Long-term abacus training gains in children are predicted by medial temporal lobe anatomy and circuitry.

Abacus-based mental calculation (AMC) is a widely used educational tool for enhancing math learning, offering an accessible and cost-effective method for classroom implementation. Despite its universal appeal, the neurocognitive mechanisms that drive the efficacy of AMC training remain poorly understood. Notably, although abacus training relies heavily on the rapid recall of number positions and sequences, the role of memory systems in driving long-term AMC learning remains unknown. Here, we sought to address this gap by investigating the role of the medial temporal lobe (MTL) memory system in predicting long-term AMC training gains in second-grade children, who were longitudinally assessed up to fifth grade. Leveraging multimodal neuroimaging data, we tested the hypothesis that MTL systems, known for their involvement in associative memory, are instrumental in facilitating AMC-induced improvements in math skills. We found that gray matter volume in bilateral MTL, along with functional connectivity between the MTL and frontal and ventral temporal-occipital cortices, significantly predicted learning gains. Intriguingly, greater gray matter volume but weaker connectivity of the posterior parietal cortex predicted better learning outcomes, offering a more nuanced view of brain systems at play in AMC training. Our findings not only underscore the critical role of the MTL memory system in AMC training but also illuminate the neurobiological factors contributing to individual differences in cognitive skill acquisition. A video abstract of this article can be viewed at https://youtu.be/StVooNRc7T8. RESEARCH HIGHLIGHTS: We investigated the role of medial temporal lobe (MTL) memory system in driving children's math learning following abacus-based mental calculation (AMC) training. AMC training improved math skills in elementary school children across their second and fifth grade. MTL structural integrity and functional connectivity with prefrontal and ventral temporal-occipital cortices predicted long-term AMC training-related gains.

Foundational Number Sense Training Gains Are Predicted by Hippocampal-Parietal Circuits.

The development of mathematical skills in early childhood relies on number sense, the foundational ability to discriminate among quantities. Number sense in early childhood is predictive of academic and professional success, and deficits in number sense are thought to underlie lifelong impairments in mathematical abilities. Despite its importance, the brain circuit mechanisms that support number sense learning remain poorly understood. Here, we designed a theoretically motivated training program to determine brain circuit mechanisms underlying foundational number sense learning in female and male elementary school-age children (7-10 years). Our 4 week integrative number sense training program gradually strengthened the understanding of the relations between symbolic (Arabic numerals) and nonsymbolic (sets of items) representations of quantity. We found that our number sense training program improved symbolic quantity discrimination ability in children across a wide range of math abilities including children with learning difficulties. Crucially, the strength of pretraining functional connectivity between the hippocampus and intraparietal sulcus, brain regions implicated in associative learning and quantity discrimination, respectively, predicted individual differences in number sense learning across typically developing children and children with learning difficulties. Reverse meta-analysis of interregional coactivations across 14,371 fMRI studies and 89 cognitive functions confirmed a reliable role for hippocampal-intraparietal sulcus circuits in learning. Our study identifies a canonical hippocampal-parietal circuit for learning that plays a foundational role in children's cognitive skill acquisition. Findings provide important insights into neurobiological circuit markers of individual differences in children's learning and delineate a robust target for effective cognitive interventions.SIGNIFICANCE STATEMENT Mathematical skill development relies on number sense, the ability to discriminate among quantities. Here, we develop a theoretically motivated training program and investigate brain circuits that predict number sense learning in children during a period important for acquisition of foundational cognitive skills. Our integrated number sense training program was effective in children across a wide a range of math abilities, including children with learning difficulties. We identify hippocampal-parietal circuits that predict individual differences in learning gains. Our study identifies a brain circuit critical for the acquisition of foundational cognitive skills, which will be useful for developing effective interventions to remediate learning disabilities.

Protein Lactylation Modification and Proteomics Features in Cirrhosis Patients after UC-MSC Treatment.

