Adeno-associated virus mediated gene delivery of Perm1 enhances cardiac contractility in mice.

Reduced muscle contractility and mitochondrial bioenergetics are the hallmarks of systolic heart failure. There is currently no therapy targeting both. Here, we show that gene delivery of Perm1 via adeno-associated virus (AAV) simultaneously enhances cardiac contractility and mitochondrial biogenesis in C57BL6 mice. Moreover, we found that PERM1 interacts with Troponin C (TnC), a key contractile protein in striated muscle, and that AAV-Perm1 led to upregulation of TnC. This study suggests that gene delivery of Perm1 may be a novel therapeutic approach to treat systolic heart failure by simultaneously restoring cardiac contractility and mitochondrial bioenergetics.

A visual pollination mechanism of a new specialized pollinating weevil-plant reciprocity system.

Introduction: Pollinating flower-consuming mutualisms are considered exemplary models for studying coevolution due to their rarity. Visual cues are considered to have a major role in facilitating the evolution of floral patterns in these systems. We present a new specialized pollinating flower-consuming mutualism from the plant Wurfbainia villosa, which is a traditional Chinese herbal medicine, by a pollinating weevil, Xenysmoderes sp. Methods: In this study, We utilized monochrome plates for binary-choice tests to determine weevil color preferences, conducted behavioral choice experiments, using trackballs, photographed flowers and weevils, and employed blue sticky boards to attract weevils in the field. Results: Tests were conducted using colorpreferring weevils in both indoor and outdoor field systems, and validation experiments were performed. Behavioral tests were conducted to investigate the role of the visual cues in the pollinator attraction of W. villosa, which is a selfcompatible insect-pollinated plant that relies primarily on the Xenysmoderes sp. weevil for pollination due to its specialized gynandrium-like structure. Behavioral tests demonstrated that a blue color wavelength of 480 nm and the blue color system, as along with the UV-style pattern of the flowers, particularly the parts with specialized gynandrium-like structures in the labellum, were significantly attractive to both male and female weevils. These results were further confirmed through the field blue sticky board trap method. Discussion: These findings indicated that the interaction between W. villosa and Xenysmoderes sp. weevil was a novel symbiotic relationship involving pollinator flower consumption. Additionally, Wurfbainia villosa flowers developed specific visual cues of UV patterns and specialized structures that played a crucial role in attracting pollinators.

Development and validation of a nomogram for individualizing fall risk in patients with hematologic malignancies.

Inpatient falls are common adverse events especially for patients with hematologic malignancies. A fall-risk prediction model for patients with hematologic malignancies are still needed. Here we conducted a multicenter study that prospectively included 516 hospitalized patients with hematologic malignancies, and developed a nomogram for fall risk prediction. Patients were divided into the modeling group (n = 389) and the validation group (n = 127). A questionnaire containing sociodemographic factors, general health factors, disease-related factors, medication factors, and physical activity factors was administered to all patients. Logistic regression analysis revealed that peripheral neuropathy, pain intensity, Morse fall scale score, chemotherapy courses, and myelosuppression days were risk factors for falls in patients with hematologic malignancies. The nomogram model had a sensitivity of 0.790 and specificity of 0.800. The calibration curves demonstrated acceptable agreement between the predicted and observed outcomes. Therefore, the nomogram model has promising accuracy in predicting fall risk in patients with hematologic malignancies.

Prenatal ultrasound diagnosis of fetal volvulus without malrotation: A case report.

Cases of fetal volvulus without malrotation are extremely uncommon and pose a life-threatening condition of acute abdomen. In cases of inadequate intestinal rotation, the narrowing of the attachment of the mesenteric root can easily cause intestinal torsion and consequent local blood circulation disorders within the intestinal tract, leading to aseptic necrosis and simultaneous intestinal perforation, resulting in meconium peritonitis, ascites, anemia, and potentially fetal death. In ultrasound examinations, it may be the preferred examination method for this disease. Ultrasound physicians should improve their understanding of this disease in prenatal diagnosis, as it has important clinical value for obstetric management and neonatal treatment, thereby potentially improving adverse pregnancy outcomes.

Post-transplant lymphoproliferative disorders after allogeneic hematopoietic stem cell transplantation: a case report, meta-analysis, and systematic review.

