Corrigendum: Paclitaxel-incorporated nanoparticles improve functional recovery after spinal cord injury.

[This corrects the article DOI: 10.3389/fphar.2022.957433.].

Association of serum interleukin-6 with negative symptoms in stable early-onset schizophrenia.

BACKGROUND: Accumulating evidence suggests that the inflammatory cytokine interleukin-6 (IL-6) contributes to the pathophysiology of psychiatric disorders. However, there was no study concerning the relationship between IL-6 concentrations and clinical features in the chronic phase of early-onset schizophrenia (EOS). AIM: To investigate the relationship between serum IL-6 concentration and the clinical features of EOS. METHODS: We measured serum IL-6 Levels from 74 patients with chronic schizophrenia, including 33 with age at onset < 21 years (EOS group) and 41 with onset ≥ 21 years in [adult-onset schizophrenia (AOS) group], and from 41 healthy controls. Symptom severities were evaluated using the Positive and Negative Syndrome Scale (PANSS). RESULTS: Serum IL-6 concentrations were higher in both EOS and AOS groups than healthy controls (F = 22.32, P < 0.01), but did not differ significantly between EOS and AOS groups (P > 0.05) after controlling for age, body mass index, and other covariates. Negative symptom scores were higher in the EOS group than the AOS group (F = 6.199, P = 0.015). Serum IL-6 concentrations in the EOS group were negatively correlated with both total PANSS-negative symptom score (r = -0.389, P = 0.032) and avolition/asociality subscore (r = -0.387, P = 0.026). CONCLUSION: Patients with EOS may have more severe negative symptoms than those with adult-onset schizophrenia during the chronic phase of the illness. IL-6 signaling may regulate negative symptoms and its avolition/asociality subsymptoms among the early-onset chronic schizophrenic patients.

Effects of fasudil on glial cell activation induced by tooth movement.

BACKGROUND: Orthodontic pain affects the physical and mental health of patients. The spinal trigeminal subnucleus caudalis (SPVC) contributes to the transmission of pain information and serves as a relay station for integrating orofacial damage information. Recently, glial cells have been found to be crucial for both acute and maintenance phases of pain. It has also been demonstrated that rho kinase (ROCK) inhibitors can manage different pain models by inhibiting glial cell activation. Here, we hypothesized that orthodontic pain is related to glial cells in the SPVC, and Fasudil, a representative rho/rock kinase inhibitor, can relieve orthodontic pain by regulating the function of glial cells and the related inflammatory factors. In this study, we constructed a rat model of tooth movement pain and used immunofluorescence staining to evaluate the activation of microglia and astrocytes. Quantitative real-time PCR was used to detect the release of related cytokines and the expression of pain-related genes in the SPVC. Simultaneously, we investigated the effect of Fasudil on the aforementioned indicators. RESULTS: In the SPVC, the expression of c-Fos peaked on day 1 along with the expression of OX42 (related to microglial activation), CD16 (a pro-inflammatory factor), and CD206 (an anti-inflammatory factor) on day 3 after tooth movement, followed by a gradual decrease. GFAP-staining showed that the number of activated astrocytes was the highest on day 5 and that cell morphology became complex. After Fasudil treatment, the expression of these proteins showed a downward trend. The mRNA levels of pro-inflammatory factors (IL-1ß and TNF-α) peaked on day 3, and the mRNA expression of the anti-inflammatory factor TGF-ß was the lowest 3 days after tooth movement. Fasudil inhibited the mRNA expression of pain-related genes encoding CSF-1, t-PA, CTSS, and BDNF. CONCLUSION: This study shows that tooth movement can cause the activation of glial cells in SPVC, and ROCK inhibitor Fasudil can inhibit the activation of glial cells and reduce the expression of the related inflammatory factors. This study presents for the first time the potential application of Fasudil in othodontic pain.

The effect of temperature on infectious diarrhea disease: A systematic review.

