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.

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.

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.

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.

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.

Accelerating 3D genomics data analysis with Microcket.

The three-dimensional (3D) organization of genome is fundamental to cell biology. To explore 3D genome, emerging high-throughput approaches have produced billions of sequencing reads, which is challenging and time-consuming to analyze. Here we present Microcket, a package for mapping and extracting interacting pairs from 3D genomics data, including Hi-C, Micro-C, and derivant protocols. Microcket utilizes a unique read-stitch strategy that takes advantage of the long read cycles in modern DNA sequencers; benchmark evaluations reveal that Microcket runs much faster than the current tools along with improved mapping efficiency, and thus shows high potential in accelerating and enhancing the biological investigations into 3D genome. Microcket is freely available at https://github.com/hellosunking/Microcket .

Functionalizing tetrahedral framework nucleic acids-based nanostructures for tumor in situ imaging and treatment.

Timely in situ imaging and effective treatment are efficient strategies in improving the therapeutic effect and survival rate of tumor patients. In recent years, there has been rapid progress in the development of DNA nanomaterials for tumor in situ imaging and treatment, due to their unsurpassed structural stability, excellent material editability, excellent biocompatibility and individual endocytic pathway. Tetrahedral framework nucleic acids (tFNAs), are a typical example of DNA nanostructures demonstrating superior stability, biocompatibility, cell-entry performance, and flexible drug-loading ability. tFNAs have been shown to be effective in achieving timely tumor in situ imaging and precise treatment. Therefore, the progress in the fabrication, characterization, modification and cellular internalization pathway of tFNAs-based functional systems and their potential in tumor in situ imaging and treatment applications were systematically reviewed in this article. In addition, challenges and future prospects of tFNAs in tumor in situ imaging and treatment as well as potential clinical applications were discussed.

ShuYu capsule alleviates emotional and physical symptoms of premenstrual dysphoric disorder: Impact on ALLO decline and GABAA receptor δ subunit in the PAG area.

Premenstrual dysphoric disorder (PMDD) is a severe subtype of premenstrual syndrome in women of reproductive age, with its pathogenesis linked to the heightened sensitivity of type A γ -aminobutyric acid receptors (GABAAR) to neuroactive steroid hormone changes, particularly allopregnanolone (ALLO). While a low dose of fluoxetine, a classic selective serotonin reuptake inhibitor, is commonly used as a first-line drug to alleviate emotional disorders in PMDD in clinical settings, its mechanism of action is related to ALLO-GABAA receptor function. However, treating PMDD requires attention to both emotional and physical symptoms, such as pain sensitivity. This study aims to investigate the efficacy of ShuYu capsules, a traditional Chinese medicine, in simultaneously treating emotional and physical symptoms in a rat model of PMDD. Specifically, our focus centres on the midbrain periaqueductal grey (PAG), a region associated with emotion regulation and susceptibility to hyperalgesia. Considering the underlying mechanisms of ALLO-GABAA receptor function in the PAG region, we conducted a series of experiments to evaluate and define the effects of ShuYu capsules and uncover the relationship between the drug's efficacy and ALLO concentration fluctuations on GABAA receptor function in the PAG region. Our findings demonstrate that ShuYu capsules significantly improved oestrous cycle-dependant depression-like behaviour and reduced stress-induced hyperalgesia in rats with PMDD. Similar to the low dose of fluoxetine, ShuYu capsules targeted and mitigated the sharp decline in ALLO, rescued the upregulation of GABAAR subunit function, and activated PAG neurons in PMDD rats. The observed effects of ShuYu capsules suggest a central mechanism underlying PMDD symptoms, involving ALLO_GABAA receptor function in the PAG region. This study highlights the potential of traditional Chinese medicine in addressing both emotional and physical symptoms associated with PMDD, shedding light on novel therapeutic approaches for this condition.

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.

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.

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.

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.

Self-Distillation for Randomized Neural Networks.

Knowledge distillation (KD) is a conventional method in the field of deep learning that enables the transfer of dark knowledge from a teacher model to a student model, consequently improving the performance of the student model. In randomized neural networks, due to the simple topology of network architecture and the insignificant relationship between model performance and model size, KD is not able to improve model performance. In this work, we propose a self-distillation pipeline for randomized neural networks: the predictions of the network itself are regarded as the additional target, which are mixed with the weighted original target as a distillation target containing dark knowledge to supervise the training of the model. All the predictions during multi-generation self-distillation process can be integrated by a multi-teacher method. By induction, we have additionally arrived at the methods for infinite self-distillation (ISD) of randomized neural networks. We then provide relevant theoretical analysis about the self-distillation method for randomized neural networks. Furthermore, we demonstrated the effectiveness of the proposed method in practical applications on several benchmark datasets.

