The development of autism spectrum disorders (ASDs) involves both environmental factors such as maternal diabetes and genetic factors such as neuroligins (NLGNs). NLGN2 and NLGN3 are two members of ...NLGNs with distinct distributions and functions in synapse development and plasticity. The relationship between maternal diabetes and NLGNs, and the distinct working mechanisms of different NLGNs currently remain unclear. Here, we first analyzed the expression levels of NLGN2 and NLGN3 in a streptozotocin-induced ASD mouse model and different brain regions to reveal their differences and similarities. Then, cryogenic electron microscopy (cryo-EM) structures of human NLGN2 and NLGN3 were determined. The overall structures are similar to their homologs in previous reports. However, structural comparisons revealed the relative rotations of two protomers in the homodimers of NLGN2 and NLGN3. Taken together with the previously reported NLGN2-MDGA1 complex, we speculate that the distinct assembly adopted by NLGN2 and NLGN3 may affect their interactions with MDGAs. Our results provide structural insights into the potential distinct mechanisms of NLGN2 and NLGN3 implicated in the development of ASD.
Hysterectomy is a widely used surgical approach for benign gynecological conditions, although recently there have been differences in the surgical route selected in different regions.
To estimate ...recent temporal trends, this study collected data on surgical approaches and adnexal surgeries during hysterectomies for benign diseases at a single institute from 2015 to 2021.
We retrospectively analyzed data from Xiangyang No.1 People's Hospital, Hubei University of Medicine in Xiangyang, China, and identified 1828 women who underwent hysterectomies for benign gynecologic conditions performed with or without bilateral salpingectomy (BS) or bilateral salpingo-oophorectomy (BSO) between January 2015 and December 2021.
There was an upward trend in the performance of hysterectomy and hysterectomy with BS, and there was a difference in the trends of concomitant adnexal surgery between AH, TLH, and VH, especially in TLH with BS. Patient characteristics data demonstrated that the most frequent indication for hysterectomy was leiomyoma, especially in women aged 45 to 65. Compared to AH, TLH, and VH, the operative bleeding, duration of surgery, and length of hospital stays of patients undergoing TLH with BS and BSO was the lowest. The surgical approach to benign diseases has changed dramatically due to a growing proportion of patients choosing minimally invasive procedures. The laparoscopic approach is becoming popular due to its capacity to decrease intraoperative blood loss and reduce hospitalization.
We should put more emphasis on surgical training for the TLH approach and help gynecologic surgeons provide the proposed added benefit of BS to their patients.
Adolescents are the primary target population for human papillomavirus (HPV) vaccination. The objective of this study is to explore the acceptability of HPV vaccines and evaluate factors related to ...willingness to be vaccinated among Chinese adolescents.
A nation-wide survey was conducted across 14 schools in mainland China. The questionnaire consisted of questions relating to socio-demographic characteristics, knowledge of adolescent sexual health, cervical cancer, HPV and HPV-related disease, and students' willingness to be vaccinated. Chi-square tests and multivariable logistic regression were conducted in the data analysis.
A total of 4,062 students participated in this study. Among them, only 17.1% of students reported having heard of HPV vaccines; however, 67.3% were willing to receive the HPV vaccine. Multivariable regression analysis showed that students who were from rural areas, have received sexual health education, have heard of cervical cancer or HPV vaccine, have a positive attitude toward vaccination, reported they were at the risk of developing cervical cancer, and those who value their parents' and teachers' opinions were more willing to receive HPV vaccination.
Awareness about the HPV vaccine is low among Chinese adolescents. The factors that most related to willingness to vaccinate among Chinese adolescents were school location, education about vaccination, HPV, and HPV vaccines. Integrating health education on HPV vaccination into existing school-based sexual health curricula may be an effective way to increase HPV vaccination coverage in mainland China.
ClC-2 transports chloride ions across plasma membranes and plays critical roles in cellular homeostasis. Its dysfunction is involved in diseases including leukodystrophy and primary aldosteronism. ...AK-42 was recently reported as a specific inhibitor of ClC-2. However, experimental structures are still missing to decipher its inhibition mechanism. Here, we present cryo-EM structures of apo ClC-2 and its complex with AK-42, both at 3.5 Å resolution. Residues S162, E205 and Y553 are involved in chloride binding and contribute to the ion selectivity. The side-chain of the gating glutamate E205 occupies the putative central chloride-binding site, indicating that our structure represents a closed state. Structural analysis, molecular dynamics and electrophysiological recordings identify key residues to interact with AK-42. Several AK-42 interacting residues are present in ClC-2 but not in other ClCs, providing a possible explanation for AK-42 specificity. Taken together, our results experimentally reveal the potential inhibition mechanism of ClC-2 inhibitor AK-42.
