1-Methyltryptophan treatment ameliorates high-fat diet-induced depression in mice through reversing changes in perineuronal nets.

Depression and obesity are prevalent disorders with significant public health implications. In this study, we used a high-fat diet (HFD)-induced obese mouse model to investigate the mechanism underlying HFD-induced depression-like behaviors. HFD-induced obese mice exhibited depression-like behaviors and a reduction in hippocampus volume, which were reversed by treatment with an indoleamine 2,3-dioxygenase (IDO) inhibitor 1-methyltryptophan (1-MT). Interestingly, no changes in IDO levels were observed post-1-MT treatment, suggesting that other mechanisms may be involved in the anti-depressive effect of 1-MT. We further conducted RNA sequencing analysis to clarify the potential underlying mechanism of the anti-depressive effect of 1-MT in HFD-induced depressive mice and found a significant enrichment of shared differential genes in the extracellular matrix (ECM) organization pathway between the 1-MT-treated and untreated HFD-induced depressive mice. Therefore, we hypothesized that changes in ECM play a crucial role in the anti-depressive effect of 1-MT. To this end, we investigated perineuronal nets (PNNs), which are ECM assemblies that preferentially ensheath parvalbumin (PV)-positive interneurons and are involved in many abnormalities. We found that HFD is associated with excessive accumulation of PV-positive neurons and upregulation of PNNs, affecting synaptic transmission in PV-positive neurons and leading to glutamate-gamma-aminobutyric acid imbalances in the hippocampus. The 1-MT effectively reversed these changes, highlighting a PNN-related mechanism by which 1-MT exerts its anti-depressive effect.

Clinical Features Post Anterior Cruciate Ligament Reconstruction Associated with Structural Alterations in Corticospinal Tract.

CONTEXT: Structural evidence for corticospinal tract (CST) abnormality between patients with ACLR and healthy controls, and the relationships between CST structure and clinical features of the patients (e.g., objective sensorimotor outcomes, postoperative duration) are lacking. OBJECTIVES: To investigate whether the structural features of CST 1) differ between patients with ACLR and healthy controls, and 2) were associated with clinical features in patients following ACLR. DESIGN: Cross-sectional study. SETTING: Sports medicine laboratory. PATIENTS OR OTHER PARTICIPANTS: Twenty-six patients who had undergone ACLR and twenty-six healthy controls were enrolled in this cross-sectional investigation. MAIN OUTCOME MEASURE(S): Using the CST as the region of interest, we performed diffusion tensor imaging to measure the microstructure of white matter tracts. Between-group comparisons and correlation analyses with clinical features in patients with ACLR were performed. RESULTS: The patients with ACLR showed significant, moderate lower fractional anisotropy (FA, Cohen's d = -0.666, 95% CIs -1.221 to -0.104), lower axial diffusivity (AD, Cohen's d = -0.526, 95% CIs -1.077 to 0.030), and higher radial diffusivity (RD, Cohen's d = 0.514, 95% CIs -0.042 to 1.064) when compared to that of healthy controls, with the RD values being significantly correlated with the postoperative duration (r = 0.623, p < 0.001) after controlling the age, sex, and BMI in patients with ACLR. CONCLUSIONS: This study revealed that patients with ACLR have impaired integrity (lower FA values and higher RD values) in the CST contralateral to the ACLR injured limb in comparison with healthy controls. Decreased integrity (higher RD) of the CST in patients was significantly associated with longer postoperative duration, which hinted that impaired structural integrity of the CST may be a maladaptive process of neuroplasticity in ACLR.

Evaluation of the feeding safety of Moringa (Moringa oleifera L.) in the Sprague Dawley rat.