This study aimed to ascertain the delayed effects of various exposure temperatures on infectious diarrhea. We performed a Bayesian random-effects network meta-analysis to calculate relative risks (RR) with 95 % confidence intervals (95 % CI). The heterogeneity was analyzed by subgroup analysis. There were 25 cross-sectional studies totaling 6858735 patients included in this analysis, with 12 articles each investigating the effects of both hyperthermia and hypothermia. Results revealed that both high temperature (RRsingle = 1.22, 95%CI:1.04-1.44, RRcum = 2.96, 95%CI:1.60-5.48, P < 0.05) and low temperature (RRsingle = 1.17, 95%CI:1.02-1.37, RRcum = 2.19, 95%CI:1.33-3.64, P < 0.05) significantly increased the risk of infectious diarrhea, while high temperature caused greater. As-sociations with strengthening in bacillary dysentery were found for high temperatures (RRcum = 2.03, 95%CI:1.41-3.01, P < 0.05; RRsingle = 1.17, 95%CI:0.90-1.62, P > 0.05), while the statistical significance of low temperatures in lowering bacterial dysentery had vanished. This investigation examined that high temperature and low temperature were the conditions that posed the greatest risk for infectious diarrhea. This research offers fresh perspectives on preventing infectious diarrhea and will hopefully enlighten future studies on the impact of temperature management on infectious diarrhea.

A systematic review and meta-analysis of the association between air pollutants and the incidence of tuberculosis.

Objective: To investigate the association between air pollutants and the incidence of tuberculosis (TB) through a systematic review and meta-analysis, and to provide directions for future research and prevention of TB. Methods: A search was conducted for all literature related to the incidence of TB and air pollution in the database. We screened the retrieved articles and proceeded statistical analyses using random effects models to investigate the relationships between five air pollutants (PM2.5, PM10, SO2, NO2 and O3) and the incidence of TB. Results: The initial search identified 100 pieces of literature and 9 studies met the screening criteria after the screening. The single-day lagged risk ratio (RR) and 95% Confidence Intervals (CIs) for the combined effects estimates are as follows: PM2.5: 1.059 (0.966, 1.160); PM10: 1.000 (0.996, 1.004); SO2: 0.980 (0.954, 1.007); NO2: 1.011 (0.994, 1.027); O3: 0.994 (0.980,1.008). The cumulative lagged results for these five pollutants are listed like this: PM2.5: 1.095 (0.983, 1.219); PM10: 1.035 (1.006, 1.066); SO2: 0.964 (0.830, 1.121); NO2: 1.037 (1.010, 1.065); O3: 0.982 (0.954, 1.010). Conclusion: The single-day lag effects of PM2.5, PM10, SO2, NO2, and O3 are not statistically significantly relevant for the occurrence of TB. However, the cumulative lag results show that both PM10 and NO2 contribute to the prevalence of TB, while the statistical relationship between the cumulative lag effects of PM2.5, SO2, and O3 and the onset of TB remains unknown.

Polyamide Membranes with Tunable Surface Charge Induced by Dipole-Dipole Interaction for Selective Ion Separation.

Nanofiltration (NF) has the potential to achieve precise ion-ion separation at the subnanometer scale, which is necessary for resource recovery and a circular water economy. Fabricating NF membranes for selective ion separation is highly desirable but represents a substantial technical challenge. Dipole-dipole interaction is a mechanism of intermolecular attractions between polar molecules with a dipole moment due to uneven charge distribution, but such an interaction has not been leveraged to tune membrane structure and selectivity. Herein, we propose a novel strategy to achieve tunable surface charge of polyamide membrane by introducing polar solvent with a large dipole moment during interfacial polymerization, in which the dipole-dipole interaction with acyl chloride groups of trimesoyl chloride (TMC) can successfully intervene in the amidation reaction to alter the density of surface carboxyl groups in the polyamide selective layer. As a result, the prepared positively charged (PEI-TMC)-NH2 and negatively charged (PEI-TMC)-COOH composite membranes, which show similarly high water permeance, demonstrate highly selective separations of cations and anions in engineering applications, respectively. Our findings, for the first time, confirm that solvent-induced dipole-dipole interactions are able to alter the charge type and density of polyamide membranes and achieve tunable surface charge for selective and efficient ion separation.

Aberrant degree centrality profiles during rumination in major depressive disorder.

