Effects of paternal ionizing radiation exposure on fertility and offspring's health.

Purpose: The intergenerational effects of ionizing radiation remain controversial. Extensive insights have been revealed for DNA mutations and cancer incidence in progeny, yet many of these results were obtained by immediate post-radiation mating. However, conception at short times after radiation exposure is likely to be avoided. After a long period of fertility recovery, whether unexposed sperm derived from exposed spermatogonia would challenge the health of the offspring is not yet clearly demonstrated. Methods: Ten-week-old C57BL/6J males underwent whole-body acute γ irradiation at 0 and 6.4 Gy. Testes and sperm were collected at different times after radiation to examine reproductive changes. The reproductive, metabolic, and neurodevelopmental parameters were measured in the offspring of controls and the offspring derived from irradiated undifferentiated spermatogonia. Results: Paternal fertility was lost after acute 6.4 Gy γ radiation and recovered at 10-11 weeks post irradiation in mice. The reproductive, metabolic, and neurodevelopmental health of offspring born to irradiated undifferentiated spermatogonia were comparable to those of controls. Conclusion: The male mice could have healthy offspring after recovery from the damage caused by ionizing radiation.

Robotic-assisted bronchoscopy for the diagnosis of peripheral pulmonary lesions: A systematic review and meta-analysis.

Robotic-assisted bronchoscopy (RAB) is a newly developed bronchoscopic technique for the diagnosis of peripheral pulmonary lesions (PPLs). The objective of this meta-analysis was to analyze the diagnostic yield and safety of RAB in patients with PPLs. Five databases (PubMed, Embase, Web of Science, CENTRAL, and ClinicalTrials.gov) were searched from inception to April 2023. Two independent investigators screened retrieved articles, extracted data, and assessed the study quality. The pooled diagnostic yield and complication rate were estimated. Subgroup analysis was used to explore potential sources of heterogeneity. Publication bias was assessed using funnel plots and the Egger test. Sensitivity analysis was also conducted to assess the robustness of the synthesized results. A total of 725 lesions from 10 studies were included in this meta-analysis. No publication bias was found. Overall, RAB had a pooled diagnostic yield of 80.4% (95% CI: 75.7%-85.1%). Lesion size of >30 mm, presence of a bronchus sign, and a concentric radial endobronchial ultrasound view were associated with a statistically significantly higher diagnostic yield. Heterogeneity exploration showed that studies using cryoprobes reported better yields than those without cryoprobes (90.0%, 95% CI: 83.2%-94.7% vs. 79.0%, 95% CI: 75.8%-82.2%, p < 0.01). The pooled complication rate was 3.0% (95% CI: 1.6%-4.4%). In conclusion, RAB is an effective and safe technique for PPLs diagnosis. Further high-quality prospective studies still need to be conducted.

Predictive Role of Pre-Thrombolytic Neutrophil-Platelet Ratio on Hemorrhagic Transformation After Intravenous Thrombolysis in Acute Ischemic Stroke.

To investigate the predictive role of the neutrophil-platelet ratio (NPR) before intravenous thrombolysis (IVT) on hemorrhagic transformation (HT) in patients with acute ischemic stroke (AIS). AIS patients treated with IVT without endovascular therapy between June 2019 and February 2023 were included. Patients were divided into high NPR (>35) and low NPR (≤35) groups according to the optimal threshold NPR value for identifying high-risk patients before IVT. The baseline data and the incidence of HT and symptomatic intracranial hemorrhage (sICH) were compared between the two groups. The predictive role of the NPR and other related factors on HT after IVT was analyzed by multivariate logistic regression. A total of 247 patients were included, with an average age of 67.5 ± 12.4 years. Post-thrombolytic HT was observed in 18.6% of the patients, and post-thrombolytic sICH was observed in 1.2% of the patients. There were 69 patients in the high NPR group and 178 patients in the low NPR group. The incidence of HT in the high NPR group was significantly higher than that in the low NPR group (30.4% vs 16.3%, P < .05). The incidence of sICH was significantly higher in the high NPR group than in the low NPR group (14.5% vs 1.7%, P < .001). Multivariate logistic regression analysis showed that NPR > 35 was positively correlated with HT (odds ratio (OR) = 3.236, 95% confidence interval (CI): 1.481-7.068, P = .003) and sICH (OR = 13.644, 95% CI: 2.392-77.833, P = .003). A high NPR (>35) before IVT may be a predictor of HT in AIS patients. This finding may help clinicians make clinical decisions before IVT in AIS patients.