BACKGROUND: Post-transplant lymphoproliferative disorders (PTLD) are rare but severe complications that occur after solid organ or allogeneic hematopoietic stem cell transplantations (allo-HSCT), with rapid progression and high mortality. Primary central nervous system (CNS)-PTLD are rarely recognized histo-pathologically. In addition, the diagnostic value of the Epstein-Barr virus (EBV) DNA copies in CNS-PTLD remains poorly understood. OBJECTIVES: We herein report a case of monomorphic EBV-associated CNS-PTLD (diffuse large B-cell lymphoma, DLBCL) after allo-HSCT and perform a meta-analysis to assess the efficacy of PTLD treatment strategies in recent years. METHODS: We present the case report covering clinical manifestations, diagnosis, treatment, and outcomes of a patient with primary CNS-PTLD. Additionally, we include a systematic review and meta-analysis of the clinical characteristics of 431 patients with PTLD after allo-HSCT. We evaluate the main treatment options and outcomes of PTLD management, including rituximab, chemotherapies, and autologous or human leukocyte antigen (HLA)-matched EBV-specific cytotoxic T lymphocyte infusion (EBV-CTLs)/donor lymphocyte infusion (DLI). RESULTS: The meta-analysis revealed an overall response rate of 69.0% for rituximab alone (95% CI: 0.47-0.84), 45.0% for rituximab plus chemotherapies (95% CI: 0.15-0.80), and 91.0% for rituximab plus EBV-CTLs/DLI (95% CI: 0.83-0.96). The complete response (CR) rate after treatments for PTLD was 67.0% (95% CI: 0.56-0.77). Moreover, the 6-month and 1-year overall survival (OS) rate was 64.0% (95% CI: 0.31-0.87) and 49.0% (95% CI: 0.31-0.68), respectively. CONCLUSIONS: This case highlighted the urgent need for effective, low-toxic treatment regimens for CNS-PTLD. Our meta-analysis suggested that rituximab combined with EBV-CTLs/DLI could be a favorable strategy for the management of PTLD after allo-HSCT.

Effects of Life-Long Exercise on Age-Related Inflammation, Apoptosis, Oxidative Stress, Ferroptosis Markers, and NRF2/KAEP 1/Klotho Pathway in Rat Kidneys.

Xi-Kun Yuan Pin-Shi Ni Zhen-Hao Yan Zhi Yu Zhuang-Zhi Wang Chen-Kai Zhang Fang-Hui Li Xiao-Ming Yu 1Sports Department, Nanjing University of Science and Technology ZiJin College, Nanjing, China, 2School of Sport Sciences, Nanjing Normal University, Nanjing, China, 3Shanghai Seventh People's Hospital, Shanghai, China To investigate the effects of life-long exercise (LLE) on age-related inflammatory cytokines, apoptosis, oxidative stress, ferroptosis markers, and the NRF2/KAEP 1/Klotho pathway in rats. Eight-month-old female Sprague-Dawley rats were divided into four groups: 1) LLE: 18-month LLE training starting at 8 months of age, 2) Old moderate-intensity continuous training (OMICT): 8 months of moderate-intensity continuous training starting at 18 months of age, 3) Adult sedentary (ASED): 8 month-old adult sedentary control group, and 4) Old sedentary (OSED): a 26-month-old sedentary control group. Hematoxylin eosin staining was performed to observe the pathological changes of kidney tissue injury in rats; Masson's staining to observe the deposition of collagen fibers in rat kidney tissues; and western blotting to detect the expression levels of IL-6, IL 1beta, p53, p21, TNF-alpha, GPX4, KAEP 1, NRF2, SLC7A11, and other proteins in kidney tissues. Results: Compared with the ASED group, the OSED group showed significant morphological changes in renal tubules and glomeruli, which were swollen and deformed, with a small number of inflammatory cells infiltrated in the tubules. Compared with the OSED group, the expression levels of inflammation-related proteins such as IL-1beta, IL-6, TNF alpha, and MMP3 were significantly lower in the LLE group. Quantitative immunofluorescence analysis and western blotting revealed that compared with the ASED group, KAEP 1 protein fluorescence intensity and protein expression levels were significantly enhanced, while Klotho and NRF2 protein fluorescence intensity and protein expression levels were reduced in the OSED group. Compared with the OSED group, KAEP 1 protein fluorescence intensity and protein expression levels were reduced in the LLE and OMICT groups. Klotho and KAEP 1 protein expression levels and immunofluorescence intensity were higher in the LLE group than in the OSED group. The expression levels of GPX4 and SLC7A11, two negative marker proteins associated with ferroptosis, were significantly higher in the LLE group than in the OSED group, while the expression of p53 a cellular senescence-associated protein that negatively regulates SLC7A11, and the downstream protein p21 were significantly decreased. LLE may ameliorated aging-induced oxidative stress, inflammatory response, apoptosis, and ferroptosis by regulating Klotho and synergistically activating the NRF2/KAEP 1 pathway. Keywords: Life-long exercise, Moderate intensity continuous training, Aging, Kidney tissue, Ferroptosis.

