume and cross-sectional area (CSAmin), were measured using the Dolphin Imaging software (Dolphin Imaging and Management Solutions, Chatsworth, Calif). RESULTS: After treatment, the median volume and CSAmin increased by 2357 mm3 and 43 mm2, respectively, and median Rin and Vmaxex decreased by 0.15 Pa/L/min and 0.24 m×s-1, respectively, in decreased lower vertical facial height group. In contrast, the median CSAmin decreased by 9.5 mm2 in the increased lower vertical facial height group. All the changes were statistically significant (all P <0.05). Significant differences in volume, CSAmin, Rin, and Vmaxex were observed between the 2 groups. CONCLUSIONS: Vertical control might improve the anatomic and aerodynamic characteristics of the oropharyngeal airway during premolar extraction treatment of Class II hyperdivergent malocclusion with nonsevere crowding.

Comparison of post-treatment recurrence between ranibizumab injection and laser photocoagulation for type 1 retinopathy of prematurity.

OBJECTIVE: To compare post-treatment recurrence between ranibizumab injection and laser photocoagulation (LP) for type 1 retinopathy of prematurity (ROP), and explore the associated risk factors. METHODS: The clinical data of ROP infants treated with LP or ranibizumab in a NICU of China from October 2007 to November 2021 were retrospectively analyzed and compared, such as general condition, degree of ROP, therapeutic effectiveness and post-treatment recurrence. The dependent variable was recurrence after ROP treatment. Univariate and regression analysis of risk factors was performed. RESULTS: Of the 298 ROP infants (556 eyes), 58% of the eyes were treated with LP and the other 42% with ranibizumab. There was no significant difference in gestational age at birth, birth weight, sex, delivery mode, prenatal corticosteroids, ROP diagnosed before admission or after admission, and the duration of oxygen therapy between the two groups. However, the ratio of type 1 ROP and aggressive retinopathy of prematurity (A-ROP) in ranibizumab group was higher than that in LP group. The number of treatments, recurrence rate and recurrence interval in ranibizumab group were higher than those in LP group. However, there was no difference in the recurrence rate between the two groups after stratified analysis by the lesion area and the presence or absence of A-ROP. There was no significant difference in the final lesion regression between the two groups. Regression analysis showed that plus disease and ROP located in zone I were independent risk factors for post-treatment recurrence. CONCLUSION: There is no significant difference in the recurrence rate of ROP between ranibizumab injection and LP, and recurrence is mainly related to the severity of ROP. In half of our patients treated with A-ROP recurrences occur.

Enhance the stability of oxygen vacancies in SrTiO3 via metallic Ag modification for efficient and durable photocatalytic NO abatement.

Oxygen vacancy engineering is an appealing strategy in the direction of photocatalytic pollutant purification. Unfortunately, the short lifetime of oxygen vacancies significantly limits photocatalytic efficiencies and their application. Herein, we report that such a scenario can be resolved via plasmonic silver metal modification SrTiO3 containing oxygen vacancies, which can achieve a high NO removal rate of 70.0% and long stability. This outstanding photocatalytic activity can be attributed to the increased optical response range and carrier separation by metallic Ag with the unique character of localized surface plasmonic resonance (LSPR) effect. Moreover, the intrinsic mechanism of how the plasmonic metal could enhance the stability of oxygen vacancies is proposed. The plasmon-driven hot carriers inject SrTiO3 support that promotes the regeneration of oxygen vacancies around the interface, meanwhile, the introduction of Ag nanoparticles prevents the oxygen vacancies from being filled by the reactant. This work elucidates the unique role of plasmonic metal in photocatalysis, providing an innovative idea for improving catalytic stability.

Clinical characteristics, risk factors and short-term prognosis of retinopathy of prematurity complicated with retinal hemorrhage.

