Neural substrates of L2-L1 transfer effects on phonological awareness in young Chinese-English bilingual children.

The growing trend of bilingual education between Chinese and English has contributed to a rise in the number of early bilingual children, who were exposed to L2 prior to formal language instruction of L1. The L2-L1 transfer effect in an L1-dominant environment has been well established. However, the threshold of L2 proficiency at which such transfer manifests remains unclear. This study investigated the behavioral and neural processes involved when manipulating phonemes in an auditory phonological task to uncover the transfer effect in young bilingual children. Sixty-two first graders from elementary schools in Taiwan were recruited in this study (29 Chinese monolinguals, 33 Chinese-English bilinguals). The brain activity was measured using fNIRS (functional near-infrared spectroscopy). Bilingual children showed right lateralization to process Chinese and left lateralization to process English, which supports more on the accommodation effect within the framework of the assimilation-accommodation hypothesis. Also, compared to monolinguals, bilingual children showed more bilateral frontal activation in Chinese, potentially reflecting a mixed influence from L2-L1 transfer effects and increased cognitive load of bilingual exposure. These results elucidate the developmental adjustments in the neural substrates associated with early bilingual exposure in phonological processing, offering valuable insights into the bilingual learning process.

Ternary heterostructure-driven photoinduced electron-hole separation enhanced oxidative stress for triple-negative breast cancer therapy.

Zinc oxide nanoparticles (ZnO NPs) stand as among the most significant metal oxide nanoparticles in trigger the formation of reactive oxygen species (ROS) and induce apoptosis. Nevertheless, the utilization of ZnO NPs has been limited by the shallowness of short-wavelength light and the constrained production of ROS. To overcome these limitations, a strategy involves achieving a red shift towards the near-infrared (NIR) light spectrum, promoting the separation and restraining the recombination of electron-hole (e--h+) pairs. Herein, the hybrid plasmonic system Au@ZnO (AZ) with graphene quantum dots (GQDs) doping (AZG) nano heterostructures is rationally designed for optimal NIR-driven cancer treatment. Significantly, a multifold increase in ROS generation can be achieved through the following creative initiatives: (i) plasmonic Au nanorods expands the photocatalytic capabilities of AZG into the NIR domain, offering a foundation for NIR-induced ROS generation for clinical utilization; (ii) elaborate design of mesoporous core-shell AZ structures facilitates the redistribution of electron-hole pairs; (iii) the incorporation GQDs in mesoporous structure could efficiently restrain the recombination of the e--h+ pairs; (iv) Modification of hyaluronic acid (HA) can enhance CD44 receptor mediated targeted triple-negative breast cancer (TNBC). In addition, the introduced Au NRs present as catalysts for enhancing photothermal therapy (PTT), effectively inducing apoptosis in tumor cells. The resulting HA-modified AZG (AZGH) exhibits efficient hot electron injection and e--h+ separation, affording unparalleled convenience for ROS production and enabling NIR-induced PDT for the cancer treanment. As a result, our well-designed mesoporous core-shell AZGH hybrid as photosensitizers can exhibit excellent PDT efficacy.

Axial Length Control Is Associated With a Choroidal Thickness Increase in Myopic Adolescents After Orthokeratology.

OBJECTIVE: To investigate the changes in choroidal thickness and axial length after orthokeratology in adolescents with low-to-moderate myopia and to explore the relationship between choroidal thickness and axial length variation. METHODS: Thirty eyes with low-to-moderate myopia were retrospectively studied, and optometric data were collected before and after 6 months of continuous orthokeratology. Axial length and choroidal and foveal thicknesses were measured using optical biometry and enhanced depth imaging-spectral domain optical coherence tomography, respectively. RESULTS: Axial length in the low myopia group increased ( P <0.001) after 6 months of orthokeratology, and the variation was greater than that in the moderate myopia group ( P <0.05). The subfoveal choroidal thickness in low and moderate myopia groups increased ( P <0.01), and the variation was greater in the moderate myopia group ( P <0.05). Choroidal thickness in all seven measured spots increased, with the variation of subfovea, nasal 1 mm to fovea, and temporal 1 mm to fovea being statistically significant ( P <0.001, P <0.05, and P <0.05). The change in axial length was negatively associated with subfoveal and average choroidal thicknesses ( P <0.01). CONCLUSION: Adolescents with moderate myopia presented better axial length control after 6 months of orthokeratology. The choroidal thickness of low and moderate myopic eyes increased, and the variation was more significant in moderate myopic eyes. The axial length control effects can be associated with an increase in the subfoveal and average choroidal thickness.