[Relationship between the Age of Diagnosis and Clinical Outcomes in Children with Chronic Immune Thrombocytopenia].

OBJECTIVE: To explore the relationship between age at diagnosis and clinical outcomes in children with chronic immune thrombocytopenia (cITP). METHODS: A retrospective analysis was conducted on 117 children with cITP, according to the age at which the patient was diagnosed with ITP, they were divided into two groups: the<10 year old group and the ≥10 year old group, the general information and clinical outcomes of the two groups of children were compared and analyzed. Logistic regression analysis was used to analyzed the impact of age at the time of diagnosis on clinical outcomes, and the predictive evaluation value of age on outcomes was assessed by the receiver operation characteristic. RESULTS: Compared with the group with diagnosed age<10 years old, the proportion of second-line drug treatment (41.46% vs 18.42%) in the diagnosed age group ≥10 years old was significantly higher, and the proportion of ≥grade 3 bleeding (36.59% vs 13.16%) was significantly higher, which was significant statistical differences ( P < 0.05). However, there was no statistically significant difference in the proportion of untreated CR between the two groups after 5 years of diagnosis (P >0.05). Logistic regression results show that age (older) was an unfavorable/dangerous influencing factor for the occurrence of ≥grade 3 bleeding after second-line treatment (OR >1, P < 0.05). For the occurrence of CR after 5 years of diagnosis without treatment, age was not the influencing factor (P >0.05). ROC analysis showed that age have a certain predictive and evaluative effect on the use of second-line treatment and the occurrence of ≥grade 3 bleeding, with AUC of 0.741(95%CI : 0.549-0.938) and 0.786(95%CI : 0.605-0.940), respectively. However, there was basically no predictive evaluation value for the occurrence of CR after 5 years of diagnosis without treatment. CONCLUSION: Older age at the time of diagnosis is not conducive to the prognosis of cITP patients.

[Clinical Significance of the Levels of Peripheral Blood Tregs and Cytokines IL-35, TGF-ß and IL-10 in Hemophilia A Patients with Fâ § Inhibitor].

OBJECTIVE: To explore the levels of regulatory T cells (Tregs) and cytokines IL-35, TGF-ß and IL-10 in peripheral blood of hemophilia A(HA) patients with FⅧ inhibitor and their clinical significance. METHODS: 43 HA patients admitted to the Hematology Department of the Affiliated Hospital of North China University of Science and Technology from October 2019 to December 2020 were selected, including 6 cases with FⅧ inhibitor and 37 cases without FⅧ inhibitor. In addition, 20 healthy males who underwent physical examinations were selected as healthy controls. Flow cytometry was used to detect the levels of CD4 + CD25 + CD127 - Tregs in peripheral blood of the HA patients and healthy controls, and ELISA assay was used to detect the expression levels of IL-35, TGF-ß and IL-10 in serum, and their differences between different groups were compared. RESULTS: Compared with the healthy control group, the level of Tregs in HA patients was decreased, and the level of Tregs in the FⅧ inhibitor positive group was the lowest, the difference was statistically significant (P <0.05). There was no significant difference in the expression level of Tregs in HA patients of different severity levels. The serum IL-35, TGF-ß, and IL-10 levels in both FⅧ inhibitor negative and positive groups were significantly lower than those in healthy control group, and those in FⅧ inhibitor positive group were significantly lower than those in FⅧ inhibitor negative group (all P <0.05). CONCLUSION: The decrease of Tregs, IL-35, TGF-ß, and IL-10 levels in HA patients may be related to the formation of FⅧ inhibitors.

