Controlled Fabrication of Metallic MoO2 Nanosheets towards High-Performance p-Type 2D Transistors.

Two-dimensional (2D) semiconducting transition metal dichalcogenides (TMDCs) are extensively employed as channel materials in advanced electronic devices. The electrical contacts between electrodes and 2D semiconductors play a crucial role in the development of high-performance transistors. While numerous strategies for electrode interface engineering have been proposed to enhance the performance of n-type 2D transistors, upgrading p-type ones in a similar manner remains a challenge. In this work, significant improvements in a p-type WSe2 transistor are demonstrated by utilizing metallic MoO2 nanosheets as the electrode contact, which are controllably fabricated through physical vapor deposition and subsequent annealing. The MoO2 nanosheets exhibit an exceptional electrical conductivity of 8.4 × 104 S m‒1 and a breakdown current density of 3.3 × 106 A cm‒2. The work function of MoO2 nanosheets is determined to be ≈5.1 eV, making them suitable for contacting p-type 2D semiconductors. Employing MoO2 nanosheets as the electrode contact in WSe2 transistors results in a notable increase in the field-effect mobility to 92.0 cm2 V‒1 s‒1, which is one order of magnitude higher than the counterpart devices with conventional electrodes. This study not only introduces an intriguing 2D metal oxide to improve the electrical contact in p-type 2D transistors, but also offers an effective approach to fabricating all-2D devices.

Transformation of Diffusion and Local Structure of CH4 , CO2 , SO2 and H2 O Mixtures in Graphene Under Wide Temperature and Pressure Range: A Molecular Dynamics Simulation Study.

As a material with high specific surface area and excellent chemical stability, graphene exhibited remarkable adsorption and separation performance as well as a wide range of potential applications. The graphene layer played a significant role in influencing gas transmission. In this study, we employed molecular dynamics simulation to investigate the diffusion characteristics and local structures of a mixed system consisting of CH4 , CO2 , SO2 and H2 O. Additionally, we further examined the transformation of the behavior of these mixtures within graphene layers. The order of diffusion coefficients of the four molecules without graphene was H2 O>SO2 >CO2 ≫CH4 . However, in the double-layer graphene, the order changed to CH4 >CO2 ≫H2 O>SO2 . Higher temperatures and lower pressures were found to facilitate gas diffusion. Temperature and pressure had great effects on the local structures of CH4 , CO2 and SO2 , while their impact on H2 O was limited due to the extensive network of hydrogen bonds formed by H2 O molecules. The statistical results of average coordination number revealed that CH4 tended to aggregate with itself, whereas CO2 and SO2 exhibited a tendency to aggregate with H2 O. The graphene structure enhanced the separation and transportation of CH4 from mixed systems.

Theoretical study on intramolecular hydrogen bonds of flavonoid cocrystals.

This study investigates the role of intramolecular hydrogen bonds in the formation of cocrystals involving flavonoid molecules, focusing on three active pharmaceutical ingredients (APIs): chrysin (CHR), isoliquiritigenin (ISO), and kaempferol (KAE). These APIs form cocrystals with different cocrystal formers (CCFs) through intramolecular hydrogen bonding. We found that disruption of these intramolecular hydrogen bonds leads to decreased stability compared to molecules with intact bonds. The extrema of molecular electrostatic potential surfaces (MEPS) show that flavonoid molecules with disrupted intramolecular hydrogen bonds have stronger hydrogen bond donors and acceptors than those with intact bonds. Using the artificial bee colony algorithm, dimeric structures of these flavonoid molecules were explored, representing early-stage structures in cocrystal formation, including API-API, API-CCF, and CCF-CCF dimers. It was observed that the number and strength of dimeric interactions significantly increased, and the types of interactions changed when intramolecular hydrogen bonds were disrupted. These findings suggest that disrupting intramolecular hydrogen bonds generally hinders the formation of cocrystals. This theoretical study provides deeper insight into the role of intramolecular hydrogen bonds in the cocrystal formation of flavonoids.

Efficacy of platelet-rich plasma in the treatment of thin endometrium: a meta-analysis of randomized controlled trials.