Developmental differences in neural connectivity for semantic processing in youths with autism.

BACKGROUND: Youths with autism spectrum disorder (ASD) rely more on lower-level visual processing as revealed by greater occipital activation, yet less effectively engage higher-level processing of modality-independent semantic knowledge as indicated by reduced frontal activation, compared to typically developing (TD) youths. However, little is known about age-dependent differences in neural connectivity during semantic processing in youths with ASD as compared to TD youths. METHODS: Four groups were recruited: 31 ASD children (mean age = 10.5 years old), 33 TD children (mean age = 10.4), 30 ASD adolescents (mean age = 14.9), and 34 TD adolescents (mean age = 15.1). We explored their differences in neural connectivity by using functional magnetic resonance imaging (fMRI) with psychophysiological interaction (PPI) during semantic judgments. RESULTS: In comparison with TD children, children with ASD showed greater activation in the left cuneus and weaker connectivity between the left cuneus and left middle temporal gyrus (MTG). In comparison with TD adolescents, adolescents with ASD showed less activation in the left inferior frontal gyrus (IFG) and weaker functional connectivity between the left IFG and left MTG. CONCLUSIONS: Children with ASD may rely more on visual processes in the occipital cortex that are disconnected from modality-independent semantics in the temporal cortex. However, adolescents with ASD may less effectively engage frontal mechanisms involved in the top-down control of modality-independent semantic knowledge in the temporal cortex. Our findings provide evidence of developmental differences in the neural substrates of the alterations in semantic processing in youths with ASD compared to TD youths.

Inhibition of SF3B1 by molecules targeting the spliceosome results in massive aberrant exon skipping.

The recent identification of compounds that interact with the spliceosome (sudemycins, spliceostatin A, and meayamycin) indicates that these molecules modulate aberrant splicing via SF3B1 inhibition. Through whole transcriptome sequencing, we have demonstrated that treatment of Rh18 cells with sudemycin leads to exon skipping as the predominant aberrant splicing event. This was also observed following reanalysis of published RNA-seq data sets derived from HeLa cells after spliceostatin A exposure. These results are in contrast to previous reports that indicate that intron retention was the major consequence of SF3B1 inhibition. Analysis of the exon junctions up-regulated by these small molecules indicated that these sequences were absent in annotated human genes, suggesting that aberrant splicing events yielded novel RNA transcripts. Interestingly, the length of preferred downstream exons was significantly longer than the skipped exons, although there was no difference between the lengths of introns flanking skipped exons. The reading frame of the aberrantly skipped exons maintained a ratio of 2:1:1, close to that of the cassette exons (3:1:1) present in naturally occurring isoforms, suggesting negative selection by the nonsense-mediated decay (NMD) machinery for out-of-frame transcripts. Accordingly, genes involved in NMD and RNAs encoding proteins involved in the splicing process were enriched in both data sets. Our findings, therefore, further elucidate the mechanisms by which SF3B1 inhibition modulates pre-mRNA splicing.

Visual processing as a potential endophenotype in youths with attention-deficit/hyperactivity disorder: A sibling study design using the counting Stroop functional MRI.

