Allele-selective lowering of mutant HTT protein by HTT-LC3 linker compounds.

Accumulation of mutant proteins is a major cause of many diseases (collectively called proteopathies), and lowering the level of these proteins can be useful for treatment of these diseases. We hypothesized that compounds that interact with both the autophagosome protein microtubule-associated protein 1A/1B light chain 3 (LC3)1 and the disease-causing protein may target the latter for autophagic clearance. Mutant huntingtin protein (mHTT) contains an expanded polyglutamine (polyQ) tract and causes Huntington's disease, an incurable neurodegenerative disorder2. Here, using small-molecule-microarray-based screening, we identified four compounds that interact with both LC3 and mHTT, but not with the wild-type HTT protein. Some of these compounds targeted mHTT to autophagosomes, reduced mHTT levels in an allele-selective manner, and rescued disease-relevant phenotypes in cells and in vivo in fly and mouse models of Huntington's disease. We further show that these compounds interact with the expanded polyQ stretch and could lower the level of mutant ataxin-3 (ATXN3), another disease-causing protein with an expanded polyQ tract3. This study presents candidate compounds for lowering mHTT and potentially other disease-causing proteins with polyQ expansions, demonstrating the concept of lowering levels of disease-causing proteins using autophagosome-tethering compounds.

Suppression of toxicity of the mutant huntingtin protein by its interacting compound, desonide.

Identifying inhibitors of pathogenic proteins is the major strategy of targeted drug discoveries. This strategy meets challenges in targeting neurodegenerative disorders such as Huntington's disease (HD), which is mainly caused by the mutant huntingtin protein (mHTT), an "undruggable" pathogenic protein with unknown functions. We hypothesized that some of the chemical binders of mHTT may change its conformation and/or stability to suppress its downstream toxicity, functioning similarly to an "inhibitor" under a broader definition. We identified 21 potential mHTT selective binders through a small-molecule microarray­based screening. We further tested these compounds using secondary phenotypic screens for their effects on mHTT-induced toxicity and revealed four potential mHTT-binding compounds that may rescue HD-relevant phenotypes. Among them, a Food and Drug Administration­approved drug, desonide, was capable of suppressing mHTT toxicity in HD cellular and animal models by destabilizing mHTT through enhancing its polyubiquitination at the K6 site. Our study reveals the therapeutic potential of desonide for HD treatment and provides the proof of principle for a drug discovery pipeline: target-binder screens followed by phenotypic validation and mechanistic studies.

(3+1)-dimensional Pearcey-Gaussian wave packet with arbitrary velocity driven by flying focus.

The group velocity (GV) modulation of space-time wave packets (STWPs) along the transverse and longitudinal directions in free space is constrained by various factors. To surmount this limitation, a technique called "flying focus" has been developed, which enables the generation of laser pulses with dynamic focal points that can propagate at arbitrary velocities independent of GV. In this Letter, we propose a (3+1)-dimensional Pearcey-Gauss wave packet based on the "flying focus" technique, which exhibits superluminal propagation, transverse focus oscillation, and longitudinal periodic autofocusing. By selecting appropriate parameters, we can flexibly manipulate the position, the size, and the number of focal points- or make the wave packet follow a desired trajectory. This work may pave the way for the advancement of space-time structured light fields.

Automatic measurement of the patellofemoral joint parameters in the Laurin view: a deep learning-based approach.