This study aimed to evaluate the safety of Moringa by comparing the effects of different gavage doses of Moringa. The general behavior, body weight, food intake, blood indexes, serum biochemical indexes, and histopathology of rats were used to determine the safety threshold and to provide a reference for the further development and use of Moringa as animal feed. 40 Sprague Dawley rats were selected and given transoral gavage for 28 consecutive days. The T1, T2 and T3 groups were observed for general behavior, body weight, and food intake. Blood and serum biochemical indices were quantified, and histopathology was performed to evaluate the effect and safety of Moringa. The results of the toxicological test showed that (1) Only T1 groups experienced diarrhea. (2) The body weight and food intake of rats in each group were normal compared with the control group. (3) The hematological and serum biochemical indices of rats in the T1 group were significantly different from those of CK but were in the normal range; (4) The results of microscopic examination of the heart, liver, spleen, lung, and kidney of rats in each group were normal, but inflammation occurred in stomach and jejunum of rats in the T1 group, but not in the ileum. The gastrointestinal tract of rats in the T2 and T3 groups were normal. (5) No abnormal death occurred in any of the treatment groups.The results of this study revealed that gavage of Moringa homogenate at a dose of 6 g/kg BW can cause diarrhea in rats. Although there is no pathological effect on weight, food intake, blood and serum biochemical indicators in rats, there are pathological textures in the gastrointestinal tissue caused by diarrhea. Therefore, the safety threshold of Moringa homogenate should be ≤ 3 g/kg BW.

Electroacupuncture modulates abnormal brain connectivity after ischemia reperfusion injury in rats: A graph theory-based approach.

BACKGROUND: Electroacupuncture (EA) has been shown to facilitate brain plasticity-related functional recovery following ischemic stroke. The functional magnetic resonance imaging technique can be used to determine the range and mode of brain activation. After stroke, EA has been shown to alter brain connectivity, whereas EA's effect on brain network topology properties remains unclear. An evaluation of EA's effects on global and nodal topological properties in rats with ischemia reperfusion was conducted in this study. METHODS AND RESULTS: There were three groups of adult male Sprague-Dawley rats: sham-operated group (sham group), middle cerebral artery occlusion/reperfusion (MCAO/R) group, and MCAO/R plus EA (MCAO/R + EA) group. The differences in global and nodal topological properties, including shortest path length, global efficiency, local efficiency, small-worldness index, betweenness centrality (BC), and degree centrality (DC) were estimated. Graphical network analyses revealed that, as compared with the sham group, the MCAO/R group demonstrated a decrease in BC value in the right ventral hippocampus and increased BC in the right substantia nigra, accompanied by increased DC in the left nucleus accumbens shell (AcbSh). The BC was increased in the right hippocampus ventral and decreased in the right substantia nigra after EA intervention, and MCAO/R + EA resulted in a decreased DC in left AcbSh compared to MCAO/R. CONCLUSION: The results of this study provide a potential basis for EA to promote cognitive and motor function recovery after ischemic stroke.

Structure and genome editing of type I-B CRISPR-Cas.

Type I CRISPR-Cas systems employ multi-subunit effector Cascade and helicase-nuclease Cas3 to target and degrade foreign nucleic acids, representing the most abundant RNA-guided adaptive immune systems in prokaryotes. Their ability to cause long fragment deletions have led to increasing interests in eukaryotic genome editing. While the Cascade structures of all other six type I systems have been determined, the structure of the most evolutionarily conserved type I-B Cascade is still missing. Here, we present two cryo-EM structures of the Synechocystis sp. PCC 6714 (Syn) type I-B Cascade, revealing the molecular mechanisms that underlie RNA-directed Cascade assembly, target DNA recognition, and local conformational changes of the effector complex upon R-loop formation. Remarkably, a loop of Cas5 directly intercalated into the major groove of the PAM and facilitated PAM recognition. We further characterized the genome editing profiles of this I-B Cascade-Cas3 in human CD3+ T cells using mRNA-mediated delivery, which led to unidirectional 4.5 kb deletion in TRAC locus and achieved an editing efficiency up to 41.2%. Our study provides the structural basis for understanding target DNA recognition by type I-B Cascade and lays foundation for harnessing this system for long range genome editing in human T cells.