BACKGROUND: Thin endometrium (TE) is a common cause of female infertility in clinical practice. Platelet-rich Plasma (PRP) therapy becomes a novel treatment for thin endometrium; however, its clinical application remains controversial. This meta-analysis aims to evaluate the therapeutic effects of intrauterine autologous PRP infusion in women with thin endometrium through relevant randomized controlled trials (RCTs). METHODS: We systematically searched studies published in English from inception until June 2024 in databases such as PubMed, The Cochrane Library, Embase, Web of Science, and MEDLINE. Search terms included "Platelet-Rich Plasma," "thin endometrium," "endometrial thickness," "infertility," "pregnancy," "reproduction," and "adverse reactions". RCTs identified through the search were subjected to systematic review and meta-analysis, and data were analyzed using fixed-effects or random-effects models based on heterogeneity. RESULTS: Eight RCTs involving 678 patients with thin endometrium were included. Patients receiving PRP infusion demonstrated significantly superior outcomes compared to the control group in endometrial thickness (MD: 1.23, 95%CI: 0.87 to 1.59, P = 0.000), clinical pregnancy rate (RR: 2.04, 95%CI: 1.52 to 2.76, P = 0.000), live birth rate (RR: 2.46; 95%CI: 1.57 to 3.85, P = 0.000), cycle cancellation rate (RR: 0.46, 95%CI: 0.23 to 0.93, P = 0.000), and embryo implantation rate (RR: 2.71; 95%CI: 1.91 to 3.84, P = 0.000). There were no statistically significance in spontaneous abortion rate (RR: 0.85, 95%CI: 0.40 to 1.78, P = 0.659), chemical pregnancy rate (RR: 1.84, 95%CI: 0.72 to 4.72, P = 0.204) and endometrial vascular improvement rate (RR: 1.10; 95%CI: 0.89 to 1.38, P = 0.367) between the two groups. The limitations of this study includes that, we only included single lauguage for literature research, the sample size and heterogeneity which could cause criteria bias. CONCLUSION: Intrauterine PRP infusion may be an effective and safe treatment for women with thin endometrium. Further high-quality, large-sample, randomized controlled trials are needed to validate the reliability of our results. TRIAL REGISTRATION: The review protocol is registered on PROSPERO with registration number CRD42023490421, and no modifications were made to the information provided at registration.

Extraordinary-log Universality of Critical Phenomena in Plane Defects.

The recent discovery of the extraordinary-log (E-Log) criticality is a celebrated achievement in modern critical theory and calls for generalization. Using large-scale Monte Carlo simulations, we study the critical phenomena of plane defects in three- and four-dimensional O(n) critical systems. In three dimensions, we provide the first numerical proof for the E-Log criticality of plane defects. In particular, for n=2, the critical exponent q[over ^] of two-point correlation and the renormalization-group parameter α of helicity modulus conform to the scaling relation q[over ^]=(n-1)/(2πα), whereas the results for n≥3 violate this scaling relation. In four dimensions, it is strikingly found that the E-Log criticality also emerges in the plane defect. These findings have numerous potential realizations and would boost the ongoing advancement of conformal field theory.

Comparing methods of detecting and segmenting unruptured intracranial aneurysms on TOF-MRAS: The ADAM challenge.