OBJECTIVES: To explore the performance of a deep learning-based algorithm for automatic patellofemoral joint (PFJ) parameter measurements from the Laurin view. METHODS: A total of 1431 consecutive Laurin views of the PFJ were retrospectively collected and divided into two parts: (1) the model development dataset (dataset 1, n = 1230) and (2) the hold-out test set (dataset 2, n = 201). Dataset 1 was used to develop the U-shaped fully convolutional network (U-Net) model to segment the landmarks of the PFJ. Based on the predicted landmarks, the PFJ parameters were calculated, including the sulcus angle (SA), congruence angle (CA), patellofemoral ratio (PFR), and lateral patellar tilt (LPT). Dataset 2 was used to assess the model performance. The mean of three radiologists who independently measured the PFJ parameters was defined as the reference standard. Model performance was assessed by the intraclass correlation coefficient (ICC), mean absolute difference (MAD), and root mean square (RMS) compared to the reference standard. Ninety-five percent limits of agreement (95% LoA) were calculated pairwise for each radiologist, reference standard, and model. RESULTS: Compared with the reference standard, U-Net showed good performance for predicting SA, CA, PFR, and LPT, with ICC = 0.85-0.97, MAD = 0.06-5.09, and RMS = 0.09-6.90 in the hold-out test set. Except for the PFR, the remaining parameters measured between the reference standard and the model were within the 95% LoA in the hold-out test dataset. CONCLUSIONS: The U-Net-based deep learning approach had a relatively high model performance in automatically measuring SA, CA, PFR, and LPT. KEY POINTS: • The U-Net model could be used to segment the landmarks of the PFJ and calculate the SA, CA, PFR, and LPT, which could be used to evaluate the patellar instability. • In the hold-out test, the automatic measurement model yielded comparable performance with reference standard. • The automatic measurement model could still accurately predict SA, CA, PFR, and LPT in patients with PI and/or PFOA.

Automatic diagnosis and grading of patellofemoral osteoarthritis from the axial radiographic view: a deep learning-based approach.

BACKGROUND: Patellofemoral osteoarthritis (PFOA) has a high prevalence and is assessed on axial radiography of the patellofemoral joint (PFJ). A deep learning (DL)-based approach could help radiologists automatically diagnose and grade PFOA via interpreting axial radiographs. PURPOSE: To develop and assess the performance of a DL-based approach for diagnosing and grading PFOA on axial radiographs. MATERIAL AND METHODS: A total of 1280 (dataset 1) axial radiographs were retrospectively collected and utilized to develop the high-resolution network (HRNet)-based classification models. The ground truth was the interpretation from two experienced radiologists in consensus according to the K-L grading system. A binary-class model was trained to diagnose the presence (K-L 2∼4) or absence (K-L 0∼1) of PFOA. A multi-class model was used to grade the stage of PFOA, i.e. from K-L 0 to K-L 4. Model performances were evaluated using the receiver operating characteristics (ROC), confusion matrix, and the corresponding evaluation metrics (positive predictive value [PPV], negative predictive value [NPV], F1 score, sensitivity, specificity, accuracy) of the internal test set (n = 129) from dataset 1 and an external validation set (dataset 2, n = 187). RESULTS: For the binary-class model, the area under the curve (AUC) was 0.91 in the internal test set and 0.90 in the external validation set. For grading PFOA, moderate to severe stage of PFOA exhibited a good performance in these two datasets (AUC = 0.91-0.98, PPV = 0.69-0.90, NPV = 0.92-0.99, F1 score = 0.72-0.87, sensitivity = 0.75-0.87, specificity = 0.90-0.99, accuracy = 0.87-0.98). CONCLUSION: The HRNet-based approach performed well in diagnosing and grading radiographic PFOA, especially for the moderate to severe cases.

Analysis of Correlation Between Serum Hypoxia-Inducible Factor-1α, Uric Acid, and Inflammatory Factor Levels and Lung Function in Patients with AECOPD.

Objective: To investigate the correlation between the serum hypoxia-inducible factor-1α, uric acid, inflammatory factor levels, and lung function in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods: The clinical data of patients with chronic obstructive pulmonary disease (40 cases) from March 2020 to March 2021 were retrospectively analyzed. According to the disease condition in patients with chronic obstructive pulmonary disease, they were divided into acute exacerbation stage (observation group, 20 cases) and stable stage (control group, 20 cases). All patients' basic data such as age, sex, and course of disease were collected and sorted out, and the serum hypoxia-inducible factor-1α, uric acid, inflammatory factor levels (procalcitonin, interleukin-6, and high-sensitivity C-reactive protein), and the index of their pulmonary function were measured. The profiles of serum hypoxia-inducible factor-1 alpha and uric acid, levels of inflammatory factors, and pulmonary function indices were measured and compared between the observation and control groups. The correlation between patients' serum hypoxia-inducible factor-1α, uric acid, and inflammatory factors and lung function was analyzed. Results: There was no difference in basic data between the observation group and the control group, P > .05. Serum hypoxia-inducible factor-1α, uric acid, and levels of inflammatory factors were all higher in the observation group than the control group, and the differences are significant (P < .05). There was significant difference in lung function indexes between the observation group and the control group (P < .05). Serum hypoxia-inducible factor-1α, uric acid, and inflammatory factor levels were negatively associated with pulmonary function indices. Conclusion: The more serious the condition of AECOPD patients is, the levels of serum hypoxia inducible factor -1α, uric acid and inflammatory factors gradually increase, and the lung function tends to decline.