Deficits in inhibitory control and visual processing are common in youths with attention-deficit/hyperactivity disorder (ADHD), but little is known about endophenotypes for unaffected siblings of youths with ADHD. This study aimed to investigate the potential endophenotypes of brain activation and performance in inhibitory control and visual processing among ADHD probands, their unaffected siblings, and neurotypical youths. We assessed 27 ADHD probands, 27 unaffected siblings, and 27 age-, gender-, and IQ-matched neurotypical youths using the counting Stroop functional magnetic resonance imaging and two tasks of the Cambridge Neuropsychological Test Automated Battery (CANTAB): rapid visual information processing (RVP) for inhibitory control and spatial span (SSP) for visual processing. ADHD probands showed greater activation than their unaffected siblings and neurotypical youths in the right inferior frontal gyrus (IFG) and anterior cingulate cortex. Increased activation in the right IFG was positively correlated with the mean latency of the RVP in ADHD probands. Moreover, ADHD probands and their unaffected siblings showed less activation in the left superior parietal lobule (SPL) than neurotypical youths. Increased activation in the left SPL was positively correlated with the spatial length of the SSP in neurotypical youths. Our findings suggest that less activation in the left SPL might be considered as a candidate imaging endophenotype for visual processing in ADHD.

Underwater Acoustic Target Tracking: A Review.

Advances in acoustic technology and instrumentation now make it possible to explore marine resources. As a significant component of ocean exploration, underwater acoustic target tracking has aroused wide attention both in military and civil fields. Due to the complexity of the marine environment, numerous techniques have been proposed to obtain better tracking performance. In this paper, we survey over 100 papers ranging from innovative papers to the state-of-the-art in this field to present underwater tracking technologies. Not only the related knowledge of acoustic tracking instrument and tracking progress is clarified in detail, but also a novel taxonomy method is proposed. In this paper, algorithms for underwater acoustic target tracking are classified based on the methods used as: (1) instrument-assisted methods; (2) mode-based methods; (3) tracking optimization methods. These algorithms are compared and analyzed in the aspect of dimensions, numbers, and maneuvering of the tracking target, which is different from other survey papers. Meanwhile, challenges, countermeasures, and lessons learned are illustrated in this paper.

Research on Localization Algorithms Based on Acoustic Communication for Underwater Sensor Networks.

The water source, as a significant body of the earth, with a high value, serves as a hot topic to study Underwater Sensor Networks (UWSNs). Various applications can be realized based on UWSNs. Our paper mainly concentrates on the localization algorithms based on the acoustic communication for UWSNs. An in-depth survey of localization algorithms is provided for UWSNs. We first introduce the acoustic communication, network architecture, and routing technique in UWSNs. The localization algorithms are classified into five aspects, namely, computation algorithm, spatial coverage, range measurement, the state of the nodes and communication between nodes that are different from all other survey papers. Moreover, we collect a lot of pioneering papers, and a comprehensive comparison is made. In addition, some challenges and open issues are raised in our paper.

Neural correlates of atomoxetine improving inhibitory control and visual processing in Drug-naïve adults with attention-deficit/hyperactivity disorder.

Atomoxetine improves inhibitory control and visual processing in healthy volunteers and adults with attention-deficit/hyperactivity disorder (ADHD). However, little is known about the neural correlates of these two functions after chronic treatment with atomoxetine. This study aimed to use the counting Stroop task with functional magnetic resonance imaging (fMRI) and the Cambridge Neuropsychological Test Automated Battery (CANTAB) to investigate the changes related to inhibitory control and visual processing in adults with ADHD. This study is an 8-week, placebo-controlled, double-blind, randomized clinical trial of atomoxetine in 24 drug-naïve adults with ADHD. We investigated the changes of treatment with atomoxetine compared to placebo-treated counterparts using the counting Stroop fMRI and two CANTAB tests: rapid visual information processing (RVP) for inhibitory control and delayed matching to sample (DMS) for visual processing. Atomoxetine decreased activations in the right inferior frontal gyrus and anterior cingulate cortex, which were correlated with the improvement in inhibitory control assessed by the RVP. Also, atomoxetine increased activation in the left precuneus, which was correlated with the improvement in the mean latency of correct responses assessed by the DMS. Moreover, anterior cingulate activation in the pre-treatment was able to predict the improvements of clinical symptoms. Treatment with atomoxetine may improve inhibitory control to suppress interference and may enhance the visual processing to process numbers. In addition, the anterior cingulate cortex might play an important role as a biological marker for the treatment effectiveness of atomoxetine. Hum Brain Mapp 38:4850-4864, 2017. © 2017 Wiley Periodicals, Inc.