Tomo-seq identifies NINJ1 as a potential target for anti-inflammatory strategy in thoracic aortic dissection.

BACKGROUND: Thoracic aortic dissection (TAD) is a life-threatening disease caused by an intimal tear in the aorta. The histological characteristics differ significantly between the tear area (TA) and the distant area. Previous studies have emphasized that certain specific genes tend to cluster at the TA. Obtaining a thorough understanding of the precise molecular signatures near the TA will assist in discovering therapeutic strategies for TAD. METHODS: We performed a paired comparison of the pathological patterns in the TA with that in the remote area (RA). We used Tomo-seq, genome-wide transcriptional profiling with spatial resolution, to obtain gene expression signatures spanning from the TA to the RA. Samples from multiple sporadic TAD patients and animal models were used to validate our findings. RESULTS: Pathological examination revealed that the TA of TAD exhibited more pronounced intimal hyperplasia, media degeneration, and inflammatory infiltration compared to the RA. The TA also had more apoptotic cells and CD31+α-SMA+ cells. Tomo-seq revealed four distinct gene expression patterns from the TA to the RA, which were inflammation, collagen catabolism, extracellular matrix remodeling, and cell stress, respectively. The spatial distribution of genes allowed us to identify genes that were potentially relevant with TAD. NINJ1 encoded the protein-mediated cytoplasmic membrane rupture, regulated tissue remodeling, showed high expression levels in the tear area, and co-expressed within the inflammatory pattern. The use of short hairpin RNA to reduce NINJ1 expression in the beta-aminopropionitrile-induced TAD model led to a significant decrease in TAD formation. Additionally, it resulted in reduced infiltration of inflammatory cells and a decrease in the number of CD31+α-SMA+ cells. The NINJ1-neutralizing antibody also demonstrated comparable therapeutic effects and can effectively impede the formation of TAD. CONCLUSIONS: Our study showed that Tomo-seq had the advantage of obtaining spatial expression information of TAD across the TA and the RA. We pointed out that NINJ1 may be involved in inflammation and tissue remodeling, which played an important role in the formation of TAD. NINJ1 may serve as a potential therapeutic target for TAD.

[Quality of Life and Its Influencing Factors Among Schizophrenia Patients Living in Urban and Rural Areas].

Objective: To investigate the status quo of the quality of life of schizophrenia patients in a city in Sichuan Province and to explore, thereof, the urban-rural differences in the factors influencing their quality of life. Methods: A total of 824 schizophrenia patients were selected for the study through multistage stratified cluster random sampling method. All the subjects were selected from a pool of patients covered by the Sichuan Provincial Information System for the Comprehensive Management of Severe Mental Disorders. Questionnaire surveys were conducted with the Schizophrenia Quality of Life Scale (SQLS), the Social Support Rating Scale (SSRS), the general circumstance questionnaire, and the lifestyle questionnaire. In addition, univariate and multiple linear regression models were used to analyze the influencing factors of quality of life among schizophrenia patients living in urban areas and those in rural areas. Results: Rural patients had poorer quality of life than urban patients did in all measurement domains ( P<0.05). Marital status, vocational skills, physical exercise, and social support were influencing factors of the quality of life among urban patients ( P<0.05). Age, marital status, annual household income, vocational skills, participation in community rehabilitation activities, and the time required to walk to the nearest medical institution were influencing factors of the quality of life among rural patients ( P<0.05). Conclusion: Targeted measures for the enhancement of the quality of life of schizophrenia patients should be formulated on the basis of urban and rural characteristics in terms of economic support, vocational skills training, input in mental health services, community rehabilitation services, and social support.

A novel maxillary transverse deficiency diagnostic method based on ideal teeth position.