Umbilical cord mesenchymal stem cell (UC-MSC) therapy improves liver function in liver cirrhosis patients. This study aimed to elucidate the therapeutic mechanism underlying cell therapy by analyzing changes in the modification and expression of proteins 1 month post-treatment with UC-MSCs. This prospective study included 11 cirrhosis patients who received MSC injection. The laboratory indexes before and after treatment were collected to evaluate the clinical treatment effect of UC-MSCs, and the protein expression and lactylation modification in the liver were comprehensively revealed. Meanwhile, weighted gene co-expression network analysis was used to analyze the co-expression protein modules and their relationship with clinical features. The patients with liver cirrhosis showed an improvement trend after receiving UC-MSC treatment; specifically, the liver protein synthesis function was significantly improved and the coagulation function was also significantly improved. Proteomics combined with lactic acid proteomics revealed 160 lysine lactylation (Kla) sites of 119 proteins. Functional analysis showed that the lactylation-modified proteins were enriched in the pathway of glucose and other substances' metabolism, and many key enzymes of glycolysis and gluconeogenesis were lactated. UC-MSC therapy has a certain clinical effect in the treatment of liver cirrhosis and may act by regulating material metabolism, because the lactylation protein points to energy metabolism.

Tumor cell density dependent IL-8 secretion induces the fluctuation of tregs/CD8 + T cells infiltration in hepatocellular carcinoma: one prompt for the existence of density checkpoint.

BACKGROUND: Tumor cell density is a basic pathological feature of solid tumors. Chemotherapy, radiotherapy, and targeted therapy reduce tumor cell density, whereas unrestricted tumor cell proliferation promotes this feature. The impact of tumor cells on the microenvironment following changes in tumor cell density is still unclear. In this study, we focused on the response of key immune cell subsets to tumor cell density in hepatocellular carcinoma (HCC). METHODS: We determined the density of tumor and immune cells in the same area by section staining. We then identified potential mediators using polymerase chain reaction (PCR), enzyme-linked immunofluorescence assay (ELISA), 3D and co-culture, flow cytometry, and lentivirus intervention. The mechanism of lactate promotion was verified using lactate tests, bioinformatics, western blotting, and the above methods. The IL-8/DAPK1/lactate/regulatory T cell (Treg) axis was verified using a mouse liver cancer model. Tumor mutation burden was calculated using maftools in R. RESULTS: We found that the Treg/CD8 + T cell ratio is not consistent with tumor cell density in HCC, and a decreased Treg/CD8 + T cell ratio in the range of 5000-6000 cells/mm2 may elicit the possibility for immunotherapy in an immunosuppressive microenvironment. We showed that IL-8 mediates this immune fluctuation and promotes the infiltration of Tregs through the DAPK1/pyruvate kinase activity/lactate axis in HCC. Based on tumor ploidy and mutation burden data, we discussed the potential significance of immune fluctuation in the homeostasis of HCC mutation burden and proposed a "density checkpoint" and "entropy model" to describe this phenomenon. CONCLUSIONS: In summary, we report the mode of infiltration of Tregs/CD8 + T cells in response to tumor cell density and provide a new theoretical basis for IL-8 as a therapeutic target and the selection of an immunotherapy window in HCC.

Pretreatment of UC-MSCs with IFN-α2 improves treatment of liver fibrosis by recruiting neutrophils.

BACKGROUND: The use of umbilical cord mesenchymal stem cells (UC-MSCs) is a burgeoning method for the treatment of liver cirrhosis. However, the secretory phenotype and regulatory ability of UC-MSCs are easily affected by their microenvironment. Ensuring a specific microenvironment to enhance the UC-MSCs phenotype is a potential strategy for improving their therapeutic efficacy. The aim of this study was to explore therapeutic UC-MSCs phenotypes for improving liver fibrosis. METHODS: RNA-sequencing was used to analyze the response pattern of UC-MSCs after exposure to the serum of cirrhotic patients with HBV. Using immunohistochemistry, quantitative polymerase chain reaction, and immunofluorescence techniques, we evaluated the therapeutic effect of UC-MSCs pretreated with interferon alpha 2 (IFN-α2) (pre-MSCs) in an animal model of cirrhosis. Immunoblotting, ELISA, and other techniques were used to analyze the signaling pathways underlying the IFN-induced changes in UC-MSCs. RESULTS: UC-MSCs exposed to the serum of patients with hepatitis B-induced cirrhosis showed an enhanced response to type I IFN. The activated type I IFN signal induced the highest secretion of colony-stimulating factor 3 (CSF-3), interleukin (IL)-8, and chemokine (C-C motif) ligand 20 (CCL20) by the UC-MSCs. Pre-MSCs showed a higher therapeutic efficacy than untreated UC-MSCs in an animal model of liver fibrosis. Immunohistochemical analysis revealed that pre-MSCs could recruit neutrophils resulting in an increase in the secretion of matrix metalloprotease 8 that alleviated fibrosis. When neutrophils in animals were depleted, the therapeutic effect of pre-MSCs on fibrosis was inhibited. IFN-α2 altered the secretory phenotype of UC-MSCs by activating phosphorylated signal transducer and activator of transcription 1 and 2 (p-STAT1 and p-STAT2). CONCLUSIONS: Pre-MSCs exhibited enhanced secretion of CSF-3, IL-8, and CCL20 and recruited neutrophils to alleviate fibrosis. This new strategy can improve cell therapy for liver cirrhosis.