In-situ construction of biomineralized cadmium sulfide-Rhodopseudomonas palustris hybrid system: Mechanism of synergistic light utilization.

Sulfide biomineralization is a microorganism-induced process for transforming the environmentally hazardous cadmium into useful resource utilization. This study successfully constructed cadmium sulfide nanoparticles-Rhodopseudomonas palustris (Bio-CdS NPs-R. palustris) hybrids. For the self-assembling hybrids, Bio-CdS NPs were treated as new artificial-antennas to enhance photosynthesis, especially under low light (LL). Bacterial physiological results of hybrids were significantly increased, particularly for cells under LL, with higher enhancement photon harvesting ability. The enhancement included the pigment contents, and the ratio of the peripheral light-harvesting complex Ⅱ (LH2) to light-harvesting Ⅰ (1.33 ± 0.01 under LL), leading to the improvements of light-harvesting, transfer, and antenna conversion efficiencies. Finally, the stimulated electron chain of hybrids improved bacterial metabolism with increased nicotinamide adenine dinucleotide (NADH, 174.5% under LL) and adenosine triphosphate (ATP, 41.1% under LL). Furthermore, the modified photosynthetic units were induced by the up-regulated expression of fixK, which was activated by reduced oxygen tension of the medium for hybrids. fixK up-regulated genes encoding pigments (crt, and bch) and complexes (puf, pucAB, and pucC), leading to improved light-harvesting and transfer, and transform ability. This study provides a comprehensive understanding of the solar energy utilization mechanism of in-situ semiconductor-phototrophic microbe hybrids, contributing to further theoretical insight into their practical application.

Micropeptide MPM regulates cardiomyocyte proliferation and heart growth via the AKT pathway.

The role of micropeptide in cardiomyocyte proliferation remains unknown. We found that MPM (micropeptide in mitochondria) was highly expressed in cardiomyocytes. Compared to MPM+/+ mice, MPM knockout (MPM-/-) mice exhibited reduction in left ventricular (LV) mass, myocardial thickness and LV fractional shortening. RNA-sequencing analysis in H9c2, a rat cardiomyocyte cell line, identified downregulation of cell cycle-promoting genes as the most significant alteration in MPM-silencing cells. Consistently, gain- and loss-of-function analyses in H9c2 cells revealed that cardiomyocyte proliferation was repressed by silencing MPM but was promoted by overexpressing MPM. Moreover, the cardiomyocytes in the hearts of MPM-/- mice displayed reduced proliferation rates. Mechanism investigations disclosed that MPM is crucial for AKT activation in cardiomyocytes. We also identified an interaction between MPM and PTPMT1, and found that silencing PTPMT1 attenuated the effect of MPM in activating the AKT pathway, whereas inhibition of the AKT pathway abrogated the role of MPM in promoting cardiomyocyte proliferation. Collectively, these results indicate that MPM may promote cardiomyocyte proliferation and thus heart growth by interacting with PTPMT1 to activate the AKT pathway. Our findings identify the novel function and regulatory network of MPM and highlight the importance of micropeptides in cardiomyocyte proliferation and heart growth.

Characteristics and Genesis of Carbonate Weathering Crust Reservoirs: A Case from the Ma5Member of Ordovician in Gaoqiao Area, Ordos Basin, China.