Accurate detection and quantification of unruptured intracranial aneurysms (UIAs) is important for rupture risk assessment and to allow an informed treatment decision to be made. Currently, 2D manual measures used to assess UIAs on Time-of-Flight magnetic resonance angiographies (TOF-MRAs) lack 3D information and there is substantial inter-observer variability for both aneurysm detection and assessment of aneurysm size and growth. 3D measures could be helpful to improve aneurysm detection and quantification but are time-consuming and would therefore benefit from a reliable automatic UIA detection and segmentation method. The Aneurysm Detection and segMentation (ADAM) challenge was organised in which methods for automatic UIA detection and segmentation were developed and submitted to be evaluated on a diverse clinical TOF-MRA dataset. A training set (113 cases with a total of 129 UIAs) was released, each case including a TOF-MRA, a structural MR image (T1, T2 or FLAIR), annotation of any present UIA(s) and the centre voxel of the UIA(s). A test set of 141 cases (with 153 UIAs) was used for evaluation. Two tasks were proposed: (1) detection and (2) segmentation of UIAs on TOF-MRAs. Teams developed and submitted containerised methods to be evaluated on the test set. Task 1 was evaluated using metrics of sensitivity and false positive count. Task 2 was evaluated using dice similarity coefficient, modified hausdorff distance (95th percentile) and volumetric similarity. For each task, a ranking was made based on the average of the metrics. In total, eleven teams participated in task 1 and nine of those teams participated in task 2. Task 1 was won by a method specifically designed for the detection task (i.e. not participating in task 2). Based on segmentation metrics, the top two methods for task 2 performed statistically significantly better than all other methods. The detection performance of the top-ranking methods was comparable to visual inspection for larger aneurysms. Segmentation performance of the top ranking method, after selection of true UIAs, was similar to interobserver performance. The ADAM challenge remains open for future submissions and improved submissions, with a live leaderboard to provide benchmarking for method developments at https://adam.isi.uu.nl/.

Platelet transcriptome profiles provide potential therapeutic targets for elderly acute myelocytic leukemia patients.

BACKGROUND: Acute myeloid leukemia (AML) is the most common acute leukemia in adults, with a median age of 68 in clinical diagnosis. About 60% patients are over 60 years old. There are various treatment options for AML patients. But for elderly patients, the complete remission rates are disappointing due to genetic, molecular, and age-related factors. Development of next-generation sequencing technologies makes it possible to seek individual strategies for patients in different ages. This study analyzed transcriptome profiles in platelets of AML patients in different ages for the first time. METHODS: Platelet RNA sequencing in AML of ten elderly and seven young patients were performed with Illumina TruSeq Stranded mRNA library Prep Kit and Illumina HiSeq4000 sequencing instrument. With the FASTQ sequencing data obtained, statistical analyses between elderly with young AML patients were analyzed by R program. GO and KEGG enrichment analyses were performed via R package clusterProfiler. TOP 10 down-regulated/up-regulated genes in elderly patients compared to young patients were selected with the threshold of |L2FC| > 2 and padj ≤ 0.0001. The down-regulated gene ATF4 was chosen by GSEA analysis and ROC analysis with AUC > 0.95. RESULTS: We found 3059 genes with differential transcript levels (GDTLs) in AML patients of different age. Among them, 2048 genes are down-regulated and 651 genes are up-regulated in elderly patients. We found that gene transcript profiles in elderly patients is obviously different from those in young patients, including a collection of down-regulated genes related to proteins processing in endoplasmic reticulum and immunity. We further identified that genes of pathway in cancer and mitogen activated protein kinase (MAPK) pathway, involved in natural immunity and metabolism, are significantly down-regulated in elderly patients. Among all screened genes with decreased transcript levels, we believe that activating transcription factor 4 (ATF4) is a biomarker indicating different chemotherapy strategies for elderly patients. CONCLUSIONS: In summary, gene transcript profiles are different in platelets of elderly and young AML patients. And ATF4 can be a useful biomarker indicating different chemotherapy strategies for AML patients with different ages.

Extraordinary-Log Surface Phase Transition in the Three-Dimensional XY Model.

Universality is a pillar of modern critical phenomena. The standard scenario is that the two-point correlation algebraically decreases with the distance r as g(r)∼r^{2-d-η}, with d the spatial dimension and η the anomalous dimension. Very recently, a logarithmic universality was proposed to describe the extraordinary surface transition of the O(N) system. In this logarithmic universality, g(r) decays in a power of logarithmic distance as g(r)∼(lnr)^{-η[over ^]}, dramatically different from the standard scenario. We explore the three-dimensional XY model by Monte Carlo simulations, and provide strong evidence for the emergence of logarithmic universality. Moreover, we propose that the finite-size scaling of g(r,L) has a two-distance behavior: simultaneously containing a large-distance plateau whose height decays logarithmically with L as g(L)∼(lnL)^{-η[over ^]^{'}} as well as the r-dependent term g(r)∼(lnr)^{-η[over ^]}, with η[over ^]^{'}≈η[over ^]-1. The critical exponent η[over ^]^{'}, characterizing the height of the plateau, obeys the scaling relation η[over ^]^{'}=(N-1)/(2πα) with the RG parameter α of helicity modulus. Our picture can also explain the recent numerical results of a Heisenberg system. The advances on logarithmic universality significantly expand our understanding of critical universality.

