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Insecticides are commonly utilized in agriculture and forestry for pest control, but their dispersal can pose hazards to humans and environment. Understanding resistance, inheritance patterns, and fitness costs can help manage resistance. A λ-cyhalothrin-resistant population (LCR) of Cydia pomonella , a global pest of pome fruits and walnuts, was obtained through selective insecticide breeding for 15 generations, showing stable moderate resistance (23.85-fold). This population was cross-resistant to deltamethrin (4.26-fold) but not to β-cypermethrin, chlorantraniliprole, chlorpyrifos, and avermectin. Genetic analysis revealed the resistance was autosomal, incompletely dominant, and controlled by multiple genes. Increased activity of glutathione S-transferases and cytochrome P450 monooxygenases (P450s) played a primary role in resistance, with specific genes up-regulated in LCR, and exhibited significant expression in midgut. LCR also exhibited fitness costs, including delays in development, reduced fecundity, and slower population growth. These findings contribute to understanding λ-cyhalothrin resistance in C. pomonella and can guide resistance management strategies.

Objective: In the Asian population, SOD1 variants are the most common cause of amyotrophic lateral sclerosis (ALS). To date, more than 200 variants have been reported in SOD1 . This study aimed to summarize the genotype-phenotype correlation and determine whether the patients carrying common variants derive from a common ancestor., Methods: A total of 103 sporadic ALS (SALS) and 11 familial ALS (FALS) probands were included and variants were screened by whole exome sequencing. Functional analyses were performed on fibroblasts derived from patients with SOD1 p.V48A and control. Haplotype analysis was performed in the probands with p.H47R or p.V48A and their familial members., Results: A total of 25 SOD1 variants were identified in 44 probands, in which p.H47R, p.V48A and p.C112Y variants were the most common variants. 94.3% and 60% of patients with p.H47R or p.V48A had lower limb onset with predominant lower motor neurons (LMNs) involvement. Patients with p.H47R had a slow progression and prolonged survival time, while patients with p.V48A exhibited a duration of 2-5 years. Patients with p.C112Y variant showed remarkable phenotypic variation in age at onset and disease course. SOD1 V48A fibroblasts showed mutant SOD1 aggregate formation, enhanced intracellular reactive oxygen species level, and decreased mitochondrial membrane potential compared to the control fibroblast. Haplotype analysis showed that seven families had two different haplotypes. p.H47R and p.V48A variants did not originate from a common founder., Conclusions: Our study expanded the understanding of the genotype-phenotype correlation of ALS with SOD1 variants and revealed that the common p.H47R or p.V48A variant did not have a founder effect.

Cadmium (Cd), a prevalent environmental contaminant, has attracted widespread attention due to its serious health hazards. Ferroptosis is a form of iron-dependent oxidative cell death that contributes to the development of various kidney diseases. However, the mechanisms underlying the occurrence of ferroptosis in Cd-induced renal tubular epithelial cells (TECs) have not been fully elucidated. Hereby, both in-vitro and in-vivo experiments were established to elucidate this issue. In this study, we found that Cd elicited accumulation of lipid peroxides due to intracellular ferrous ion (Fe 2+ ) overload and glutathione depletion, contributing to ferroptosis. Inhibition of ferroptosis via chelation of Fe 2+ or reduction of lipid peroxidation can significantly mitigate Cd-induced cytotoxicity. Renal transcriptome analysis revealed that the activation of heme oxygenase 1 (HO-1) was closely related to ferroptosis in Cd-induced TECs injury. Cd-induced ferroptosis and resultant TECs injury are significantly alleviated due to HO-1 inhibition, demonstrating the crucial role of HO-1 in Cd-triggered ferroptosis. Further studies showed that accumulation of lipid peroxides due to iron overload and mitochondrial ROS (mtROS) generation was responsible for HO-1-triggered ferroptosis in Cd-induced cytotoxicity. In conclusion, the current study demonstrates that excessively upregulating HO-1 promotes iron overload and mtROS overproduction to trigger ferroptosis in Cd-induced TECs injury, highlighting that targeting HO-1-mediated ferroptosis may provide new ideas for preventing Cd-induced nephrotoxicity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Granular sludge is an alternative technology for the direct treatment of acidic nitrate-containing wastewater. Rapid remediation of disintegrated granules is essential to achieve efficient nitrogen removal. In this study, denitrifying granules were inactivated and disintegrated when the influent nitrate-nitrogen concentration was elevated from 240 to 360 mg L -1 in acidic wastewater (pH = 4.1) in a sequencing batch reactor. Tightly bound extracellular polymeric substances (TB-EPS) decreased by 60%, and extracellular protein (PN) was the main component of the reduced EPS. The three-dimensional excitation emission matrices (3D-EEM) results confirmed that the PNs that decreased were mainly tryptophan-like, tyrosine-like, and aromatic. This study further confirmed that the decrease in PN was mainly from the destruction of C=O (amide I) and N-H functional groups. Overloading of nitrogen-inhibited denitrifying activity and the destruction and dissolution of TB-EPS by acidic pH were responsible for granule disintegration, with PNs playing a major role in maintaining granule stability. Based on this, new granules with an average particle size of 454.4 μm were formed after calcium chloride addition; EPS nearly doubled during granule formation with PN as the dominant component, accounting for 64.7-78.4% of the EPS. Atomic force microscopy (AFM) revealed that PN-PN adhesion increased by 1.6-4.9 times in the presence of calcium ions, accelerating the re-granulation of disintegrated particles. This study provides new insights into the disintegration and remediation of granular sludge under acidic conditions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The biological treatment of wastewater generates a substantial amount of waste sludge that requires dewatering before final disposal. Efficient sludge dewatering is essential to minimize storage and transportation costs. In this study, the sludge conditioners polydimethyldiallylammonium chloride (PDMDAAC) and ferric chloride (FeCl 3 ) were sequentially dosed, and the pH was adjusted to 3. As a result, the sludge moisture content (MC) was reduced to 59.4%, achieving deep dewatering. After conditioning, the tightly bound extracellular polymeric substances (TB-EPS) were reduced from 34.5 to 10.2 mg g -1 VSS, with the majority of the reduced fractions being composed of protein (PN). In contrast, soluble EPS increased more than 8 times. Subsequent studies revealed that the decrease in PN from TB-EPS primarily involved tryptophan and tyrosine proteins, accompanied by a significant reduction in the N-H and C[double bond, length as m-dash]C absorption peaks. These results highlight the critical role of TB-EPS dissolution in achieving deep dehydration, with the N-H in PN was identified as the key group influencing sludge dewatering. Combined with the changes in sludge particle size and morphology, the dewatering mechanism can be summarized as follows: PDMDAAC dissolves TB-EPS, simultaneously disrupting the floc structure and refining the sludge. Subsequently, FeCl 3 reconstructs these elements, forming larger particle sizes. Finally, hydrochloric acid reduces TB-EPS once again, releasing bound water. This study offers alternative methods and new insights for achieving deep dewatering of waste sludge., Competing Interests: There were no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Glyphosate (GLY), a widely used herbicide, can adversely affect the male reproductive health by inhibiting testosterone synthesis. Ferroptosis is a form of iron-dependent oxidative cell death that contributes to inhibition of testosterone secretion. However, it still remains unclear whether ferroptosis is involved in GLY-inhibited testosterone synthesis. Hereby, an in vitro model of 1 mM GLY-exposed testicular Leydig (TM3) cells was established to elucidate this issue. Data firstly showed that GLY causes cytotoxicity and testosterone synthesis inhibition via ferroptosis, while accumulation of lipid peroxides due to intracellular ferrous ion (Fe 2+ ) overload and glutathione depletion is confirmed as a determinant of ferroptosis. Blockage of ferroptosis via chelation of Fe 2+ or inhibition of lipid peroxidation can markedly mitigate GLY-induced testosterone synthesis inhibition. Also, autophagy activation is revealed in GLY-treated TM3 cells and nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy is involved in ferroptosis through the release of excess Fe 2+ . GLY-induced cytotoxicity and testosterone synthesis inhibition are significantly alleviated by NCOA4 knockdown, demonstrating the crucial role of NCOA4-mediated ferritinophagy in GLY-inhibited testosterone synthesis. In summary, this study provides solid evidence that NCOA4-mediated ferritinophagy promotes ferroptosis to inhibit testosterone synthesis, highlighting that targeting NCOA4 may be a potential therapeutic approach in GLY-induced male reproductive toxicity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