MiR-29c Inhibits TNF-α-Induced ROS Production and Apoptosis in Mouse Hippocampal HT22 Cell Line.

Recent reports have suggested that abnormal miR-29c expression in hippocampus have been implicated in the pathophysiology of some neurodegenerative and neuropsychiatric diseases. However, the underlying effect of miR-29c in regulating hippocampal neuronal function is not clear. In this study, HT22 cells were infected with lentivirus containing miR-29c or miR-29c sponge. Cell counting kit-8 (CCK8) and lactate dehydrogenase (LDH) assay kit were applied to evaluate cell viability and toxicity before and after TNF-α administration. Reactive oxygen species (ROS) generation and mitochondrial membrane potential (MMP) were measured with fluorescent probes. Hoechst 33258 staining and TUNEL assay were used to evaluate cell apoptosis. The expression of key mRNA/proteins (TNFR1, Bcl-2, Bax, TRADD, FADD, caspase-3, -8 and -9) in the apoptosis pathway was detected by PCR or WB. In addition, the protein expression of microtubule-associated protein-2 (MAP-2), nerve growth-associated protein 43 (GAP-43) and synapsin-1 (SYN-1) was detected by WB. As a result, we found that miR-29c overexpression could improve cell viability, attenuate LDH release, reduce ROS production and inhibit MMP depolarization in TNF-α-treated HT22 cells. Furthermore, miR-29c overexpression was found to decrease apoptotic rate, along with decreased expression of Bax, cleaved caspase-3, cleaved caspase-9, and increased expression of Bcl-2 in TNF-α-treated HT22 cells. However, miR-29c sponge exhibited an opposite effects. In addition, in TNF-α-treated HT22 cells, miR-29c overexpression could decrease the expressions of TNFR1, TRADD, FADD and cleaved caspase-8. However, in HT22 cells transfected with miR-29c sponge, TNF-α-induced the expressions of TNFR1, TRADD, FADD and cleaved caspase-8 was significantly exacerbated. At last, TNF-α-induced the decreased expression of MAP-2, GAP-43 and SYN-1 was reversed by miR-29c but exacerbated by miR-29c sponge. Overall, our study demonstrated that miR-29c protects against TNF-α-induced HT22 cells injury through alleviating ROS production and reduce neuronal apoptosis. Therefore, miR-29c might be a potential therapeutic agent for TNF-α accumulation and toxicity-related brain diseases.

Comprehensive analysis on subchondral bone marrow lesions of human osteoarthritis by integrating bulk and single-cell transcriptomes.

OBJECTIVE: This study aims to demonstrate the cellular composition and underlying mechanisms in subchondral bone marrow lesions (BMLs) of knee osteoarthritis (OA). METHODS: BMLs were assessed by MRI Osteoarthritis Knee Score (MOAKS)≥2. Bulk RNA-sequencing (bulk-seq) and BML-specific differentially expressed genes (DEGs) analysis were performed among subchondral bone samples (including OA-BML=3, paired OA-NBML=3; non-OA=3). The hub genes of BMLs were identified by verifying in independent datasets and multiple bioinformatic analyses. To further estimate cell-type composition of subchondral bone, we utilized two newly developed deconvolution algorithms (MuSiC, MCP-counter) in transcriptomic datasets, based on signatures from open-accessed single-cell RNA sequencing (scRNA-seq). Finally, competing endogenous RNA (ceRNA) and transcription factor (TF) networks were constructed through multiple predictive databases, and validated by public non-coding RNA profiles. RESULTS: A total of 86 BML-specific DEGs (up 79, down 7) were identified. IL11 and VCAN were identified as core hub genes. The "has-miR-424-5p/lncRNA PVT1" was determined as crucial network, targeting IL11 and VCAN, respectively. More importantly, two deconvolution algorithms produced approximate estimations of cell-type composition, and the cluster of heterotopic-chondrocyte was discovered abundant in BMLs, and positively correlated with the expression of hub genes. CONCLUSION: IL11 and VCAN were identified as the core hub genes of BMLs, and their molecular networks were determined as well. We profiled the characteristics of subchondral bone at single-cell level and determined that the heterotopic-chondrocyte was abundant in BMLs and was closely linked to IL11 and VCAN. Our study may provide new insights into the microenvironment and pathological molecular mechanism of BMLs, and could lead to novel therapeutic strategies.