A Two-Phase Time Synchronization-Free Localization Algorithm for Underwater Sensor Networks.

Underwater Sensor Networks (UWSNs) can enable a broad range of applications such as resource monitoring, disaster prevention, and navigation-assistance. Sensor nodes location in UWSNs is an especially relevant topic. Global Positioning System (GPS) information is not suitable for use in UWSNs because of the underwater propagation problems. Hence, some localization algorithms based on the precise time synchronization between sensor nodes that have been proposed for UWSNs are not feasible. In this paper, we propose a localization algorithm called Two-Phase Time Synchronization-Free Localization Algorithm (TP-TSFLA). TP-TSFLA contains two phases, namely, range-based estimation phase and range-free evaluation phase. In the first phase, we address a time synchronization-free localization scheme based on the Particle Swarm Optimization (PSO) algorithm to obtain the coordinates of the unknown sensor nodes. In the second phase, we propose a Circle-based Range-Free Localization Algorithm (CRFLA) to locate the unlocalized sensor nodes which cannot obtain the location information through the first phase. In the second phase, sensor nodes which are localized in the first phase act as the new anchor nodes to help realize localization. Hence, in this algorithm, we use a small number of mobile beacons to help obtain the location information without any other anchor nodes. Besides, to improve the precision of the range-free method, an extension of CRFLA achieved by designing a coordinate adjustment scheme is updated. The simulation results show that TP-TSFLA can achieve a relative high localization ratio without time synchronization.

Safer-use strategies in the context of harm-reduction treatment for people experiencing homelessness and alcohol use disorder.

BACKGROUND: Two, randomized controlled trials found harm-reduction treatment for AUD (HaRT-A) improves alcohol outcomes for adults experiencing homelessness. HaRT-A, which neither requires nor precludes abstinence, entails tracking alcohol-related harm, harm-reduction goals, and safer-use strategies. This secondary dual study qualitatively describes this last component, safer-use strategies, and their quantitative association with treatment outcomes. METHODS: Participants were people who experienced homelessness and AUD and were enrolled in the active HaRT-A treatment arms in 2 randomized control trials (Trial 1 N = 86; Trial 2 N = 208). Trial 1was a 2-arm study with randomization to HaRT-A or services as usual. Trial 2 was a 4-arm study combining HaRT-A and extended release naltrexone. In HaRT-A sessions, participants received a list of 3 categories of safer-use strategies (i.e., buffering alcohol's effects on the body, changing the manner of drinking to be safer and healthier, and reducing alcohol use). Mixed methods were used to qualitatively describe safer-use strategies implemented and quantitatively test their association with alcohol outcomes (i.e., peak quantity, frequency, alcohol-related harm). RESULTS: In Trial 1, but not Trial 2, participants committed to more safer-use strategies across time, which was associated with reductions in alcohol frequency over the past 30 days. In both trials, participants committing to reducing alcohol consumption drank on a quarter fewer days overall, and in Trial 2, experienced 15 % less alcohol-related harm. In Trial 1, participants who committed to changing the manner of drinking were heavier drinkers overall, and although they showed significant reductions in alcohol-related harm, their reduction rate was slower than for participants who selected other strategies. In Trial 2, strategies to buffer alcohol's effects were associated with a monthly 14 % decrease of alcohol-related harm. CONCLUSION: This study replicated prior findings that people experiencing homelessness and AUD regularly adopt strategies to reduce alcohol-related harm. The implementation of safer-use strategies was favorably associated with alcohol outcomes, but specific associations differed by trial and outcome. Discussion of safer-use strategies appears helpful; however, further research is needed to firmly establish how this HaRT-A component works.

Efficacy and Safety Evaluation of Scleral Cross-Linking Using Genipin in the Treatment of Juvenile Guinea Pigs with High Myopia.