To investigate the prevalence, types, and risk factors of functional gastrointestinal diseases (FGIDs) in Hainan Province, China, in order to provide insights for future prevention and treatment strategies. A questionnaire survey was conducted from July 2022 to May 2023, using stratified sampling to sample local residents in five cities (20 townships) in Hainan Province. Out of 2057 local residents surveyed, 659 individuals (32.0%) reported experiencing at least one FGID. The most prevalent FGIDs were functional dyspepsia (FD) (10.7%), functional constipation (FC) (9.3%), irritable bowel syndrome (IBS) (6.8%), functional bloating (2.2%), belching disorder (2.2%), functional diarrhea (FDr) (1.5%), functional heartburn (1.5%), and fecal incontinence (0.98%). The study revealed significant associations between FGIDs and factors such as age, sleep quality, anxiety, smoking, alcohol consumption, and the consumption of pickled food (P < 0.05). Older age, poor sleep quality, anxiety, and the consumption of pickled food were identified as independent risk factors for the prevalence of FGIDs (P < 0.05). In Hainan Province, the overall prevalence of FGIDs was found to be 32.0%, with higher prevalences of FC and FD. Older age, poor sleep quality, anxiety, and the consumption of pickled food were identified as risk factors for FGIDs., (© 2024. The Author(s).)

Background: We examined the impact of the Clonorchis sinensis (C. sinensis) infection on the survival outcomes of spontaneous rupture Hepatocellular Carcinoma (srHCC) patients undergoing hepatectomy., Methods: Between May 2013 and December 2021, 157 consecutive srHCC patients who underwent hepatectomy were divided into an no C. sinensis group (n = 126) and C. sinensis group (n = 31). To adjust for differences in preoperative characteristics an inverse probability of treatment weighting (IPTW) analysis was done, using propensity scores. Overall survival (OS) and recurrence-free survival (RFS) were compared before and after IPTW. Multivariate Cox regression analysis was performed to determine whether the C. sinensis infection was an independent prognostic factor after IPTW., Results: In original cohort, the no C. sinensis group did not show a survival advantage over the C. sinensis group. After IPTW adjustment, the median OS for the C. sinensis group was 9 months, compared to 29 months for the no C. sinensis group. C. sinensis group have worse OS than no C. sinensis group (p = 0.024), while it did not differ in RFS(p = 0.065). The multivariate Cox regression analysis showed that C. sinensis infection and lower age were associated with worse OS., Conclusions: The C. sinensis infection has an adverse impact on os in srHCC patients who underwent hepatectomy., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ni et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Many resting-state functional magnetic resonance imaging (rs-fMRI) studies have explored abnormal regional spontaneous brain activity in migraine. However, these results are inconsistent. To identify the consistent regions with abnormal neural activity, we meta-analyzed these studies. We gathered whole-brain rs-fMRI studies measuring differences in the amplitude of low-frequency fluctuations (ALFF), fractional ALFF (fALFF), or regional homogeneity (ReHo) methods. Then, we performed a voxel-wise meta-analysis to identify consistent abnormal neural activity in migraine by anisotropic effect size seed-based d mapping (AES-SDM). To confirm the AES-SDM meta-analysis results, we conducted two meta-analyses: activation likelihood estimation (ALE) and multi-level kernel density analysis (MKDA). We found that migraine showed increased regional neural activities in the bilateral postcentral gyrus (PoCG), left hippocampus (HIP.L), right pons, left superior frontal gyrus (SFG.L), triangular part of right inferior frontal gyrus (IFGtriang.R), right middle frontal gyrus (MFG.R), and left precentral gyrus (PreCG.L) and decreased regional intrinsic brain activities were exhibited in the right angular gyrus (ANG.R), left superior occipital gyrus (SOG.L), right lingual gyrus (LING.R). Moreover, the meta-analysis of ALE further validated the abnormal neural activities in the PoCG, right pons, ANG.R, and HIP. Meta-regression demonstrated that headache intensity was positively associated with the abnormal activities in the HIP.L, ANG.R, and LING.R. These findings suggest that migraine is associated with abnormal spontaneous brain activities of some pain-related regions, which may contribute to a deeper understanding of the neural mechanism of migraine., (© 2023 Wiley Periodicals LLC.)