Investigation of a novel biofilm model close to the original oral microbiome.

A more optimized culture medium used in vitro to mimic the bacterial composition of original oral flora as similar as possible remains difficult at present, and the goal of this study is to develop a novel oral biofilm medium to restore the original oral microbiome. Firstly, we conducted a systematic literature review by searching PubMed and summarized the current reported culture media in vitro. Seven culture media were found. We used mixed saliva as the origin of oral species to compare the effects of the above media in culturing oral multispecies biofilms. Results indicated that among the seven media brain heart infusion containing 1% sucrose (BHIs) medium, PG medium, artificial saliva (AS) medium, and SHI medium could obviously gain large oral biofilm in vitro. The nutrients contained in different culture media may be suitable for the growth of different oral bacteria; therefore, we optimized several novel media accordingly. Notably, results of crystal violet staining showed that the biofilm cultured in our modified artificial saliva (MAS) medium had the highest amount of biofilm biomass. 16S rRNA gene sequencing showed that the operational taxonomic units (OTUs) and Shannon index of biofilm cultured in MAS medium were also the highest among all the tested media. More importantly, the 16S rRNA gene sequencing analysis indicated that the biofilm cultured in MAS medium was closer to the original saliva species. Besides, biofilm cultured by MAS was denser and produced more exopolysaccharides. MAS supported stable biofilm formation on different substrata. In conclusion, this study demonstrated a novel MAS medium that could culture oral biofilm in vitro closer to the original oral microbiome, showing a good application prospect. KEY POINTS: • We compare the effects of different media in culturing oral biofilms • A novel modified artificial saliva (MAS) medium was obtained in our study • The MAS medium could culture biofilm that was closer to oral microbiome.

Epidemiological and molecular investigations of sequential outbreaks of Campylobacter jejuni infecting adults and schoolchildren in southeastern China, 2021-2022.

OBJECTIVES: To investigate cases of five Campylobacter jejuni outbreaks and describe laboratory characteristics of these infections. METHODS: Whole-genome sequencing and conventional methods were combined to thoroughly investigate the outbreaks, and data of contemporaneous sporadic cases was included for comparison. RESULTS: Seven sequence types (STs) of C. jejuni caused 83 cases, including ST9079 which recurred across 2 years. Trace-back investigation could not identify any food items of infection but detected identical campylobacters from food contacts. Phylogenetic analysis unveiled genetic closeness between outbreak strains and some concurrent sporadic strains, indicating local campylobacteriosis may not be wholly sporadic but rather a series of linked cases. Virulence genes disclosed species/case-specific signatures to differentiate outbreaks from truly non-outbreak strains. Resistance to fluoroquinolones and/or macrolides was prevalent (90.8%, 108/119), with a noteworthy portion exhibiting multidrug resistance (31.1%, 37/119). Five types of plasmids were harbored among outbreak isolates, of which one plasmid harboring anti-stress and resistant genes was rarely found in C. jejuni. CONCLUSIONS: This is the first reported sequential outbreak of C. jejuni in China. Our observations help to define the genomic landscape and antimicrobial resistance patterns of Campylobacter, emphasizing the need for a broader 'One Health' perspective to combat the threats posed by campylobacteriosis.

CEPs suppress auxin signaling but promote cytokinin signaling to inhibit root growth in Arabidopsis.