Purpose: To investigate the efficacy and safety of scleral cross-linking (CXL) using Genipin in the treatment of juvenile guinea pigs with high myopia. Methods: Twenty-four 4-week-old tricolor guinea pigs with high myopia of diopter ≤ -6.0 DS in the right eye were randomly divided into two groups: Genipin CXL group and control group (n = 12 for each group). They received separately form-deprivation (FD) combined with sub-tenon injection, and the former was 0.5% Genipin solution, while the latter was 0.9% saline solution. Refractive error, axial length (AL), intraocular pressure (IOP), and structural and vasculature optic disc changes in optical coherence tomography (OCT) and OCT angiography (OCTA) were analyzed at baseline and at 3 weeks after injection. Results: Baseline parameters were similar between the two groups (P > 0.05). After 3 weeks of the intervention, the difference of AL between the two groups was statistically significant (t = -11.28, P < 0.001). Besides, IOP increased in both groups, and the changes of IOP between the two groups were statistically significant (t = 2.80, P = 0.01). The average cup-disc ratio (C/D) (t = 3.11, P = 0.006) and the vertical C/D (t = 2.96, P = 0.009) of OCT-related optic disc parameters in the Genipin CXL group increased, and the differences were statistically significant compared with the control group. Conclusion: The CXL method of sub-tenon injection of Genipin solution could effectively inhibit the progression of myopia in juvenile guinea pigs with highly myopic eyes combined with FD. The slightly elevated IOP and increased C/D of some fundus optic discs should be further assessed.

Range of motion of the mid-cervical spine: human versus goat.

BACKGROUND: The goat cervical spine represents a promising alternative for human specimen in spinal implant testing, but the range of motion (ROM) of the spine is lacking. We aimed to evaluate and compare the ROMs of fresh goat and human mid-cervical spine specimens. METHODS: Ten fresh adult healthy male goat cervical spine specimens (G group) and ten fresh frozen adult healthy human cervical spine specimens (average age: 49.5 ± 12.1 years; 6 males, 4 females) (H group) were included. The ROMs of each specimen were biomechanically tested at the C2-3, C3-4, C4-5 and C2-5 levels at 1.5 Nm and 2.5 Nm torque and recorded. The ROMs of different levels of goat cervical samples were compared to those of human cervical samples using an independent sample t test. Significance was defined as a P value of less than 0.05. RESULTS: At the C2-3, C3-4 and C4-5 levels, the ROMs of the goat cervical spine were significantly larger than those of the human cervical spine in all directions except extension under 1.5 Nm torque; under 2.5 Nm torque, the ROMs of the goat cervical spine at the C2-3 and C3-4 levels were significantly larger than those of humans in the pure movement of flexion, lateral bending and axial rotation, and the ROMs for axial rotation of the goat specimens and human specimens were comparable. Under both 1.5 Nm and 2.5 Nm torque, the goat cervical spine displayed a much greater ROM in all directions at the C2-5 level. CONCLUSIONS: Several segmental ROMs of fresh goat and human cervical spine specimens were recorded in this investigation. We recommend using goat cervical specimens as an alternative to fresh human cervical specimens in future studies when focusing only on the ROMs of C2-3, C3-4 and C4-5 in flexion under a torque of 1.5 Nm or the ROMs of C2-3 and C3-4 in flexion and rotation under a torque of 2.5 Nm.

Specialization of the posterior temporal lobes for audio-motor processing - evidence from a functional magnetic resonance imaging study of skilled drummers.

Sounds of hammering or clapping can evoke simulation of the arm movements that have been previously associated with those sounds. This audio-motor transformation also occurs at the sequential level and plays a role in speech and music processing. The present study aimed to demonstrate how the activation pattern of the sensorimotor network was modulated by the sequential nature of the auditory input and effector. Fifteen skilled drum set players participated in our functional magnetic resonance imaging study. Prior to the scan, these drummers practiced six drumming grooves. During the scan, there were four rehearsal conditions: covertly playing the drum set under the guidance of its randomly-presented isolated stroke sounds, covertly playing the drum set along with the sounds of learned percussion music, covertly reciting the syllable representation along with this music, and covertly reciting along with the syllable representation of this music. We found greater activity in the bilateral posterior middle temporal gyri for active listening to isolated drum strokes than for active listening to learned drum music. These regions might mediate the one-to-one mappings from sounds to limb movements. Compared with subvocal rehearsals along with learned drum music, covert rehearsals of limb movements along with the same music additionally activated a lateral subregion of the left posterior planum temporale. Our results illustrate a functional specialization of the posterior temporal lobes for audio-motor processing.