A Review on Map-Merging Methods for Typical Map Types in Multiple-Ground-Robot SLAM Solutions.

When multiple robots are involved in the process of simultaneous localization and mapping (SLAM), a global map should be constructed by merging the local maps built by individual robots, so as to provide a better representation of the environment. Hence, the map-merging methods play a crucial rule in multi-robot systems and determine the performance of multi-robot SLAM. This paper looks into the key problem of map merging for multiple-ground-robot SLAM and reviews the typical map-merging methods for several important types of maps in SLAM applications: occupancy grid maps, feature-based maps, and topological maps. These map-merging approaches are classified based on their working mechanism or the type of features they deal with. The concepts and characteristics of these map-merging methods are elaborated in this review. The contents summarized in this paper provide insights and guidance for future multiple-ground-robot SLAM solutions.

Apoptosis in human myelodysplastic syndrome CD34+ cells is modulated by the upregulation of TLRs and histone H4 acetylation via a ß-arrestin 1 dependent mechanism.

Excessive apoptosis of hematopoietic precursors in the bone marrow underlies the ineffective hematopoiesis characteristic of myelodysplastic syndrome (MDS). Toll-like receptor (TLR) signaling is abnormally activated in MDS and may be involved in excessive programmed cell death in the pathogenesis of MDS. TLRs expression and global histone H3/H4 acetylation were analyzed in bone marrow (BM) CD34+ cells from 20 lower-risk and 20 higher-risk MDS patients and 10 healthy controls. Apoptosis of BM CD34+ cells was examined by flow cytometry, and its correlation to histone acetylation and the expression of TLR2 and ß-arrestin1 (ß-arr1), measured by enzyme-linked immunosorbent assay and qRT-PCR, was assessed. TLR1, TLR2 and TLR6 expression and H4 acetylation levels were higher in lower-risk MDS patients than in higher-risk MDS patients or controls, and TLR2 expression and H4 acetylation levels were positively correlated with an increased rate of apoptosis. Lower-risk MDS was associated with increased ß-arr1 expression and histone acetyltransferase p300 activity. In in vitro-cultured primary normal and lower-risk MDS CD34+ cells, TLR2 activation-induced apoptosis was mediated by the upregulation of ß-arr1 leading to the recruitment of p300 and increased histone H4 acetylation. The nuclear accumulation of ßarr1 following TLR2 activation promote H4 acetylation at specific target gene promoters and may thus affect transcription of target genes in BM CD34+ cells. The mechanisms underlying the deregulation of TLR2 and increased apoptosis in MDS may involve the ß-arr1 mediated recruitment of p300 leading to increased levels of histone H4 acetylation.

Inward-facing conformation of the zinc transporter YiiP revealed by cryoelectron microscopy.

YiiP is a dimeric Zn(2+)/H(+) antiporter from Escherichia coli belonging to the cation diffusion facilitator family. We used cryoelectron microscopy to determine a 13-Å resolution structure of a YiiP homolog from Shewanella oneidensis within a lipid bilayer in the absence of Zn(2+). Starting from the X-ray structure in the presence of Zn(2+), we used molecular dynamics flexible fitting to build a model consistent with our map. Comparison of the structures suggests a conformational change that involves pivoting of a transmembrane, four-helix bundle (M1, M2, M4, and M5) relative to the M3-M6 helix pair. Although accessibility of transport sites in the X-ray model indicates that it represents an outward-facing state, our model is consistent with an inward-facing state, suggesting that the conformational change is relevant to the alternating access mechanism for transport. Molecular dynamics simulation of YiiP in a lipid environment was used to address the feasibility of this conformational change. Association of the C-terminal domains is the same in both states, and we speculate that this association is responsible for stabilizing the dimer that, in turn, may coordinate the rearrangement of the transmembrane helices.

