Restoration of HMGCS2-mediated ketogenesis alleviates tacrolimus-induced hepatic lipid metabolism disorder.

Tacrolimus, one of the macrolide calcineurin inhibitors, is the most frequently used immunosuppressant after transplantation. Long-term administration of tacrolimus leads to dyslipidemia and affects liver lipid metabolism. In this study, we investigated the mode of action and underlying mechanisms of this adverse reaction. Mice were administered tacrolimus (2.5 mg·kg-1·d-1, i.g.) for 10 weeks, then euthanized; the blood samples and liver tissues were collected for analyses. We showed that tacrolimus administration induced significant dyslipidemia and lipid deposition in mouse liver. Dyslipidemia was also observed in heart or kidney transplantation patients treated with tacrolimus. We demonstrated that tacrolimus did not directly induce de novo synthesis of fatty acids, but markedly decreased fatty acid oxidation (FAO) in AML12 cells. Furthermore, we showed that tacrolimus dramatically decreased the expression of HMGCS2, the rate-limiting enzyme of ketogenesis, with decreased ketogenesis in AML12 cells, which was responsible for lipid deposition in normal hepatocytes. Moreover, we revealed that tacrolimus inhibited forkhead box protein O1 (FoxO1) nuclear translocation by promoting FKBP51-FoxO1 complex formation, thus reducing FoxO1 binding to the HMGCS2 promoter and its transcription ability in AML12 cells. The loss of HMGCS2 induced by tacrolimus caused decreased ketogenesis and increased acetyl-CoA accumulation, which promoted mitochondrial protein acetylation, thereby resulting in FAO function inhibition. Liver-specific HMGCS2 overexpression via tail intravenous injection of AAV8-TBG-HMGCS2 construct reversed tacrolimus-induced mitochondrial protein acetylation and FAO inhibition, thus removing the lipid deposition in hepatocytes. Collectively, this study demonstrates a novel mechanism of liver lipid deposition and hyperlipidemia induced by long-term administration of tacrolimus, resulted from the loss of HMGCS2-mediated ketogenesis and subsequent FAO inhibition, providing an alternative target for reversing tacrolimus-induced adverse reaction.

Evaluating the effectiveness and feasibility of a digital health intervention to community-based rehabilitation in older adults: A cluster randomized controlled trial study protocol.

Objective: The escalating global aging population underscores the need to effectively manage geriatric diseases, constituting a significant public health concern. Community-based rehabilitation has emerged as a crucial and accessible paradigm for the rehabilitation of older adults. In China, however, the practical implementation of community-based rehabilitation faces formidable challenges, including a dearth of specialized rehabilitation therapists, substantial disparities between demand and supply, and suboptimal satisfaction rates. We aimed to develop a community-based rehabilitation management platform for older adults centered around digital health technology, with the plan to conduct a cluster randomized controlled trial to gather more evidence to explore the best practices and service models of community-based rehabilitation based on digital health technology. Methods: This cluster randomized controlled trial will be conducted in Zunyi City, China. We will recruit 286 adults aged ≥60 years and randomly allocate 20 subdistricts in a 1:1 ratio into either the intervention group, which will use the Rehabilitation Journey application, or the control group, which will be given a Rehabilitation Information Booklet for Older Adults. Both groups will undergo a 12-month rehabilitation management program, encompassing six months of guidance and an additional six months of follow-up through online and offline methods. The evaluation indicators will be assessed at enrollment and at 3rd, 6th, and 12th month. Discussion: This study endeavors to furnish novel insights to develop a tailored community-based rehabilitation management program for older adults, delivering customized, intelligent, and precise rehabilitation services.

Multi-omics explores the potential regulatory role of acetylation modification in flavonoid biosynthesis of Ginkgo biloba.