The hydrocarbon reserves in carbonate rocks account for about half of the global hydrocarbon reserves and are an important reservoir type. The Ordovician Majiagou Formation in the central Ordos Basin is a representative weathering crust reservoir. The Caledonian movement uplifted the stratum as a whole, and subsequently, 120 million years of exposed weathering, denudation, and leaching created this unique karst paleomorphology. Dolomite reservoirs have developed dissolved pores and microfractures, which are the best reserved spaces for natural gas and good hydrocarbon migration channels. This paper takes the Ma5Member (hereinafter referred to as Ma51+2) carbonate reservoir in Gaoqiao Gas Field as the research target, based on the core, thin section, cathodoluminescence, logging data, etc., and systematically study the effect of karstification on the reservoir and the genesis of the dolomite reservoir. The results show that the depositional period of the Ordovician Majiagou strata is a regression cycle and the depositional environment is a limited evaporative tidal flat. The reservoir lithology of Ma51+2 is mainly gypsiferous dolomite and micrite dolomite. The reservoir space types consist of intergranular pores, gypsum mold pore, intragranular dissolution pores, intercrystalline pores, and microfractures. The porosity has values from 0.3 to 11.2% (mostly less than 5.0%) with an average of 3.3%, and the permeability ranges from 0.003 to 13.2 mD (mostly less than 1 mD) with an average of 0.36 mD. Karstification is divided into three periods, including syngenetic karst, eogenetic karst, and burial karst. The sedimentary microfacies determine the material basis of the reservoir, and multistage karstification finally modifies the physical properties. By deeply exploring the formation mechanism and influencing factors of the carbonate reservoir in the Ordovician Majiagou Formation, it provides an important theoretical basis and practical guidance for oil and gas exploration and development. At the same time, it also has important reference value for understanding and predicting the development law and distribution characteristics of carbonate reservoirs under similar geological background.

Single-Probe-Based Sensor Array for Fingerprint Recognition of Trivalent Metal Ions and Application in Water Identification.

Abnormal concentration levels of trivalent metal ions (M3+) might hinder their natural biological activities in physiological processes and cause severe health hazards. Herein, a dual-chromophore probe (RhB-TPE) composed of rhodamine and tetraphenylethene (TPE) units was synthesized and explored for discriminating M3+ ions. It exhibited special aggregation and AIE properties in aqueous media. Its ensemble with anionic surfactant SDBS assemblies (RhB-TPE/SDBS) could be utilized as fluorescent sensors for selective and sensitive detection of M3+ ions such as Fe3+, Al3+, and Cr3+ by illustrating quenched TPE emission and switched-on rhodamine emission. Moreover, the use of SDBS assemblies at two concentrations could provide a single-probe-based sensor array and realize four-signal pattern recognition of different concentrations of the three M3+ ions and identify M3+ mixtures or unknown samples. The cross-reactive fluorescence variation was attributed to the M3+ influence on the FRET process from TPE to open-ring form rhodamine in the two ensemble sensors. With the coexistence of Al3+, the optimized RhB-TPE/SDBS ensemble sensor array was successfully applied to differentiate commercially available brand mineral water and purified water, as well as tap water. The present work provides a novel strategy to generate a single-probe-based sensor array and realizes fingerprint recognition of three trivalent metal ions and efficient discrimination of different types of water. The modulation FRET process of a dual chromophore in different surfactant ensembles inspires the future construction of novel and effective sensing platforms.

Polydopamine-induced biomimetic mineralization strategy to generate hydroxyapatite for the preparation of carbon fiber composites with excellent mechanical properties.

Living organisms have developed a miraculous biomineralization strategy to form multistage organic-inorganic composites through the orderly assembly of hard/soft substances, achieving mechanical enhancement of materials from the nanoscale to the macroscale. Inspired by biominerals, this study used polydopamine (PDA) coating as a template to induce the growth of hydroxyapatite (HAP) on the surface of carbon fibers (CFs) for enhancing the interfacial properties of the CF/epoxy resin composites. This polydopamine-assisted hydroxyapatite formation (pHAF) biomimetic mineralization strategy constructs soft/hard ordered structure on the CF surface, which not only improves the chemical reaction activity of the CFs but also increases the fiber surface roughness. This, in turn, enhances the interaction and loading delivery among the fibers and the matrix. Compared to the untreated carbon fiber/epoxy resin (CF/EP) composites, the prepared composites showed a substantial enhancement in interlaminar shear strength (ILSS), flexural strength, and interfacial shear strength (IFSS), with improvements of 45.2 %, 46.9 %, and 60.5 %, respectively. This can be attributed to the HAP nanolayers increasing the adhesion and mechanical interlocking with the CFs to the matrix. This study provides an interface modification method of biomimetic mineralization for the preparation of high strength CF composites.

Conservation and specialization of the Ycf2-FtsHi chloroplast protein import motor in green algae.

