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.

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.

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.

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.

[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.

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.

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.

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.

Rare-Earth Elements Can Structurally and Energetically Replace the Calcium in a Synthetic Mn4CaO4-Cluster Mimicking the Oxygen-Evolving Center in Photosynthesis.

The oxygen-evolving center (OEC) in photosynthesis is a unique biological Mn4CaO5 cluster catalyzing the water-splitting reaction. A great current challenge is to achieve a robust and precise mimic of the OEC in the laboratory. Herein, we report synthetic Mn4XO4 clusters (X = calcium, yttrium, gadolinium) that closely resemble the OEC with regard to the main metal-oxide core and peripheral ligands, as well as the oxidation states of the four Mn ions and the redox potential of the cluster. We demonstrate that rare-earth elements can structurally replace the calcium in neutral Mn4XO4 clusters. All three Mn4XO4 clusters with different redox-inactive metal ions display essentially the same redox properties, challenging the conventional view that the Lewis acidity of the redox-inactive metal ions could modulate the redox potential of the heteronuclear-oxide clusters. The new synthetic rare-earth element-containing Mn4XO4 clusters reported here provide robust and structurally well-defined chemical models and shed new light on the design of new water-splitting catalysts in artificial photosynthesis.

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.

Temperature Hysteresis Mechanism and Compensation of Quartz Flexible Accelerometer in Aerial Inertial Navigation System.

Strap-down inertial navigation systems (INSs) with quartz flexible accelerometers (QFAs) are widely used in many conditions, particularly in aerial vehicles. Temperature is one of the significant issues impacting the performance of INS. The variation and the gradient of temperature are complex under aerial conditions, which severely degrades the navigation performance of INS. Previous work has indicated that parts of navigation errors could be restrained by simple temperature compensation of QFA. However, the temperature hysteresis of the accelerometer is seldom considered in INS. In this paper, the temperature hysteresis mechanism of QFA and the compensation method would be analyzed. Based on the fundamental model, a comprehensive temperature hysteresis model is proposed and the parameters in this model were derived through a temperature cycling test. Furthermore, the comparative experiments in the laboratory were executed to refine the temperature hysteresis model and to verify the effectiveness of the new compensation method. Applying the temperature hysteresis compensation in flight condition, the result shows that the position error (CEP) is restrained from 1.54 nmile/h to 1.29 nmile/h. The proposed temperature hysteresis compensation method improves the performance of INS effectively and feasibly, which could be promoted to other applications of INS in similar temperature changing environment correspondingly.

Reliability of 2 methods in maxillary transverse deficiency diagnosis.

INTRODUCTION: The objective of this research was to evaluate the reliability of 2 methods (Andrews' Element III analysis and Yonsei transverse analysis) in maxillary transverse deficiency diagnosis. METHODS: Plaster casts and cone-beam computed tomography images of 80 outpatients with skeletal Class I malocclusion (29 males and 51 females, mean age, 20.16 ± 8.22 years) were selected. Maxillary and mandibular width were measured, respectively, and independently by 2 examiners at an interval of 2 weeks, using Andrews' Element III analysis and Yonsei transverse analysis. Intraclass correlation coefficients and Bland-Altman plots of intraexaminer and interexaminer reliability were evaluated. After diagnosis, Cohen's kappa statistics were calculated to evaluate the diagnostic agreement. RESULTS: The intraclass correlation coefficients were all above 0.85, indicating good to excellent reliability. Compared with Andrews' Element III analysis, Yonsei transverse analysis had higher intraexaminer and interexaminer reliability in both maxillary and mandibular width measurements. Thirty-one to 42 of the patients were diagnosed with maxillary transverse deficiency by 2 examiners using 2 methods. The intraexaminer and interexaminer Cohen's kappa values of Yonsei transverse analysis were all higher than those of Andrews' Element III analysis. CONCLUSIONS: Both Andrews' Element III analysis and Yonsei transverse analysis had good to excellent reliability and substantial diagnostic agreement. Yonsei transverse analysis had higher reliability in maxillary and mandibular width measurements and higher diagnostic agreement, compared with Andrews' Element III analysis.

A Study on the Characteristics of the Ionospheric Gradient under Geomagnetic Perturbations.