C-terminally encoded peptides (CEPs) are peptide hormones that function as mobile signals coordinating crucial developmental programs in plants. Previous studies have revealed that CEPs exert negative regulation on root development through interaction with CEP receptors (CEPRs), CEP DOWNSTREAMs (CEPDs), the cytokinin receptor ARABIDOPSIS HISTIDINE KINASE (AHKs) and the transcriptional repressor Auxin/Indole-3-Acetic Acid (AUX/IAA). However, the precise molecular mechanisms underlying CEPs-mediated regulation of root development via auxin and cytokinin signaling pathways still necessitate further detailed investigation. In this study, we examined prior research and elucidated the underlying molecular mechanisms. The results showed that both synthetic AtCEPs and overexpression of AtCEP5 markedly supressed primary root elongation and lateral root (LR) formation in Arabidopsis. Molecular biology and genetics elucidated how CEPs inhibit root growth by suppressing auxin signaling while promoting cytokinin signaling. In summary, this study elucidated the inhibitory effects of AtCEPs on Arabidopsis root growth and provided insights into their potential molecular mechanisms, thus enhancing our comprehension of CEP-mediated regulation of plant growth and development.

P2X7 receptor: a potential target for treating comorbid anxiety and depression.

In clinical practice, depression and anxiety frequently coexist, and they are both comorbid with somatic diseases. The P2X7R is an adenosine 5'-triphosphate (ATP)-gated non-selective cation channel that is widely expressed in immune-related cells. Under conditions of stress, chronic pain, and comorbid chronic physical illness, P2X7R activation in glial cells leads to neuroinflammation. This could contribute to the development of anxiety and depression-related emotional disturbances. Previous studies have shown that the P2X7 receptor (P2X7R) plays an important role in the pathogenesis of both anxiety and depression. Thus, the P2X7R may play a role in the comorbidity of anxiety and depression. Positron emission tomography can be used to assess the degree and location of neuroinflammation by monitoring functional and expression-related changes in P2X7R, which can facilitate clinical diagnoses and guide the treatment of patients with anxiety and depression. Moreover, single nucleotide polymorphisms (SNPs) in the P2X7R gene are associated with susceptibility to different types of psychiatric disorders. Thus, evaluating the SNPs of the P2X7R gene could enable personalized mood disorder diagnoses and treatments. If the P2X7R were set as a therapeutic target, selective P2X7R antagonists may modulate P2X7R function, thereby altering the balance of intra- and extra-cellular ATP. This could have therapeutic implications for treating anxiety and depression, as well as for pain management. According to in vitro and in vivo studies, the P2X7R plays an important role in anxiety and depression. In this review, we consider the potential of the P2X7R as a therapeutic target for comorbid anxiety and depression, and discuss the potential diagnostic and therapeutic value of this receptor.

Tensor Network Message Passing.

When studying interacting systems, computing their statistical properties is a fundamental problem in various fields such as physics, applied mathematics, and machine learning. However, this task can be quite challenging due to the exponential growth of the state space as the system size increases. Many standard methods have significant weaknesses. For instance, message-passing algorithms can be inaccurate and even fail to converge due to short loops, while tensor network methods can have exponential computational complexity in large graphs due to long loops. In this Letter, we propose a new method called "tensor network message passing." This approach allows us to compute local observables like marginal probabilities and correlations by combining the strengths of tensor networks in contracting small subgraphs with many short loops and the strengths of message-passing methods in globally sparse graphs, thus addressing the crucial weaknesses of both approaches. Our algorithm is exact for systems that are globally treelike and locally dense-connected when the dense local graphs have a limited tree width. We have conducted numerical experiments on synthetic and real-world graphs to compute magnetizations of Ising models and spin glasses, and have demonstrated the superiority of our approach over standard belief propagation and the recently proposed loopy message-passing algorithm. In addition, we discuss the potential applications of our method in inference problems in networks, combinatorial optimization problems, and decoding problems in quantum error correction.

Endogenous AND Logic DNA Nanomachine for Highly Specific Cancer Cell Imaging.