The protein import motor in chloroplasts plays a pivotal role in their biogenesis and homeostasis by driving the translocation of preproteins into chloroplasts. While the Ycf2-FtsHi complex serves as the import motor in land plants, its evolutionary conservation, specialization, and mechanisms across photosynthetic organisms are largely unexplored. Here, we isolated and determined the cryogenic electron microscopy (cryo-EM) structures of the native Ycf2-FtsHi complex from Chlamydomonas reinhardtii, uncovering a complex composed of up to 19 subunits, including multiple green-algae-specific components. The heterohexameric AAA+ ATPase motor module is tilted, potentially facilitating preprotein handover from the translocon at the inner chloroplast membrane (TIC) complex. Preprotein interacts with Ycf2-FtsHi and enhances its ATPase activity in vitro. Integrating Ycf2-FtsHi and translocon at the outer chloroplast membrane (TOC)-TIC supercomplex structures reveals insights into their physical and functional interplay during preprotein translocation. By comparing these findings with those from land plants, our study establishes a structural foundation for understanding the assembly, function, evolutionary conservation, and diversity of chloroplast protein import motors.

Structural insights into the chloroplast protein import in land plants.

Chloroplast proteins are imported via the translocon at the outer chloroplast membrane (TOC)-translocon at the inner chloroplast membrane (TIC) supercomplex, driven by an ATPase motor. The Ycf2-FtsHi complex has been identified as the chloroplast import motor. However, its assembly and cooperation with the TIC complex during preprotein translocation remain unclear. Here, we present the structures of the Ycf2-FtsHi and TIC complexes from Arabidopsis and an ultracomplex formed between them from Pisum. The Ycf2-FtsHi structure reveals a heterohexameric AAA+ ATPase motor module with characteristic features. Four previously uncharacterized components of Ycf2-FtsHi were identified, which aid in complex assembly and anchoring of the motor module at a tilted angle relative to the membrane. When considering the structures of the TIC complex and the TIC-Ycf2-FtsHi ultracomplex together, it becomes evident that the tilted motor module of Ycf2-FtsHi enables its close contact with the TIC complex, thereby facilitating efficient preprotein translocation. Our study provides valuable structural insights into the chloroplast protein import process in land plants.

Organolanthanide Single-Molecule Magnets with Heterocyclic Ligands.

Lanthanide (Ln) based mononuclear single-molecule magnets (SMMs) provide probably the finest ligand regulation model for magnetic property. Recently, the development of such SMMs has witnessed a fast transition from coordination to organometallic complexes because the latter provides a fertile, yet not fully excavated soil for the development of SMMs. Especially those SMMs with heterocyclic ligands have shown the potential to reach higher blocking temperature. In this minireview, we give an overview of the design principle of SMMs and highlight those "shining stars" of heterocyclic organolanthanide SMMs based on the ring sizes of ligands, analysing how the electronic structures of those ligands and the stiffness of subsequently formed molecules affect the dynamic magnetism of SMMs. Finally, we envisaged the future development of heterocyclic Ln-SMMs.

PBI derivatives/surfactant-based fluorescent ensembles: Sensing of multiple aminoglycoside antibiotics and interaction mechanism studies.

Fluorescent aggregates and ensembles have been widely applied in fabrication of fluorescent sensors due to their capacity of encapsulating fluorophores and modulating their photophysical properties. In the present work, fluorescent ensembles based on anionic surfactant SDS assemblies and perylene derivatives (PBIs) were particularly constructed. Three newly synthesized neutral PBI derivatives with different structures, PO, PC1 and PC2, were used for the purpose to evaluate probe structure influence on constructing fluorescent ensembles. The one with hydrophilic side chains, PO, experienced distinct photophysical modulation effect by SDS assemblies. The ensemble based on PO@SDS assemblies displayed effective fluorescence variation to antibiotic aminoglycosides (AGs). To improve cross-reactivity and discrimination capability of ensembles, a second probe, coumarin, was introduced into PO@SDS assemblies. The resultant ternary sensor, CM-PO@SDS, exhibited good qualitative and quantitative detection capabilities, and achieved differentiation of eight AGs and mixed AG samples both in aqueous solution and actual biological fluid, like human serum. Sensing mechanism studies revealed that hydrogen bonding, electrostatic and hydrophobic interactions are involved in the sensing process. This surfactant-based fluorescent ensemble provides a simple and feasible method for assessing AGs levels. Meanwhile, this work may provide some insights to design reasonable probes for constructing effective single-system based discriminative fluorescent amphiphilic sensors.