BACKGROUND: This study proposed a novel maxillary transverse deficiency diagnostic method and evaluated the skeletal Class I and the mild skeletal Class III groups. METHODS: Pre-treatment data from 30 mild skeletal Class III and 30 skeletal Class I patients were collected and uploaded to the Emeiqi Case Management System to design the ideal teeth positions. On these positions, the first bi-molars width was measured at the central fossa and center resistance, the maxillary first bi-premolars width was measured at the central fossa, and the mandibular first bi-premolars width was measured at the distal contact point by Mimics, then width differences of two groups were calculated respectively. RESULTS: At ideal teeth positions, there was no statistically significant difference in the maxillomandibular width in the premolar area between the two groups, but there was in the molar area, and this difference was caused by the difference in mandible width between the two groups. CONCLUSIONS: We proposed a new transverse diagnostic method and found that even the Class I group was not quite up to standard in the molar area on ideal teeth positions, and the Class III group had more severe maxillary transverse deficiency than the Class I group. Meanwhile, the maxillary transverse deficiency in the Class III group was mainly caused by the larger width of the mandible.

Maxillary transverse deficiency diagnosed by 3 methods and its relationship with molar angulation in patients with skeletal Class III malocclusion.

INTRODUCTION: The objective of this study was to evaluate the relationship between maxillary transverse deficiency (MTD) diagnosed by 3 methods and molar angulation measured in 3-dimensions in patients with skeletal Class III malocclusion, which could give reference to the selection of diagnostic methods in MTD patients. METHODS: Cone-beam computed tomography data of 65 patients with skeletal Class III malocclusion (mean age 17.35 ± 4.45 years) were selected and imported into MIMICS software. Transverse deficiencies were evaluated by 3 methods, and molar angulations were measured after reconstructing 3-dimensional planes. Two examiners performed repeated measurements to assess the intraexaminer and interexaminer reliability. Pearson correlation coefficient analyses and linear regressions were performed to determine the relationship between a transverse deficiency and molar angulations. One-way analysis of variance was used to compare the diagnostic results of 3 methods. RESULTS: The novel molar angulation measurement method and 3 MTD diagnostic methods have the interexaminer and intraexaminer intraclass correlation coefficient values >0.6. The transverse deficiency diagnosed by 3 methods was significantly and positively correlated with the sum of molar angulation. There was a statistically significant difference for the transverse deficiencies diagnosed by the 3 methods. The transverse deficiency was significantly higher in Boston University's analysis than in Yonsei's analysis. CONCLUSIONS: Clinicians ought to choose the diagnostic methods properly, considering the feature of the 3 methods and the individual difference of each patient.

Condylar morphology and position changes after miniscrew-assisted rapid palatal expansion in skeletal Class III malocclusion adult patients with mandibular deviation and unilateral posterior crossbite.

BACKGROUND: To evaluate the morphological and positional changes of mandibular condyle after miniscrew-assisted rapid palatal expansion (MARPE) in skeletal Class III malocclusion adult patients with horizontal mandibular deviation (MD). METHODS: The sample consisted of 15 patients with MD (6 males and 9 females, mean age 21.58 ± 3.12 years). The CBCT scans were taken before and after MARPE immediately. The pre- and post-registered images of the cranial base and mandible were measured, respectively, by Mimics. RESULTS: After expansion, the distance between superior condylar point and the Frankfort horizontal plane on the deviated side and the non-deviated side increased by 0.96 ± 0.60 mm (P = 0.011) and 0.70 ± 0.65 mm (P = 0.046); coronal condylar angle of the deviated side increased by 0.39° ± 0.34 (P = 0.028) and 0.06° ± 0.49 (P = 0.917) on the non-deviated side. No statistically significant differences were found when comparing the condylar position on both sides before and after treatment. The degree of mandibular deviation decreased 0.43 mm (P = 0.270). CONCLUSIONS: This study suggested that for skeletal Class III malocclusion adult patients with horizontal MD, the condyle on the deviated side rotated toward the non-deviated side in the coronal direction; the condylar remodeling occurred mainly on the deviated side after MARPE in the vertical direction.

Mimicking the Oxygen-Evolving Center in Photosynthesis.