Introduction: Default mode network (DMN) is the most involved network in the study of brain development and brain diseases. Resting-state functional connectivity (rsFC) is the most used method to study DMN, but different studies are inconsistent in the selection of seed. To evaluate the effect of different seed selection on rsFC, we conducted an image-based meta-analysis (IBMA)., Methods: We identified 59 coordinates of seed regions of interest (ROIs) within the default mode network (DMN) from 11 studies (retrieved from Web of Science and Pubmed) to calculate the functional connectivity; then, the uncorrected t maps were obtained from the statistical analyses. The IBMA was performed with the t maps., Results: We demonstrate that the overlap of meta-analytic maps across different seeds' ROIs within DMN is relatively low, which cautions us to be cautious with seeds' selection., Discussion: Future studies using the seed-based functional connectivity method should take the reproducibility of different seeds into account. The choice of seed may significantly affect the connectivity results., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Sun, Zhan, Antwi, Lv, Jia and Ren.)

The Slack channel (KCNT1, Slo2.2) is a sodium-activated and chloride-activated potassium channel that regulates heart rate and maintains the normal excitability of the nervous system. Despite intense interest in the sodium gating mechanism, a comprehensive investigation to identify the sodium-sensitive and chloride-sensitive sites has been missing. In the present study, we identified two potential sodium-binding sites in the C-terminal domain of the rat Slack channel by conducting electrophysical recordings and systematic mutagenesis of cytosolic acidic residues in the rat Slack channel C terminus. In particular, by taking advantage of the M335A mutant, which results in the opening of the Slack channel in the absence of cytosolic sodium, we found that among the 92 screened negatively charged amino acids, E373 mutants could completely remove sodium sensitivity of the Slack channel. In contrast, several other mutants showed dramatic decreases in sodium sensitivity but did not abolish it altogether. Furthermore, molecular dynamics (MD) simulations performed at the hundreds of nanoseconds timescale revealed one or two sodium ions at the E373 position or an acidic pocket composed of several negatively charged residues. Moreover, the MD simulations predicted possible chloride interaction sites. By screening predicted positively charged residues, we identified R379 as a chloride interaction site. Thus, we conclude that the E373 site and the D863/E865 pocket are two potential sodium-sensitive sites, while R379 is a chloride interaction site in the Slack channel. SIGNIFICANCE STATEMENT The research presented here identified two distinct sodium and one chloride interaction sites located in the intracellular C-terminal domain of the Slack (Slo2.2, KCNT1) channel. Identification of the sites responsible for the sodium and chloride activation of the Slack channel sets its gating property apart from other potassium channels in the BK channel family. This finding sets the stage for future functional and pharmacological studies of this channel., (Copyright © 2023 the authors.)

Post-ovulatory aging, a major problem faced by oocytes cultured in vitro, causes oxidative damage and mitochondrial dysfunction in oocytes. The ginsenoside Rh2 is one of the main monomeric components of ginseng, but its effects on porcine oocytes are unknown. In the present study, in vitro aging (IVA) and accelerated induction of aging using H 2 O 2 resulted in DNA damage and an increased incidence of abnormal spindle formation in porcine oocytes. Rh2 supplementation increased the antioxidant capacity, reduced the occurrence of early apoptosis, and improved the development of in vitro fertilized blastocysts. It also rescued the abnormal aggregation of mitochondria and the decrease of the mitochondrial membrane potential under mitochondrial dysfunction. Meanwhile, Rh2 enhanced mRNA expression of the anti-aging and mitochondrial biogenesis-related genes silent information regulator of transcription 1 (SIRT1) and peroxisome proliferator-activated receptor coactivator 1-α (PGC-1α), and the antioxidant gene superoxide dismutase 1 (SOD1). The protection of porcine oocytes against aging and oxidative stress by Rh2 was confirmed using the SIRT1-specific inhibitor EX-527. Our results reveal that Rh2 upregulates SIRT1/PGC-1α to enhance mitochondrial function in porcine oocytes and improve their quality. Our study indicates that Rh2 can be used to prevent mitochondrial dysfunction in oocytes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Acidic nitrogenous wastewater often requires alkali pretreatment before biological treatment, which results in increased system complexity and operating costs. The demonstration of denitrification under acidic conditions would provide a theoretical basis for the direct treatment of such wastewater. In this study, the denitrification performance, microbial community, and nitrous oxide (N 2 O) emissions under acidic conditions were investigated using a sequencing batch reactor. When the influent pH decreased from 5.5 to 4.5, the sequencing batch reactor removed 99.8 ± 0.2% of the nitrate and 92.5 ± 1.6% (n = 171) of the chemical oxygen demand, and the production efficiency of N 2 O increased significantly to 11.45%. This was 2.6-fold higher than that observed at pH 5.5. The long-term denitrification treatment of acidic wastewater (pH 4.5) led to the formation of granular sludge, and Thauera, Allorhizobium-Neorhizobium-Parararhizobium-Rhizobium, and Diaphorobacter became the dominant microbes with a collective abundance of 81.3%. More importantly, only 0.25% of the nitrate was denitrified as N 2 O, and the batch test revealed that the emissions of N 2 O decreased with the increase in sludge size. These results indicate that denitrifying granular sludge formed under acidic conditions and denitrifying bacteria capable of N 2 O reduction proliferated, which both resulted in a significant reduction in the release of N 2 O., (Copyright © 2022 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.)