Adverse Childhood Experiences, Family Support, and Depression: Evidence from Internal Migrants in China.

Previous studies have linked poor family support and adverse childhood experiences (ACEs) to increased risk of depression; however, little is known about the interplay between the two when it comes to their effects on depression. Therefore, the current study examined if family support moderated the cumulative effect of ACEs on depression. Based on data from a migrant survey in Shiyan, Hubei Province, in 2019 (N = 1,326), this study used the ordinary least squares method to analyze the effect of ACEs on depression and evaluate whether family support moderated this effect. Higher exposure to ACEs and lower scores of family support were associated with higher depression levels in adulthood. The moderation model indicated that family support significantly moderated the relationship between ACEs and depression. Appropriate interventions to reduce depression should target internal migrants with history of ACEs. Community nurses should consider ACEs as an integral part of psychosocial assessment. Negative effects of ACEs can be reduced through teaching skills that increase effective family interaction and maintain supportive family networks. [Journal of Psychosocial Nursing and Mental Health Services, 61(3), 19-25.].

Field measurements of PM2.5 emissions from typical solid fuel combustion in rural households in Fenhe Basin, China.

Solid fuel is the most widely used energy source for cooking and heating in the rural households in developing countries. In this study, emissions from 13 fuel-stove combinations were studied in two typical rural villages in the Fenhe Basin, Shanxi Province, China. This study gathered data on the emission characteristics of particles with an aerodynamic diameter of ≤2.5 µm (PM2.5), organic carbon (OC), elemental carbon (EC), and 21 parent and oxygenated polycyclic aromatic hydrocarbons (pPAHs and oPAHs, respectively); the mechanism of gas formation was also determined. The PM2.5 EFs of biomass burning ranged from 4.11 ± 2.12 to 138 ± 47.2 g/kg, which was higher than that of coal combustion (1.57 ± 0.89 to 4.11 ± 0.63 g/kg). Notably, the average PM2.5 EFs of biomass burning in a traditional stove and elevated kang were 50.9 ± 13.8 and 23.0 ± 3.99 g/kg, respectively, suggesting that the elevated kang had superior emission mitigation. Wood pellet burning in a biomass furnace yielded lower PM2.5 EFs than firewood burning in the biomass furnace, which demonstrated wood pellet combustion's superior emission reduction effect. The relative contribution of OC4 to OC subfractions may be useable as tools for identifying the sources of coal and biomass burning. Regarding PAHs, biomass with abundant lignin pyrolysis produced numerous hydroxyl radicals that were conducive to the release of greater proportions of oPAHs. By contrast, pPAHs had greater relative contributions in coal combustion. Regarding gaseous pollutants, its formation mechanism varied with combustion phase. Emission differences between the two phases were mainly determined by the relative contributions of volatile C/N and char. Clarifying the pollutant formation mechanism can better guide the implementation of emission control from household solid fuel combustion.

Antifungal Substances Produced by Xenorhabdus bovienii and Its Inhibition Mechanism against Fusarium solani.