The Earth's ionosphere is greatly influenced by geomagnetic activities, especially geomagnetic storms. During a geomagnetic storm, the ionosphere suffers many perturbations, leading to a spatial gradient that are neglected during geomagnetically quiet periods. An ionospheric gradient generates potential hazards for a ground-based argumentation system (GBAS) by enlarging the errors in the delay corrections between ground monitor stations and users. To address this problem, this work investigates the characteristics of the ionospheric gradient under geomagnetic storms. Global Navigation Satellite System (GNSS) observations from the continuously operating reference station (CORS) network were used to analyze the ionospheric gradients during the geomagnetic storm on 8 September 2017. The statistical behavior of the ionospheric gradient was further discussed. Experiments show that strong geomagnetic perturbations lead to large ionospheric gradients, and the gradients also vary with the geomagnetic location.

Effects of Twin-block vs sagittal-guidance Twin-block appliance on alveolar bone around mandibular incisors in growing patients with Class II Division 1 malocclusion.

INTRODUCTION: The purpose of this study was to comparatively evaluate the effects of Twin-block (TB) appliance and sagittal-guidance Twin-block (SGTB) appliance on alveolar bone around mandibular incisors in growing patients with Class II Division 1 malocclusion, using cone-beam computed tomography. METHODS: The sample consisted of 25 growing patients with Class II Division 1 malocclusion (14 boys and 11 girls, mean age 11.92 ± 1.62 years) and was randomly distributed into the TB group (n = 13) and the SGTB group (n = 12). The treatment duration was 11.56 ± 1.73 months. Pretreatment (T1) and posttreatment (T2) cone-beam computed tomography scans were taken in both groups. Height, thickness at apex level, and volume of the alveolar bone around mandibular left central incisors were measured respectively on labial and lingual side, using Mimics software (version 19.0; Materialise, Leuven, Belgium). Based on the stable structures, 3-dimensional (3D) registrations of T1 and T2 models were taken to measure the sagittal displacement of incisors. Intragroup comparisons were evaluated by paired-samples t tests and Wilcoxon tests. Independent-samples t tests and Mann-Whitney U tests were used for intergroup comparisons. RESULTS: In both groups, alveolar bone height and volume on the labial side of the incisors significantly decreased after treatment (P <0.05). Lingual alveolar bone height, lingual and total alveolar bone volume, labial, lingual and total alveolar bone thickness showed no significant difference between T1 and T2 (P >0.05). In both groups the incisors tipped labially and drifted to the labial side. Compared with the TB group, less labial alveolar bone loss, less incisor proclination and crown edge drift were found in the SGTB group (P <0.05). CONCLUSIONS: Labial alveolar bone loss around mandibular incisors was observed after both types of appliances treatment in growing patients with Class II Division 1 malocclusion. Less labial alveolar bone loss, less incisor proclination, and crown edge drift were found in the SGTB group than in the TB group during treatment.

Suppression of the quantization error in a fiber optic gyroscope using a double-electrode-pair multifunction integrated-optic circuit.

The measuring accuracy of the fiber optic gyroscope (FOG) for weak signals under very short sampling time is significantly impacted by the quantization error, impeding its application in high-speed measurement and real-time control. In this work, we propose and implement a double-electrode-pair multifunction integrated-optic circuit (MIOC), which contains an additional pair of short electrodes besides the conventional electrode-pair. Taking advantage of the better modulating precision of the additional electrode-pair, the digital feedback is more refined and the quantization error in the FOG output is significantly suppressed. The driving circuits and the control scheme of the proposed MIOC are specially designed for FOGs. Experimental results show that the resolution for extremely small angular rates at short smoothing times is significantly improved. This work provides the potential of the applications in high-speed measuring and controlling systems for high-precision FOGs.

High-performance fully differential photodiode amplifier for miniature fiber-optic gyroscopes.

Electrical cross coupling is regarded as a major obstacle to achieving high-performance miniature fiber-optic gyroscopes (FOGs), because it can cause dead bands, which are critical errors in FOGs. Using a differential photodiode amplifier has proven to be effective in rejecting coupled interference. However, the conventional three-op-amp instrumentation amplifier cannot provide a miniature FOG's bandwidth requirements, because of the large photodiode capacitance and parasitic capacitance. We present a high-performance, fully differential photodiode amplifier, where the bandwidth limitations are removed by applying a reverse bias to the photodiode and replacing the feedback resistor with a modified tee-network and a DC cancellation loop. For an experimental FOG with a 300 m fiber coil, we demonstrate a fully differential photodiode amplifier with 880 kΩ gain and 3.5 MHz bandwidth. In the FOG performance test, it not only reduces the angular random walk and bias drift, but also eliminates the approximately 1°/h dead band observed in the same FOG using a PINFET receiver, demonstrating its effectiveness in suppressing coupled interference.