Background: Mycoplasma pneumoniae (M. Pneumoniae ) is a common pathogen of respiratory tract infections, but there is still a lack of detailed investigation on the large sample of M. Pneumoniae infection in the all age population. And patients with severe M. Pneumoniae pneumonia (SMPP) still have a certain risk of death. How to identify the clinical characteristics and population of patients with SMPP as soon as possible is still an urgent problem in clinical practice., Methods: Demographic characteristics, patient clinical information, and laboratory data of 81,131 patients with respiratory tract infections (RTIs) in the Affiliated Suzhou Hospital of Nanjing Medical University from 2014 to 2020 were retrospectively collected from all patient records. The serum particle agglutination (PA) test was used to determine M. Pneumoniae infection by detecting specific antibodies. The white blood cell count, the proportion of neutrophils and lymphocytes, C-reactive protein (CRP) and lactate dehydrogenase (LDH) levels between children and adults with SMPP were compared by Student's t -test; other clinical features were analyzed by χ 2 test or Fisher's exact test., Results: A total of 81,131 patients with RTIs were included, and 21,582 (26.60%) M. Pneumoniae immunoglobulin M (IgM)-positive patients were detected. From 2014 to 2020, the annual proportions of M. Pneumoniae RTIs were 23.60%, 28.18%, 38.08%, 27.05%, 23.44%, 25.26%, and 18.33%, respectively. In terms of seasonal distribution, April-June and September-November were the peak seasons of M. Pneumoniae infection each year. Children and women have a high proportion of M. Pneumoniae infection. The peak age of M. Pneumoniae infection was between 4 and 14 years old. There were 301 cases of SMPP, including 281 children and 20 adults (8 cases of pregnant women). Children and pregnant women accounted for a high proportion of SMPP. Children with SMPP had more extrapulmonary symptoms, multilobar infiltrates, and increased CRP and LDH levels compared with adults., Conclusions: M. Pneumoniae infection has seasonal, sex, and age distribution trends. Children and pregnant women accounted for a high proportion of SMPP. Extrapulmonary symptoms, multilobar infiltrates, and increased CRP and LDH levels may be helpful to identify SMPP in children than in adults., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-4304/coif). The authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Aim: This study aimed to investigate the key points in the transformation of the functions of the Drug and Therapeutics Committee (DTC) of the Shandong Provincial Third Hospital and how to provide full authority to its role in the control of rational drug use, especially in the management of antibiotic use. Method: A prescription review management group, antimicrobial stewardship group, and rational drug use service group were established under the DTC. From January 2016 to December 2021, each group played a role in promoting rational drug use and antimicrobial stewardship. In addition, we performed statistics on typical management cases, irrational drug use, bacterial resistance rate, and drug costs from 2015 to 2021 to evaluate the effect of management by the DTC. Results: Intervention by the DTC led to a significant reduction in prescribing errors (71.43%, p < 0.05), the intervention acceptance rate increased by 16.03%, and the problem solved rate increased by 32.41% ( p < 0.05). Resistance rates of general spectrum antibiotics were reduced remarkably after the intervention. The quality of drug treatment was improved and patient drug expenses was continuously reduced. Conclusion: Giving full play to the functions of the DTC can significantly improve the level of drug treatment and reduce unreasonable drug use to save unnecessary drug expenses and slow the development of drug resistance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yang, Zheng, Guan and Lv.)

What Is Known and Objective: This study aimed to explore methods to optimize the function of Drug and Therapeutics Committees (DTCs) in controlling irrational drug use. Clinical pharmacologists contribute their specific knowledge and skills to DTCs and help guide rational therapeutics. The DTC is the highest organization of hospital pharmacy management., Methods: From January 2016 to August 2021, the DTC promoted the optimization of clinical drug treatment schemes and reduced unreasonable drug use by improving the organizational framework, clarifying the division of functions, regularly monitoring drug use, organizing expert comments, scientific decision-making and functional intervention. During this time, we statistically analysed typical management cases, irrational drug use and drug cost to evaluate the effectiveness of the DTC's management., Results and Discussion: The DTC's intervention led to a significant reduction in prescribing errors (65.98%, p < 0.05); the intervention acceptance rate increased by 16.37%; and the rate of problem resolution increased by 45.84% (p < 0.05). The level of drug treatment was improved, and the proportion of patients' drug expenses was reduced., What Is New and Conclusion: The DTC carried out a series of continuous improvement work that played a significant normative role in clinical drug use. Giving more power to the DTCs can significantly improve the level of drug treatment and reduce unreasonable drug use, which reduces unnecessary drug expenses., (© 2022 John Wiley & Sons Ltd.)

Diabetes mellitus (DM), a high incidence metabolic disease, is related to the impairment of male spermatogenic function. Spermidine (SPM), one of the biogenic amines, was identified from human seminal plasma and believed to have multiple pharmacological functions. However, there exists little evidence that reported SPM's effects on moderating diabetic male spermatogenic function. Thus, the objective of this study was to investigate the SPM's protective effects on testicular spermatogenic function in streptozotocin (STZ)-induced type 1 diabetic mice. Therefore, 40 mature male C57BL/6 J mice were divided into four main groups: the control group (n = 10), the diabetic group (n = 10), the 2.5 mg/kg SPM-treated diabetic group (n = 10) and the 5 mg/kg SPM-treated diabetic group (n = 10), which was given intraperitoneally for 8 weeks. The type 1 diabetic mice model was established by a single intraperitoneal injection of STZ 120 mg/kg. The results showed that, compare to the control group, the body and testis weight, as well the number of sperm were decreased, while the rate of sperm malformation was significantly increased in STZ-induced diabetic mice. Then the testicular morphology was observed, which showed that seminiferous tubule of testis were arranged in mess, the area and diameter of which was decreased, along with downregulated anti-apoptotic factor (Bcl-2) expression, and upregulated pro-apoptotic factor (Bax) expression in the testes. Furthermore, testicular genetic expression levels of Sertoli cells (SCs) markers (WT1, GATA4 and Vimentin) detected that the pathological changes aggravated observably, such as the severity of tubule degeneration increased. Compared to the saline-treated DM mice, SPM treatment markedly improved testicular function, with an increment in the body and testis weight as well as sperm count. Pro-apoptotic factor (Bax) was down-regulated expression with the up-regulated expression of Bcl-2 and suppression of apoptosis in the testes. What's more, expression of WT1, GATA4, Vimentin and the expressions of glycolytic rate-limiting enzyme genes (HK2, PKM2, LDHA) in diabetic testes were also upregulated by SPM supplement. The evidence derived from this study indicated that the SMP's positive effect on moderating spermatogenic disorder in T1DM mice's testis. This positive effect is delivered via promoting spermatogenic cell proliferation and participating in the glycolytic pathway's activation., (© 2022. The Author(s).)