The oxygen-evolving center (OEC) in photosystem II (PSII) of oxygenic photosynthetic organisms is a unique heterometallic-oxide Mn4CaO5-cluster that catalyzes water splitting into electrons, protons, and molecular oxygen through a five-state cycle (Sn, n = 0 ~ 4). It serves as the blueprint for the developing of the man-made water-splitting catalysts to generate solar fuel in artificial photosynthesis. Understanding the structure-function relationship of this natural catalyst is a great challenge and a long-standing issue, which is severely restricted by the lack of a precise chemical model for this heterometallic-oxide cluster. However, it is a great challenge for chemists to precisely mimic the OEC in a laboratory. Recently, significant advances have been achieved and a series of artificial Mn4XO4-clusters (X = Ca/Y/Gd) have been reported, which closely mimic both the geometric structure and the electronic structure, as well as the redox property of the OEC. These new advances provide a structurally well-defined molecular platform to study the structure-function relationship of the OEC and shed new light on the design of efficient catalysts for the water-splitting reaction in artificial photosynthesis.

Exosomal non-coding RNAs have a significant effect on tumor metastasis.

Exosomes are produced by the majority of eukaryotic cells and are capable of transporting a variety of substances, including non-coding RNAs, between cells. Metastasis is a significant cause of death from cancer. Numerous studies have established an important role for exosomal non-coding RNAs in tumor metastasis. Exosomal non-coding RNAs from a variety of cells have been shown to affect tumor metastasis via several mechanisms. Exosomes transmit non-coding RNAs between tumor cells, fibroblasts, endothelial cells, and immune cells within the tumor microenvironment. Exosomal non-coding RNAs also have an effect on epithelial-mesenchymal transition, angiogenesis, and lymphangiogenesis. Exosomes derived from tumor cells have the ability to transport non-coding RNAs to distant organs, thereby facilitating the formation of the metastatic niche. Due to their role in tumor metastasis, exosomal non-coding RNAs have the potential to serve as diagnostic or prognostic markers as well as therapeutic targets for tumors. The purpose of this paper is to review and discuss the mechanisms of exosomal non-coding RNAs, their role in tumor metastasis, and their clinical utility, aiming to establish new directions for tumor metastasis, diagnosis, and treatment research.

Redox-Induced Structural Change in Artificial Heterometallic-Oxide Cluster Mimicking the Photosynthetic Oxygen-Evolving Center.

The oxygen-evolving center (OEC) in photosynthesis is a unique Mn4 CaO5 -cluster that catalyzes the water-splitting reaction in nature. Understanding its catalytic mechanism for the O=O bond formation is of great challenge and long-standing issue, which is severely restricted by the lack of precise structure and mechanism mimics of this heterometallic-oxide cluster. Herein, we report two synthetic (Mn3 XO4 )2 O-clusters (X=Sr2+ , La3+ ) that closely mimic the heterometallic-oxide Mn3 XO4 cubane and three different types of µ-oxide bridges (µ2 -O2- , µ3 -O2- , and µ4 -O2- ) simultaneously as seen in the OEC. By resolving the crystal structures of both oxidized and reduced forms of the cluster, we have identified significant redox-induced structural changes that take place on the µ2 -oxide bridge, rather than the µ4 -oxide or µ3 -oxide bridges. Our results provide chemical insights into understanding the reactivity of three different types of oxide bridges in the biological Mn4 CaO5 -cluster in PSII.

Embryo morphologic quality in relation to the metabolic and cognitive development of singletons conceived by in vitro fertilization and intracytoplasmic sperm injection: a matched cohort study.