PPE11 of Mycobacterium tuberculosis can alter host inflammatory response and trigger cell death.

Tuberculosis (TB), which is caused by Mycobacterium tuberculosis (Mtb), remains a serious global health problem. The PE/PPE family, featuring unique sequences, structures and expression in Mtb, is reported to interfere with the macrophage response to the pathogen and facilitate its infection. PPE11 (Rv0453) existed in pathogenic mycobacteria and was persistently expressed in the infected guinea pig lungs. However, the role it played in the pathogenesis remains unclear. Here, to investigate the interaction and potential mechanism of PPE11 between pathogens and hosts, we heterologously expressed PPE11 in non-pathogenic, rapidly growing Mycobacterium smegmatis strains. We found that the overexpression of the cell wall-associated protein, PPE11, can improve the viability of bacteria in the presence of lysozyme, hydrogen peroxide and acid stress. Expression of PPE11 enhanced the early survival of M. smegmatis in macrophages and sustained a higher bacterial load in mouse tissues that showed exacerbated organ pathology. Macrophages infected with recombinant M. smegmatis produced significantly greater amounts of interleukin (IL)-1ß, IL-6, tumour necrosis factor (TNF)-α and an early decrease in IL-10 along with higher levels of host cell death. Similar cytokines changes were observed in the sera of infected mice. Accordingly, PPE11 protein causes histopathological changes by disrupting the dynamic balance of the inflammatory factors and promoting host-cell death, indicating a potential role in the virulence of Mtb.

[Mycobacterium Tuberculosis Rv3084 Encodes Functional Esterase and Suppresses the Pro-inflammatory Cytokines in vivo].

OBJECTIVE: To explore the biological characteristics of the esterase LipR encoded by Mycobacterium tuberculosis (MTB) Rv3084 and its immunomodulatory function in vivo. METHODS: The LipR gene was amplified from MTB H37Rv strain to construct recombinant expression plasmid. After sequencing, the recombinant plasmid was transformed into E. coli for expression and purification of LipR protein. The expressed protein was confirmed with Western blot assay. The hydrolyzing activity of LipR was detected and the factors affecting LipR enzyme activity were analyzed. Mice were intramuscularly injected with 0.1 mL (containing plasmid DNA 100 µg) recombinant eukaryotic plasmid three times (day 1, 8, and 15); seven days after the last injection, the mice were executed, and the lung and spleen were taken for cytokine detection. RESULTS: The recombinant expression plasmid was successfully constructed and it was found that LipR protein was mainly expressed in the form of inclusion bodies in E. coli with the relative molecular mass of about 33×10 3. LipR was demonstrated as an alkaline eurythermic esterase, due to the preference of hydrolyzing short carbon chain esters with optimal hydrolyzing activity on pNP-acetate (pNPA, C2) and the capability in tolerance of high pH and temperature; in the presence of different detergents or metal ions, the activity of LipR hydrolyzing pNP-butyrate (pNPB, C4) was inhibited to some extent. In the mouse model, it was found that LipR could inhibit the secretion of interferon-γ (IFN- γ) and interleukin-2 (IL-2), but to stimulate the secretion of IL-10. CONCLUSION: The esterase LipR may be one of the esterases help M. tuberculosis withstand harsh environment inside the host in collaboration, and simultaneously act as an immune modulator to inhibit the secretion of pro-inflammatory cytokines and consequently impact the killing effect of host immune system against M. tuberculosis.

Artificial Mn4 Ca Clusters with Exchangeable Solvent Molecules Mimicking the Oxygen-Evolving Center in Photosynthesis.

The natural Mn4 Ca cluster in photosystem II serves as a blueprint to develop artificial water-splitting catalysts for the generation of solar fuel in artificial photosynthesis. Although significant advances have recently been achieved, it remains a great challenge to prepare robust artificial Mn4 Ca clusters that precisely mimic the structure and function of the biological catalyst. Herein, we report the isolation and structural characterization of two Mn4 CaO4 complexes with polar solvent molecules, acetonitrile or N,N-dimethylformamide, which closely mimics the two water molecules on the calcium ion, as well as the oxidation states of the four manganese ions and the main geometric structure of the natural Mn4 Ca cluster. These new artificial Mn4 Ca complexes provide important chemical clues to understand the structure and mechanism of the biological system.