Obesity is an important public-health problem worldwide. This study aimed to determine effects of porphyromonas gingivalis lipopolysaccharide (Pg-LPS) on adipocytes injuries and explore associated mechanisms. Adipocytes were isolated from SD rats. pLVX-XBP1 (XBP1 over-expression) and pLVX-XBP1-RNAi (silencing XBP1) were structured and transfected into adipocytes. All adipocytes were divided into pLVX-NC, pLVX-XBP1, pLVX-NC+Pg-LPS and pLVX-XBP1+ Pg-LPS group. Oil-Red O staining was employed to identify isolated adipocytes. Quantitative real-time PCR (qRT-PCR) was used to examine gene transcription of IL-6, TNF-α, leptin, adiponectin. Western blotting was used to detect Bax and caspase-3 expression. Adipocytes were successfully isolated and identified with Oil-Red O staining. Both XBP1 mimic and XBP1 RNAi were effectively transfected into adipocytes with higher expressing efficacy. XBP1 over-expression significantly aggravated Pg-LPS induced inflammatory response compared to adipocytes without Pg-LPS treatment (p<0.05). Pg-LPS significantly enhanced leptin and inhibited adiponectin expression by up-regulating XBP1 expression (p<0.05). XBP1 silence significantly alleviated Pg-LPS induced inflammatory response and reduced leptin, enhanced adiponectin expression in Pg-LPS treated adipocytes compared to adipocytes without Pg-LPS treatment (p<0.05). Pg-LPS induced apoptosis of adipocytes by enhancing XBP1 expression and modulating Bcl-2/Bax pathway associated molecules. In conclusion, Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) induces adipocytes injuries through modulating XBP1 expression and initialling mitochondria-mediated apoptosis.

Increasing evidence has shown that the resting state brain connectivity of default mode network (DMN) which are important for social cognition are disrupted in autism spectrum disorder (ASD). However, previous neuroimaging studies did not present consistent results. Therefore, we performed a meta-analysis of resting-state functional connectivity (rsFC) studies of DMN in the individuals with ASD and healthy controls (HCs) to provide a new perspective for investigating the pathophysiology of ASD. We carried out a search using the terms: ("ASD" OR "Autism") AND ("resting state" OR "rest") AND ("DMN" OR "default mode network") in PubMed, Web of Science and Embase to identify the researches published before January 2020. Ten resting state datasets including 203 patients and 208 HCs were included. Anisotropic Effect Size version of Signed Differential Mapping (AES-SDM) method was applied to identify group differences. In comparison with the HCs, the patients with ASD showed increased connectivity in cerebellum, right middle temporal gyrus, superior occipital gyrus, right supramarginal gyrus, supplementary motor area and putamen. Decreased connectivity was discovered in some nodes of DMN, such as medial prefrontal cortex, precuneus and angular gyrus. These results may help us to further clarify the neurobiological mechanisms in patients with ASD., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

Local activity metrics of resting-state functional MRI (RS-fMRI), such as the amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), regional homogeneity (ReHo), and degree centrality (DC), are widely used to detect brain abnormalities based on signal fluctuations. Although signal changes with echo time (TE) have been widely studied, the effect of TE on local activity metrics has not been investigated. RS-fMRI datasets from 12 healthy subjects with eyes open (EO) and eyes closed (EC) were obtained with a four-echo gradient-echo-planar imaging pulse sequence with the following parameters: repetition time/TE1/TE2/TE3/TE4 = 2,000/13/30.93/48.86/66.79 ms. Six representative regions were selected for simulating the spatial feature of TE dependency of local activity metrics. Moreover, whole-brain local activity metrics were calculated from each echo dataset and compared between EO and EC conditions. Dice overlap coefficient (DOC) was then employed to calculate the overlap between the T maps. We found that all the local activity metrics displayed different TE dependency characteristics, while their overall change patterns were similar: an initial large change followed by a slow variation. The T maps for local activity metrics also varied greatly with TE. For ALFF, fALFF, ReHo, and DC, the DOCs for voxels in four TE datasets were 6.87, 0.73, 5.08, and 0.93%, respectively. Collectively, these findings demonstrate that local metrics are greatly dependent on TE. Therefore, TE should be carefully considered for the optimization of data acquisition and multi-center data analysis in RS-fMRI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yuan, Zhao, Wang, Lv and He.)

The amplitude of low-frequency fluctuation (ALFF) measures resting-state functional magnetic resonance imaging (RS-fMRI) signal of each voxel. However, the unit of blood oxygenation level-dependent (BOLD) signal is arbitrary and hence ALFF is sensitive to the scale of raw signal. A well-accepted standardization procedure is to divide each voxel's ALFF by the global mean ALFF, named mALFF. Although fractional ALFF (fALFF), a ratio of the ALFF to the total amplitude within the full frequency band, offers possible solution of the standardization, it actually mixes with the fluctuation power within the full frequency band and thus cannot reveal the true amplitude characteristics of a given frequency band. The current study borrowed the percent signal change in task fMRI studies and proposed percent amplitude of fluctuation (PerAF) for RS-fMRI. We firstly applied PerAF and mPerAF (i.e., divided by global mean PerAF) to eyes open (EO) vs. eyes closed (EC) RS-fMRI data. PerAF and mPerAF yielded prominently difference between EO and EC, being well consistent with previous studies. We secondly performed test-retest reliability analysis and found that (PerAF ≈ mPerAF ≈ mALFF) > (fALFF ≈ mfALFF). Head motion regression (Friston-24) increased the reliability of PerAF, but decreased all other metrics (e.g. mPerAF, mALFF, fALFF, and mfALFF). The above results suggest that mPerAF is a valid, more reliable, more straightforward, and hence a promising metric for voxel-level RS-fMRI studies. Future study could use both PerAF and mPerAF metrics. For prompting future application of PerAF, we implemented PerAF in a new version of REST package named RESTplus., Competing Interests: NO authors have competing interests.