Flavonoids are crucial medicinal active ingredients in Ginkgo biloba. However, the effect of protein post-translational modifications (PTMs) on flavonoid biosynthesis remains poorly explored. Lysine acetylation, a reversible PTM, plays a crucial role in metabolic regulation. This study aims to investigate the potential role of acetylation in G. biloba flavonoid biosynthesis. Through comprehensive analysis of transcriptomes, metabolomes, proteomes, and acetylated proteins in different tissues, a total of 11,788 lysine acetylation sites were identified on 4324 acetylated proteins, including 89 acetylation sites on 23 proteins. Additionally, 128 types of differentially accumulated flavonoids were identified among tissues, and a dataset of differentially expressed genes related to the flavonoid biosynthesis pathway was constructed. Twelve (CHI, C3H1, ANR, DFR, CCoAOMT1, F3H1, F3H2, CCoAOMT2, C3H2, HCT, F3'5'H, and FG2) acetylated proteins that might be involved in flavonoid biosynthesis were identified. Specifically, we found that the modification levels of CCoAOMT1 and F3'5'H sites correlated with the catalytic production of homoeriodictyol and dihydromyricetin, respectively. Inhibitors of lysine deacetylase (trichostatin A, TSA) impacted total flavonoid content in different tissues and increased flavonoid levels in G. biloba roots. Treatment with TSA revealed that expression levels of GbF3'5'H and GbCCoAOMT1 in stems and leaves aligned with total flavonoid content variations, while in roots, expression levels of GbC3H2 and GbFG2 corresponded to total flavonoid content changes. Collectively, these findings reveal for the first time the important role of acetylation in flavonoid biosynthesis.

MOFs-Based Materials with Confined Space: Opportunities and Challenges for Energy and Catalytic Conversion.

Metal-Organic Frameworks (MOFs) are a very promising material in the fields of energy and catalysis due to their rich active sites, tunable pore size, structural adaptability, and high specific surface area. The concepts of "carbon peak" and "carbon neutrality" have opened up huge development opportunities in the fields of energy storage, energy conversion, and catalysis, and have made significant progress and breakthroughs. In recent years, people have shown great interest in the development of MOFs materials and their applications in the above research fields. This review introduces the design strategies and latest progress of MOFs are included based on their structures such as core-shell, yolk-shell, multi-shelled, sandwich structures, unique crystal surface exposures, and MOF-derived nanomaterials in detail. This work comprehensively and systematically reviews the applications of MOF-based materials in energy and catalysis and reviews the research progress of MOF materials for atmospheric water harvesting, seawater uranium extraction, and triboelectric nanogenerators. Finally, this review looks forward to the challenges and opportunities of controlling the synthesis of MOFs through low-cost, improved conductivity, high-temperature heat resistance, and integration with machine learning. This review provides useful references for promoting the application of MOFs-based materials in the aforementioned fields.

A fluorescent terbium-metal-organic framework material for high-sensitivity detection of vomitoxin and oxytetracycline hydrochloride in water.

A unique luminescent lanthanide metal-organic framework (LnMOF)-based fluorescence detection platform was utilized to achieve sensitive detection of vomitoxin (VT) and oxytetracycline hydrochloride (OTC-HCL) without the use of antibodies or biomolecular modifications. The sensor had a fluorescence quenching constant of 9.74 × 106 M-1 and a low detection limit of 0.68 nM for vomitoxin. Notably, this is the first example of a Tb-MOF sensor for fluorescence detection of vomitoxin. We further investigated its response to two mycotoxins, aflatoxin B1 and ochratoxin A, and found that their Stern-Volmer fluorescence quenching constants were lower than those of VT. In addition, the fluorescence sensor realized sensitive detection of OTC-HCL with a detection limit of 0.039 µM. In conclusion, the method has great potential as a sensitive and simple technique to detect VT and OTC-HCL in water.

Metabolomics reveals the implication of acetoacetate and ketogenic diet therapy in radioiodine-refractory differentiated thyroid carcinoma.