Intracellular cancer-related biomarker imaging strategy has been used for specific identification of cancer cells, which was of great importance to accurate cancer clinical diagnosis and prognosis studies. Localized DNA circuits with improved sensitivity showed great potential for intracellular biomarkers imaging. However, the ability of localized DNA circuits to specifically image cancer cells is limited by off-site signal leakage associated with a single-biomarker sensing strategy. Herein, we integrated the endogenous enzyme-powered strategy with logic-responsive and localized signal amplifying capability to construct a self-assembled endogenously AND logic DNA nanomachine (EDN) for highly specific cancer cell imaging. When the EDN encountered a cancer cell, the overexpressed DNA repairing enzyme apurinic/apyrimidinic endonuclease 1 (APE1) and miR-21 could synergistically activate a DNA circuit via cascaded localized toehold-mediated strand displacement (TMSD) reactions, resulting in amplified fluorescence resonance energy transfer (FRET) signal. In this strategy, both endogenous APE1 and miR-21, served as two "keys" to activate the AND logic operation in cancer cells to reduce off-tumor signal leakage. Such a multiplied molecular recognition/activation nanomachine as a powerful toolbox realized specific capture and reliable imaging of biomolecules in living cancer cells.

Bioorthogonal microglia-inspired mesenchymal stem cell bioengineering system creates livable niches for enhancing ischemic stroke recovery via the hormesis.

Mesenchymal stem cells (MSCs) experience substantial viability issues in the stroke infarct region, limiting their therapeutic efficacy and clinical translation. High levels of deadly reactive oxygen radicals (ROS) and proinflammatory cytokines (PC) in the infarct milieu kill transplanted MSCs, whereas low levels of beneficial ROS and PC stimulate and improve engrafted MSCs' viability. Based on the intrinsic hormesis effects in cellular biology, we built a microglia-inspired MSC bioengineering system to transform detrimental high-level ROS and PC into vitality enhancers for strengthening MSC therapy. This system is achieved by bioorthogonally arming metabolic glycoengineered MSCs with microglial membrane-coated nanoparticles and an antioxidative extracellular protective layer. In this system, extracellular ROS-scavenging and PC-absorbing layers effectively buffer the deleterious effects and establish a micro-livable niche at the level of a single MSC for transplantation. Meanwhile, the infarct's inanimate milieu is transformed at the tissue level into a new living niche to facilitate healing. The engineered MSCs achieved viability five times higher than natural MSCs at seven days after transplantation and exhibited a superior therapeutic effect for stroke recovery up to 28 days. This vitality-augmented system demonstrates the potential to accelerate the clinical translation of MSC treatment and boost stroke recovery.

High-frequency repetitive transcranial magnetic stimulation promotes ipsilesional functional hyperemia and motor recovery in mice with ischemic stroke.

Neurovascular decoupling plays a significant role in dysfunction following an ischemic stroke. This study aimed to explore the effect of low- and high-frequency repetitive transcranial magnetic stimulation on neurovascular remodeling after ischemic stroke. To achieve this goal, we compared functional hyperemia, cerebral blood flow regulatory factors, and neurochemical transmitters in the peri-infract cortex 21 days after a photothrombotic stroke. Our findings revealed that low- and high-frequency repetitive transcranial magnetic stimulation increased the real-time cerebral blood flow in healthy mice and improved neurobehavioral outcomes after stroke. Furthermore, high-frequency (5-Hz) repetitive transcranial magnetic stimulation revealed stronger functional hyperemia recovery and increased the levels of post-synaptic density 95, neuronal nitric oxide synthase, phosphorylated-endothelial nitric oxide synthase, and vascular endothelial growth factor in the peri-infract cortex compared with low-frequency (1-Hz) repetitive transcranial magnetic stimulation. The magnetic resonance spectroscopy data showed that low- and high-frequency repetitive transcranial magnetic stimulation reduced neuronal injury and maintained excitation/inhibition balance. However, 5-Hz repetitive transcranial magnetic stimulation showed more significant regulation of excitatory and inhibitory neurotransmitters after stroke than 1-Hz repetitive transcranial magnetic stimulation. These results indicated that high-frequency repetitive transcranial magnetic stimulation could more effectively promote neurovascular remodeling after stroke, and specific repetitive transcranial magnetic stimulation frequencies might be used to selectively regulate the neurovascular unit.