We investigate non-Gaussian noise second-order filtering and fixed-order smoothing problems for non-Gaussian stochastic discrete systems with packet dropouts. We present a novel Kalman-like nonlinear ...non-Gaussian noise estimation approach based on the packet dropout probability distribution and polynomial filtering technique. By means of properties of Kronecker product we first introduce a second-order polynomial extended system and then analyze the means and variances of the Kronecker powers of the extended system noises. To generate noise estimators in forms of filtering and smoothing, we use the innovation approach. We give an example to illustrate that the presented algorithm has better robustness against packet dropouts than conventional linear minimum variance estimation.
Currently, acute ischemic stroke (AIS) is one of the most common and serious diseases in the world and is associated with very high mortality and morbidity even after thrombolysis therapy. This study ...aims to research the relationship between lactic dehydrogenase (LDH) and prognosis in AIS patients treated with intravenous rtPA.
This study (a Multicenter Clinical Trial of Revascularization Treatment for Acute Ischemic Stroke, TRAIS) included 527 AIS patients in 5 cooperative medical institutions in China from January 2018 to February 2021. The primary outcome was major disability and death within 3 months (mRS score of 3-6), and the secondary outcomes were early neurological improvement (ENI), early neurological deterioration (END), moderate-severe cerebral edema (CE), and symptomatic intracranial hemorrhage (sICH).
The mean age of the 527 patients was 65.6 ± 11.7 years, and the median baseline NIHSS score was 4 (interquartile range, 2-7). The median serum LDH level was 184 U/L (interquartile range, 163-212 U/L). In total, 287 (54.5%) patients acquired ENI, 68 (13.0%) patients suffered END, 53 (12.1%) patients were observed with moderate-severe CE, and 28 (6.2%) patients showed sICH. Within 3 months, 127 (25.15%) patients experienced the primary outcome and 42 (8.3%) patients died. Serum LDH levels before thrombolysis showed an independent association with the risk of primary outcome adjusted odds ratio, 3.787; (95% CI, 1.525-9.404);
= 0.014. When log-transformed LDH increased each standard deviation, the risk of primary outcome was raised by 80.1% (95% CI, 28.9-251.7%). A positive linear dependence between the risk of primary outcome and serum LDH levels (
of linearity = 0.0248,
of non-linearity = 0.8284) was shown in multivariable-adjusted spline regression models. Pre-thrombolysis LDH quartile also provided a conventional risk model and significant improvement of the prediction for clinical outcomes, with a net reclassification improvement index (NRI) = 41.86% (
< 0.001) and integrated discrimination improvement (IDI) = 4.68% (
< 0.001).
Elevated serum LDH levels predicted unfavorable clinical outcomes after intravenous thrombolysis in AIS patients.
Preoperative neoadjuvant treatment in locally advanced breast cancer is recognized as an effective adjuvant therapy, as it improves treatment outcomes. However, the potential complications remain a ...threat, so there is an urgent clinical need to assess both the tumor response and changes in its microenvironment using non-invasive and precise identification techniques. Here, two-photon microscopy was employed to detect morphological alterations in breast cancer progression and recession throughout chemotherapy. The changes in structure were analyzed based on the autofluorescence and collagen of differing statuses. Parameters, including optical redox ratio, the ratio of second harmonic generation and auto-fluorescence signal, collagen density, and collagen shape orientation, were studied. Results indicate that these parameters are potential indicators for evaluating breast tumors and their microenvironment changes during progression and chemotherapy. Combined analyses of these parameters could provide a quantitative, novel method for monitoring tumor therapy.
Substantial rates of fetal loss plague all in vitro procedures involving embryo manipulations, including human-assisted reproduction, and are especially problematic for mammalian cloning where over ...90% of reconstructed nuclear transfer embryos are typically lost during pregnancy. However, the epigenetic mechanism of these pregnancy failures has not been well described. Here we performed methylome and transcriptome analyses of pig induced pluripotent stem cells and associated cloned embryos, and revealed that aberrant silencing of imprinted genes, in particular the retrotransposon-derived RTL1 gene, is the principal epigenetic cause of pregnancy failure. Remarkably, restoration of RTL1 expression in pig induced pluripotent stem cells rescued fetal loss. Furthermore, in other mammals, including humans, low RTL1 levels appear to be the main epigenetic cause of pregnancy failure.
Multiphoton microscopy was employed for monitoring the structure changes of mouse dermis collagen in the intrinsic- or the extrinsic-age-related processes
. The characteristics of textures in ...different aging skins were uncovered by fast Fourier transform in which the orientation index and bundle packing of collagen were quantitatively analyzed. Some significant differences in collagen-related changes are found in different aging skins, which can be good indicators for the statuses of aging skins. The results are valuable to the study of aging skin and also of interest to biomedical photonics.
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