OBJECTIVE: Patients with radioiodine-refractory (RAIR) differentiated thyroid carcinoma (DTC; RAIR-DTC) have a poor prognosis. The aim of this study was to provide new insights and possibilities for the diagnosis and treatment of RAIR-DTC. METHODS: The metabolomics of 24 RAIR-DTC and 18 non-radioiodine-refractory (NonRAIR) DTC patients samples were analyzed by liquid chromatograph-mass spectrometry. Cellular radioiodine uptake was detected with γ counter. Sodium iodide symporter (NIS) expression and thyroid stimulating hormone receptor (TSHR) were measured by Western blot analysis. CCK8 and colony formation assays were used to measure cellular proliferation. Scratch and transwell assays were performed to assess cell migration and invasion. Annexin V/PI staining was used to detect cell apoptosis. Cell growth in vivo was evaluated by a tumor xenograft model. The acetoacetate (AcAc) level was measured by ELISA. Pathological changes, Ki67, NIS, and TSHR expression were investigated by immunohistochemistry. RESULTS: The metabolite profiles of RAIR could be distinguished from those of NonRAIR, with AcAc significantly lower in RAIR. The significantly different metabolic pathway was ketone body metabolism. AcAc increased NIS and TSHR expression and improved radioiodine uptake. AcAc inhibited cell proliferation, migration, and invasion, and as well promoted cell apoptosis. Ketogenic diet (KD) elevated AcAc levels and significantly suppressed tumor growth, as well as improved NIS and TSHR expression. CONCLUSION: Significant metabolic differences were observed between RAIR and NonRAIR, and ketone body metabolism might play an important role in RAIR-DTC. AcAc improved cellular iodine uptake and had antitumor effects for thyroid carcinoma. KD might be a new therapeutic strategy for RAIR-DTC.

HHLA2 promotes hepatoma cell proliferation, migration, and invasion via SPP1/PI3K/AKT signaling pathway.

Hepatocellular carcinoma (HCC) stands as one of the most malignant tumors characterized by poor prognosis and high mortality rates. Emerging evidence underscores the crucial role of the B7 protein family in various cancers, including HCC. However, the involvement of the human endogenous retrovirus H long-terminal repeat-associated protein 2 (HHLA2, or B7-H5) in HCC remains unclear. Immunohistochemistry was employed to assess the differential expression of HHLA2 between HCC and normal liver tissues. A battery of assays, including CCK8, EdU, tablet clone-forming, Transwell, and wound healing assays, were conducted to elucidate the function and potential mechanisms of HHLA2 in the malignant biological behaviors of HCC. Additionally, a xenograft mouse model was established to evaluate the tumorigenicity of hepatoma cell lines exhibiting different HHLA2 expression levels in vivo. Western blot analysis was used to analyze HHLA2, secretory phosphoprotein 1 (SPP1), and PI3K/AKT/mTOR levels. HHLA2 exhibited elevated expression in HCC tissues, correlating with poor tumor differentiation and shortened overall survival in HCC patients. In vitro experiments demonstrated that HHLA2 overexpression (OE) promoted the proliferation, migration, and invasion of hepatoma cells, while in vivo experiments revealed that HHLA2 OE enhanced HCC tumor growth. Conversely, inhibition of HHLA2 expression yielded the opposite effect. Downregulation of SPP1 inhibited the proliferation, migration, and invasion induced by HHLA2 OE, and this effect was linked to the PI3K/AKT/mTOR signaling pathway. Our findings indicate that HHLA2 promotes the proliferation, migration, and invasion of hepatoma cells via the SPP1/PI3K/AKT signaling pathway, establishing it as a potential therapeutic target for HCC.

Weak-Interaction Environment in a Composite Electrolyte Enabling Ultralong-Cycling High-Voltage Solid-State Lithium Batteries.

Poly(vinylidene fluoride) (PVDF)-based solid electrolytes with a Li salt-polymer-little residual solvent configuration are promising candidates for solid-state batteries. Herein, we clarify the microstructure of PVDF-based composite electrolyte at the atomic level and demonstrate that the Li+-interaction environment determines both interfacial stability and ion-transport capability. The polymer works as a "solid diluent" and the filler realizes a uniform solvent distribution. We propose a universal strategy of constructing a weak-interaction environment by replacing the conventional N,N-dimethylformamide (DMF) solvent with the designed 2,2,2-trifluoroacetamide (TFA). The lower Li+ binding energy of TFA forms abundant aggregates to generate inorganic-rich interphases for interfacial compatibility. The weaker interactions of TFA with PVDF and filler achieve high ionic conductivity (7.0 × 10-4 S cm-1) of the electrolyte. The solid-state Li||LiNi0.8Co0.1Mn0.1O2 cells stably cycle 4900 and 3000 times with cutoff voltages of 4.3 and 4.5 V, respectively, as well as deliver superior stability at -20 to 45 °C and a high energy density of 300 Wh kg-1 in pouch cells.