Relationship between demoralization of the college student with their individual- and social-oriented self.

Demoralization has become increasingly prevalent among college students who have lost motivation in life and feel hopeless about their future. Many college students who demonstrate symptoms of demoralization are neglected because they might fail to typical symptoms of depression. Taiwanese college students are simultaneously influenced by bicultural-self system, such as individual- and social-oriented views of self, which vary considerably in the view of self, achievement motivation, and the value of self-realization, and may even create contradictory expectations and behavioral standard. The purpose of this study was to investigate the extent of the relationship between attitude towards demoralization, individual- and social-oriented views of self. Three-hundred fifty-six college students completed the online questionnaire, which was designed to explore their demoralization status and cultural differences. Four groups were divided into bicultural self, individual-oriented self, social-oriented self, and unintegrated self. Bicultural group demonstrated significantly lower demoralization overall scores than other groups. Moreover, the five dimensions of demoralization in college students were mostly significantly and negatively correlated with individual- and social-oriented views of self, indicating that college students' bicultural views of self may contribute to or prevent demoralization.

Biomechanics of a novel artificial cervical vertebra from an in vivo caprine cervical spine non-fusion model.

Objective: Anterior cervical corpectomy and fusion (ACCF) has been widely used in the treatment of cervical spondylotic myelopathy (CSM) but is accompanied by unavoidable motion loss and destruction of vertebra. We aim to evaluate the range of motion (ROM) of caprine cervical spine constructs implanted with cervical artificial disc and vertebra system (ADVS). The purpose of this study was to investigate the biomechanical properties of the ADVS from an in vivo caprine cervical spine non-fusion model. Methods: Twelve goats were randomly divided into ADVS or control group, with 6 animals in each group. The animals in the ADVS group were implanted with ADVS at the C4 level. The cervical spine constructs were harvested 6 months after the operation. The ROM of cervical spine specimens in the ADVS group was recorded. Biomechanical testing of the specimens in the control group were conducted to evaluate the ROM of the cervical spine specimens under intact and fixed condition (C3-C5) by an anterior plate, respectively. Results: The biomechanical outcomes showed that the ROM of the levels (C3-C5) implanted with ADVS was maintained. The ROM in the adjacent level (C2-3) did not increase significantly comparing with intact group. Conclusions: In general, ADVS could preserve the ROM of operative levels and could reconstruct the height of the vertebra. ADVS did not increase the ROM of upper adjacent level. This device provides a non-fusion method for the treatment of patients suffering from CSM. However, improvements on the design of ADVS are still needed. Translational potential statement: This study introduced a novel cervical spinal implant, which was designed to have the ability of motion preservation and vertebra construction. Our study provided a non-fusion procedure in the treatment of CSM after ACCF.

Prognostic significance of the expression of metastasis-associated in colon cancer-1 in gynecologic cancers and breast cancer: A protocol for systematic review and meta-analysis.

BACKGROUND: The prognostic role of the expression of metastasis-associated in colon cancer-1 (MACC1) in gynecologic cancers and breast cancer remains unclear. The aim of this systematic review and meta-analysis was to determine the prognostic significance of MACC1 expression in gynecologic cancers and breast cancer. MATERIALS AND METHODS: PubMed, Web of Science and Embase were comprehensively searched up to February 9, 2020. Studies focusing on the relationship between the expression of MACC1 and prognosis in gynecologic cancers and breast cancer were included into the analysis. Pooled hazard ratio (HR) or odd ratio with 95% confidence interval (CI) was used to estimate the prognostic value of the expression of MACC1. RESULTS: A total of 1,811patients with gynecologic cancers or breast cancer were included into the analysis. Patients with high expression of MACC1 tended to suffer a shorter overall survival (HR = 2.76, 95%CI = 2.12-3.59, P < .01) and recurrence-free survival (HR = 2.37, 95%CI = 1.44-3.90, P < .01) compared to those with low expression of MACC1. High expression of MACC1 was significantly associated with worse tumor differentiation (P = .04), more advanced FIGO stage (P < .01) and earlier lymph node metastasis (P < .01) compared to low expression of MACC1. CONCLUSION: Compared to low expression of MACC1, high expression of MACC1 predicts a worse prognosis of gynecologic cancers and breast cancer. The expression of MACC1 can serve as a prognostic indicator of gynecologic cancers and breast cancer.