Indirect co-culture of osteoblasts and endothelial cells in vitro based on a biomimetic 3D composite hydrogel scaffold to promote the proliferation and differentiation of osteoblasts.

The field of orthopedics has long struggled with the challenge of repairing and regenerating bone defects, which involves a complex process of osteogenesis requiring coordinated interactions among different types of cells. The crucial role of endothelial cells and osteoblasts in bone vascularization and osteogenesis underscores the importance of their intimate interaction. However, efforts to bioengineer bone tissue have been impeded by the difficulty in establishing proper angiogenesis and osteogenesis in tissue structures. This study presents a novel approach to bone tissue engineering, involving a three-dimensional composite hydrogel scaffold composed of sodium alginate microspheres encapsulated in type I collagen. Using this scaffold, a three-dimensional indirect co-culture system was established for osteoblasts and endothelial cells to evaluate the osteogenic differentiation potential of osteoblasts. Results demonstrate that the non-contact co-culture system of endothelial cells and osteoblasts constructed by the composite hydrogel scaffold loaded with microspheres holds promise for bone tissue engineering. The innovative concept of an indirect co-culture system presents exciting prospects for conducting intercellular communication studies and offers a valuable in vitro tissue platform to investigate tissue regeneration.

Biogeography and diversity patterns of abundant and rare bacterial communities in paddy soils along middle and lower Yangtze River.

The middle and lower reaches of the Yangtze River serve as principal rice production bases in China, yet the biodiversity and ecological processes of bacterial communities in paddy soils are not well understood. This study explores the diversity, composition, ecological function, and assembly processes of abundant and rare bacterial communities in paddy soils. A total of 129 paddy soil samples from 43 sites along the middle and lower reaches of the Yangtze River were collected and analyzed using NovaSeq sequencing. The results showed that the dominant phylum for both abundant and rare taxa was Proteobacteria, with a greater relative abundance of the abundant taxa. The diversity of the abundant community was lower than that of the rare community. Soil properties and geographic variables explained more of the variation in the abundant community than in the rare community. The rare community exhibited a significant distance-decay relationship. The assembly of the abundant community was more influenced by stochastic processes, although both the abundant and rare communities were governed by stochastic processes. It is concluded that both abundant and rare bacterial communities exhibit differing biogeographic patterns, yet they undergo similar ecological processes in the paddy soils along the middle and lower reaches of the Yangtze River. These observations offer a theoretical framework for a deeper comprehension of the function of both abundant and rare bacteria, as well as the development and preservation of soil bacterial diversity within agricultural ecosystems.

[Clinical research and the rules of acupoint selection on acupuncture treatment of psoriasis in the past 20 years]. / 近20å¹´é’ˆç¸æ²»ç–—é“¶å±‘ç— çš„ä¸´åºŠç ”ç©¶ä¸Žé€‰ç©´è§„å¾‹.

OBJECTIVES: To sum up clinical researches and the rule of acupoint selection on the treatment of psoriasis by acupuncture and moxibustion in the past 20 years, so as to provide new ideas and reference for improving the clinical effect of acupuncture for psoriasis. METHODS: Research papers, published from January 1, 2002 to December 31, 2022 in both Chinese and English, were searched from databases of China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform (WanFang), and Chinese Science and Technology Journal (CSTJ), PubMed, Embase and Web of Science by using key words of psoriasis, psoriases, psoriasis vulgaris, acupuncture, needle, acupoint and moxibustion. Then, Microsoft Excel 2021 was used for data entry, extraction and sorting of the included literature, data extraction mainly includes diagnostic criteria, treatment methods, treatment frequency, total course of treatment, selection of acupoints, efficacy evaluation and outcomes. SPSS Modeler 18.1 software was used to make analysis on the association rules of acupoints. RESULTS: A total of 26 papers were included, and the diagnostic criteria of clinical studies on acupuncture treatment of psoriasis are constantly updated. Of the 26 clinical studies, 23 had both treatment group and control group, 21 were randomized controlled trials. The main methods for treatment of psoriasis included fire needle, acupuncture, electroacupuncture, acupuncture combined with moxibustion or fire needle, fire needle plus western medicines, etc. with the acupuncture combined with moxibustion, and fire needle combined with western medicines being most frequently used. The observation index and clinical efficacy evaluation were effective rate, psoriasis area and severity index, dermatology life quality index, Traditional Chinese Medicine syndrome score, etc., with the effective rate being about 40% to 100%. Comparison of clinical efficacy of acupuncture in treating psoriasis showed that the simple fire needle, simple acupuncture, acupuncture combined with moxibustion, fire needle or acupuncture combined with western medicines were superior to simple western medicines, etc. In regard to acupoint selection, a total of 35 acupoints were found in the 26 studies included, among which the top 5 frequently used were Ashi points (skin lesion region), Geshu (BL17), Feishu (BL13), Ganshu (BL18) and Quchi (LI11), and there were strong association rules among BL17, BL13, BL18 and Shenshu (BL23). CONCLUSIONS: Acupuncture is safe and effective in the treatment of psoriasis, and acupuncture combined with moxibustion and fire acupuncture needle combined with western medicines are recommended as the main intervention method, with Ashi-point, BL13, BL17, BL18 and BL23 as the main acupoints.