Conjunctive encoding of exploratory intentions and spatial information in the hippocampus.

The hippocampus creates a cognitive map of the external environment by encoding spatial and self-motion-related information. However, it is unclear whether hippocampal neurons could also incorporate internal cognitive states reflecting an animal's exploratory intention, which is not driven by rewards or unexpected sensory stimuli. In this study, a subgroup of CA1 neurons was found to encode both spatial information and animals' investigatory intentions in male mice. These neurons became active before the initiation of exploration behaviors at specific locations and were nearly silent when the same fields were traversed without exploration. Interestingly, this neuronal activity could not be explained by object features, rewards, or mismatches in environmental cues. Inhibition of the lateral entorhinal cortex decreased the activity of these cells during exploration. Our findings demonstrate that hippocampal neurons may bridge external and internal signals, indicating a potential connection between spatial representation and intentional states in the construction of internal navigation systems.

The detection methods currently available for protein aggregation in neurological diseases.

Protein aggregation is a pathological feature in various neurodegenerative diseases and is thought to play a crucial role in the onset and progression of neurological disorders. This pathological phenomenon has attracted increasing attention from researchers, but the underlying mechanism has not been fully elucidated yet. Researchers are increasingly interested in identifying chemicals or methods that can effectively detect protein aggregation or maintain protein stability to prevent aggregation formation. To date, several methods are available for detecting protein aggregates, including fluorescence correlation spectroscopy, electron microscopy, and molecular detection methods. Unfortunately, there is still a lack of methods to observe protein aggregation in situ under a microscope. This article reviews the two main aspects of protein aggregation: the mechanisms and detection methods of protein aggregation. The aim is to provide clues for the development of new methods to study this pathological phenomenon.

Nanosurface-reconstructed perovskite for highly efficient and stable active-matrix light-emitting diode display.

Perovskite quantum dots (QDs) are promising for various photonic applications due to their high colour purity, tunable optoelectronic properties and excellent solution processability. Surface features impact their optoelectronic properties, and surface defects remain a major obstacle to progress. Here we develop a strategy utilizing diisooctylphosphinic acid-mediated synthesis combined with hydriodic acid-etching-driven nanosurface reconstruction to stabilize CsPbI3 QDs. Diisooctylphosphinic acid strongly adsorbs to the QDs and increases the formation energy of halide vacancies, enabling nanosurface reconstruction. The QD film with nanosurface reconstruction shows enhanced phase stability, improved photoluminescence endurance under thermal stress and electric field conditions, and a higher activation energy for ion migration. Consequently, we demonstrate perovskite light-emitting diodes (LEDs) that feature an electroluminescence peak at 644 nm. These LEDs achieve an external quantum efficiency of 28.5% and an operational half-lifetime surpassing 30 h at an initial luminance of 100 cd m-2, marking a tenfold improvement over previously published studies. The integration of these high-performance LEDs with specifically designed thin-film transistor circuits enables the demonstration of solution-processed active-matrix perovskite displays that show a peak external quantum efficiency of 23.6% at a display brightness of 300 cd m-2. This work showcases nanosurface reconstruction as a pivotal pathway towards high-performance QD-based optoelectronic devices.

Research on the mitigation of redeposition defects on the fused silica surface during wet etching process.

The laser-induced damage of ultraviolet fused silica optics is a critical factor that limits the performance enhancement of high-power laser facility. Currently, wet etching technology based on hydrofluoric acid (HF) can effectively eliminate absorbing impurities and subsurface defects, thereby significantly enhancing the damage resistance of fused silica optics. However, with an increase in the operating fluence, the redeposition defects generated during wet etching gradually become the primary bottleneck that restricts its performance improvement. The composition and morphology of redeposition defects were initially identified in this study, followed by an elucidation of their formation mechanism. A mitigation strategy was then proposed, which combines a reduction in the generation of precipitation with an acceleration of the precipitation dissolution process. Additionally, we systematically investigated the influence of various process parameters such as extrinsic impurity, etching depth, and megasonic excitation on the mitigation of deposition defects. Furthermore, a novel multiple-step dynamic etching method was developed. Through comprehensive characterization techniques, it has been confirmed that this new etching process not only effectively mitigate redeposition defects under low fluence conditions but also exhibits significant inhibition effects on high fluence precursors. Consequently, it significantly enhances the laser damage resistance performance of fused silica optics.