Rumination is closely linked to the onset and maintenance of major depressive disorder (MDD). Prior neuroimaging studies have identified the association between self-reported rumination trait and the functional coupling among a network of brain regions using resting-state functional magnetic resonance imaging (MRI). However, little is known about the underlying neural circuitry mechanism during active rumination in MDD. Degree centrality (DC) is a simple metric to denote network integration, which is critical for higher-order psychological processes such as rumination. During an MRI scan, individuals with MDD (N = 45) and healthy controls (HC, N = 46) completed a rumination state task. We examined the interaction effect between the group (MDD vs. HC) and condition (rumination vs. distraction) on vertex-wise DC. We further characterized the identified brain region's functional involvement with Neurosynth and BrainMap. Network-wise seed-based functional connectivity (FC) analysis was also conducted for the identified region of interest. Finally, exploratory correlation analysis was conducted between the identified region of interest's network FCs and self-reported in-scanner affect levels. We found that a left superior frontal gyrus (SFG) region, generally overlapped with the frontal eye field, showed a significant interaction effect. Further analysis revealed its involvement with executive functions. FCs between this region, the frontoparietal, and the dorsal attention network (DAN) also showed significant interaction effects. Furthermore, its FC to DAN during distraction showed a marginally significant negative association with in-scanner affect level at the baseline. Our results implicated an essential role of the left SFG in the rumination's underlying neural circuitry mechanism in MDD and provided novel evidence for the conceptualization of rumination in terms of impaired executive control.

A lightweight ship target detection model based on improved YOLOv5s algorithm.

Real-time and accurate detection of ships plays a vital role in ensuring navigation safety and ship supervision. Aiming at the problems of large parameters, large computation quantity, poor real-time performance, and high requirements for memory and computing power of the current ship detection model, this paper proposes a ship target detection algorithm MC-YOLOv5s based on YOLOv5s. First, the MobileNetV3-Small lightweight network is used to replace the original feature extraction backbone network of YOLOv5s to improve the detection speed of the algorithm. And then, a more efficient CNeB is designed based on the ConvNeXt-Block module of the ConvNeXt network to replace the original feature fusion module of YOLOv5s, which improves the spatial interaction ability of feature information and further reduces the complexity of the model. The experimental results obtained from the training and verification of the MC-YOLOv5s algorithm show that, compared with the original YOLOv5s algorithm, MC-YOLOv5s reduces the number of parameters by 6.98 MB and increases the mAP by about 3.4%. Even compared with other lightweight detection models, the improved model proposed in this paper still has better detection performance. The MC-YOLOv5s has been verified in the ship visual inspection and has great application potential. The code and models are publicly available at https://github.com/sakura994479727/datas.

Impact of PM2.5 and ozone on incidence of influenza in Shijiazhuang, China: a time-series study.

Most of the studies are focused on influenza and meteorological factors for influenza. There are still few studies focused on the relationship between pollution factors and influenza, and the results are not consistent. This study conducted distributed lag nonlinear model and attributable risk on the relationship between influenza and pollution factors, aiming to quantify the association and provide a basis for the prevention of influenza and the formulation of relevant policies. Environmental data in Shijiazhuang from 2014 to 2019, as well as the data on hospital-confirmed influenza, were collected. When the concentration of PM2.5 was the highest (621 µg/m3), the relative risk was the highest (RR: 2.39, 95% CI: 1.10-5.17). For extremely high concentration PM2.5 (348 µg/m3), analysis of cumulative lag effect showed statistical significance from cumulative lag0-1 to lag0-6 day, and the minimum cumulative lag effect appeared in lag0-2 (RR: 0.760, 95% CI: 0.655-0.882). In terms of ozone, the RR value was 2.28(1.19,4.38), when O3 concentration was 310 µg/m3, and the RR was 1.65(1.26,2.15), when O3 concentration was 0 µg/m3. The RR of this lag effect increased with the increase of lag days, and reached the maximum at lag0-7 days, RR and 95% CI of slightly low concentration and extremely high concentration were 1.217(1.108,1.337) and 1.440(1.012,2.047), respectively. Stratified analysis showed that there was little difference in gender, but in different age groups, the cumulative lag effect of these two pollutants on influenza was significantly different. Our study found a non-linear relationship between two pollutants and influenza; slightly low concentrations were more associated with contaminant-related influenza. Health workers should encourage patients to get the influenza vaccine and wear masks when going out during flu seasons.