Targeting epigenetic enzymes for autism treatment.

Emerging preclinical autism research has shown the therapeutic promise of pharmacological inhibitors for epigenetic enzymes, such as histone deacetylases (HDAC), euchromatic histone methyltransferases (EHMT), and lysine-specific histone demethylase 1A (LSD1). These interventions restore gene expression, synaptic function, and behavioral performance in autism models, highlighting a new strategy for autism treatment.

Efficacy of cognitive-behavioral therapy combined with habit reversal training on anxiety disorders in children with Tourette's syndrome.

BACKGROUND: Cognitive-behavioral therapy (CBT) and habit reversal training (HRT) have shown application potential in addressing tic symptoms and comorbid psychiatric conditions. Despite their theoretical potential, empirical evidence on their combined efficacy remains limited. AIM: To evaluate the efficacy of CBT combined with HRT on anxiety disorders in children with Tourette's syndrome (TS). METHODS: Clinical data of children with TS admitted to our hospital from January 2022 to June 2023 were collected, and the patients were grouped into the conventional therapy (control) group and the CBT combined with HRT group. Baseline characteristics, anxiety scores, tic severity scores, treatment adherence, and parental satisfaction were assessed. Statistical analysis was performed using t-tests, chi-square tests, and correlation analysis. RESULTS: A total of 136 patients, including 65 patients in the control group and 71 patients in the CBT combined with HRT group, were included. The CBT combined with HRT group showed remarkable improvements compared with the control group. Post-intervention assessment revealed a decrease in anxiety scores from 63.52 ± 1.81 to 40.53 ± 1.64 (t = 2.022, P = 0.045), and the Yale Global Tic Severity Scale total score decreased from 22.14 ± 5.67 to 16.28 ± 4.91 (t = 2.288, P = 0.024). Treatment adherence was significantly higher in the CBT combined with HRT group (85.47 ± 7.62%) compared with the control group (82.32 ± 6.54%; t = 2.596, P = 0.010). Parental satisfaction scores were also higher in the CBT combined with HRT group (8.69 ± 1.77) compared with the control group (7.87 ± 1.92; t = 2.592, P = 0.011). CONCLUSION: This study demonstrates that CBT combined with HRT significantly reduces anxiety symptoms and tic severity in children with TS, with higher treatment adherence and parental satisfaction. These findings support the potential application of this comprehensive therapeutic approach for TS treatment.

High methionine intake alters gut microbiota and lipid profile and leads to liver steatosis in mice.

Methionine is an important sulfur-containing amino acid. Health effects of both methionine restriction (MR) and methionine supplementation (MS) have been studied. This study aimed to investigate the impact of a high-methionine diet (HMD) (1.64% methionine) on both the gut and liver functions in mice through multi-omic analyses. Hepatic steatosis and compromised gut barrier function were observed in mice fed the HMD. RNA-sequencing (RNA-seq) analysis of liver gene expression patterns revealed the upregulation of lipid synthesis and degradation pathways, cholesterol metabolism and inflammation-related nucleotide-binding oligomerization domain (NOD)-like receptor signaling pathway. Metagenomic sequencing of cecal content demonstrated a shift in gut microbial composition with an increased abundance of opportunistic pathogens and gut microbial functions with up-regulated lipopolysaccharide (LPS) biosynthesis in mice fed HMD. Metabolomic study of cecal content showed an altered gut lipid profile and the level of bioactive lipids, including docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), palmitoylethanolamide (PEA), linoleoyl ethanolamide (LEA) and arachidonoyl ethanolamide (AEA), that carry anti-inflammatory effects significantly reduced in the gut of mice fed the HMD. Correlation analysis demonstrated that gut microbiota was highly associated with liver and gut functions and gut bioactive lipid content. In conclusion, this study suggested that the HMD exerted negative impacts on both the gut and liver, and an adequate amount of methionine intake should be carefully determined to ensure normal physiological function without causing adverse effects.