The Dual-Mode Transition of Myofibroblasts Derived from Hepatic Stellate Cells in Liver Fibrosis.

Hepatic stellate cells (HSCs) are the key promoters of liver fibrosis. In response to liver-fibrosis-inducing factors, HSCs express alpha smooth muscle actin (α-SMA) and obtain myofibroblast phenotype. Collagen secretion and high expression of α-SMA with related high cell tension and migration limitation are the main characteristics of myofibroblasts. How these two characteristics define the role of myofibroblasts in the initiation and progression of liver fibrosis is worth exploring. From this perspective, we explored the correlation between α-SMA expression and collagen secretion in myofibroblasts and the characteristics of collagen deposition in liver fibrosis. Based on a reasonable hypothesis and experimental verification, we believe that the myofibroblast with the α-SMAhighcollagenhigh model do not effectively explain the initial stage and progression characteristics of liver fibrosis. Therefore, we propose a myofibroblast dual-mode transition model in fibrotic liver (DMTM model). In the DMTM model, myofibroblasts have dual modes. Myofibroblasts obtain enhanced α-SMA expression, accompanied by collagen expression inhibition in the high-concentration region of TGF-ß. At the edge of the TGF-ß positive region, myofibroblasts convert to a high-migration and high-collagen secretion phenotype. This model reasonably explains collagen deposition and expansion in the initial stage of liver fibrosis.

Heterogeneous matrix stiffness regulates the cancer stem-like cell phenotype in hepatocellular carcinoma.

BACKGROUND: Solid tumors are stiffer than their surrounding normal tissues; however, their interior stiffness is not uniform. Under certain conditions, cancer cells can acquire stem-like phenotypes. However, it remains unclear how the heterogeneous physical microenvironment affects stemness expression in cancer cells. Here, we aimed to evaluate matrix stiffness heterogeneity in hepatocellular carcinoma (HCC) tissues and to explore the regulation effect of the tumor microenvironment on stem-like phenotypic changes through mechanical transduction. METHODS: First, we used atomic force microscopy (AFM) to evaluate the elastic modulus of HCC tissues. We then used hydrogel with adjustable stiffness to investigate the effect of matrix stiffness on the stem-like phenotype expression of HCC cells. Moreover, cells cultured on hydrogel with different stiffness were subjected to morphology, real-time PCR, western blotting, and immunofluorescence analyses to explore the mechanotransduction pathway. Finally, animal models were used to validate in vitro results. RESULTS: AFM results confirmed the heterogenous matrix stiffness in HCC tissue. Cancer cells adhered to hydrogel with varying stiffness (1.10 ± 0.34 kPa, 4.47 ± 1.19 kPa, and 10.61 kPa) exhibited different cellular and cytoskeleton morphology. Higher matrix stiffness promoted the stem-like phenotype expression and reduced sorafenib-induced apoptosis. In contrast, lower stiffness induced the expression of proliferation-related protein Ki67. Moreover, mechanical signals were transmitted into cells through the integrin-yes-associated protein (YAP) pathway. Higher matrix stiffness did not affect YAP expression, however, reduced the proportion of phosphorylated YAP, promoted YAP nuclear translocation, and regulated gene transcription. Finally, application of ATN-161 (integrin inhibitor) and verteporfin (YAP inhibitor) effectively blocked the stem-like phenotype expression regulated by matrix stiffness. CONCLUSIONS: Our experiments provide new insights into the interaction between matrix stiffness, cancer cell stemness, and heterogeneity, while also providing a novel HCC therapeutic strategy.

Huc-MSC-derived exosomes modified with the targeting peptide of aHSCs for liver fibrosis therapy.