The association between air pollution, meteorological factors, and daily outpatient visits for urticaria in Shijiazhuang, Hebei Province, China: a time series analysis.

The associations of air pollution and meteorological factors with the outpatient visits of urticaria remain poorly studied. This study aimed to assess the association between air pollution, meteorological factors, and daily outpatient visits for urticaria in Shijiazhuang, China, during 2014-2019. Daily recordings of air pollutant concentrations, meteorological data, and outpatient visits data for urticaria were collected during the 6 years. Descriptive research methods were used to describe the distribution characteristics and demographic features of urticaria. A combination of the generalized linear regression model (GLM) and distribution lag nonlinear model (DLNM) was used to evaluate the lag association between environmental factors and daily outpatient visits for urticaria. Stratified analyses by gender (male; female) and age (< 18 years; 18-39 years; > 39 years) were further conducted. The dose-response relationship between daily urticaria visits and CO, NO2, O3, temperature, and relative humidity was nonlinear. High concentrations of CO, NO2, O3, and high temperatures increased the risk of urticaria outpatient visits. The maximum cumulative association of high concentrations of CO, NO2, and O3 was lag 0-14 days (CO: RR = 1.10, 95%CI: 1.06, 1.31; NO2: RR = 1.09, 95%CI: 1.01, 1.08; O3: RR = 1.16, 95%CI: 1.08, 1.25), and high temperatures was lag 0-7 days (RR = 1.27, 95%CI: 1.14, 1.41). Low concentrations of NO2, O3, and high humidity, on the other hand, act as protective factors for urticaria outpatient. The maximum cumulative association of low concentrations of NO2 was the 0-day lag (RR = 0.97, 95%CI: 0.95, 0.99), O3 was lag 0-5 days (RR = 0.94, 95%CI: 0.88, 0.99), and high humidity was lag 0-10 days (RR = 0.93, 95%CI: 0.89, 0.98). Stratified analyses showed that the risk of urticaria outpatient visits was higher for the males and in the < 18 years age group. In conclusion, we found that the development of urticaria in Shijiazhuang has a distinct seasonal and cyclical nature. Air pollutants and meteorological factors had varying degrees of influence on the risk of urticaria outpatient visits. This study provides indirect evidence for a link between air pollution, meteorological factors, and urticaria outpatient visits.

The effect of orthodontic vertical control on the changes in the upper airway size and tongue and hyoid position in adult patients with hyperdivergent skeletal class II.

BACKGROUND: At present, there are still controversies about the influence of orthodontic treatment on the size of upper airway and the position of hyoid bone. We investigated the effect of orthodontic vertical control therapy on the size of the upper airway and position of the tongue and hyoid bone in adult patients with hyperdivergent skeletal Class II. METHODS: Overall, 15 adults with hyperdivergent skeletal Class II and normal occlusion, respectively, were selected as the experimental and control groups. The angle and line of the craniofacial structure, upper airway, hyoid bone position and three-dimensional (3D) upper airway indexes were measured using the Uceph 4.2.1 standard version and Mimics 21.0 software, respectively. The paired t-test, Wilcoxon symbol rank test, t-test of two independent samples, two independent sample nonparametric tests, Mann-Whitney U test, Pearson correlation analysis, the Univariate linear regression analysis and Multiple linear regression analysis were performed. RESULTS: After treatment, the S-Go/N-Me (%) and the MP-SN and XiPm-SN angles were significantly different (P < 0.01). The U-MPW and PAS significantly increased (P < 0.05), sagittal diameter L2 increased significantly, and transverse diameter L2 decreased significantly (P < 0.01). Although no significant correlation was observed between the vertical change in the jaw and that in U-MPW and PAS, the sagittal diameter L2 showed a significant correlation (P < 0.05). The Multiple linear regression analysis showed that there was a significant negative correlation between the variables MP-SN and sagittal diameter L2 and positive correlation between S-Go/N-Me(%) and H-MP (P < 0.05). Furthermore, significant differences between the Hv (P < 0.01) and sagittal diameter L1(P < 0.05) were observed before and after treatment. CONCLUSIONS: After the orthodontic vertical control therapy in patients with hyperdivergent skeletal Class II, the upper airway only underwent adaptive changes during treatment without substantial size changes, the position of tongue body and hyoid bone did not change significantly. Furthermore, compared with normal occlusion, the velopharyngeal segment airway of patients with hyperdivergent skeletal Class II remains narrow and long after treatment.