Fungal colonization can severely damage artifacts. Nematode endosymbiotic bacteria exhibit good prospects in protecting artifacts from fungal damage. We previously found that supernatant from the fermentation of nematode endosymbiotic bacterium, Xenorhabdus bovienii, is effective in inhibiting the growth of Fusarium solani NK-NH1, the major disease fungus in the Nanhai No.1 Shipwreck. Further experiments proved that X. bovienii produces volatile organic compounds (VOCs) that inhibit NK-NH1. Here, using metabolomic analysis, GC-MS, and transcriptomic analysis, we explored the antifungal substances and VOCs produced by X. bovienii and investigated the mechanism underlying its inhibitory effect against NK-NH1. We show that X. bovienii produces several metabolites, mainly lipids and lipid-like molecules, organic acids and derivatives, and organoheterocyclic compounds. The VOCs produced by X. bovienii showed two specific absorption peaks, and based on the library ratio results, these were predicted to be of 2-pentanone, 3-(phenylmethylene) and 1-hexen-3-one, 5-methyl-1-phenyl. The inhibition of F. solani by VOCs resulted in upregulation of genes related to ribosome, ribosome biogenesis, and the oxidative phosphorylation and downregulation of many genes associated with cell cycle, meiosis, DNA replication, and autophagy. These results are significant for understanding the inhibitory mechanisms employed by nematode endosymbiotic bacteria and should serve as reference in the protection of artifacts.

Speech acquisition within a 3-generation Vietnamese-English family: the influence of maturation and ambient phonology.

The emergence approach to speech acquisition theorises the influence of intrinsic capabilities (e.g., maturation), interactional capabilities, and extrinsic contexts (e.g., ambient phonology). Intrinsic and extrinsic influences were examined via a case study of a 3-generation Vietnamese-English family with two brothers (C1 aged 5;6 and C2 aged 3;10), their mother (M), grandfather (GF) and grandmother (GM). Their speech was assessed using the Diagnostic Evaluation of Articulation and Phonology (DEAP) and the Vietnamese Speech Assessment (VSA). Standard Australian English/Standard Vietnamese productions were defined as 'correct', even though the adults spoke different Vietnamese dialects. Their percentage of standard consonants correct (PSCC) was: C1 (English:92.27%, Vietnamese:89.05%), C2 (E:86.47%, VN:86.13%), M (E:90.34%, VN:96.35%), GF (E:82.61%, VN:97.81%), GM (VN:99.27%). Percentages were higher when dialectal variants were included. C1 and C2 had more pronunciation matches with English (86.96%) than Vietnamese (79.56%). C1's pronunciation matched: M (E:85.02%, VN:83.94%), GF (E:79.23%, VN:77.37%), GM (VN:73.72%) and C2's pronunciation matched: M (E:79.23%, VN:73.72%), GF (E:73.91%, VN:75.18%), GM (VN:72.26%). There was evidence of ambient phonology influences and cross-linguistic transfer. For example, in Vietnamese 'r' is produced as /ʐ/ or /r/ , but was produced by C1 as [ɹ] (English approximant) and by C2 [w] (age-appropriate/ɹ/substitution). The children demonstrated maturation influences for late-occurring English consonants (e.g., English /θ/ →[f]). This study found evidence for the emergence approach and recommends knowledge of the ambient phonology augments traditional child-focused understandings of children's speech acquisition.

[Regulatory roles of microRNAs in sarcopenia and exercise intervention].

Sarcopenia is an age-related degenerative disease, in which skeletal muscle mass and function are reduced during aging process. Physical intervention is one of the most effective strategies available for the treatment of sarcopenia. Studies have shown that microRNAs (miRNAs), as important regulators of gene expression, play an important role in maintaining the homeostasis of senescent skeletal muscle cells by regulating skeletal muscle cell development (proliferation and differentiation), mitochondrial biogenesis, protein synthesis and degradation, inflammatory response and metabolic pathways. Furthermore, exercise can combat age-related changes in muscle mass, composition and function, which is associated with the changes in the expression and biological functions of miRNAs in skeletal muscle cells. In this article, we systematically review the regulatory mechanisms of miRNAs in skeletal muscle aging, and discuss the regulatory roles and molecular targets of exercise-mediated miRNAs in muscular atrophy during aging process, which may provide novel insights into the prevention and treatment of sarcopenia.

Ankyrin-B Q1283H Variant Linked to Arrhythmias Via Loss of Local Protein Phosphatase 2A Activity Causes Ryanodine Receptor Hyperphosphorylation.