PURPOSE: To investigate the incidence, clinical characteristics and short-term prognosis of retinal hemorrhage (RH) in premature infants with retinopathy of prematurity (ROP). METHODS: From July 2015 to December 2021, the incidence and clinical characteristics of RH in premature infants with ROP diagnosed in a NICU of China before treatment were retrospectively analyzed. RESULTS: A total of 670 premature infants were diagnosed with ROP, including 406 males and 254 females, with a mean gestational age (GA) of 29.51 ± 2.15w and a mean birth weight of 1240.56 ± 292.97g, excluding 10 premature infants who had progressed to stage 4 or 5 at the time of transfer and receiving vitrectomy. Of them, 322 (48.8%) premature infants had Type 1 ROP and received laser or anti-VEGF therapy, and 142 (21.3%) premature infants developed RH before treatment. The GA and birth weight of RH group were lower than those of non-RH group (29.19 ± 2.19w vs. 29.60 ± 2.13w; 1178.11 ± 282.01g vs. 1257.69 ± 293.85g, both P < 0.05), and the proportion of premature infants receiving treatment was also higher than that of non-RH group (97/142, 68.3% vs. 225/518, 43.4%). The lower the GA and the birth weight, the higher the incidence of RH. The incidence of RH was 45.5% in GA <26w and 30.5% in birth weight <1000g. After treatment, 7 eyes (2.6%) of 5 cases (3.5%) in RH group developed retinal detachment vs. 4 eyes (0.4%) of 3 cases (0.6%) in non-RH group, showing a significant difference between the two groups (χ2 = 8.043, P < 0.01). Regression analysis showed that RH, Zone I lesions, plus lesions, and the postnatal time of ocular lesions were independent risk factors for Type 1 ROP. CONCLUSION: The lower the GA and the birth weight, the higher the incidence of ROP complicated with RH. RH is an indicator of severe ROP associated with poor retinal prognosis.

The Causal Effects of Lipid Profiles on Sleep Apnea.

Introduction: Observational studies have suggested that lipid profiles were associated with risk of sleep apnea (SA). However, the specific lipid types and whether this relationship has a causal effect are uncertain. This study conducted two-sample Mendelian randomization (MR) and multivariable Mendelian randomization (MVMR) to investigate the potential causal relationship between lipid profiles and risk of SA. Materials and Methods: We used the largest genome-wide association study (GWAS) on European participants on the UK Biobank. After a rigorous single nucleotide polymorphism screening process to remove confounding effects, we performed MR and MVMR to explore the causal relationship between lipid profiles and SA risk. Results: Both MR and MVMR showed causal effects of increased triglyceride on SA risk [MR: per 10 units, odds ratio (OR): 1.0156; 95% CI: 1.0057-1.0257; P value = 0.002; MVMR: per 10 units, OR: 1.0229; 95% CI: 1.0051-1.0411; P value = 0.011]. The sensitivity analysis including Cochran's Q test, MR-Egger intercept, and MR pleiotropy residual sum and outlier (MR-PRESSO) test indicated that our findings were robust. The causal effects of triglyceride on SA did not change after adjusting for potential confounders (obesity, age, sex, and airway obstruction). Conclusion: Genetically increased triglyceride levels have independent causal effects on risk of sleep apnea without the confounding effects of obesity, suggesting that lowering triglyceride concentrations may help to reduce the risk of sleep apnea.

A comparative analysis of aerodynamic and anatomic characteristics of upper airway before and after mini-implant-assisted rapid maxillary expansion.

INTRODUCTION: The objective of this research was to observe changes in aerodynamics and anatomic characteristics of the upper airway after mini-implants assisted rapid maxillary expansion and to evaluate the correlation between the 2 changes of the upper airway in young adults. METHODS: Thirty consecutive patients (mean age, 23.82 ± 3.90 years; median, 24.5 years; 9 males, 21 females) were involved. Cone-beam computed tomography was taken before activation and over 3 months. Three-dimensional models of the upper airway were reconstructed on the basis of cone-beam computed tomography. The anatomic characteristics of the upper airway, including volume, area, transverse, and sagittal diameter, were measured. The aerodynamic characteristics of the upper airway were calculated on the basis of 3-dimensional models using computational fluid dynamics. The correlation between the changes in aerodynamics and anatomic characteristics of the upper airway was explored. RESULTS: The enlargements of the volume of the total pharynx, nasopharynx, and oropharynx were found (9.99%, 20.7%, and 8.84%, respectively). The minimum cross-sectional area increased significantly (13.6%). The airway resistance (R) and maximum velocity (Vmax) decreased significantly in both the inspiration and expiration phase (inspiration: R, -26.8%, Vmax, -15.7%; expiration: R, -24.7%, Vmax, -16.5%). The minimum wall shear stress reduced significantly only in the inspiration phase (-26.3%). The correlations between decreased R and increased volume and minimum cross-sectional area were observed. CONCLUSIONS: Mini-implants assisted rapid maxillary expansion is an effective device for improving anatomic characteristics represented by the total volume of the upper airway and minimum cross-sectional area, which contributed to the respiratory function depending on the favorable changes of aerodynamic characteristics including resistance, velocity, and minimum wall shear stress.

Skeletal width changes after mini-implant-assisted rapid maxillary expansion (MARME) in young adults.