Online dynamic ensemble deep random vector functional link neural network for forecasting.

This paper proposes a three-stage online deep learning model for time series based on the ensemble deep random vector functional link (edRVFL). The edRVFL stacks multiple randomized layers to enhance the single-layer RVFL's representation ability. Each hidden layer's representation is utilized for training an output layer, and the ensemble of all output layers forms the edRVFL's output. However, the original edRVFL is not designed for online learning, and the randomized nature of the features is harmful to extracting meaningful temporal features. In order to address the limitations and extend the edRVFL to an online learning mode, this paper proposes a dynamic edRVFL consisting of three online components, the online decomposition, the online training, and the online dynamic ensemble. First, an online decomposition is utilized as a feature engineering block for the edRVFL. Then, an online learning algorithm is designed to learn the edRVFL. Finally, an online dynamic ensemble method, which can measure the change in the distribution, is proposed for aggregating all layers' outputs. This paper evaluates and compares the proposed model with state-of-the-art methods on sixteen time series.

The dosage of curcumin to alleviate movement symptoms in a 6-hydroxydopamine-induced Parkinson's disease rat model.

Background: Curcumin is a natural compound with extensive pharmacological effects. This research is to verify the optimal dose and administration duration efficacy of curcumin in alleviating the movement symptoms of Parkinson's disease (PD). Methods: Wistar rats were divided into six groups including control, model, levodopa treatment and low/middle/high (40/80/160 mg/kg/d) curcumin treatment groups. After stereotactic brain injection of 6-hydroxydopamine (6-OHDA), curcumin was given by intragastric administration for 2 weeks. To evaluate the drug effect, the rats received behavioral tests including apomorphine (APO)-induced rotation test, rotarod test and open field test. Then the rats were sacrificed and the brain slices including substantia nigra pars compacta (SNc) were used for immunofluorescence staining. Results: After 6-OHDA injection, the model group showed typical movement symptoms including the severe APO-induced rotation to the healthy side, decreased latency in the rotarod with constant or accelerative mode, and decreased total distance and average speed in the open field test. In the results of immunofluorescence staining, the 6-OHDA induced a severe damage of dopaminergic neurons in SNc. The 160 mg/kg/d treatment of curcumin to intervene for 2 weeks alleviated most of the behavioral disorders but the 40/80 mg/kg/d treatment showed limitations. Then, we compared the effect of 1 week intervention to the 2 weeks with 160 mg/kg/d treatment of curcumin to intervene and results indicated that the treatment of 2 weeks could better alleviate the symptoms. Conclusions: Curcumin alleviated 6-OHDA-induced movement symptoms in a PD rat model. Additionally, the effect of curcumin against PD indicated dose and duration dependent and the intervention of 160 mg/kg/d for 2 weeks showed optimally therapeutic effect.

Enhancer RNAs in transcriptional regulation: recent insights.

Enhancers are a class of cis-regulatory elements in the genome that instruct the spatiotemporal transcriptional program. Last decade has witnessed an exploration of non-coding transcripts pervasively transcribed from active enhancers in diverse contexts, referred to as enhancer RNAs (eRNAs). Emerging evidence unequivocally suggests eRNAs are an important layer in transcriptional regulation. In this mini-review, we summarize the well-established regulatory models for eRNA actions and highlight the recent insights into the structure and chemical modifications of eRNAs underlying their functions. We also explore the potential roles of eRNAs in transcriptional condensates.

Curcumin (CUMINUP60®) mitigates exercise fatigue through regulating PI3K/Akt/AMPK/mTOR pathway in mice.

Curcumin is a chemical constituent extracted from Curcuma longa L. Several clinical and preclinical studies have demonstrated that it can mitigate exercise fatigue, but the exact mechanism is still unknown. Therefore, we applied a mouse model of exercise fatigue to investigate the possible molecular mechanisms of curcumin's anti-fatigue effect. Depending on body mass, Kunming mice were randomly divided into control, caffeine (positive drug), and curcumin groups, and were given 28 days intragastric administration. Both the caffeine group and curcumin group showed significant improvement in exercise fatigue compared to the control group, as evidenced by the increase in time to exhaustion, as well as the higher quadriceps coefficient, muscle glycogen (MG) content, and increase in the expression of Akt, AMPK, PI3K, and mTOR proteins. While the curcumin group also significantly improved the exercise fatigue of the mice, demonstrating a lower AMP/ATP ratio and lactic acid (LA) content, and increased glycogen synthase (GS), and myonectin content compared to the caffeine group. Therefore, in the present study, we found that curcumin can exert a similar anti-fatigue effect to caffeine and may act by regulating energy metabolism through modulating the expression of the proteins in the PI3K/Akt/AMPK/mTOR pathway.