The cardiac mechanosensitive BK (Slo1) channels are gated by Ca 2+ , voltage, and membrane stretch. The neuropeptide GsMTx4 is a selective inhibitor of mechanosensitive (MS) channels. It has been reported to suppress stretch-induced cardiac fibrillation in the heart, but the mechanism underlying the specificity and even the targeting channel(s) in the heart remain elusive. Here, we report that GsMTx4 inhibits a stretch-activated BK channel (SAKcaC) in the heart through a modulation specific to mechano-gating. We show that membrane stretching increases while GsMTx4 decreases the open probability ( P o ) of SAKcaC. These effects were mostly abolished by the deletion of the STREX axis-regulated (STREX) exon located between RCK1 and RCK2 domains in BK channels. Single-channel kinetics analysis revealed that membrane stretch activates SAKcaC by prolonging the open-time duration (τ O ) and shortening the closed-time constant (τ C ). In contrast, GsMTx4 reversed the effects of membrane stretch, suggesting that GsMTx4 inhibits SAKcaC activity by interfering with mechano-gating of the channel. Moreover, GsMTx4 exerted stronger efficacy on SAKcaC under membrane-hyperpolarized/resting conditions. Molecular dynamics simulation study revealed that GsMTx4 appeared to have the ability to penetrate deeply within the bilayer, thus generating strong membrane deformation under the hyperpolarizing/resting conditions. Immunostaining results indicate that BK variants containing STREX are also expressed in mouse ventricular cardiomyocytes. Our results provide common mechanisms of peptide actions on MS channels and may give clues to therapeutic suppression of cardiac arrhythmias caused by excitatory currents through MS channels under hyper-mechanical stress in the heart., (© 2019 Li et al.)

General anesthesia is an unconscious state induced by anesthetics for surgery. The molecular targets and cellular mechanisms of general anesthetics in the mammalian nervous system have been investigated during past decades. In recent years, K + channels have been identified as important targets of both volatile and intravenous anesthetics. This review covers achievements that have been made both on the regulatory effect of general anesthetics on the activity of K + channels and their underlying mechanisms. Advances in research on the modulation of K + channels by general anesthetics are summarized and categorized according to four large K + channel families based on their amino-acid sequence homology. In addition, research achievements on the roles of K + channels in general anesthesia in vivo, especially with regard to studies using mice with K + channel knockout, are particularly emphasized.

Hepatic transcatheter arterial chemoembolization (TACE), a minimally invasive procedure to block the blood supply of tumors and release of cytotoxic agents, is preferentially applied to patients with hepatocellular carcinoma (HCC) who are not able to receive radical treatments. However, the long-term effects of TACE are unsatisfactory, as the microenvironment following procedure stimulates tumor angiogenesis, which promotes recurrence and metastasis of residual tumors. Tumor associated macrophages (TAMs) have been revealed to stimulate tumor growth and angiogenesis associated with poor prognosis in HCC. The present study focused on the changes in TAMs following TACE, and explored the effects of TACE in combination with the TAM inhibitor zoledronic acid (ZA) in rat HCC models. Orthotropic HCC rats were divided into three groups: Sham TACE, TACE alone and TACE combined with ZA treatment. At 7 or 14 days following TACE, tumor growth was evaluated by magnetic resonance imaging (MRI). Infiltration of TAMs was assessed by histological analysis and flow cytometry. Tumor angiogenesis was measured as the mean vessel density, and initial slope was calculated from dynamic contrast enhancement MRI. Local and systemic levels of vascular endothelial growth factor (VEGF) were determined by western blotting or an ELISA, respectively. The results revealed that TACE inhibited tumor growth at 7 days following the procedure, but this inhibition was attenuated at 14 days following the procedure compared with the sham TACE control. If combined with ZA treatment, TACE exhibited a stable inhibition effect on tumor growth until the end of observation. Investigation of the underlying mechanisms demonstrated that TACE combined with ZA treatment inhibited infiltration of F4/80 positive TAMs and tumor angiogenesis compared with the TACE alone group at 14 days following the procedure. Additionally, the combination treatment significantly inhibited secretion of VEGF in the present models. In conclusion, ZA treatment enhanced the effects of TACE through inhibiting TAM infiltration and tumor angiogenesis in rat HCC models.

The three-dimensional quantitative structure-activity relationships (3D-QSAR) were established for 30 oxindole derivatives as vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase inhibitors by using comparative molecular field analysis (CoMFA) and comparative similarity indices analysis comparative molecular similarity indices analysis (CoMSIA) techniques. With the CoMFA model, the cross-validated value (q(2)) was 0.777, the non-cross-validated value (R(2)) was 0.987, and the external cross-validated value ([Formula: see text]) was 0.72. And with the CoMSIA model, the corresponding q(2), R(2) and [Formula: see text] values were 0.710, 0.988 and 0.78, respectively. Docking studies were employed to bind the inhibitors into the active site to determine the probable binding conformation. The binding mode obtained by molecular docking was in good agreement with the 3D-QSAR results. Based on the QSAR models and the docking binding mode, a set of new VEGFR-2 tyrosine kinase inhibitors were designed, which showed excellent predicting inhibiting potencies. The result revealed that both QSAR models have good predictive capability to guide the design and structural modification of homologic compounds. It is also helpful for further research and development of new VEGFR-2 tyrosine kinase inhibitors.

Objectives: After development and differentiation, megakaryocytes (MKs) can produce platelets. As is well known, thrombopoietin (TPO) can induce MKs to differentiate. The effect of thrombin on MKs differentiation is not clear. In this study, we used a human megakaryoblastic leukemia cell line (Meg-01) to assess the effect of thrombin on MKs differentiation., Methods: In order to interrogate the role of thrombin in Meg-01 cells differentiation, the changes of morphology, cellular function, and expression of diverse factors were analyzed., Results: The results show that thrombin suppresses Meg-01 cells proliferation and induces apoptosis and cell cycle arrest. Thrombin upregulates the expression of CD41b, which is one of the most important MK markers. Globin transcription factor 1 (GATA-1), an important transcriptional regulator, controls MK development and maturation. The expression of GATA-1 is also upregulated by thrombin in Meg-01 cells. The expression of B-cell lymphoma 2 (Bcl-2), an apoptosis-inhibitory protein, is downregulated by thrombin. Phosphorylated protein kinase B (p-AKT) and phosphorylated extracellular signal-regulated kinase (p-ERK) were upregulated by thrombin in Meg-01 cells. All the results are consistent with Meg-01 cells treated with TPO., Discussion and Conclusion: In conclusion, all these data indicate that thrombin maybe plays an important role in MK differentiation into platelets. However, whether the platelet-like particles are certainly platelets remains unknown.