Fully-Automatic Detection and Diagnosis System for Thyroid Nodules Based on Ultrasound Video Sequences by Artificial Intelligence.

Background: Interpretation of ultrasound findings of thyroid nodules is subjective and labor-intensive for radiologists. Artificial intelligence (AI) is a relatively objective and efficient technology. We aimed to establish a fully automatic detection and diagnosis system for thyroid nodules based on AI technology by analyzing ultrasound video sequences. Patients and Methods: We prospectively acquired dynamic ultrasound videos of 1067 thyroid nodules (804 for training and 263 for validation) from December 2018 to January 2021. All the patients underwent hemithyroidectomy or total thyroidectomy. Dynamic ultrasound videos were used to develop an AI system consisting of two deep learning models that could automatically detect and diagnose thyroid nodules. Average precision (AP) was used to estimate the performance of the detection model. The area under the receiver operating characteristic curve (AUC) was used to measure the performance of the diagnostic model. Results: Location and shape were accurately detected with a high AP of 0.914 in the validation cohort. The AUC of the diagnostic model was 0.953 in the validation cohort. The sensitivity and specificity of junior and senior radiologists were 76.9% vs 78.3% and 68.4% vs 81.1%, respectively. The diagnostic performance of the AI diagnostic model was superior to that of junior radiologists (P = 0.016) and was not significantly different from that of senior radiologists (P = 0.281). Conclusion: We established a fully automatic detection and diagnosis system for thyroid nodules based on ultrasound video using an AI approach that can be conveniently applied to optimize the management of patients with thyroid nodules.

Success rate of current human-derived gastric cancer organoids establishment and influencing factors: A systematic review and meta-analysis.

BACKGROUND: Human-derived gastric cancer organoids (GCOs) are widely used in gastric cancer research; however, the culture success rate is generally low. AIM: To explore the potential influencing factors, and the literature on successful culture rates of GCOs was reviewed using meta-analysis. METHODS: PubMed, Web of Science, and EMBASE were searched for studies. Two trained researchers selected the studies and extracted data. STATA 17.0 software was used for meta-analysis of the incidence of each outcome event. The adjusted Methodological Index for Non-Randomized Studies scale was used to assess the quality of the included studies. Funnel plots and Egger's test were used to detect publication bias. Subgroup analyses were conducted for sex, tissue source, histological classification, and the pathological tumor-node-metastasis (pTNM) cancer staging system. RESULTS: Eight studies with a pooled success rate of 66.6% were included. GCOs derived from women and men had success rates of 67% and 46.7%, respectively. GCOs from surgery or biopsy/endoscopic submucosal dissection showed success rates of 70.9% and 53.7%, respectively. GCOs of poorly-differentiated, moderately-differentiated and signet-ring cell cancer showed success rates of 64.6%, 31%, and 32.7%, respectively. GCOs with pTNM stages I-II and III-IV showed success rates of 38.3% and 65.2%, respectively. Y-27632 and non-Y-27632 use showed success rates of 58.2% and 70%, respectively. GCOs generated with collagenase were more successful than those constructed with Liberase TH and TrypLE (72.1% vs 71%, respectively). EDTA digestion showed a 50% lower success rate than other methods (P = 0.04). CONCLUSION: GCO establishment rate is low and varies by sex, tissue source, histological type, and pTNM stage. Omitting Y-27632, and using Liberase TH, TrypLE, or collagenase yields greater success than EDTA.

Mendelian randomization study supports positive bidirectional causal relationships between genetically predicted insomnia symptom and liability to benign prostatic hyperplasia.