Preparation and characterization of Y-doped microarc oxidation coating on AZ31 magnesium alloys.

The rapid degradation characteristics of magnesium alloys limit its application in the field of orthopedic fracture fixation and cardiovascular stents. This study aimed to improve the corrosion resistance and biocompatibility of AZ31 magnesium alloys and prepare degradable implant materials. Micro-arc oxidation (MAO) was used to change the concentration of yttrium acetate in the electrolyte to prepare coatings with different yttrium content on the surface of AZ31 magnesium alloy. Through characterization, it is proved that the yttrium in the coating mainly exists in the form of Y3+. The polarization potential experiment shows that the micro-arc oxidation coating significantly improves the corrosion resistance of magnesium alloys. With the increase of yttrium acetate concentration in the electrolyte, the corrosion resistance of the coating first increases and then weakens. When the concentration is 0.0035 mol/L, the coating has the highest corrosion resistance. The results of CCK-8 cytotoxicity experiment and cell morphology observation also proved that the cell viability in each group was greater than 140%, and the yttrium-doped coating on the surface of AZ31 magnesium alloy has no cytotoxicity, can promote cell growth, and has good biocompatibility.

Paclitaxel-incorporated nanoparticles improve functional recovery after spinal cord injury.

As a worldwide medical problem, spinal cord injury has no clear and effective treatment to improve its prognosis. Hence, new treatment strategies for spinal cord injury with good therapeutic efficacy have been actively pursued. As a new drug loading system, acetal dextran nanoparticles (SAD) have good biocompatibility and biodegradability. Therefore, we designed spermine-functionalized acetal-dextran (SAD) nanoparticles and encapsulated paclitaxel (PCL) into them. This design can ensure the sustained release of paclitaxel in the injured area for 4 days and promote the extension of nerve processes in vitro. In our experiment, we found that paclitaxel-loaded SAD nanoparticles (PCL@SAD) decreased the level of chondroitin sulfate proteoglycan in the rat spinal cord injury model, which reduced the scar repair of the injured site and changed the inhibitory environment after spinal cord injury. This reveals that PCL@SAD can effectively protect the injured spinal cord and ultimately improve the functional recovery of the injured spinal cord. One single injection of PCL@SAD shows better therapeutic effect than that of PCL. This study opens an exciting perspective toward the application of neuroprotective PCL@SAD for the treatment of severe neurological diseases.

Discovery of Isoindoline Amide Derivatives as Potent and Orally Bioavailable ADAMTS-4/5 Inhibitors for the Treatment of Osteoarthritis.

Osteoarthritis (OA) treatment is a highly unmet medical need. Development of a disease-modifying OA drug (DMOAD) is challenging with no approved drugs on the market. Inhibition of ADATMS-4/5 is a promising OA therapeutics to target cartilage degradation and potentially can reduce joint pain and restore its normal function. Starting from the reported ADAMTS-5 inhibitor GLPG1972, we applied a scaffold hopping strategy to generate a novel isoindoline amide scaffold. Representative compound 18 showed high potency in ADATMS-4/5 inhibition, as well as good selectivity over a panel of other metalloproteases. In addition, compound 18 exhibited excellent druglike properties and showed better pharmacokinetic (PK) profiles than GLPG1972 cross-species. Compound 18 demonstrated dose-dependent efficacy in two in vivo rat osteoarthritis models.

Rosa1, a Transposable Element-Like Insertion, Produces Red Petal Coloration in Rose Through Altering RcMYB114 Transcription.