OBJECTIVES: To observe skeletal width changes after mini-implant-assisted rapid maxillary expansion (MARME) and determine the possible factors that may affect the postexpansion changes using cone-beam computed tomography (CBCT) in young adults. MATERIALS AND METHODS: Thirty-one patients (mean age 22.14 ± 4.76 years) who were treated with MARME over 1 year were enrolled. Four mini-implants were inserted in the midpalatal region, and the number of activations ranged from 40 to 60 turns (0.13 per turn). CBCT was performed before MARME (T0), after activation (T1), and after 1 year of retention (T2). The mean period between T1 and T0 was 6 ± 1.9 months and between T2 and T1 was 13 ± 2.18 months. A paired t-test was performed to compare T0, T1, and T2. The correlations between the postexpansion changes and possible contributing factors were analyzed by Pearson correlation analysis. RESULTS: The widths increased significantly after T1. After T2, the palatal suture width decreased from 2.50 mm to 0.75 mm. From T1 to T2, decreases recorded among skeletal variables varied from 0.13 mm to 0.41 mm. This decrease accounted for 5.75% of the total expansion (2.26 mm) in nasal width (N-N) and 19.75% at the lateral pterygoid plate. A significant correlation was found between postexpansion change and palatal cortical bone thickness and inclination of the palatal plane (ANS-PNS/SN; P < .05). CONCLUSIONS: Expanded skeletal width was generally stable after MARME. However, some amount of relapse occurred over time. Patients with thicker cortical bone of the palate and/or flatter palatal planes seemed to demonstrate better stability.

Comparison of dimensions and volume of upper airway before and after mini-implant assisted rapid maxillary expansion.

OBJECTIVES: To evaluate changes in dimensions and volume of upper airway before and after mini-implant assisted rapid maxillary expansion (MARME) and observe correlations between changes of upper airway and vertical skeletal pattern in young adults. MATERIALS AND METHODS: In this retrospective study, 22 patients (mean age, 22.6 ± 4.5 years; 4 male 18 female) with transverse discrepancy underwent MARME. Cone beam computed tomography was taken before and 3 months after expansion. Vertical and horizontal dimensions and volume of the nasal cavity, nasopharyngeal, retropalatal, retroglossal and hypopharyngeal airway were compared before and after MARME. Correlations between changed volume and dimensions were explored, as well as the vertical skeletal pattern. RESULTS: Nasal osseous width, maxillary width, volume of the nasal cavity and nasopharynx increased significantly (P < .05). Enlarged nasopharyngeal volume correlated with increased nasal width at the PNS plane (P < .05). There were no correlations between expanded volume and maxillary width. No measurements except nasal cavity volume had a correlation with Sum angle. Increased maxillary width correlated negatively with hard palate thickness (P < .05). CONCLUSIONS: (1) MARME caused an increase in volume of the nasal cavity and nasopharynx, with expansion of nasal osseous width and maxillary width. (2) Enlarged nasal width at the PNS plane contributed to the increase in nasopharynx volume. Enlarged maxillary width showed no direct relation with increased volume. (3) In this study, it was unclear about the association between changes of the upper airway and vertical skeletal pattern because of complex structures. (4) Palate thickness affected skeletal expansion of the maxilla in MARME.

A Prospective Study of the Incidence of Retinopathy of Prematurity in China: Evaluation of Different Screening Criteria.

To investigate the incidence of Retinopathy of Prematurity (ROP) in Beijing, North China, and to evaluate the effectiveness of different ROP screening criteria, we conducted a prospective cohort study in a single-neonatal intensive care unit (NICU). A total of 2997 premature infants with birth weight (BW) ≤ 2000 g and/or gestational age (GA) ≤ 34 weeks had completed ROP screening. ROP was diagnosed in 356 (11.9%) infants. The mean GA was 30.46 ± 1.98 weeks and the mean BW was 1477.35 ± 371.29 g. Of the 59 (2.0%) infants receiving treatment, the mean GA was 29.37 ± 2.10 weeks, and the mean BW was 1240.80 ± 330.71 g. The incidence of ROP declined from 14.7% in 2009 and 11.1% in 2010 to 9.5% in 2011. The United Kingdom (UK) criteria could reduce the screening number by 40.8%, and 3 infants with type I ROP needing treatment were missed, but none in 2011. The United States (US) criteria could reduce the screening number by 66.5%, and 10 infants with type I ROP needing treatment were missed, including one in 2011. So the UK criteria may be appropriate for screening of ROP in our NICU in 2011. Future multisite epidemiologic studies are required to establish suitable ROP screening criteria in China.