Current status of common cold-related knowledge, attitude, and practices among nursing students as well as relevant factors in China.

To understand the current status of cold-related knowledge, attitude, and practices (KAP) among nursing students as well as relevant factors, and provide a scientific basis for offering effective health education and promoting health care levels among nursing students. We conducted a survey of 668 nursing students using a self-designed "General Condition Questionnaire" and "Survey of common cold-related knowledge, attitude, and practices among students majoring in nursing." We used SPSS22.0 for data sorting and analysis; mean ±â€…standard deviation was used for statistical description of the questionnaire scores, and t-test and ANOVA (analysis of variance) were used for differences comparison between binary variables and polytomous variables of the relevant factors. The test level α was 0.05, and the difference was considered statistically significant when P < .05. The total KAP score of the nursing students was 128.47 ±â€…13.91 points, which is a good level. There were significant differences in the KAP scores based on gender, educational background, grade, whether relevant knowledge had been acquired, extracurricular activities, weekly exercise frequency, exercise time per session, coping method after catching a cold, and medicine purchase methods (P < .05). The KAP level for cold among nursing students is at a good level. It is recommended that the relevant departments of nursing schools strengthen the education of nursing students on the knowledge about cold and physical exercise.

Population Pharmacokinetics and Individualized Medication of Azithromycin for Injection in Children Under 6 Years Old.

Pharmacokinetic data for injectable azithromycin in children remain limited. This study aims to develop and validate a population pharmacokinetic model of azithromycin for injection in children under 6 years old and optimize its dosage regimen in this population. We prospectively enrolled patients under 6 years old who received azithromycin for injection at Beijing Friendship Hospital, Capital Medical University. Demographic information, clinical characteristics, and venous blood samples were collected in accordance with the research protocol. Azithromycin concentrations were determined using a validated UPLC-MS/MS method. The population pharmacokinetic model was structured using Phoenix NLME. The adequacy and robustness of the model was evaluated using VPC and bootstrap. We optimized azithromycin's dosing regimen for injection through Monte Carlo simulations. We included 254 plasma concentration data from 148 patients to establish the model. The clearance and volume were 1.27 L/h/kg and 45.6 L/kg, respectively. The covariates included were weight and age. VPC plots and nonparametric bootstrap showed that the final PPK model was reliable and robust. Based on Monte Carlo simulation, we derived a simple and practical dosing scheme. The results provided reference for individualized dosing in this population. The individualized dosing scheme based on Monte Carlo simulation can optimize clinical decision-making and guide personalized therapy.

Simulation-Assisted DNA Nanodevice Serve as a General Optical Platform for Multiplexed Analysis of Micrornas.

Small frame nucleic acids (FNAs) serve as excellent carrier materials for various functional nucleic acid molecules, showcasing extensive potential applications in biomedicine development. The carrier module and function module combination is crucial for probe design, where an improper combination can significantly impede the functionality of sensing platforms. This study explores the effect of various combinations on the sensing performance of nanodevices through simulations and experimental approaches. Variances in response velocities, sensitivities, and cell uptake efficiencies across different structures are observed. Factors such as the number of functional molecules loaded, loading positions, and intermodular distances affect the rigidity and stability of the nanostructure. The findings reveal that the structures with full loads and moderate distances between modules have the lowest potential energy. Based on these insights, a multisignal detection platform that offers optimal sensitivity and response speed is developed. This research offers valuable insights for designing FNAs-based probes and presents a streamlined method for the conceptualization and optimization of DNA nanodevices.

Effects of electroacupuncture on imaging and behavior in rats with ischemic stroke through miR-212-5p.