Rose (Rosa sp.) flowers have a rich diversity of colors resulting from the differential accumulation of anthocyanins, flavonols, and carotenoids. However, the genetic and molecular determinants of the red-petal trait in roses remains poorly understood. Here we report that a transposable element-like insertion (Rosa1) into RcMYB114, a R2R3-MYB transcription factor's promoter region causes its transcription, resulting in red petals. In red-petal varieties, RcMYB114 is expressed specifically in flower organs, but is absent from non-red varieties. Sequencing, yeast two-hybrid, transient transformation, and promoter activity assays of RcMYB114 independently confirmed the role of Rosa1 in altering RcMYB114's transcription and downstream effects on flower color. Genetic and molecular evidence confirmed that the Rosa1 transposable element-like insertion, which is a previously unknown DNA transposable element, is different from those in other plants and is a reliable molecular marker to screen red-petal roses.

SHR1032, a novel STING agonist, stimulates anti-tumor immunity and directly induces AML apoptosis.

Stimulator of interferon genes (STING) activation induces type I interferons and pro-inflammatory cytokines which stimulate tumor antigen cross presentation and the adaptive immune responses against tumor. The first-generation of STING agonists, cyclic di-nucleotide (CDN), mimicked the endogenous STING ligand cyclic guanosine monophosphate adenosine monophosphate, and displayed limited clinical efficacy. Here we report the discovery of SHR1032, a novel small molecule non-CDN STING agonist. Compared to the clinical CDN STING agonist ADU-S100, SHR1032 has much higher activity in human cells with different STING haplotypes and robustly induces interferon ß (IFNß) production. When dosed intratumorally, SHR1032 induced strong anti-tumor effects in the MC38 murine syngeneic tumor model. Pharmacodynamic studies showed induction of IFNß, tumor necrosis factor α (TNFα) and interleukin-6 (IL-6) in the tumors and, to a lower extent, in the plasma. More importantly, we found SHR1032 directly causes cell death in acute myeloid leukemia (AML) cells. In conclusion, our findings demonstrate that in addition to their established ability to boost anti-tumor immune responses, STING agonists can directly eradicate AML cells, and SHR1032 may present a new and promising therapeutic agent for cancer patients.

A Clinical Study on the Effect of Different Ratios of Recombinant Human Bone Morphogenetic Protein-2 Compound to Autogenous Bone on Cervical Interbody Fusion Based on Smart Healthcare.

With an increasing elderly population worldwide, the incidence of spine degenerative diseases with neck and shoulder pain as the main symptom is rising obviously, which has now become one of the important and difficult problems in sociomedical science. This study was to explore the effects of different ratios of recombinant human bone morphogenetic protein-2 (rhBMP-2) compound to the autogenous bone on cervical interbody fusion. 90 cervical degeneration patients with the need of surgical treatment admitted to our hospital from January 2019 to January 2020 were selected as the research objects and equally divided into group A, group B, and group C according to the order of admission, with 30 cases in each group and the ratios of rhBMP-2 compound to autogenous bone being 2 : 1, 1 : 1, and 1 : 2 respectively, and standard anterior cervical diskectomy and fusion (ACDF) treatment was performed to all patients to compare their surgery-related indexes, the Japanese Orthopaedic Association (JOA) score, the visual analog scale (VAS) score, the effect of cervical interbody fusion, and the postoperative complication rate (CR). Compared with group A and group C, group B achieved the significantly better surgery-related indexes (P < 0.05), significantly higher postoperative JOA scores (P < 0.05), significantly lower postoperative neck and upper limb VAS scores (P < 0.05), significantly better effect of cervical interbody fusion (P < 0.05), and significantly lower postoperative CR (P < 0.05). 1 : 1 is the best ratio of rhBMP-2 compound to the autogenous bone, for it can optimize patients' perioperative indexes, reduce the postoperative pain, lower the possibility of complications, and improve the effect of cervical interbody fusion, which should be promoted and applied in practice.

A new sex-specific underlying mechanism for female schizophrenia: accelerated skewed X chromosome inactivation.