Neovibsanins are believed to be promising candidates for the development of novel therapeutic agents to treat neurological diseases like Alzheimer's disease. It has been shown that chronic cerebral hypoperfusion is linked to neurodegenerative disorders and their subsequent cognitive impairment. In the present study effect of neovibsanin B (NVB) on spatial cognitive functions of rats with lobal cerebrovascular hypoperfusion was investigated. The cerebrovascular hypoperfusion rat model was prepared by bilateral common carotid arteries occlusion (2VO). Morris water maze (MWM) test was employed to examine the effect of NVB on spatial cognitive function before and after 2VO intervention. The animals were divided into two groups; long-term memory (LTM) and short-term memory (STM) groups. Each of the groups was subdivided into 3 subgroups: control, untreated and NVB treated groups. After ten weeks of the surgery, all the subgroups were tested with MWM. The results of working memory test for both control and NVB treated groups revealed that escape latency time and total distance travelled were significantly lower compared to untreated group. Similarly, the maze test performance was observed to be significantly improved for control and NVB treated groups. Moreover, the probe memory test performance for control and NVB treated groups was markedly better than untreated group. Thus NVB has a significant effect on the spatial cognitive preservation in rats with chronic cerebral hypoperfusion. Thus NVB can be a promising agent for the spatial cognitive functions improvement.

Vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase has two conformations, active and inactive conformations. Type II inhibitors bind to inactive conformation. It has two possible binding/unbinding paths. To explore the unbinding path of inhibitor 01-435 that was generated by fragment build in the binding pocket of VEGFR-2, molecular dynamics (MD) simulation was performed on the crystal structure of VEGFR-2 in complex with 01-435, then steered molecular dynamics (SMD) simulation was executed on the crystal structure of VEGFR-2 in complex with 01-435. Pull force, van der Waals and electrostatic interaction along the two paths were calculated by using SMD simulation. The SMD simulation results indicate that the more favorable path for inhibitor dissociation is along with the traditional ATP-channel rather than the allosteric-pocket-channel, which is mainly due to the less electrostatic interaction that the ligand suffers during dissociation process along the traditional ATP-channel., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Malignant melanoma is a melanocytic tumor with a high potential of invasion and metastasis. Curcumin is extracted from Curcuma longa L.; curcumin has anti-tumor efficacy in multiple systemic malignancies. Here, we investigated the effect of curcumin on A375 human melanoma cells. A375 cells were cultivated, passaged, and treated with different concentrations of curcumin. We observed the cellular morphology and determined the migration, invasion, proliferation, and apoptosis of A375 cells in vitro. Our results showed that curcumin induced a significant change in the morphology of A375 cells. Compared to the control group, the groups treated with curcumin showed significantly wider scratches, and the number of A375 cells significantly decreased in the 12.5, 25, and 50 mM curcumin groups (P < 0.05 or < 0.01). The rates of proliferation inhibition in the 5 curcumin groups were 19.38 ± 3.57%, 35.56 ± 4.37%, 63.98 ± 5.95%, 86.38 ± 3.91%, and 95.56 ± 3.15%. The half-maximal inhibitory concentration of curcumin at 48 h was 10.05 mM. The rates of apoptosis in 6.25 and 12.5 mM curcumin groups were significantly higher (P < 0.05), phosphorylation levels of JAK-2 and STAT-3 in 10 and 20 mM curcumin groups were significantly lower (P < 0.05), and Bcl-2 protein expression in 1, 2.5, 5, 10, and 20 curcumin groups was significantly lower (P < 0.05) than that in the control group. In conclusion, curcumin has antiproliferative and proapoptotic activities on A375 cells, the mechanism of which may be related to the inhibition of JAK-2/STAT-3 signaling pathway.

Purpose: To clarify the association between clinically defined simple stress urinary incontinence (SUI) symptoms and urodynamic SUI, we examined the relationship between Valsalva leak point pressure (VLPP) as measured by the Q-tip test and Stamey grade in simple female SUI., Methods: Two hundred grade I or II female SUI patients with SUI symptom were examined by reviewing medical history; physical examination; urethral mobility as assessed by Q-tip test; stress test; and cystometry, including VLPP measurement. On the basis of the VLPP, patients were classified into urethral hypermobility [UH, subdivided into anatomical incontinence (AI) and equivocal incontinence (EI)] or intrinsic sphincter deficiency groups for analysis of the relationship between VLPP and Stamey grade and Q-tip angle., Results: Seventy-eight patients were included, and the mean patient age was 54 ± 7.5 years, mean SUI symptom duration 2.8 years (range 0.5-6 years), mean VLPP 103.6 ± 18.4 cm H2O, and mean Q-tip angle 28.6° ± 7.2°. Fifty-three patients were categorized as Stamey grade I, 25 as Stamey grade II, 51 as AI, and 27 as EI. VLPP was found to be negatively correlated with Q-tip angle (Rs = -0.798, Y = -0.313X + 60.95, P < 0.001), and classifications of VLPP and Stamey grade have positive correlation (χ (2) = 4.9130, P = 0.0267)., Conclusions: In simple female SUI, VLPP is associated with the Q-tip angle and Stamey grade, which may help to reduce some of urodynamic items.