BACKGROUND: Ischemic stroke is a serious disease leading to significant disability in humans worldwide. Increasing evidence suggests that some microRNAs (miRNAs) participate in the pathophysiology of ischemic stroke. A key role for MiR-212 has been found in neuronal function and synaptic plasticity. Ischemic stroke can be effectively treated with electroacupuncture (EA); however, there is a lack of understanding of the relevant mechanisms. In this study, we employed behavioral test and resting-state functional magnetic resonance imaging (rs-fMRI) to detect behavioral and brain function alterations in rats suffering from ischemic stroke. The efficacy of EA therapy and miR-212-5p's role in this process were also evaluated. METHODS AND RESULTS: Forty rats were randomly divided into the following groups: Sham, middle cerebral artery occlusion/reperfusion (MCAO/R), MCAO/R + EA, MCAO/R + EA + antagomir-negative control and MCAO/R + EA + antagomir-212-5p groups. Behavioral changes were assessed by Catwalk gait analysis prior to and after modeling. Rs-fMRI was performed at one week after EA treatment, amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) were calculated to reveal neural activity. Furthermore, neuronal apoptosis in the ischemic penumbra was analyzed using a TUNEL assay. Treatment with EA significantly improved the performance of rats in the behavioral test. The motor and cognition-related brain regions showed decreased ALFF and ReHo following focal cerebral ischemia-reperfusion, and EA treatment could reactivate these brain regions. Moreover, EA treatment significantly decreased MCAO/R-induced cell death. However, the transfection of antagomir-212-5p attenuated the therapeutic effect of EA. CONCLUSIONS: In conclusion, the results suggested that EA improved the behavioral and imaging outcomes of ischemic stroke through miR-212-5p.

Thin and Plain Supplementary Motor Area in Chronic Ankle Instability: A Volume and Surface-based Morphometric Study.

CONTEXT: The supplementary motor area (SMA) is involved in the functional deficits of chronic ankle instability (CAI), but the structural basis of its abnormalities remains unclear. OBJECTIVE: To determine the differences in volume and surface-based morphological features of SMA between patients with CAI and healthy controls, and their relationship with the clinical features of CAI. DESIGN: Cross-sectional study. SETTING: Sports medicine laboratory. PATIENTS OR OTHER PARTICIPANTS: A total of 32 CAI patients (10 females; age: 32.46 ± 7.51 years) and 31 healthy controls (12 females; age: 29.70 ± 8.07 years) participated in this study. MAIN OUTCOME MEASURE(S): Participants perform T1 structural magnetic resonance imaging and calculate volume and surface-based morphological features of SMA subregions. These included anterior and posterior subdivisions of Brodmann's area 6 m (6 ma/6 mp), and supplementary and cingulate eye fields. Between-group comparisons and correlation analysis with clinical features of CAI were performed. RESULTS: Moderately thinner 6 mp (Cohen's d = -0.61) and moderately plainer 6 ma (Cohen's d = -0.70) were observed in patients compared with controls. Before and after regressing out the covariates, the thinner 6 mp was correlated with the lower foot and ankle ability measure scores of daily activities (r-before=0.400, r-after = 0.449). CONCLUSIONS: Patients with CAI had a thinner posterior subdivision (motor-output site) and a plainer anterior subdivision (motor-planning site) of SMA than that of controls. The thin motor-output site of the SMA is associated with ankle dysfunction in patients. These morphologic evidence of maladaptive neuroplasticity in SMA might promote more targeted rehabilitation of CAI.

Long-term grazing improved soil chemical properties and benefited community traits under climatic influence in an alpine typical steppe.