BACKGROUND: X chromosome inactivation (XCI) is the mechanism by which the X-linked gene dosage is adjusted between the sexes. Evidence shows that many sex-specific diseases have their basis in X chromosome biology. While female schizophrenia patients often have a delayed age of disease onset and clinical phenotypes that are different from those of males, it is unknown whether the sex differences in schizophrenia are associated with X-linked gene dosage and the choice of X chromosome silencing in female cells. Previous studies demonstrated that sex chromosome aneuploidies may be related to the pathogeneses of some psychiatric diseases. Here, we examined the changes in skewed XCI in patients with schizophrenia. METHODS: A total of 109 female schizophrenia (SCZ) patients and 80 age- and sex-matched healthy controls (CNTLs) were included in this study. We evaluated clinical features including disease onset age, disease duration, clinical symptoms by the Positive and Negative Syndrome Scale (PANSS) and antipsychotic treatment dosages. The XCI skewing patterns were analyzed by the methylation profile of the HUMARA gene found in DNA isolated from SCZ patient and CNTL leukocytes in the three age groups. RESULTS: First, we found that the frequency of skewed XCI in SCZ patients was 4 times more than that in the age- and sex-matched CNTLs (p < 0.01). Second, we found an earlier onset of severe XCI skewing in the SCZ patients than in CNTLs. Third, we demonstrated a close relationship between the severity of skewed XCI and schizophrenic symptoms (PANSS score ≥ 90) as well as the age of disease onset. Fourth, we demonstrated that the skewed XCI in SCZ patients was not transmitted from the patients' mothers. LIMITATIONS: The XCI skewing pattern might differ depending on tissues or organs. Although this is the first study to explore skewed XCI in SCZ, in the future, samples from different tissues or cells in SCZ patients might be important for understanding the impact of skewed XCI in this disease. CONCLUSION: Our study, for the first time, investigated skewed XCI in female SCZ patients and presented a potential mechanism for the sex differences in SCZ. Our data also suggested that XCI might be a potential target for the development of female-specific interventions for SCZ.

Brain estrogen alters the effects of the antidepressant sertraline in middle-aged female and male mice.

Estrogens are important in regulating mood, especially for females. However, whether tissue-specific estrogen, such as brain estrogen, contributes to the effects of antidepressant treatment has not been determined. The present study used middle-aged aromatase gene knockout (Ar-/-) mice or overexpression (Thy1-Ar; hGFAP-Ar) mice as brain estrogen models to investigate whether brain estrogen synthesis alters the anti-depressive behaviors of sertraline treatment. Our results showed that depletion of brain estrogen increased depressive-like behavior in females, and elevated brain estrogen reduced depression-like behavior, regardless of sex. These genotype-related behaviors correlated with alterations of monoamine metabolism in the hippocampus (HPC) and the prefrontal cortex (PFC). We also demonstrated that male and female Ar-/- mice exhibited an attenuation of sertraline-induced anti-depressive behaviors compared to wild-type (WT) mice. The present data suggest that brain estrogen alters depressive-like behaviors and changes the effectiveness of antidepressants in middle-aged mice, regardless of sex.

Male mice adjust courtship behavior in response to female multimodal signals.

Multimodal signaling is nearly ubiquitous across animal taxa. While much research has focused on male signal production contributing to female mate-choice or preferences, females often give their own multimodal signals during intersexual communication events. Multimodal signal components are often classified based on whether they contain redundant information (e.g., the backup hypothesis) or non-redundant information (e.g., the multiple messages hypothesis) from the perspective of the receiver. We investigated the role of two different female vocalizations produced by the female house mouse (Mus musculus): the broadband, relatively low-frequency squeaks (broadband vocalizations or BBVs,), and the higher-frequency ultrasonic vocalizations (USVs). These female vocalizations may convey differently valenced information to the male receivers. We paired these vocalizations with and without female urine to examine the influence of combining information across multiple modalities. We found evidence that female urine and vocalizations act as non-redundant multimodal cues as males responded with different behaviors and vocalization rates depending on the female signal presented. Additionally, male mice responded with greater courtship effort to the multimodal combination of female USVs paired with female urine than any other signal combination. These results suggest that the olfactory information contained in female urine provides the context by which males can then evaluate potentially ambiguous female vocalizations.