BACKGROUND: Effective therapeutics to stop or reverse liver fibrosis have not emerged, because these potential agents cannot specifically target activated hepatic stellate cells (aHSCs) or are frequently toxic to parenchymal cells. Human umbilical cord mesenchymal stem cell (Huc-MSC)-derived exosomes show promise in nanomedicine for the treatment of liver fibrosis. However, systemic injection showed that unmodified exosomes were mainly taken up by the mononuclear phagocyte system. The discovery of ligands that selectively bind to a specific target plays a crucial role in clinically relevant diagnostics and therapeutics. Herein, we aimed to identify the targeting peptide of aHSCs by screening a phage-displayed peptide library, and modify Huc-MSC-derived exosomes with the targeting peptide. RESULTS: In this study, we screened a phage-displayed peptide library by biopanning for peptides preferentially bound to HSC-T6 cells. The identified peptide, HSTP1, also exhibited better targeting ability to aHSCs in pathological sections of fibrotic liver tissues. Then, HSTP1 was fused with exosomal enriched membrane protein (Lamp2b) and was displayed on the surface of exosomes through genetic engineering technology. The engineered exosomes (HSTP1-Exos) could be more efficiently internalized by HSC-T6 cells and outperformed both unmodified exosomes (Blank-Exos) and Lamp2b protein overexpressed exosomes (Lamp2b + Exos) in enhancing the ability of exosomes to promote HSC-T6 reversion to a quiescent phenotype. In vivo results showed HSTP1-Exos could specifically target to the aHSC region after intravenous administration, as demonstrated by coimmunofluorescence with the typical aHSCs marker α-SMA, and enhance the therapeutic effect on liver fibrosis. CONCLUSION: These results suggest that HSTP1 is a reliable targeting peptide that can specifically bind to aHSCs and that HSTP1-modified exosomes realize the precise treatment for aHSCs in complex liver tissue. We provide a novel strategy for clinical liver fibrosis therapy.

Transcription profiling of cadmium-exposed livers reveals alteration of lipid metabolism and predisposition to hepatic steatosis.

1. Cadmium (Cd) is a ubiquitous environmental toxicant that can cause liver steatosis and nonalcoholic fatty liver disease (NAFLD) on long-term exposure.2. Sixteen Sprague Dawley rats were randomly divided into two groups, and were administered normal saline and 5 mg/(kg·d) cadmium chloride by gavage. In vitro, BRL3A cells, a rat normal liver cell line, were treated with different concentrations of Cd to verify the sequencing results.3. The RNA-seq revealed 146 upregulated genes and 127 downregulated genes in the Cd intervention group. The key genes of lipid metabolism were significantly overexpressed, such as Cyp1a1 and Pla2g2d. The GO enrichment analysis showed that the 'sterol biosynthetic process' was the most obvious difference. The KEGG analysis showed that six of the top 10 differential pathways were related to lipid metabolism. The expression of the essential genes in BRL3A was consistent with the sequencing results. The protein-protein interaction (PPI) yielded that Cyp1a1 is in the central region of the differentially expressed gene network.4. The chronic Cd exposure is still an important environmental health problem with a probable tendency to cause NAFLD. It may possibly act by affecting the lipid metabolism in the liver, especially the synthesis and decomposition of unsaturated fatty acids.

[The relationship between brain networks and symptoms of schizophrenia].

The pathogenesis of schizophrenia (SCZ) is not yet clear, and the pathological changes of the brain activity remains debatable. There are still numerous unresolved issues and debates regarding the relationship between functional connection of the brain network and the symptoms of SCZ. In this paper, we provide a comprehensive review of recent research progresses on resting-state and task-based brain networks, which covers the symptoms of SCZ. Furthermore, we discuss the relationship between large-scale brain networks and SCZ symptoms, and propose possible future research directions in the field of SCZ diagnosis and treatment.

Copper-catalyzed C-H [3 + 2] annulation of N-substituted anilines with α-carbonyl alkyl bromides via C(sp3)-Br/C(sp2)-H functionalization.

A copper-catalyzed C-H [3 + 2] annulation of N-substituted anilines with α-carbonyl alkyl bromides for the synthesis of 3,3'-disubstituted oxindoles is developed. Tandem C-H cycloamidation reactions of various α-carbonyl alkyl bromide derivatives including tertiary-α-bromoalkyl ketone esters, malonic esters and cycloalkanes, with N-aryl or alkyl substituted anilines, can be performed using this system, affording a vast array of valuable 3,3'-disubstituted oxindoles in moderate to good yields.

Association of trimethylamine N-Oxide with cardiovascular and all-cause mortality in hemodialysis patients.