BACKGROUND: Sleep quality may be related to benign prostatic hyperplasia (BPH), however causal associations have not been established. This study aimed to evaluate causal relationships between six sleep traits ([i] day time napping, [ii] daytime sleepiness, [iii] insomnia, [iv] long sleep duration, [v] short sleep duration, and [vi] sleep duration per hour) and BPH through a bidirectional Mendelian randomization (MR) study. METHODS: Genome-wide association summary statistics of sleep traits and BPH were downloaded from public databases. Inverse variance weighting (IVW) was used as the main approach for causal inference. For causal estimates identified by IVW, various sensitivity analyses were performed to assess the reliability of the results: (i) four additional MR methods to complement IVW; (ii) Cochran's Q test to assess heterogeneity; (iii) MR-Egger intercept test and MR-PRESSO global test to assess horizontal pleiotropy; and (iv) leave-one-out method to assess stability. RESULTS: Forward MR analyses indicated that genetically predicted insomnia symptom significantly increased BPH risk (OR = 1.267, 95% CI: 1.003-1.601, P = 0.048), while reverse MR analyses identified that genetically predicted liability to BPH significantly increased the incidence of insomnia (OR = 1.026, 95% CI: 1.000-1.052, P = 0.048). In a replicate MR analysis based on summary statistics including exclusively male participants, the finding of increased risk of BPH due to genetically predicted insomnia symptom was further validated (OR = 1.488, 95% CI: 1.096-2.022, P = 0.011). No further causal links were identified. In addition, sensitivity tests demonstrated the reliability of the MR results. CONCLUSION: This study identified that a higher prevalence of genetically predicted insomnia symptoms may significantly increase the risk of BPH, while genetically predicted liability to BPH may in turn increase the incidence of insomnia symptom. Therefore, improving sleep quality and reducing the risk of insomnia could be a crucial approach for the prevention of BPH.

Causal association between 25-Hydroxyvitamin D and risk of abnormal spermatozoa: A bidirectional Mendelian randomization study.

Previous studies indicated conflicting findings regarding the association between vitamin D and abnormal spermatozoa. Herein, we assessed the causal association between circulating 25-Hydroxyvitamin D (25OHD) levels and the risk of abnormal spermatozoa by utilizing bidirectional Mendelian randomization (MR) analysis. Genome-wide association study summary statistics for 25OHD and abnormal spermatozoa were obtained from publicly accessible databases. Single nucleotide polymorphisms (SNPs) associated with 25OHD and SNPs associated with abnormal spermatozoa were used as instrumental variables (IVs) for forward MR analysis and reverse MR analysis, respectively. Inverse variance weighted (IVW) was the main MR approach, while weighted median, MR-Egger, and maximum likelihood methods were employed to supplement IVW. In addition, several sensitivity tests assessed the reliability of MR analysis. Forward MR analysis showed that elevated 25OHD levels significantly reduced abnormal spermatozoa risk (odds ratio [OR] = 0.75, 95 % confidence interval [CI]: 0.56-1.00, P = 4.98E-02), and the effect remained statistically significant after excluding SNPs associated with confounders (OR = 0.73, 95 % CI: 0.54-0.98, P = 3.83E-02) or only utilizing SNPs located near 25OHD-associated genes only as IVs (OR = 0.58, 95 % CI: 0.41-0.81, P = 1.67E-03). Reverse MR analysis indicated abnormal spermatozoa not affecting 25OHD level (P > 0.05). Sensitivity tests showed that MR analyses were not affected by heterogeneity and horizontal polytropy. Overall, the present MR study supports that elevated 25OHD levels reduce the risk of abnormal spermatozoa. Therefore, ensuring adequate vitamin D intake and maintaining stable levels of 25OHD may be effective strategies to optimize reproductive outcomes.

Contrasting roles of plant, bacterial, and fungal diversity in soil organic carbon accrual during ecosystem restoration: A meta-analysis.