Unlike the mammalian fetus, development of the avian embryo is independent of the maternal uterus and is potentially vulnerable to physiological and environmental stresses close to hatch. In contrast to the fetus of late gestation in mammals, skeletal muscle in avian embryos during final incubation shows differential developmental characteristics: 1) muscle mobilization (also called atrophy) is selectively enhanced in the type II fibers (pectoral muscle) but not in the type I fibers (biceps femoris and semimembranosus muscle), involving activation of ubiquitin-mediated protein degradation and suppression of S6K1-mediated protein translation; 2) the proliferative activity of satellite cells is decreased in the atrophied muscle of late-term embryos but enhanced at the day of hatch, probably preparing for the postnatal growth. The mobilization of muscle may represent an adaptive response of avian embryos to external (environmental) or internal (physiological) changes, considering there are developmental transitions both in hormones and requirements for glycolytic substrates from middle-term to late-term incubation. Although the exact mechanism triggering muscle fiber atrophy is still unknown, nutritional and endocrine changes may be of importance. The atrophied muscle fiber recovers as soon as feed and water are available to the hatchling. In ovo feeding of late-term embryos has been applied to improve the nutritional status and therein enhances muscle development. Similarly, in ovo exposure to higher temperature or green light during the critical period of muscle development are also demonstrated to be potential strategies to promote pre- and posthatch muscle growth.

Background: Autism is a pervasive neurodevelopmental disorder. At present there are no defined mechanisms of pathogenesis and therapy is mostly limited to behavioral interventions. Stem cell transplantation may offer a unique treatment strategy for autism due to immune and neural dysregulation observed in this disease. This non-randomized, open-label, single center phase I/II trial investigated the safety and efficacy of combined transplantation of human cord blood mononuclear cells (CBMNCs) and umbilical cord-derived mesenchymal stem cells (UCMSCs) in treating children with autism., Methods: 37 subjects diagnosed with autism were enrolled into this study and divided into three groups: CBMNC group (14 subjects, received CBMNC transplantation and rehabilitation therapy), Combination group (9 subjects, received both CBMNC and UCMSC transplantation and rehabilitation therapy), and Control group (14 subjects, received only rehabilitation therapy). Transplantations included four stem cell infusions through intravenous and intrathecal injections once a week. Treatment safety was evaluated with laboratory examinations and clinical assessment of adverse effects. The Childhood Autism Rating Scale (CARS), Clinical Global Impression (CGI) scale and Aberrant Behavior Checklist (ABC) were adopted to assess the therapeutic efficacy at baseline (pre-treatment) and following treatment., Results: There were no significant safety issues related to the treatment and no observed severe adverse effects. Statistically significant differences were shown on CARS, ABC scores and CGI evaluation in the two treatment groups compared to the control at 24 weeks post-treatment (p < 0.05)., Conclusions: Transplantation of CBMNCs demonstrated efficacy compared to the control group; however, the combination of CBMNCs and UCMSCs showed larger therapeutic effects than the CBMNC transplantation alone. There were no safety issues noted during infusion and the whole monitoring period., Trial Registration: ClinicalTrials.gov: NCT01343511, Title "Safety and Efficacy of Stem Cell Therapy in Patients with Autism".

Thymidylate synthase (TS) catalyzes the transfer of a methyl group from methylenetetrahydrofolate to dUMP to form dTMP. It is a primary target in the chemotherapy of colorectal cancers and some other neoplasms. In order to obtain pure protein for analysis of structure and biological function, an expression vector TS-pET28b (+) was constructed by inserting wild-type human thymidylate synthase (hTS) cDNA into pET28b (+). Then an expression strain was selected after transformation of the recombined plasmid into Rosetta (DE3). Fusion protein with His-tag was efficiently expressed in the form of inclusion bodies after IPTG induction and the content was approximately 40.0% of total bacteria proteins after optimizing expression conditions. When inclusion bodies were washed, dissolved and purified by Ni-NTA under denatured conditions, the purity was up to 90%. On SDS-PAGE and West-blotting, the protein band was found to match well with the predicted relative molecular mass-36kDa. Bioactivity was 0.1 U/mg. The results indicated that high-level expression of wild-type hTS cDNA can be achieved in prokaryotes with our novel method, facilitating research into related chemotherapy.

DCs infiltrated tumors appears to be phenotypically and functionally defective. B7-H4 was highlighted for its inhibitory role in T cell responses. In this study, we showed that B7-H4 was moderately expressed in imDCs, and up-regulated by IL-10, and TNF-α could counteract the up-regulatory effects of IL-10 on expression of B7-H4 in DCs in vitro. Furthermore, tumor infiltrated DCs expressed B7-H4 at high levels. Blockade of B7-H4 expressed in DCs highly resulted in enhanced T cell proliferation and IFN-γ production significantly. Otherwise, the high level of IL-10 and TNF-α was both detected in the tumor, which suggested that TNF-α can not antagonize the effects of IL-10 on expression of B7-H4 in DCs in vivo. These data indicate that tumor environment may condition local DCs to become dysfunctional in the phenotype, and that the high expression of B7-H4 may contribute to the tumor infiltrated DCs to mediate immune invasion.

The current study combined structural magnetic resonance imaging (sMRI) and diffusion tensor MRI (DT-MRI) to investigate both gray matter density (GMD) and white matter integrity (WMI) in 18 pianists and 21 age-matched non-musicians. The pianists began their piano training at a mean age of 12. Voxel-based morphometry of the sMRI data showed that the pianists had higher GMD in the left primary sensorimotor cortex and right cerebellum. Voxel-based analysis of the DT-MRI data showed that pianists had higher fractional anisotropy (FA) (indicating higher WMI) in the right posterior limb of the internal capsule. The sMRI and DT-MRI results indicate that both the GMD and WMI of pianists may exhibit movement-related increases during adolescence or even early adulthood compared with non-musicians.

Resting-state functional MRI and structural MRI were used to study correlations of spontaneous activity and gray matter density between the left and right primary sensorimotor areas in pianists and nonmusicians. Functional MRI analysis showed significant correlation of spontaneous activity between the left and right primary sensorimotor area in both groups; however, there was no between-group difference. Structural MRI analysis showed significant correlation in gray matter density between the left and right sensorimotor areas in nonmusicians (r=0.65, P=0.001), but not in pianists (r=0.07, P=0.78), with a significant between-group difference (P=0.035). The lack of correlation of gray matter density between the left and right sensorimotor areas might be the basis of bimanual coordination of the pianists.