BACKGROUND: Human loss-of-function variants of ANK2 (ankyrin-B) are linked to arrhythmias and sudden cardiac death. However, their in vivo effects and specific arrhythmogenic pathways have not been fully elucidated. METHODS: We identified new ANK2 variants in 25 unrelated Han Chinese probands with ventricular tachycardia by whole-exome sequencing. The potential pathogenic variants were validated by Sanger sequencing. We performed functional and mechanistic experiments in ankyrin-B knockin (KI) mouse models and in single myocytes isolated from KI hearts. RESULTS: We detected a rare, heterozygous ANK2 variant (p.Q1283H) in a proband with recurrent ventricular tachycardia. This variant was localized to the ZU5C region of ANK2, where no variants have been previously reported. KI mice harboring the p.Q1283H variant exhibited an increased predisposition to ventricular arrhythmias after catecholaminergic stress in the absence of cardiac structural abnormalities. Functional studies illustrated an increased frequency of delayed afterdepolarizations and Ca2+ waves and sparks accompanied by decreased sarcoplasmic reticulum Ca2+ content in KI cardiomyocytes on isoproterenol stimulation. The immunoblotting results showed increased levels of phosphorylated ryanodine receptor Ser2814 in the KI hearts, which was further amplified on isoproterenol stimulation. Coimmunoprecipitation experiments demonstrated dissociation of protein phosphatase 2A from ryanodine receptor in the KI hearts, which was accompanied by a decreased binding of ankyrin-B to protein phosphatase 2A regulatory subunit B56α. Finally, the administration of metoprolol or flecainide decreased the incidence of stress-induced ventricular arrhythmias in the KI mice. CONCLUSIONS: ANK2 p.Q1283H is a disease-associated variant that confers susceptibility to stress-induced arrhythmias, which may be prevented by the administration of metoprolol or flecainide. This variant is associated with the loss of protein phosphatase 2A activity, increased phosphorylation of ryanodine receptor, exaggerated delayed afterdepolarization-mediated trigger activity, and arrhythmogenesis.

Targeting Gpr52 lowers mutant HTT levels and rescues Huntington's disease-associated phenotypes.

See Huang and Gitler (doi:10.1093/brain/awy112) for a scientific commentary on this article.Lowering the levels of disease-causing proteins is an attractive treatment strategy for neurodegenerative disorders, among which Huntington's disease is an appealing disease for testing this strategy because of its monogenetic nature. Huntington's disease is mainly caused by cytotoxicity of the mutant HTT protein with an expanded polyglutamine repeat tract. Lowering the soluble mutant HTT may reduce its downstream toxicity and provide potential treatment for Huntington's disease. This is hard to achieve by small-molecule compound drugs because of a lack of effective targets. Here we demonstrate Gpr52, an orphan G protein-coupled receptor, as a potential Huntington's disease drug target. Knocking-out Gpr52 significantly reduces mutant HTT levels in the striatum and rescues Huntington's disease-associated behavioural phenotypes in a knock-in Huntington's disease mouse model expressing endogenous mutant Htt. Importantly, a novel Gpr52 antagonist E7 reduces mutant HTT levels and rescues Huntington's disease-associated phenotypes in cellular and mouse models. Our study provides an entry point for Huntington's disease drug discovery by targeting Gpr52.

[Study on simulation method of knee hydrops based on biologcal impedance].

The injury of the knee joint is usually accompanied with the generation of hydrops. The volume of hydrops can be used as a reference to evaluate the extent of knee joint injuries. Based on the principle of bioimpedance detection, in this paper, a new method is proposed to detect knee joint hydrops. Firstly, a three-dimensional model of the knee joint was established according to the physiological and anatomical structure of the knee joint. Secondly, a knee impedance detection system was constructed based on the four-electrode theory, and the relationship between the knee impedance change and the volume of hydrops was calculated by linear regression. Finally, the model of rat knee joint hydrops was established, and the knee joint impedance was measured under different hydrops content to deduce the relationship between the fluid content and the knee joint impedance. The fluid volume in the joint was calculated by measuring the knee joint impedance, and the error rate was less than 10%. The experimental results show that the method proposed in this paper can establish the relationship between the impedance of the knee and the volume of fluid and realize the detection of the fluid volume.

Early Shared Reading, Socioeconomic Status, and Children's Cognitive and School Competencies: Six Years of Longitudinal Evidence.