BACKGROUND: Trimethylamine-N-Oxide (TMAO) is a proatherogenic and prothrombotic metabolite. Our study examined the association of plasma TMAO level with cardiovascular and all-cause mortality in hemodialysis (HD) patients. METHODS: Patients who were at least 18 years-old and received HD for at least 6 months were enrolled within 6 months. Patients with coronary heart disease, congestive heart failure, arrhythmia, or stroke within 3 months before study onset were excluded. The primary endpoints were cardiovascular and all-cause death, and the secondary endpoint was cerebrovascular death. RESULTS: We recruited 252 patients and divided them into a high-TMAO group (>4.73 µg/mL) and a low-TMAO group (≤4.73 µg/mL). The median follow-up time was 73.4 months (interquartile range: 42.9, 108). A total of 123 patients died, 39 from cardiovascular disease, 19 from cerebrovascular disease, and 65 from other causes. Kaplan-Meier analysis indicated that the high-TMAO group had a greater incidence of cardiovascular death (Log-Rank: p = 0.006) and all-cause death (Log-Rank: p < 0.001). Cox regression analysis showed that high TMAO level was significantly associated with cardiovascular and all-cause mortality. After adjustment for confounding, this association remained significant for cardiovascular mortality (TMAO as a continuous variable: HR: 1.18, 95%CI: 1.07, 1.294, p < 0.001; TMAO as a dichotomous variable: HR: 3.44, 95%CI: 1.68, 7.08, p < 0.001) and all-cause mortality (TMAO as a continuous variable: HR: 1.14, 95%CI: 1.08, 1.21, p < 0.001; TMAO as a dichotomous variable: HR: 2.54, 95%CI: 1.71, 3.76, p < 0.001). CONCLUSIONS: High plasma TMAO level is significantly and independently associated with cardiovascular and all-cause mortality in HD patients.

Proximal femoral nail anti-rotation (PFNA) and hemi-arthroplasty in the treatment of elderly intertrochanteric fractures.

To determine reasonable treatment of intertrochanteric fractures with proximal femoral nail anti-rotation (PFNA) or hemi-arthroplasty (HA) in elderly patients. Between January 2009 and June 2013, a total of 367 patients were admitted to the Orthopedics Department of The Second Affiliated Hospital of Soochow University. Patient data were retrospectively analyzed and included 160 males and 207 females. The ages of the patients were between 60 and 97 years and the average age was 72 +/- 3.9 years. According to the Evans-Jensen classification scheme, the fracture types were type IA (n = 18), type IB (n =3 1), type II (n=154), and type III (n = 164). A comparison between the two surgical methods (PFNA and HA) included the duration of surgery, intra-operative blood loss, post-operative weight-bearing time, implant complications, and the Harris hip score. The data were analyzed after 14-50 months (average 24 months) of follow-up. The gender and age of the patients did not differ significantly between the two methods of treatment; however, the duration of surgery between the PFNA hemi-arthroplasty groups did differ (hemi-arthroplasty required less time), the intra-operative blood loss in the PFNA group was significantly less than the hemi-arthroplasty group, and the post-operative weight-bearing time was significantly shorter in the hemi-arthroplasty group than the PFNA group. A retrospective study was conducted in 367 patients during the 42-month study period (January 2009-June 2013) to observe the efficacy of PFNA and hemi-arthroplasty. Complete data were available for analysis. There are significant advantages and disadvantages with respect to the two surgical treatment modalities. For elderly patients with unstable fractures, severe osteoporosis, and pre-operative mobility, hemi-arthroplasty is preferred because hemi-arthroplasty has fewer disadvantages compared to PFNA, which is not suitable for full weight bearing and bone union. PFNA for the treatment of intertrochanteric fractures has been increasingly accepted and widely used; however the use of arthroplasty remains controversial (3). Conservative treatment for intertrochanteric fractures in elderly patients has become a main trend and often takes longer, gives rise to more complications, and has mortality rates higher than surgical treatment.

The impact of long-term abacus training on modular properties of functional brain network.