BACKGROUND: Embryos with higher morphologic quality grading may have a greater potential to achieve clinical pregnancy that leads to a live birth regardless of the type of cleavage-stage embryos or blastocysts. Few studies have investigated the impacts of embryo grading on the long-term health of the offspring. OBJECTIVE: This pilot study aimed to examine the associations between embryo morphologic quality and the physical, metabolic, and cognitive development of singletons conceived by in vitro fertilization and intracytoplasmic sperm injection at preschool age. STUDY DESIGN: This matched cohort study included singletons born to infertile couples who underwent fresh cleavage-stage embryo transfer cycles with good- or poor-quality embryos from 2014 to 2016 at the reproductive center of the Women's Hospital, School of Medicine, Zhejiang University. A total of 144 children, aged 4 to 6 years, participated in the follow-up assessment from 2020 to 2021, and the response rate of poor-quality embryo offspring was 39%. Singletons in the good-quality embryo group were matched with singletons in the poor-quality embryo group at a 2:1 ratio according to the fertilization method and the children's age (±1 year). We measured the offspring's height, weight, body mass index, blood pressure, thyroid hormone levels, and metabolic indicators. Neurodevelopmental assessments were performed using the Chinese version of the Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition, and the Adaptive Behavior Assessment System, Second Edition. We also collected data from the medical records. A linear regression model was used to analyze the association between embryo morphologic quality and offspring health outcomes. RESULTS: A total of 48 singletons conceived with poor-quality embryo transfer and 96 matched singletons conceived with good-quality embryo transfer were included in the final analysis. Age, sex, height, weight, body mass index, blood pressure, thyroid function, and metabolic indicators were comparable between the 2 groups. After adjustment for potential risk factors by linear regression model 1 and model 2, poor-quality embryo offspring exhibited a tendency toward higher free thyroxine levels than offspring of good-quality embryo transfers (beta, 0.22; 95% confidence interval, 0.09-0.90; beta, 0.22; 95% confidence interval, 0.09-0.91, respectively), but this difference was not clinically significant. Regarding neurodevelopmental assessments, there was no difference in the full-scale intelligence quotient based on the Wechsler Preschool and Primary Scale of Intelligence (109.96±12.42 vs 109.60±14.46; P=.88) or the general adaptive index based on the Adaptive Behavior Assessment System (108.26±11.70 vs 108.08±13.44; P=.94) between the 2 groups. The subindices of the 2 tests were also comparable. These findings remained after linear regression analysis. CONCLUSION: At 4 to 6 years of age, singletons born from poor-quality embryo transfers have comparable metabolic and cognitive development as those born from good-quality embryo transfers using fresh cleavage-stage embryos. The results of this pilot study indicate that poor-quality embryos that can survive implantation and end in live birth are likely to have a developmental potential comparable to that of good-quality embryos.

Wavelength-dependence reduction of the scale factor for tactical-grade fiber optic gyroscopes.

Fiber optic gyroscopes (FOGs) suffer from the scale-factor inaccuracy induced by the wavelength instability of the broadband source, which remains a bottleneck both in theory and in practical application. In this work, we propose a simple but effective technique for reducing the wavelength dependence of the scale factor by employing the size of the digital-ramp register as the actuator in the closed-loop scheme for nulling the ramp-reset-induced errors, instead of the conventionally-used feedback-chain gain. Experiments show that, for the tactical-grade FOG equipped with the super-luminescent diode (SLD) operating under temperatures from -40 °C to +60 °C, the proposed technique reduces the compensated scale-factor inaccuracy to 282 ppm, with respect to 2065ppm in the conventional case. This technique relaxes the stringent requirements on the wavelength stability of SLDs, which contributes to the large-scale production and application of tactical-grade FOGs.

Vitamin D Levels in Early and Middle Pregnancy and Preeclampsia, a Systematic Review and Meta-Analysis.

Vitamin D (VitD) shows a beneficial role in placentation, the immune system, and angiogenesis, and thus, VitD status may link to the risk of preeclampsia. A meta-analysis was conducted to investigate the association between VitD status in early and middle pregnancy and the risk of preeclampsia. A total of 22 studies with 25,530 participants were included for analysis. Women with VitD insufficiency or deficiency had a higher preeclampsia rate compared to women with replete VitD levels (OR 1.58, 95% CI 1.39-1.79). Women with VitD deficiency had a higher preeclampsia rate compared to women with replete or insufficient VitD levels (OR 1.35, 95% CI 1.10-1.66). Women with insufficient VitD levels had a higher preeclampsia rate compared to women with replete VitD levels (OR 1.44, 95% CI 1.24-1.66). Women with deficient VitD levels had a higher preeclampsia rate compared to women with replete VitD levels (OR 1.50, 95% CI 1.05-2.14). Sensitivity analysis showed the results were stable after excluding any one of the included studies. In conclusion, our systematic review suggested that VitD insufficiency or deficiency was associated with an increased risk of preeclampsia.

Synthesizing Mechanism of the Mn4 Ca Cluster Mimicking the Oxygen-Evolving Center in Photosynthesis.