This study explored the longitudinal association between early shared reading and children's later school achievement. We also examined the mediating role of children's academic school readiness and the moderating effect of family socioeconomic status. Data were drawn from the Longitudinal Study of Australian Children (n = 4,768). Frequency of shared reading and academic school readiness were assessed at the ages of 2-3 and 4-5. School achievement was assessed at age 8-9 via standardized national tests of school literacy and mathematics achievement. Results indicated that early shared reading was associated with children's school achievement directly and indirectly through receptive language and early academic skills. The results also showed that frequency of reading predicts the outcome measures, over and above other home activities such as telling child a story or practicing music. The associations were stronger among low and middle SES groups compared to the high SES group. We conclude that shared reading is uniquely associated to indicators of children's cognitive development such as language and early academic skills as well as children's school achievement. This effect is over and above families' socioeconomic status and other activities that parents do. This may be because books offer unique opportunities to teach children new words and concepts in a systematic way, and this is something that most parents would not be able to do otherwise.

Longitudinal changes in polysyllable maturity of preschool children with phonologically-based speech sound disorders.

Children's polysyllables were investigated for changes in (1) consonant and vowel accuracy, (2) error frequency and (3) polysyllable maturity over time. Participants were 80 children (4;0-5;4) with phonologically-based speech sound disorders who participated in the Sound Start Study and completed the Polysyllable Preschool Test (Baker, 2013) three times. Polysyllable errors were categorised using the Word-level Analysis of Polysyllables (WAP, Masso, 2016a) and the Framework of Polysyllable Maturity (Framework, Masso, 2016b), which represents five maturity levels (Levels A-E). Participants demonstrated increased polysyllable accuracy over time as measured by consonant and vowel accuracy, and error frequency. Children in Level A, the lowest level of maturity, had frequent deletion errors, alterations of phonotactics and alterations of timing. Participants in Level B were 8.62 times more likely to improve than children in Level A at Time 1. Children who present with frequent deletion errors may be less likely to improve their polysyllable accuracy.

[Correlation of serum anti-Müllerian hormone with semen parameters].

OBJECTIVE: To investigate the relationship between the serum anti-Müllerian hormone (AMH) level and semen parameters. METHODS: We collected the data about 726 outpatients at the Male Infertility Clinic of Jinling Hospital from September 2015 to November 2016, including 72 with non-obstructive azoospermia, 123 with oligospermia, and 531 with normal sperm concentration. We obtained the semen volume, total sperm count, sperm concentration, sperm motility, the percentages of progressively motile sperm (PMS) and morphologically normal sperm (MNS), and the levels of serum AMH, inhibin B (INH-B), total testosterone (TT) and follicle - stimulating hormone (FSH) of the patients, analyzed the correlation of the serum AMH level with the other parameters, and compared the AMH level among different groups. RESULTS: The serum AMH level was found to be correlated positively with the total sperm count (r = 0.227, P <0.001), sperm concentration (r = 0.215, P <0.001), sperm motility (r = 0.111, P = 0.003), the percentage of PMS (r = 0.120, P = 0.001), and the levels of INH-B (r = 0.399, P <0.001) and TT (r = 0.184, P = 0.002), negatively with the FSH level (r = －0.283, P <0.001), but insignificantly with age, time of abstinence, semen volume, and the percentage of MNS (P >0.05). There was a statistically significant difference in the serum AMH level among the patients with non-obstructive azoospermia, oligozoospermia, and normal sperm concentration (ï¼»6.33 ± 4.26ï¼½ vs ï¼»8.26 ± 3.98ï¼½ vs ï¼»9.8 ± 5.19ï¼½ ng/ml, P <0.001). CONCLUSIONS: Serum AMH is a biomarker reflecting the function of Sertoli cells and its level is significantly correlated with sperm concentration and motility, suggesting that AMH may be involved in spermatogenesis and sperm maturation.

Towards a better understanding of the relationship between executive control and theory of mind: an intra-cultural comparison of three diverse samples.