Training induces cognitive and neural plasticity, and understanding of the neural mechanisms of training-induced brain plasticity has significant implications for improving children's academic achievement. Previous studies have indicated that training in abacus-based mental calculation (AMC) improves arithmetical capacities and results in brain plasticity within visuospatial brain regions. However, previous studies have reported alterations within distributed brain regions. Thus, it remains unclear whether and how AMC training influences the functional integration and separation between and/or within networks. The current study aimed to address these questions using graph theory, engaging 162 children, 90 of whom were given long-term AMC training. The AMC group exhibited greater local efficiency and intra-module connections within the visual network and less local efficiency and intra-module connections in the cingulo-opercular network (CON). Interestingly, in the AMC group, negative correlations were found between local efficiency and intra-module connections across the two networks. Furthermore, both network characteristics of the CON were negatively correlated with math ability in the AMC group. No such correlations were found in the control group. The current study delineated the enhanced neural mechanisms of visuospatial-related brain regions at an intermediate level and highlighted the intrinsic association between different brain ensembles in neural plasticity, thus furthering the understanding of the effects of AMC training on brain network reconfiguration.

Release of cadmium in contaminated paddy soil amended with NPK fertilizer and lime under water management.

Agricultural soils contaminated with cadmium (Cd) pose a risk to receiving surface water via drainage or runoff. A 90-day laboratory incubation experiment was conducted to investigate the release characteristics and transformation of Cd from contaminated paddy soil amended with agrochemical (NPK fertilizer) and lime (L) under water management regimes of continuous flooding (F) and drying-wetting cycles (DW). The result showed that the dissolved Cd concentrations in overlying water of the fertilizer treatment under flooding (NPK+F) and drying-wetting (NPK+DW) reached up to 81.0 µg/L and 276 µg/L, and were much higher than that from the corresponding controls without NPK fertilizer addition at the end of experiment. The Cd concentration showed significantly negative correlation with overlying water pH, but positive correlation with soil redox potential and concentrations of dissolved total nitrogen, sulfate and manganese in overlying water (P < 0.05), indicating that drying-wetting cycles and N fertilizer addition may enhance soil Cd release. The Cd concentrations in overlying water from all treatments except NPK+L+F treatment exceeded the Cd threshold limit of Chinese Environmental Quality Standards for Surface Water (10 µg/L Grade V) and poses potential risk to surface water quality. Meanwhile, the proportion of Cd in the acid-soluble fraction from all incubated soil except NPK+L+F treatment increased compared to before incubation. The results indicated that continuous flooding was a reasonable water management candidate coupled with lime addition for immobilizing soil Cd.

Leaf Variegation of Thylakoid Formation1 Is Suppressed by Mutations of Specific σ-Factors in Arabidopsis.

Thylakoid Formation1 (THF1) has been shown to play roles in chloroplast development, resistance to excessive light, and chlorophyll degradation in Arabidopsis (Arabidopsis thaliana). To elucidate mechanisms underlying THF1-regulated chloroplast development, we mutagenized thf1 seeds with ethyl methanesulfonate and screened second-site recessive mutations that suppress its leaf variegation phenotype. Here, we characterized a unique suppressor line, 42-6, which displays a leaf virescent phenotype. Map-based cloning and genetic complementation results showed that thf1 variegation was suppressed by a mutation in σ-FACTOR6 (SIG6), which is a plastid transcription factor specifically controlling gene expression through the plastid-encoded RNA polymerase. Northern-blot analysis revealed that plastid gene expression was down-regulated in not only 42-6 and sig6 but also, thf1 at the early stage of chloroplast development. Interestingly, mutations in SIG2 but not in other σ-factors also suppressed thf1 leaf variegation. Furthermore, we found that leaf variegation of thf1 and var2 could be suppressed by several virescent mutations, including yellow seedling1, brz-insensitive-pale green2, and nitric oxide-associated protein1, indicating that virescent mutations suppress leaf variegation. Taken together, our results provide unique insights into thf1-mediated leaf variegation, which might be triggered by defects in plastid gene transcription.

Synthesis of benzocyclohepta[b]indoles by Lewis acid catalyzed annulation of two 3-(1H-isochromen-1-yl)-1H-indoles.

A novel Lewis acid catalyzed annulation reaction has been established for the synthesis of benzocyclohepta[b]indoles. This method represents a new annulation strategy to a seven-membered carbocyclic ring system from two 3-(1H-isochromen-1-yl)-1H-indole molecules using Cu(OTf)2 catalyst; moreover, the products, benzocyclohepta[b]indoles, can be used as the rapid mercuric ion colorimetric detection reagents.

A novel microfluidic system for the rapid analysis of protein thermal stability.

We describe a simple microfluidic device for the rapid analysis of protein thermal stability using a novel imaging method. The change in UV absorption upon thermal denaturation or aggregation of proteins is used to get a spatial image of proteins' folding or aggregation state along a linear temperature gradient.