Plant and microbial diversity plays vital roles in soil organic carbon (SOC) accumulation during ecosystem restoration. However, how soil microbial diversity mediates the positive effects of plant diversity on carbon accumulation during vegetation restoration remains unclear. We conducted a large-scale meta-analysis with 353 paired observations from 65 studies to examine how plant and microbial diversity changed over 0-160 years of natural restoration and its connection to SOC accrual in the topsoil (0-10 cm). Results showed that natural restoration significantly increased plant aboveground biomass (122.09 %), belowground biomass (153.05 %), and richness (21.99 %) and SOC accumulation (32.34 %) but had no significant impact on microbial diversity. Over time, bacterial and fungal richness increased and then decreased. The responses of major microbial phyla, in terms of relative abundance, varied across restoration and ecosystem types. Specifically, Ascomycota and Zygomycota decreased more under farmland abandonment than under grazing exclusion. In forest, Bacteroidetes, Ascomycota, and Zygomycota significantly decreased after natural restoration. The increase in SOC and Basidiomycota was higher in forest than in grassland. Based on standardized estimates, structural equation modeling showed that plant diversity had the highest positive effect (0.55) on SOC accrual, and while fungal diversity (0.15) also had a positive effective, bacterial diversity (-0.20) had a negative effect. Plant diversity promoted SOC accumulation by directly impacting biomass and soil moisture and total nitrogen and indirectly influencing soil microbial richness. This meta-analysis highlights the significant roles of plant diversity and microbial diversity in carbon accumulation during natural restoration and elucidates their relative contributions to carbon accumulation, thereby aiding in more precise predictions of soil carbon sequestration.

[Clinical features and genetic analysis of 17 Chinese pedigrees affected with X-linked intellectual disability].

OBJECTIVE: To analyze the clinical features and genetic etiology of 17 Chinese pedigrees affected with X-linked intellectual disability (XLID). METHODS: Seventeen pedigrees affected with unexplained intellectual disability which had presented at Henan Provincial People's Hospital from May 2021 to May 2023 were selected as the study subjects. Clinical data of the probands and their pedigree members were collected. Trio-whole exome sequencing (Trio-WES), Sanger sequencing and X chromosome inactivation (XCI) analysis were carried out. Pathogenicity of candidate variants was predicted based on the guidelines from the American College of Medical Genetics and Genomics and co-segregation analysis. RESULTS: The 17 probands, including 9 males and 8 females with an age ranging from 0.6 to 8 years old, had all shown mental retardation and developmental delay. Fourteen variants were detected by genetic testing, which included 4 pathogenic variants (MECP2: c.502C>T, MECP2: c.916C>T/c.806delG, IQSEC2: c.1417G>T), 4 likely pathogenic variants (MECP2: c.1157_1197del/c.925C>T, KDM5C: c.2128A>T, SLC6A8: c.1631C>T) and 6 variants of uncertain significance (KLHL15: c.26G>C, PAK3: c.970A>G/c.1520G>A, GRIA3: c.2153C>G, TAF1: c.2233T>G, HUWE1: c.10301T>A). The PAK3: c.970A>G, GRIA3: c.2153C>G and TAF1: c.2233T>G variants were considered as the genetic etiology for pedigrees 12, 14 and 15 by co-segregation analysis, respectively. The proband of pedigree 13 was found to have non-random XCI (81:19). Therefore, the PAK3: c.1520G>A variant may underlie its pathogenesis. CONCLUSION: Trio-WES has attained genetic diagnosis for the 17 XLID pedigrees. Sanger sequencing and XCI assay can provide auxiliary tests for the diagnosis of XLID.

Two imprinted genes primed by DEMETER in the central cell and activated by WRKY10 in the endosperm.

The early development of the endosperm is crucial for balancing the allocation of maternal nutrients to offspring. This process is believed to be evolutionarily associated with genomic imprinting, resulting in parentally biased allelic gene expression. Beyond FertilizationIndependentSeed (FIS) genes, the number of imprinted genes involved in early endosperm development and seed size determination remains limited. This study introduces two early endosperm-expressed HAIKU (IKU) downstream Candidate F-box 1 (ICF1) and ICF2, as maternally expressed imprinted genes (MEGs). Although these genes are also demethylated by DEMETER (DME) in the central cell, their activation differs from the direct DME-mediated activation seen in classical MEGs such as the FIS genes. Instead, ICF maternal alleles carry pre-established hypomethylation in their promoters, priming them for activation by the WRKY10 transcription factor in the endosperm. On the contrary, paternal alleles are predominantly suppressed by CG methylation. Furthermore, we find that ICF genes partially contribute to the small seed size observed in iku mutants. Our discovery reveals a two-step regulatory mechanism that highlights the important role of conventional transcription factors in the activation of imprinted genes, which was previously not fully recognized. Therefore, the mechanism provides a new dimension to understand the transcriptional regulation of imprinting in plant reproduction and development.