The impact of serum uric acid on psoriasis: NHANES 2005-2014 and Mendelian randomization.

Background: Psoriasis is a chronic systemic inflammatory disease, and hyperuricemia is a common comorbidity in patients with psoriasis. However, the exact relationship between uric acid levels and psoriasis remains unclear. This study aimed to explore the association between uric acid levels and psoriasis. Methods: Observational study participant data (≥16 years, n = 23,489) from NHANES 2003-2014. We conducted analyses using a weighted multiple logistic regression model. Genetic data sets for uric acid levels and psoriasis were obtained from the IEU database. We selected genetically independent loci closely associated with serum uric acid levels as instrumental variables and performed Mendelian randomization analyses using five complementary methods: inverse variance weighting (IVW), MR-Egger, weighted median, simple mode, and weighted mode. Results: After adjusting for other covariates, the results revealed no significant association between serum uric acid levels and psoriasis (b = 0.999, 95% CI: 0.998, 1.001, p = 0.275). Subgroup analyses stratified by gender and ethnicity showed no significant association between sUA and psoriasis in any of the subgroups. Furthermore, the MR analysis involved the selection of 227 SNPs that were associated with both sUA and psoriasis. IVW results demonstrated no causal relationship between sUA and psoriasis (OR = 0.282, 95% CI: -0.094-0.657, p = 0.142). Conclusion: Our study suggests that uric acid levels are not significantly causally related to psoriasis. This finding provides valuable insights for the treatment and prevention of psoriasis, indicating that merely reducing uric acid levels may not be an effective strategy to reduce the risk of psoriasis onset.

CTH-Net: A CNN and Transformer hybrid network for skin lesion segmentation.

Automatically and accurately segmenting skin lesions can be challenging, due to factors such as low contrast and fuzzy boundaries. This paper proposes a hybrid encoder-decoder model (CTH-Net) based on convolutional neural network (CNN) and Transformer, capitalizing on the advantages of these approaches. We propose three modules for skin lesion segmentation and seamlessly connect them with carefully designed model architecture. Better segmentation performance is achieved by introducing SoftPool in the CNN branch and sandglass block in the bottleneck layer. Extensive experiments were conducted on four publicly accessible skin lesion datasets, ISIC 2016, ISIC 2017, ISIC 2018, and PH2 to confirm the efficacy and benefits of the proposed strategy. Experimental results show that the proposed CTH-Net provides better skin lesion segmentation performance in both quantitative and qualitative testing when compared with state-of-the-art approaches. We believe the CTH-Net design is inspiring and can be extended to other applications/frameworks.

Enzymatically Cyclic Activated Biosensor Based on a Tetrahedral DNA Framework for Precise Tumor in Situ Molecular Imaging.