Previous research has consistently indicated that theory of mind (ToM) is associated with executive control in the preschool years. However, interpretation of this literature is limited by the fact that most studies have focused exclusively on urbanized Western cultural samples. Consequently, it is not clear whether the association between ToM and executive control reflects the specific features of this particular cohort or instead reflects a universal pattern. The present study provides the first empirical assessment of these two constructs in three diverse groups of Iranian children. Participants were 142 preschoolers (4-5 years old) from high-socioeconomic status (SES) urban (n = 33), low-SES urban (n = 37) and rural villages (n = 77). The results show that there is a robust association between ToM and executive control in all three groups, and that executive control contributes significant unique variance to ToM understanding, even after controlling for a range of variables that have been proposed as potential confounders of this relationship. However, although the three groups were equated in ToM, significant differences in executive control were evident. Moreover, cluster analysis identified three distinct clusters that were relatively homogeneous with respect to executive control and SES. One of these clusters was characterized by both low SES and low executive functioning, and showed little evidence of ToM understanding. Taken together, these findings provide possibly the clearest evidence to date that the association between ToM and executive control is not dependent on children's previous experiences on the tasks, or their family and cultural background.

The administration of erythropoietin attenuates kidney injury induced by ischemia/reperfusion with increased activation of Wnt/ß-catenin signaling.

BACKGROUND/PURPOSE: Understanding the mechanisms of protecting the kidneys from injury is of great importance because there are no effective therapies that promote repair and the kidneys frequently do not repair adequately. Evidence has shown that erythropoietin (EPO) has a vital renoprotective role, independent of its erythropoietic effect. However, whether EPO can contribute to kidney repair after injury and the potential mechanisms are not fully understood. METHODS: To investigate the renoprotective mechanism of EPO, a kidney ischemia/reperfusion injury (IRI) model was induced in adult male Sprague-Dawley rats. The rats were subsequently randomly treated with EPO or a vehicle 6 hours after the kidney IRI. The rats were sacrificed on Day 3, Day 5, and Day 7 post kidney IRI. Renal function and histological alterations were examined. Renal interstitial macrophage infiltration, cell proliferation, apoptosis, and angiogenesis were evaluated by immunostaining. Furthermore, the effects of EPO on the Wnt/ß-catenin pathway and IRI-related micro-RNAs were investigated. RESULTS: The administration of EPO significantly improved renal function and reduced tubular injury. Furthermore, EPO treatment significantly prevented tubular cell apoptosis and promoted cell proliferation after IRI. Erythropoietin significantly suppressed macrophage infiltration, compared to the vehicle. In addition, treatment with EPO markedly prevented the loss of microvasculature. We have also demonstrated that, compared to the vehicle, EPO administration enhanced the expression of Wnt7b and ß-catenin, and downregulated miR-21, -214, -210, and -199a. CONCLUSION: Erythropoietin protects the kidneys against IRI by attenuating injury of the renal microvasculature and tubule epithelial cells, by promoting Wnt/ß-catenin pathway activation, and by regulating miRNA expression.

Study on biodegradation mechanism of Fusarium solani NK-NH1 on the hull wood of the Nanhai No. 1 shipwreck.

The Nanhai No. 1 shipwreck is an ancient wooden ship in the Southern Song Dynasty. Currently, serious challenges of microbial diseases exist on the hull wood. This study aimed to obtain microbial samples from the ship hull in December 2021 and analyze the microbial diseases through scanning electron microscopy and high-throughput sequencing to preserve the Nanhai No. 1 shipwreck. The biodegradation mechanism of diseased microorganisms was explored through whole genome sequencing and the detection of enzyme activity and gene expression levels of diseased microorganisms under different conditions. The results showed that there was obvious fungal colonization on the surface of the hull wood and Fusarium solani NK-NH1 was the dominant disease fungus on the surface. NK-NH1 has strong cellulose and lignin degradation ability. Its whole genome size is 52,389,955 bp, and it contains 17,402 genes. It has a variety of key enzyme genes involved in cellulose and lignin degradation. The NK-NH1 dominant degrading enzyme lignin peroxidase has the highest enzyme activity at pH = 4, NaCl concentration of 30%, and FeSO4 concentration of 50 mg/L, while laccase has the highest enzyme activity at pH = 4, NaCl concentration of 10%, and FeSO4 concentration of 100 mg/L. The above research results prove that NK-NH1 is a key fungus to the biodegradation of ship hull wood when it is exposed to air, low pH, high salt, and rich in sulfur iron compounds. This study provides a theoretical basis for the preservation of the Nanhai No. 1 shipwreck.