Bone marrow mesenchymal stem cells-derived exosomes reduce apoptosis and inflammatory response during spinal cord injury by inhibiting the TLR4/MyD88/NF-κB signaling pathway.

Spinal cord injury (SCI) is one of the most common destructive injuries, which may lead to permanent neurological dysfunction. Currently, transplantation of bone marrow mesenchymal stem cells (BMSCs) in experimental models of SCI shows promise as effective therapies. BMSCs secrete various factors that can regulate the microenvironment, which is called paracrine effect. Among these paracrine substances, exosomes are considered to be the most valuable therapeutic factors. Our study found that BMSCs-derived exosomes therapy attenuated cell apoptosis and inflammation response in the injured spinal cord tissues. In in vitro studies, BMSCs-derived exosomes significantly inhibited lipopolysaccharide (LPS)-induced PC12 cell apoptosis, reduced the secretion of pro-inflammatory factors including tumor necrosis factor (TNF)-α and IL (interleukin)-1ß and promoted the secretion of anti-inflammatory factors including IL-10 and IL-4. Moreover, we found that LPS-induced protein expression of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88) and nuclear transcription factor-κB (NF-κB) was significantly downregulated after treatment with BMSCs-derived exosomes. In in vivo studies, we found that hindlimb motor function was significantly improved in SCI rats with systemic administration of BMSCs-derived exosomes. We also observed that the expression of pro-apoptotic proteins and pro-inflammatory factors was significantly decreased, while the expression of anti-apoptotic proteins and anti-inflammatory factors were upregulated in SCI rats after exosome treatment. In conclusion, BMSCs-derived exosomes can inhibit apoptosis and inflammation response induced by injury and promote motor function recovery by inhibiting the TLR4/MyD88/NF-κB signaling pathway, which suggests that BMSCs-derived exosomes are expected to become a new therapeutic strategy for SCI.

The effects of MIR137HG genetic polymorphisms on the susceptibility of alcohol-induced osteonecrosis of the femoral head in a Chinese male population.

BACKGROUNDS: Osteonecrosis of the femoral head (ONFH) is one of the common and complicated diseases in the orthopedic clinic. Previous studies indicate that genetic factors play a crucial role in the occurrence of ONFH. This case-control study aimed to investigate the associations of MIR137HG genetic polymorphisms with the alcohol-induced ONFH risk. METHODS: A total of 731 participants were recruited to detect the effect of MIR137HG SNPs on the alcohol-induced ONFH risk in a Chinese male population. Odds ratios (OR) and 95% confidence intervals (CI) were calculated to evaluate the associations. Multifactor dimensionality reduction (MDR) was used to analyze the SNP-SNP interaction with the alcohol-induced ONFH risk. RESULTS: Our study showed that rs7549905 played a protective role in alcohol-induced ONFH risk (OR 0.57, p = 0.045). Stratified analysis indicated that rs9440302 was associated with an increased risk of patients aged >45 years (OR 2.00, p = 0.038), and rs7549905 showed a reduced risk in patients aged ≤ 45 years (OR 0.43, p = 0.023). In addition, we found that rs9440302 and rs7554283 exhibited a significantly increased susceptibility of III-IV grade alcohol-induced ONFH patients (OR 2.34, p = 0.003; OR 2.13, p = 0.011, respectively). We also observed that rs12138817 was related to an increased risk in patients with >21 months of course (OR 1.77, p = 0.043). Interestingly, rs17371457 showed a significant correlation with low-density lipoprotein-cholesterol (p = 0.040). CONCLUSION: Our study suggests that MIR137HG genetic variants are associated with the alcohol-induced ONFH susceptibility in a Chinese male population, which may give scientific evidence for exploring molecular mechanisms of the alcohol-induced ONFH.