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Loss-of-function mutations in MECP2 cause Rett syndrome (RTT), a severe neurological disorder that mainly affects girls. Mutations in MECP2 do occur in males occasionally and typically cause severe encephalopathy and premature lethality. Recently, we identified a missense mutation (c.353G>A, p.Gly118Glu [G118E]), which has never been seen before in MECP2, in a young boy who suffered from progressive motor dysfunction and developmental delay. To determine whether this variant caused the clinical symptoms and study its functional consequences, we established two disease models, including human neurons from patient-derived iPSCs and a knock-in mouse line. G118E mutation partially reduces MeCP2 abundance and its DNA binding, and G118E mice manifest RTT-like symptoms seen in the patient, affirming the pathogenicity of this mutation. Using live-cell and single-molecule imaging, we found that G118E mutation alters MeCP2s chromatin interaction properties in live neurons independently of its effect on protein levels. Here we report the generation and characterization of RTT models of a male hypomorphic variant and reveal new insight into the mechanism by which this pathological mutation affects MeCP2s chromatin dynamics. Our ability to quantify protein dynamics in disease models lays the foundation for harnessing high-resolution single-molecule imaging as the next frontier for developing innovative therapies for RTT and other diseases.

In response to the problems of no suitable constraint conditions in the optimization process of tooth profile modification of cycloidal pin wheel transmission, difficulty in determining the modification amount of cycloidal gear tooth profile in reverse engineering, and the inability to obtain the meshing interval when studying the characteristics of cycloidal pin wheel transmission, research has been conducted on the method for determining the meshing intervals of cycloidal gears. Firstly, the stiffness analysis is performed to determine the main components that affect the stiffness. Then, through the contact stiffness analysis of the key components, the torsional stiffness model of the needle roller bearing, the tapered roller bearing and the meshing point of the cycloid are established respectively.On this basis, the torsional stiffness equation of the cycloid with needle roller bearings, tapered roller bearings and with the torsion angle of the whole machine as variables is deduced.Finally, according to the continuity principle of meshing points, all the meshing intervals whose sum of torsional stiffness of meshing points is approximately equal to the torsional stiffness of cycloidal wheels are calculated, and according to the principle that the initial meshing point of cycloidal wheels does not change with the increase of load, the feasible meshing intervals under different loads are finally screened. The analysis results of this method are basically consistent with the actual situation, and there is no need to disassemble the reducer, which can provide necessary reference data for the design and optimization of cycloid pin gear transmission.

Postoperative cognitive dysfunction (POCD) is a common complication of cognitive decline after surgery and anesthesia. Sevoflurane, as a commonly used anesthetic, was found to cause POCD. Nudix Hydrolase 21 (NUDT21), a conserved splicing factor, has been reported to exert important functions in multiple diseases’ progression. In this study, the effect of NUDT21 on sevoflurane-induced POCD was elucidated. Results showed that NUDT21 was down-regulated in the hippocampal tissue of sevoflurane-induced rats. Morris water maze test results revealed that overexpression of NUDT21 improved sevoflurane-induced cognitive impairment. In addition, TUNEL assay results indicated that enhanced NUDT21 alleviated sevoflurane-induced apoptosis of hippocampal neurons. Furthermore, overexpression of NUDT21 suppressed the sevoflurane-induced LIMK2 expression. Taken together, NUDT21 alleviates sevoflurane-induced neurological damage in rats by down-regulating LIMK2, providing a novel target for the prevention of sevoflurane-induced POCD.

Objective To explore the related risk factors of pancreatic portal hypertension(PPH) and then establish a risk prediction model. Methods The clinical data of 185 patients with pancreatic diseases treated in the First Affiliated Hospital of Army Medical University from January 2004 to January 2022 were collected and analyzed retrospectively. They were divided into study group(n=75) and control group(n=110) according to the occurrence of portal hypertension. The risk factors of PPH were screened by univariate, correlation and multivariate analysis. Based on these variables, a risk prediction model was established by Nomogram. Results In variable screening, the results showed that smoking, history of diabetes and causes were risk factors for PPH(OR=5.008, 3.913, 3.690), and red blood cell count was a protective factor(OR=0.362). A nomogram model of PPH was constructed based on the results of variable screening. The area under the prediction curve of the model was 0.789, and the calibration curve had a good degree of fit, indicating that the model has a good prediction effect. Decision curve analysis showed that a better net gain value was obtained when the risk threshold is between 15% and 80%, and the model had high clinical applicability. Conclusion Our nomogram risk prediction model can effectively identify the high risk factors of PPH and early intervention is of great significance for disease prevention.

This paper presents a control algorithm for a micro-electro-mechanical system (MEMS) fast steering mirror (FSM), whose performance is poor in open loop control mode. Based on the characterization and parameter identification of MEMS FSM, an improved double step algorithm is proposed to shorten the settling time and improve its quasi-static working bandwidth. A characterization system is set up, in which an optical sensor is utilized to monitor the tilt angle of FSM. The performance of the FSM in the time and frequency domain are both acquired, while the critical parameters of the FSM model are identified. Finally, the closed-loop experiments for the FSM are done to verify the effectiveness of the control algorithm. The experimental results demonstrate that the settling time (98%) of the FSM is effectively reduced from 398 ms to 0.4 ms under the improved double step control mode, which has a better tracking performance and tiny overshoot, compared with the open loop control mode.

Objective To explore the role of programmed cell death-ligand 1(PD-L1) in pathogenesis of ulcerative colitis (UC). Methods A total of 29 colon tissue samples from UC patients aged 18~64 years who underwent the colonoscopy in our department from January 2022 to September 2022 were collected, and another 22 colon tissue samples from non-UC patients were also collected during the same period.The expression of PD-L1 and inflammatory factors IL-1β, IL-6, IL-17a, IL-22 and TGF-β1 were detected by immunohistochemistry and RT-qPCR.Twenty-four male C57BL/6 mice (8~10 weeks old, 23~26 g) were randomly divided into blank control group (n=4), PD-L1-Fc group (n=4), dextran sulfate sodium salt (DSS) group (n=8), and DSS+PD-L1-Fc group (n=8).The mice from the DSS group and DSS+PD-L1-Fc group were given 2.5% DSS solution for 7 consecutive days, and were changed to normal drinking water on the 8th day.The animals of the other groups were given normal drinking water.On the 3rd day, the mice in the PD-L1-Fc group and DSS+PD-L1-Fc group were injected intraperitoneally with PD-L1-Fc protein (1 mg/mL, 40 μg/animal).In 8~10 d after modeling, the expression of PD-L1 in colonic mucosa was detected, and the body weight, fecal traits, morphological changes, histopathological changes and inflammatory factors were observed in different groups. Results The expression of PD-L1 was significantly increased in the colonic mucosa of UC patients (43.03±4.044, P < 0.001) than of normal colon tissue samples, and the expression of pro-inflammatory factors IL-1β and IL-6 and anti-inflammatory factors IL-22 and TGF-β1 were increased (P < 0.05), which also existed in DSS mouse models.Intraperitoneal injection of PD-L1-Fc protein improved body weight, fecal score, gross morphology of colonic mucosa and microscopic inflammation (P < 0.05), down-regulated IL-6 and IL-17a(P < 0.05) and up-regulated IL-22 and Foxp3(P < 0.05) in the DSS+PD-L1-Fc mice when compared with the DSS group. Conclusion The upregulation of PD-L1 in UC patients and DSS-induced colitis mouse models may play an adaptive protective role.