Grazing and climate change both contribute to diversity loss and productivity fluctuations. Sensitive climate conditions and long-term grazing activities have a profound influence on community change, particularly in high-altitude mountain grassland ecosystems. However, knowledge about the role of long-term continuous grazing management on diversity, productivity and the regulation mechanisms in fragile grassland ecosystems is still rudimentary. We conducted a long-term grazing experiment on an alpine typical steppe in the Qilian Mountains to assess effects of grazing intensity on soil, diversity, productivity and the regulation mechanisms. Plants and soil were sampled along grazing gradients at different distances from the pasture entrance (0, 0.3, 0.6, 0.9, 1.2 and 1.5 km) under the non-growing (WP) and the growing season grazing pasture (SAP). The results revealed that community diversity and biomass did not change significantly on a time scale, while the concentration of soil organic carbon and total phosphorus increased significantly. Heavy grazing (0-0.3 km) decreased community diversity and biomass. Grazing increased soil chemical properties in heavy grazed areas of WP, while the opposite was recorded in SAP. Soil chemical properties explained the largest variances in community diversity and community biomass. The prediction model indicates that grazing in WP mainly affects community diversity through soil chemical properties, and promotes a positive correlation between community diversity and community biomass; in SAP, the direct effect of grazing gradients on community diversity and biomass is the main pathway, but not eliminating the single positive relationship between diversity and biomass, which means that diversity can still be used as a potential resource to promote productivity improvement. Therefore, we should focus on the regulation of soil chemical properties in WP, such as the health and quality of soil, strengthening its ability to store water, sequester carbon and increase nutrients; focus on the management of livestock in SAP, including providing fertilizer and sowing to increase diversity and production in heavily grazed regions and reducing grazing pressure through regional rotational grazing. Ultimately, we call for strengthening the stability and sustainability of ecosystems through targeted and active human intervention in ecologically sensitive areas to cope with future grazing pressures and climate disturbances.

Biomineralization-Inspired Anti-Caries Strategy Based on Multifunctional Nanogels as Mineral Feedstock Carriers.

Background: Dentin caries remains a significant public concern, with no clinically viable material that effectively combines remineralization and antimicrobial properties. To address this issue, this study focused on the development of a bio-inspired multifunctional nanogel with both antibacterial and biomineralization properties. Methods: First, p(NIPAm-co-DMC) (PNPDC) copolymers were synthesized from N-isopropylacrylamide (NIPAm) and 2-methacryloyloxyethyl-trimethyl ammonium chloride (DMC). Subsequently, PNPDC was combined with γ-polyglutamic acid (γ-PGA) through physical cross-linking to form nanogels. These nanogels served as templates for the mineralization of calcium phosphate (Cap), resulting in Cap-loaded PNPDC/PGA nanogels. The nanogels were characterized using various techniques, including TEM, particle tracking analysis, XRD, and FTIR. The release properties of ions were also assessed. In addition, the antibacterial properties of the Cap-loaded PNPDC/PGA nanogels were evaluated using the broth microdilution method and a biofilm formation assay. The remineralization effects were examined on both demineralized dentin and type I collagen in vitro. Results: PNPDC/PGA nanogels were successfully synthesized and loaded with Cap. The diameter of the Cap-loaded PNPDC/PGA nanogels was measured as 196.5 nm at 25°C and 162.3 nm at 37°C. These Cap-loaded nanogels released Ca2+ and PO43- ions quickly, effectively blocking dental tubules with a depth of 10 µm and promoting the remineralization of demineralized dentin within 7 days. Additionally, they facilitated the heavy intrafibrillar mineralization of type I collagen within 3 days. Moreover, the Cap-loaded nanogels exhibited MIC50 and MIC90 values of 12.5 and 50 mg/mL against Streptococcus mutans, respectively, with an MBC value of 100 mg/mL. At a concentration of 50 mg/mL, the Cap-loaded nanogels also demonstrated potent inhibitory effects on biofilm formation by Streptococcus mutans while maintaining good biocompatibility. Conclusion: Cap-loaded PNPDC/PGA nanogels are a multifunctional biomimetic system with antibacterial and dentin remineralization effects. This strategy of using antibacterial nanogels as mineral feedstock carriers offered fresh insight into the clinical management of caries.