The development of stimulus-responsive and amplification-based strategies is crucial for achieving improved spatial specificity and enhanced sensitivity in tumor molecular imaging, addressing challenges such as off-tumor signal leakage and limited biomarker content. Therefore, a cyclically activated enzymatic biosensor based on the modification of an AP site within a tetrahedral framework DNA (AP-tFNA) was rationally developed for tumor cell-specific molecular imaging using the endogenous enzyme apurinic/apyrimidinic endonuclease 1 (APE1) as a target, exhibiting superior spatial specificity and high sensitivity. APE1, which predominantly localizes within the nucleus in normal cells but exhibits cytosolic and nucleus expression in cancer cells, can specifically recognize and cleave the AP site in AP-tFNA, resulting in the separation of the fluorophore and quenching group, thereby inducing a fluorescence signal. Additionally, upon completion of the excision of one AP site in AP-tFNA, APE1 is released, thereby initiating a subsequent cycle of hydrolytic cleavage reactions. The experimental results demonstrated that AP-tFNA enables precise differentiation of tumor cells both in vitro and in vivo. In particular, the AP-tFNA can monitor drug resistance in neuroblastoma cells and classify the risk for neuroblastoma patients at the clinical plasma level.

Time association study on a sub-acute mouse model of Parkinson's disease.

Parkinson's disease (PD) is a severe neurodegenerative disease that disturbs human health. In the laboratory researches about PD, the mice model induced by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was widely used. However, there has been controversy about the model effectiveness to simulate PD symptoms and pathology, and the time-varying development of behavioral and pathological characteristic after MPTP treatment remains unclear. In order to solve these problems, we designed a series of experiments to evaluate this PD model at different time points. We constructed the subacute PD mouse model by intraperitoneal injection of MPTP for 5 consecutive days. The rotarod test, open field test and the immunohistochemical staining of tyrosine hydroxylase were conducted at -5, 1, 5, 7, 14, 21 and 28 days after the last injection of MPTP. The results showed that 5 days after the last MPTP administration, typical motor disorders with significant balance function damage in rotarod test began to appear and remained stable throughout the entire experiment. Simultaneously, we also observed the loss of tyrosine hydroxylase (TH) positive cells in the substantia nigra compacta and reduction of TH content in the striatum but this pathological change in the substantia nigra compacta reversed 21 days after injection. Besides, the spontaneous movement of mice in open field test remained unchanged by MPTP. This research indicated the time-dependence of MPTP neurotoxicity that impair the motor function and histological features and confirmed the symptom occurrence time after MPTP injection, which provides a reference for the future research about MPTP-induced PD.

A novel study on CXXC5: unraveling its regulatory mechanisms in hematopoietic stem cell biology through proteomics and gene editing.

BACKGROUND: This study investigates the role of CXXC5 in the self-renewal and differentiation of hematopoietic stem cells (HSCs) within the bone marrow microenvironment, utilizing advanced methodologies such as single-cell RNA sequencing (scRNA-seq), CRISPR-Cas9, and proteomic analysis. METHODS: We employed flow cytometry to isolate HSCs from bone marrow samples, followed by scRNA-seq analysis using the 10x Genomics platform to examine cell clustering and CXXC5 expression patterns. CRISPR-Cas9 and lentiviral vectors facilitated the knockout and overexpression of CXXC5 in HSCs. The impact on HSCs was assessed through qRT-PCR, Western blot, CCK-8, CFU, and LTC-IC assays, alongside flow cytometry to measure apoptosis and cell proportions. A mouse model was also used to evaluate the effects of CXXC5 manipulation on HSC engraftment and survival rates. RESULTS: Our findings highlight the diversity of cell clustering and the significant role of CXXC5 in HSC regulation. Knockout experiments showed reduced proliferation and accelerated differentiation, whereas overexpression led to enhanced proliferation and delayed differentiation. Proteomic analysis identified key biological processes influenced by CXXC5, including cell proliferation, differentiation, and apoptosis. In vivo results demonstrated that CXXC5 silencing impaired HSC engraftment in a bone marrow transplantation model. CONCLUSION: CXXC5 is crucial for the regulation of HSC self-renewal and differentiation in the bone marrow microenvironment. Its manipulation presents a novel approach for enhancing HSC function and provides a potential therapeutic target for hematological diseases.