The photosynthetic oxygen-evolving center (OEC) is a unique Mn4 CaO5 cluster that serves as a blueprint to develop superior water-splitting catalysts for the generation of solar fuels in artificial photosynthesis. It is a great challenge and long-standing issue to reveal the synthesizing mechanism of this Mn4 CaO5 cluster in both natural and artificial photosynthesis. Herein, efforts were made to reveal the synthesizing mechanism of an artificial Mn4 CaO4 cluster, a close mimic of the OEC. Four key intermediates were successfully isolated and structurally characterized for the first time. It was demonstrated that the Mn4 CaO4 cluster could be formed through a reaction between a thermodynamically stable Mn3 CaO4 cluster and an unusual four-coordinated MnIII ion, followed by stabilization process through binding an organic base (e.g., pyridine) on the "dangling" Mn ion. These findings shed new light on the synthesizing mechanism of the OEC and rational design of new artificial water-splitting catalysts.

Demethylase FTO promotes mechanical stress induced osteogenic differentiation of BMSCs with up-regulation of HIF-1α.

BACKGROUND: In orthodontics, mechanical stress plays an important role in the process of bone remodeling. Mechanical stress has an effect on osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs). However, the mechanism remains to be studied. The aim of this study is to investigate the effects of demethyltransferase fat mass and obesity-associated (FTO) on osteogenic differentiation of BMSCs under mechanical stress condition. METHODS AND RESULTS: The rat BMSCs were cultured in vitro, followed by flow cytometry to identify the cell surface antigens. Osteogenic differentiation of BMSCs was induced by mechanical stress by using the flexcell tension system for 6 h every day and 3 days in total. BMSCs were transfected by using plasmid for FTO knockdown. The expression level of FTO, hypoxia-inducible factor (HIF)-1α, runt-related transcription factor 2 (RUNX2), bone morphogenetic proteins (BMPs) and alkaline phosphatase (ALP) were measured by real-time qPCR, western blotting. ALP activity were determined by ALP staining assays. The expression of FTO and HIF-1α in BMSCs with mechanical stress were significantly higher than BMSCs without mechanical stress, also, the expression of osteogenic differentiation markers were higher in BMSCs with mechanical stress. Knockdown of FTO decreased expression of osteogenic differentiation marker and ALP activity in stretched BMSCs. In addition, the expression of HIF-1α was decreased after knocking down FTO. CONCLUSIONS: FTO promotes the expression of HIF-1α and osteogenic differentiation under the condition of mechanical stress. This finding may facilitate the clinical application of orthodontics and the mechanism research of mechanical stress-induced osteogenesis.

Structural Reorganization of a Synthetic Mimic of the Oxygen-Evolving Center in Multiple Redox Transitions Revealed by Electrochemical FTIR Spectra.

In photosynthesis, the protein-bound natural oxygen-evolving center (OEC) undergoes multiple oxidation-state transitions in the light-driven water splitting reactions with a stepwise change in the oxidation potential. Because the protein is vulnerable to electrochemical oxidation, the multiple oxidation/reduction-state transitions can hardly be achieved by electrochemical oxidation with a continuous change in the oxidation potential. An OEC mimic that can undergo four redox transitions has been synthesized (Zhang, C., Science, 2015, 348, 690-693). Here we report an electrochemical FTIR spectroscopic study of this synthetic complex at its multiple oxidation states in the low-frequency region for Mn-O bonds. Compared with those of the native OEC induced by pulsed laser flashes, our results also show the existence of two structural isomers in the S2 state, with the closed cubane conformer being more stable than the open cubane conformer, in contrast to that of the native OEC in which the open form is more stable.

Method for improving the polarization extinction ratio of multifunction integrated optic circuits.

The polarization extinction ratio (PER) of the multifunction integrated optic circuit (MIOC) is significant in maintaining polarization reciprocity in the fiber-optic gyroscope (FOG), and a high PER value is required, particularly in high-precision FOGs. Practically, the value of the PER decreases owing to the recoupling of the TM mode to the output port, thereby degrading the performance of the FOG. To improve the PER, the propagation of the leaking TM mode in the substrate is analyzed first. The variation of the PER with the chip structure is simulated based on the overlap integral algorithm of the optical mode. According to the analysis results, a structure of double absorption trenches at the bottom of the MIOC is proposed to block the TM mode from reflecting to the output port. In comparison with the traditional design, the optimized MIOC exhibits a higher PER that increases by approximately 25 dB and the average value of the PER reaches 75 dB. The MIOC design proposed in this study has good potential for application in high-precision FOGs.